Human Synovial Mesenchymal Stem Cells Expressed Immunoregulatory Factors IDO and TSG6 in a Context of Arthritis Mediated by Alphaviruses.

Infection by arthritogenic alphaviruses (aavs) can lead to reactive arthritis, which is characterized by inflammation and persistence of the virus; however, its mechanisms remain ill-characterized. Intriguingly, it has been shown that viral persistence still takes place in spite of robust innate and adaptive immune responses, characterized notably by the infiltration of macrophages (sources of TNF-alpha) as well as T/NK cells (sources of IFN-gamma) in the infected joint. Aavs are known to target mesenchymal stem cells (MSCs) in the synovium, and we herein tested the hypothesis that the infection of MSCs may promote the expression of immunoregulators to skew the anti-viral cellular immune responses. We compared the regulated expression via human synovial MSCs of pro-inflammatory mediators (e.g., IL-1ß, IL6, CCL2, miR-221-3p) to that of immunoregulators (e.g., IDO, TSG6, GAS6, miR146a-5p). We used human synovial tissue-derived MSCs which were infected with O'Nyong-Nyong alphavirus (ONNV, class II aav) alone, or combined with recombinant human TNF-α or IFN-γ, to mimic the clinical settings. We confirmed via qPCR and immunofluorescence that ONNV infected human synovial tissue-derived MSCs. Interestingly, ONNV alone did not regulate the expression of pro-inflammatory mediators. In contrast, IDO, TSG6, and GAS6 mRNA expression were increased in response to ONNV infection alone, but particularly when combined with both recombinant cytokines. ONNV infection equally decreased miR-146a-5p and miR-221-3p in the untreated cells and abrogated the stimulatory activity of the recombinant TNF-α but not the IFN-gamma. Our study argues for a major immunoregulatory phenotype of MSCs infected with ONNV which may favor virus persistence in the inflamed joint.

Inflammatory Mesenchymal Stem Cells Express Abundant Membrane-Bound and Soluble Forms of C-Type Lectin-like CD248.

CD248 (endosialin) belongs to a glycoprotein family that also includes thrombomodulin (CD141), CLEC14A, and CD93 (AA4) stem cell markers. We analyzed the regulated expression of CD248 in vitro using skin (HFFF) and synovial (FLS) mesenchymal stem cell lines, and in fluid and tissue samples of rheumatoid arthritis (RA) and osteoarthritis (OA) patients. Cells were incubated with either rhVEGF165, bFGF, TGF-ß1, IL1-ß, TNF-α, TGFß1, IFN-γ, or PMA (Phorbol ester). There was no statistically significant change in membrane expression. A soluble (s) form of cleaved CD248 (sCD248) was detected after cell treatment with IL1-ß and PMA. Matrix metalloprotease (MMP) MMP-1 and MMP-3 mRNAs were significantly up-regulated by IL1-ß and PMA. A broad MMP inhibitor blocked the release of soluble CD248. In RA synovial tissue, we identified CD90+ perivascular MSCs double-stained for CD248 and VEGF. High sCD248 levels were detected in synovial fluid from RA. In culture, subpopulations of CD90+ CD14- RA MSCs were either identified as CD248+ or CD141+ cells but CD93-. CD248 is abundantly expressed by inflammatory MSCs and shed in an MMP-dependent manner in response to cytokines and pro-angiogenic growth factors. Both membrane-bound and soluble CD248 (acting as a decoy receptor) may contribute to RA pathogenesis.

Gonococcal arthritis: case series of 58 hospital cases.

OBJECTIVES: Extra-genital manifestations of gonococcal infection are rare (0.5-3%). Among them, gonococcal arthritis (GA) is the most frequent, accounting for 30-90% of disseminated infections. Our study aimed to describe all hospital cases of GA in Reunion Island, a French overseas territory. METHODS: We conducted a retrospective, multicentric, observational study of all cases of certain, probable or possible GA from 2008 to 2020. RESULTS: We identified 58 cases of GA, mostly certain cases (n = 48). Sex ratio was balanced, but men were older than women (51 vs 27 years, p < 0.001). A total of 41% had travelled abroad during the previous 3 months, mostly in Madagascar or South-East Asia. The most frequently infected joint was the knee, followed by ankle, wrist and fingers or carpal joints. Only 16% of cases had genital symptoms, but 50% had another extra-genital manifestation, mainly skin lesions (40%). Positivity rate of joint puncture was 91%, with a purulent liquid. Only 58% had a positive culture, and 33% had only a positive PCR. There was no 3GC-resistant strain. In comparison with gonococcal infection without arthritis, patients were older and had fewer genital but more extra-genital symptoms. On discharge 60% had persistent articular symptoms. GA represented 18% of all hospitalised septic arthritis cases with microbial identification in 2019. CONCLUSIONS: GA is rare but it is important to make an early diagnosis and treat promptly, as joint destruction may be important, leading to persistent symptoms after discharge. PCR use in joint puncture is useful in cases with negative culture.

Flexor digitorum profundus tendon injuries in Zone 2 repaired with a modified Mantero technique.

From January 2010 to January 2017, 81 complete flexor digitorum profundus tendon disruptions in Zones 2B and 2C were treated using the modified Mantero technique. The patients were re-examined at a mean of 62 months (range 30-96) after operation. We analysed outcomes against ages, gender, pulley integrity, associated injuries and follow-up times. The median total range of motion of both interphalangeal joints, distal interphalangeal joint alone and Quick DASH scores were significantly better for the group with pulley vented versus no pulley vented. According to the Strickland and Glogovac criteria, 76 (91%) had excellent or good, five fair and none had poor results. There were no complications except for one deep and one superficial infection at the site of the injury. There were no tendon ruptures and only three patients (3.7%) required secondary tenolysis. The modified Mantero repair is recommended as an alternative in the repair of tendon disruptions in Zone 2B and 2C. The good results and absence of ruptures suggest that the tendon healing and strength of repair are adequate for immediate postoperative motion.Level of evidence: IV.

Epigenetic Regulation (Including Micro-RNAs, DNA Methylation and Histone Modifications) of Rheumatoid Arthritis: A Systematic Review.

The inflammatory reaction in rheumatoid arthritis (RA) is controlled by major epigenetic modifications that modulate the phenotype of synovial and immune cells. The aim of this work was to perform a systematic review focusing on miR expression, DNA methylation and histone modifications in RA. We demonstrated that, in human samples, the expressions of miR-155, miR-146a and miR-150 were significantly decreased while the expression of miR-410-3p was significantly increased in the RA group. Moreover, miR-146a significantly decreased pro-autoimmune IL-17 cytokine expression in RA. In a murine model, miR-34a inhibition can ameliorate the arthritis score. However, this evidence remain critically insufficient to support current therapeutic applications in RA patients.

Visceral adiposity in patients with psoriatic arthritis and psoriasis alone and its relationship with metabolic and cardiovascular risk.

BACKGROUND: Fat mass distribution, especially in the abdominal visceral region, has been rarely evaluated in patients with PsA or psoriasis (PsO). METHODS: Patients with PsA and patients with PsO alone were evaluated and compared with control subjects (1:1 ratio in each patient group) matched for age, sex and BMI category. Body composition and fat distribution (android and visceral fat) were evaluated by DXA. Anthropometric measurements, disease activity and the systematic coronary risk evaluation (SCORE) cardiovascular risk were assessed. Metabolic parameters (insulin, homeostasis model assessment for insulin resistance), serum adipokines [total and high-molecular-weight adiponectin, leptin, resistin and retinol-binding protein-4 (RBP4)] were measured. RESULTS: Data for 52 patients with PsA and 52 patients with PsO and their respective paired controls were analysed. Android fat and visceral fat were found to be significantly higher in patients with PsO compared with their controls, while these measurements did not differ between patients with PsA and their controls. By multivariate analysis, after adjusting for age, sex and BMI, visceral fat was higher in PsO patients compared with PsA patients (P = 0.0004) and the whole group of controls (P = 0.0013). Insulin levels and HOMA-IR were increased in both PsA and PsO groups. High-molecular-weight/total adiponectin ratio was decreased in patients with PsO. RBP4 was significantly higher in both PsA and PsO patients. In patients with PsO, visceral fat strongly correlated with SCORE (r = 0.61). CONCLUSION: Visceral fat accumulates more in PsO alone than in PsA. Visceral adiposity may be a more pressing concern in PsO relative to PsA. TRIAL REGISTRATION: The ADIPSO study (Évaluation du tissu ADIpeux et des adipokines dans le PSOriasis et le rhumatisme psoriasique et analyse de ses relations avec le risque cardiovasculaire) is a case-control study conducted in Besançon, France, and is registered on ClinicalTrials.gov under the number NCT02849795.

Uveitis occurrence in early inflammatory back pain. Five years data from the prospective French nationwide DESIR cohort.

OBJECTIVE: Uveitis is a frequent extra rheumatological manifestation in axial Spondyloarthritis (SpA). The aim of study was to evaluate the prevalence and incidence of uveitis over the first five years of a prospective nationwide cohort of patients with high suspicion of early axial SpA, and to evaluate its associated factors. METHODS: DESIR is a prospective observational cohort of patients with recent onset inflammatory back pain (more than 3 months, less than 3 years), suggestive of axial SpA, All available factors in the database were compared between patients with and without uveitis at 5 years, by uni and then multivariate analysis. Baseline factors associated with new cases of uveitis occurrence over the 5 years were also analyzed. SIGNIFICANCE: P less than 0.05. RESULTS: After 5 years, 91 patients (out of 480 with complete follow-up) had at least one uveitis episode, giving an estimated prevalence of 18.9% [95% CI: 15.4-22.4]. In multivariate analysis, uveitis was significantly associated with dactylitis, and elevated ESR. New incident uveitis occurred in 31 cases over 5 years, giving an estimated incidence rate of 1.29 [0.84-1.74]/100 patient-years. Incidence of new uveitis was associated in multivariate analysis with baseline factors: diagnosis of SpA, sacro iliac MRI inflammatory SPARCC score, dactylitis, syndesmophyte score. No significant association was found with HLA-B27, DMARDs, BASDAI, ASDAS, BASFI. CONCLUSION: Five-years data of the DESIR cohort allowed an estimation of incidence rate of uveitis of 1.3/100p-y; over five years, uveitis was associated with dactylitis, biologic and sacro iliac MRI inflammation.

1H-NMR-Based Analysis for Exploring Knee Synovial Fluid Metabolite Changes after Local Cryotherapy in Knee Arthritis Patients.

Rehabilitation using cryotherapy has widely been used in inflammatory diseases to relieve pain and decrease the disease activity. The aim of this study was to explore the metabolite changes in inflammatory knee-joint synovial fluids following local cryotherapy treatment (ice or cold CO2). We used proton nuclear magnetic resonance (1H NMR) spectroscopy to assess the metabolite patterns in synovial fluid (SF) in patients with knee arthritis (n = 46) before (D0) and after (D1, 24 h later) two applications of local cryotherapy. Spectra from aqueous samples and organic extracts were obtained with an 11.75 Tesla spectrometer. The metabolite concentrations within the SF were compared between D1 and D0 using multiple comparisons with the application of a false discovery rate (FDR) adjusted at 10% for each metabolite. A total of 32 metabolites/chemical structures were identified including amino acids, organic acids, fatty acids or sugars. Pyruvate, alanine, citrate, threonine was significantly higher at D1 vs D0 (p < 0.05). Tyrosine concentration significantly decreases after cryotherapy application (p < 0.001). We did not observe any effect of gender and cooling technique on metabolite concentrations between D0 and D1 (p > 0.05). The present study provides new insight into a short-term effect of cold stimulus in synovial fluid from patients with knee arthritis. Our observations suggest that the increased level of metabolites involved in energy metabolism may explain the underlying molecular pathways that mediate the antioxidant and anti-inflammatory capacities of cryotherapy.

Emerging Roles of Perivascular Mesenchymal Stem Cells in Synovial Joint Inflammation.

In contrast to the significant advances in our understanding of the mesenchymal stem cell (MSC) populations in bone marrow (BM), little is known about the MSCs that are resident in the synovial joint and their possible roles in the tissue homeostasis, chronic inflammation as well as in repair. Neural crest is a transient embryonic structure, generating multipotential MSC capable of migrating along peripheral nerves and blood vessels to colonize most tissue types. In adult, these MSC can provide functional stromal support as a stem cell niche for lymphocyte progenitors for instance in the BM and the thymus. Critically, MSC have major immunoregulatory activities to control adverse inflammation and infection. These MSC will remain associated to vessels (perivascular (p) MSC) and their unique expression of markers such as myelin P0 and transcription factors (e.g. Gli1 and FoxD1) has been instrumental to develop transgenic mice to trace the fate of these cells in health and disease conditions. Intriguingly, recent investigations of chronic inflammatory diseases argue for an emerging role of pMSC in several pathological processes. In response to tissue injuries and with the release of host cell debris (e.g. alarmins), pMSC can detach from vessels and proliferate to give rise to either lipofibroblasts, osteoblasts involved in the ossification of arteries and myofibroblasts contributing to fibrosis. This review will discuss currently available data that suggest a role of pMSC in tissue homeostasis and pathogenesis of the synovial tissue and joints. Graphical abstract.

Deciphering SARS-CoV-2 Virologic and Immunologic Features.

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 and its associated pathology, COVID-19, have been of particular concerns these last months due to the worldwide burden they represent. The number of cases requiring intensive care being the critical point in this epidemic, a better understanding of the pathophysiology leading to these severe cases is urgently needed. Tissue lesions can be caused by the pathogen or can be driven by an overwhelmed immune response. Focusing on SARS-CoV-2, we and others have observed that this virus can trigger indeed an immune response that can be dysregulated in severe patients and leading to further injury to multiple organs. The purpose of the review is to bring to light the current knowledge about SARS-CoV-2 virologic and immunologic features. Thus, we address virus biology, life cycle, tropism for many organs and how ultimately it will affect several host biological and physiological functions, notably the immune response. Given that therapeutic avenues are now highly warranted, we also discuss the immunotherapies available to manage the infection and the clinical outcomes.

Chikungunya-Induced Arthritis in Reunion Island: A Long-Term Observational Follow-Up Study Showing Frequently Persistent Joint Symptoms, Some Cases of Persistent Chikungunya Immunoglobulin M Positivity, and No Anticyclic Citrullinated Peptide Seroconversion After 13 Years.

BACKGROUND: Reunion Island was struck by a massive Chikungunya outbreak in 2005-2006. Chikungunya infection is characterized by inflammatory joint symptoms, which may evolve into chronic arthritis. METHODS: In this long-term longitudinal observational monocentric study, after the 2005-2006 outbreak in Reunion Island, 159 patients were first referred to a rheumatologist for post-Chikungunya chronic musculoskeletal pain, 73 of them were diagnosed with classifiable Chikungunya-related chronic inflammatory rheumatic diseases (>3 month symptom duration from the initial viral infection). Thirty of these 73 patients were clinically evaluated by a second rheumatologist in 2018-2019. The main objective of this second examination was to estimate the proportion of patients with persistent Chikungunya-related inflammatory joint symptoms after 13 years. RESULTS: Inflammatory joint symptoms persisted in 17/30 patients after 13 years (therefore in at least 23.3% of the 73 patients initially diagnosed with Chikungunya-related inflammatory joint symptoms and 10.7% of the 159 patients referred for post-Chikungunya chronic musculoskeletal pain). In the symptom persistence subgroup, the prevalence of positive autoantibodies (antinuclear or ACPA) was significantly higher - without any seroconversion, Chikungunya IgG and IgM levels were higher, long-term IgM positivity and radiographic damage were more frequent. Overall, after 13 years, pain and fatigue levels remained significant, 5 patients were still treated by methotrexate, 3 by TNF-blockers, highlighting long-term Chikungunya-related patient burden. CONCLUSIONS: Such a long-term persistence of Chikungunya-related chronic inflammatory rheumatic diseases had not been reported so far. Furthermore, the long-term Chikungunya IgM positivity we observed in some cases might corroborate the hypothesis of residual viral antigen-driven chronic arthritis.

Age-Dependent Metabolic Profiles Unravel the Metabolic Relationships Within and Between Flax Leaves (Linum usitatissimum).

Flax for oil seed is a crop of increasing popularity, but its cultivation needs technical improvement. Important agronomic traits such as productivity and resistance to stresses are to be regarded as the result of the combined responses of individual organs and their inter-communication. Ultimately, these responses directly reflect the metabolic profile at the cellular level. Above ground, the complexity of the plant phenotype is governed by leaves at different developmental stages, and their ability to synthesise and exchange metabolites. In this study, the metabolic profile of differently-developed leaves was used firstly to discriminate flax leaf developmental stages, and secondly to analyse the allocation of the metabolites within and between leaves. For this purpose, the concentration of 52 metabolites, both primary and specialized, was followed by gas chromatography (GC-) and liquid chromatography coupled to mass spectrometry (LC-MS) in alternate pairs of flax leaves. On the basis of their metabolic content, three populations of leaves in different growth stages could be distinguished. Primary and specialized metabolites showed characteristic distribution patterns, and compounds similarly evolving with leaf age could be grouped by the aid of the Kohonen self-organising map (SOM) algorithm. Ultimately, visualisation of the correlations between metabolites via hierarchical cluster analysis (HCA) allowed the assessment of the metabolic fluxes characterising different leaf developmental stages, and the investigation of the relationships between primary and specialized metabolites.

Microwave-Assisted versus Conventional Isolation of Glucosinolate Degradation Products from Lunaria annua L. and Their Cytotoxic Activity.

Glucosinolates (GSLs) from Lunaria annua L. seeds were analyzed qualitatively and quantitatively by their desulfo counterparts using UHPLC-DAD-MS/MS technique and by their volatile breakdown products, isothiocyanates (ITCs), using GC-MS technique. GSL breakdown products were obtained by conventional techniques (hydrodistillation in a Clevenger type apparatus (HD), CH2Cl2 extraction after myrosinase hydrolysis (EXT) for 24 h) as well as by modern techniques, microwave-assisted distillation (MAD) and microwave hydrodiffusion and gravity (MHG). Seven GSLs were identified as follows: isopropyl GSL (1), sec-butyl GSL (2), 5-(methylsulfinyl)pentyl GSL (3), 6-(methylsulfinyl)hexyl GSL (4), 5-(methylsulfanyl)pentyl GSL (5), 6-(methylsulfanyl)hexyl GSL (6), and benzyl GSL (7). Additionally, pent-4-enyl- and hex-5-enyl ITCs were detected in the volatile extracts. However, their corresponding GSLs were not detected using UHPLC-DAD-MS/MS. Thus, they are suggested to be formed during GC-MS analysis via thermolysis of 5-(methylsulfinyl)pentyl- and 6-(methylsulfinyl)hexyl ITCs, respectively. Volatile isolates were tested for their cytotoxic activity using MTT assay. EXT and MHG showed the best cytotoxic activity against human lung cancer cell line A549 during an incubation time of 72 h (IC50 18.8, and 33.5 µg/mL, respectively), and against breast cancer cell line MDA-MB-231 after 48 h (IC50 6.0 and 11.8 µg/mL, respectively). These activities can be attributed to the ITCs originating from 3 and 4.

Effect of Gut Involvement in Patients with High Probability of Early Spondyloarthritis: Data from the DESIR Cohort.

OBJECTIVE: Inflammatory bowel disease (IBD) is a well-known extraarticular feature of spondyloarthritis (SpA). The aims of this study were to evaluate factors associated with IBD and incidence over 5 years of followup in the DESIR cohort. METHODS: DESIR is a prospective observational cohort of patients with recent-onset inflammatory back pain suggestive of axial SpA. All available variables in the database were compared between patients with and without IBD at baseline and 5 years, and occurrence over 5 years of followup, with uni- and then multivariable analysis. RESULTS: At baseline, of 708 patients, 35 had IBD (prevalence 4.94%, CI 95% 3.3-6.5). IBD was associated (multivariable) with history of uveitis, levels of Dickkopf-1, and tumor necrosis factor, but not with phenotypic presentation (peripheral arthritis, enthesitis, dactylitis, uveitis) or baseline serum levels of other cytokines. At 5 years, 480 patients were analyzed, 58 with IBD. IBD was associated (multivariable) with fulfillment of modified New York criteria, sick leave, Bath Ankylosing Spondylitis Disease Activity Index, and smoking. There was no association with magnetic resonance imaging scores, enthesitis, psoriasis, and bone mineral density. Twenty-three incident cases of IBD were recorded: estimated occurrence rate of 0.95/100 (95% CI 0.57-1.35) patient-years (PY). Incidence of IBD is associated (multivariable) with HLA-B27 (OR 0.36, 95% CI 0.22-0.59), fulfillment of modified New York criteria (OR 3.35, 95% CI 1.85-6.08), and familial history of IBD (OR 3.31, 95% CI 1.62-6.77). CONCLUSION: In early SpA, IBD occurs with an incidence of 1/100 PY, and is associated with poor outcome, familial history of IBD, absence of HLA-B27, and fulfillment of modified New York criteria.

Methotrexate an Old Drug with New Tricks.

Methotrexate (MTX) is the first line drug for the treatment of a number of rheumatic and non-rheumatic disorders. It is currently used as an anchor disease, modifying anti-rheumatic drug in the treatment of rheumatoid arthritis (RA). Despite the development of numerous new targeted therapies, MTX remains the backbone of RA therapy due to its potent efficacy and tolerability. There has been also a growing interest in the use of MTX in the treatment of chronic viral mediated arthritis. Many viruses-including old world alphaviruses, Parvovirus B19, hepatitis B/C virus, and human immunodeficiency virus-have been associated with arthritogenic diseases and reminiscent of RA. MTX may provide benefits although with the potential risk of attenuating patients' immune surveillance capacities. In this review, we describe the emerging mechanisms of action of MTX as an anti-inflammatory drug and complementing its well-established immunomodulatory activity. The mechanisms involve adenosine signaling modulation, alteration of cytokine networks, generation of reactive oxygen species and HMGB1 alarmin suppression. We also provide a comprehensive understanding of the mechanisms of MTX toxic effects. Lastly, we discussed the efficacy, as well as the safety, of MTX used in the management of viral-related rheumatic syndromes.

Value of serum procalcitonin for the diagnosis of bacterial septic arthritis in daily practice in rheumatology.

INTRODUCTION/OBJECTIVES: Septic arthritis is a diagnostic and therapeutic emergency because of a high morbidity and mortality. Nevertheless, the etiologic diagnosis is often difficult. The aim of our study was to determine if serum procalcitonin was a discriminatory biomarker in case of arthritis of undetermined etiology. METHOD: Patients were separated in five groups: gouty arthritis, calcium pyrophosphate deposition arthritis, osteoarthritis or post-traumatic arthritis ("mechanical" arthritis), chronic inflammatory rheumatic arthritis, and septic arthritis. Levels of serum white blood cells, C-reactive protein and procalcitonin were measured. RESULTS: Ninety-eight patients were included: 18 in the "gout" group, 26 in the "calcium pyrophosphate deposition arthritis" group, 16 in the mechanical group, 18 in the "chronic inflammatory rheumatic" group, and 20 in the "sepsis" group. The area under the receiver operating characteristic curve of white blood cells, C-reactive protein, and procalcitonin levels to diagnose a septic arthritis were 0.69 (IC95% 0.55-0.83), 0.82 (IC95% 0.73-0.91), and 0.87 (IC95% 0.76-0.98) respectively. For a cutoff of 0.5 ng/ml, procalcitonin sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio and negative likelihood ratio were 65%, 91%, 65%, 91%, 7.2, and 0.4, respectively. Serum C-reactive protein and procalcitonin levels were correlated, were not different in sepsis or gout groups, and were higher in non-septic arthritis with poly-arthritis than with mono-arthritis (p < 0.05). CONCLUSIONS: Serum procalcitonin is a useful biomarker in arthritis management with diagnosis performances higher than those of other biomarkers (white blood cells, C-reactive protein).Key Points• Diagnostic performances of serum procalcitonin level in septic arthritis are higher than those of serum C-reactive protein or white blood cells levels.• Serum procalcitonin levels are not different in septic arthritis or gouty arthritis.• Serum procalcitonin levels are higher in non-septic arthritis with poly-arthritis than with mono-arthritis.

Vascular involvement in axial spondyloarthropathies.

Ankylosing spondylitis (AS) is a chronic inflammatory joint disease that involves the entheses, causing inflammatory pain and functional impairments. Patients may experience extraarticular manifestations such as uveitis, psoriasis, and inflammatory bowel disease. These, together with the increased risk of cardiovascular disease and osteoporosis and the development of spinal fusion, are the main determinants of adverse disease outcomes. As with many systemic inflammatory diseases, AS is associated with excess cardiovascular mortality due to increased risks of myocardial infarction, stroke, and venous thromboembolism. Studies of markers for subclinical atheroma (endothelial dysfunction, arterial stiffness, and intima-media thickness) have shown earlier onset of arterial disease compared to healthy controls, with the difference being greatest for patients with active AS. The potential vascular effects of drugs used to treat AS have not been established. Few studies have focused on nonsteroidal antiinflammatory drugs and biologics in patients with AS, and their results do not conclusively establish a beneficial or deleterious effect in axial spondyloarthritis. Statins have been found to improve endothelial dysfunction and to decrease mortality. The latest EULAR recommendations on cardiovascular risk management in patients with inflammatory joint disease indicate that statins should be used in compliance with national guidelines.

Aerobic exercise for axial spondyloarthritis - its effects on disease activity and function as compared to standard physiotherapy: A systematic review and meta-analysis.

AIM: To evaluate the impact of an aerobic fitness program on disease activity, defined by the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and on C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) and the Bath Ankylosing Spondylitis Functional Index (BASFI) in case of axial spondyloarthritis. METHODS: A systematic review of the literature, following the Prisma recommendations, was performed by two reviewers on the PubMed and Embase databases. Controlled trials assessing the efficacy of aerobic exercises compared to physiotherapy on axial spondyloarthritis disease activity were included. The diagnosis of axial spondyloarthritis was meeting the New York criteria and/or the Assessment in Axial Spondyloarthritis International Working Group criteria. Aerobic fitness was defined as an exercise performed at 50%-90% of the maximal heart rate or between 50% and 80% oxygen consumption (VO2 ) peak. RESULTS: Five hundred and twenty abstracts were identified and 93 abstracts were analyzed. Eight studies met the selection criteria and 6 were finally included in this study because of the presence of a control group. Both groups were similar in terms of age, sex ratio, disease duration. Aerobic exercise provided a positive impact on the BASDAI in the intervention group (148 patients) (weighted mean difference [WMD]: -0.52 [95% CI: -0.9 to -0.13]) (I2 : 10.3%, P = 0.35). However, when compared to a control group (152 patients), the improvement of BASDAI didn't reach significance (WMD: -0.25 [95% CI: -0.83 to 0.32]) (I2 : 0%, P = 0.41). Aerobic exercise did not improve BASFI, CRP or ESR. CONCLUSION: Aerobic exercise did not provide beneficial effects either on disease activity or on physical function and biological parameters when compared to a control group in axial spondyloarthritis.