An experimental model of western diet in female Wistar rats leads to cardiac hypoxia related to a stimulated contractility.

Previous studies in Western diet (WD)-fed male rats have highlighted a link between the stimulation of cardiac contractility, mitochondrial adaptations and a pro-inflammatory fatty acid profile of phospholipids in the heart. Our objectives were to determine (1) if WD-fed female Wistar rats and obese humans display a similar pro-inflammatory profile in their cardiac phospholipids and (2) if this lipid profile is associated with deleterious effects on the heart of the female rodents. Female Wistar rats were fed WD for 5 weeks or a laboratory chow as a control. Ionic homeostasis, redox status, inflammation markers, and fatty acid composition of phospholipids were analysed in the heart. WD increased the abdominal fat mass without modifying the body weight of female rats. As previously found in males, a WD induced a shift in membrane fatty acid composition toward a pro-inflammatory profile in the female rats, but not in obese humans. It was associated with an increased COX2 expression suggesting an increased pro-inflammatory eicosanoid production. Signs of increased intracellular calcium strongly supported a stimulation of cardiac contractility without any induction of apoptosis. The heart of WD-fed rats exhibited a hypoxic state as a higher HIF1-α expression was reported. The expressions of antioxidant enzymes were increased, but the redox reserves against reactive oxygen species were lowered. In conclusion, as previously observed in males, we suppose that cardiac abnormalities are magnified with severe obesity in female rats, leading to hypoxia and intense oxidative stress which could ultimately induce cell death and heart failure.

Sensitivity to change of structural outcomes in axial spondyloarthritis after 10 years of follow up. Data from the DESIR cohort.

OBJECTIVE: To evaluate the sensitivity to change in structural imaging outcomes over 10 years of follow-up in patients with axial spondyloarthritis (axSpA). METHODS: Patients with axSpA from the Devenir des Spondyloarthropathies Indifferénciées Récentes cohort were included. Radiographs and MRIs of the sacroiliac joints (SIJ) and spine were obtained at baseline and at 1, 2, 5 and 10 years. The yearly rate of change of each structural outcome was analysed using generalised estimating equation models, including all patients with ≥1 score from ≥1 reader from ≥1 reading wave, using the time (years) as an explanatory variable and adjusting for reader and wave. All outcomes were standardised, and the relative standardised rate of change was calculated (ie, the standardised rate of an outcome divided by the rate of a reference outcome). RESULTS: A total of 659 patients (46% males and mean age 33.6 years) were included. The most sensitive outcome to change in the SIJ (both MRI and radiographs) was the presence of ≥3 fatty lesions at a specific timepoint, with a relative standardised rate of change per year of 5.28 using the modified New York criteria as reference.Similarly, the most sensitive to change (in both MRI and radiographs) outcome in the spine was the modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS; relative standardised yearly change 1.76) using ≥1 syndesmophyte as reference. CONCLUSION: MRI structural outcomes in the SIJ (ie, fatty lesions) are more sensitive to change than radiographic outcomes. Conversely, the mSASSS remains the most sensitive method, even when compared with MRI of the spine.

Impact of the time of initiation and line of biologic therapy on the retention rate of secukinumab in axial spondyloarthritis (axSpA): data from the French multicentre retrospective FORSYA study.

OBJECTIVE: To compare the 1-year retention rate of secukinumab in axial spondyloarthritis (axSpA) and its predisposing factors with regard to its time of initiation (eg, right after or remotely from its launch). METHODS: Study design: Retrospective multicentre French study of patients with axSpA. Study periods: Two cohorts were evaluated regarding the time of initiation of secukinumab: cohort 1 (C1)-between 16 August 2016 and 31 August 2018-and cohort 2 (C2)-between 1 September 2018 and 13 November 2020. STATISTICAL ANALYSIS: The 1-year retention rate of secukinumab was estimated using the Kaplan-Meier method, and the log-rank test was used to compare the retention curves of the two cohorts. Preselected factors (eg, disease characterristics, line and time of secukinumab initiation) of secukinumab retention at 1 year were analysed by univariate and multivariate Cox model regression. RESULTS: In total, 906 patients in C1 and 758 in C2 from 50 centres were included in the analysis. The 1-year retention rate was better in C2 (64% (61%-68%)) vs C1 (59% (55%-62%)) (HR=1.19 (1.02-1.39); p=0.0297). In the multivariate analysis, the line of biologic therapy was the single predictive factor of the 1-year retention rate of secukinumab picked up in both cohorts, with a better retention rate when prescribed as first-line biologic therapy. CONCLUSION: The better secukinumab retention rate remotely from its launch is explained by its use at an earlier stage of the disease, suggesting a change in the behaviour of prescribing physicians. Our results emphasise the relevance of iterative evaluations of routine care treatments.

Effect of Argentine tango sessions on total physical activity time in patients with chronic inflammatory rheumatism: randomized, controlled, pilot study.

OBJECTIVE: The aim of this study was to evaluate the effect of an Argentine Tango (AT) program on total physical activity (PA) time in patients with rheumatoid arthritis (RA) and spondyloarthritis (SpA). METHODS: Prospective randomized controlled pilot study with two parallel groups. Participants were randomized 1:1 to attend a 24-week AT program from baseline to month 6 for the immediate tango group (ITG) and a 12-week AT program from month 3 to month 6 for the wait-list control group (WLCG). Total PA time was measured at baseline, month 3, and month 6 using the Global Physical Activity Questionnaire-ONAPS and an accelerometer. RESULTS: Twenty-seven participants (15 RA and 12 SpA) were enrolled in the study. Thirteen participants in the WLCG and 14 in the ITG. At month 3, there was no significant difference in the total PA time between the two groups. Longitudinal analyses revealed no significant difference between the two groups regarding PA, sedentary, fatigue, anxiety, depression, balance, physical performance, pain, and stress. However, body appreciation improved significantly in the ITG compared with the WLCG. Both groups showed improved physical abilities at 6 month, including improvements in the 6-min walk test and timed up and go test. The ITG also reported reduced pain at months 3 and 6, while the WLCG exhibited improved balance at month 6. CONCLUSION: Although the AT program did not significantly increase total PA time in patients with CIR, it positively impacted body appreciation and physical abilities suggesting its potential as a complementary therapy. Key Points • Body appreciation significantly improved after a 24-week AT program, emphasizing the positive impact of dance on self-perception. • Both groups exhibited improved physical abilities at month 6, indicating a positive influence on participants' overall mobility and functional capacity. • The 24-week AT group reported reduced pain at months 3 and 6, and the 12-week AT group exhibited improved balance at month 6.

Frequency of irritable bowel syndrome in spondyloarthritis: a multicentric cross-sectional study and meta-analysis.

OBJECTIVE: To evaluate the prevalence of symptoms and factors associated with irritable bowel syndrome (IBS) in axial spondyloarthritis (ax-SpA). METHODS: In a cross-sectional multicentric study, consecutive patients with ax-SpA treated with biologics in five rheumatology departments were asked for IBS Rome IV criteria. Demographic data, lifestyle behaviours and disease characteristics were recorded. Second, a systematic literature review and meta-analysis were performed following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. RESULTS: Of the 500 patients with ax-SpA included, 124 reported IBS symptoms (25%). Female gender, unemployment, higher Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and worse Bath Ankylosing Spondylitis Functional Index scores, multiple lines of biologics, fibromyalgia, anxiety, depression and lower physical activity were associated with IBS symptoms. In multivariate model, the risk of IBS was associated with anxiety and physical inactivity. From the literature review, the prevalence of IBS in patients with SpA was 15.4% (8.8% to 23.3%). Meta-analysis of the five studies comparing the presence of IBS in patients with SpA (323/7292) and healthy controls (484/35587) showed a significant increase of IBS in patients with SpA (OR=1.59 (1.05 to 2.40)). CONCLUSION: The prevalence of IBS symptoms was high in the ax-SpA population and should therefore be considered in the presence of gastrointestinal disorders. The presence of IBS symptoms was associated with anxiety and low physical activity in multivariate analysis. Patients with IBS symptoms tended to have more difficult to manage disease characterised by higher activity, worse functional score and multiple lines of treatment in univariate analysis.

Standardized reporting for systematic global evaluation of axial spondyloarthritis: An evidence-based and consensus-driven initiative.

INTRODUCTION: National and international scientific societies advocate for a regular, systematic, and standardized global evaluation of axial spondyloarthritis (axSpA) patients. However, there are no recommendations specifying the content of this global evaluation. This initiative aimed to propose a standardized reporting framework, using evidence-based and consensus approaches, to collect data on all domains of axSpA. METHODS: A literature review and consensus process involved a steering committee and an expert panel of 37 rheumatologists and health professionals. The first steering committee took place in March 2022 and identified the main domains for inclusion in the standardized report. A hierarchical literature review was conducted to identify items within these domains and tools for assessment. The items and tools for assessment were discussed and consensus was reached through a vote session during an expert meeting that took place in March 2023. RESULTS: The steering committee identified four main domains to include in the standardized reporting framework: disease assessment, comorbidities, lifestyle, and quality of life. Items and tools for assessment were adopted after the expert meeting. Additionally, recommendations regarding digital tools (websites, apps, social media) were provided. CONCLUSION: This initiative led to a consensus, based on evidence and expertise, on a reporting framework for use during periodic systematic global evaluations of axSpa in daily practice.

Unmet needs in axial spondyloarthritis. Proceedings of the French spondyloarthritis taskforce workshop.

The progress observed over the last 30 years in the field of axial spondyloarthritis (axSpA) has not made it possible to answer all the current questions. This manuscript represents the proceedings of the meeting of the French spondyloArthitiS Task force (FAST) in Besançon on September 28 and 29, 2023. Different points of discussion were thus individualized as unmet needs: biomarkers for early diagnosis and disease activity, a common electronic file dedicated to SpA nationwide, a better comprehension of dysbiosis in the disease, a check-list for addressing to the rheumatologist, adapt patient reported outcomes thresholds for female gender, implementation of comorbidities screening programs, new imaging tools, in research cellular and multi omics approaches, grouping, at a nationwide level, different cohorts and registries, therapeutic strategy studies, consensual definition of difficult to treat disease and management, preclinical stage of the disease, mastering AI as a tool in the various aspects of research. These elements may represent a framework for the research agenda in axSpA for the years to come.

Recommendations of the French Society of Rheumatology for the management in current practice of patients with polymyalgia rheumatica.

OBJECTIVE: To develop recommendations for the routine management of patients with polymyalgia rheumatica (PMR). METHODS: Following standard procedures, a systematic review of the literature by five supervised junior rheumatologists, based on the questions selected by the steering committee (5 senior rheumatologists), was used as the basis for working meetings, followed by a one-day plenary meeting with the working group (15 members), leading to the development of the wording and determination of the strength of the recommendations and the level of agreement of the experts. RESULTS: Five general principles and 19 recommendations were drawn up. Three recommendations relate to diagnosis and the use of imaging, and five to the assessment of the disease, its activity and comorbidities. Non-pharmacological therapies are the subject of one recommendation. Three recommendations concern initial treatment based on general corticosteroid therapy, five concern the reduction of corticosteroid therapy and follow-up, and two concern corticosteroid dependence and steroid-sparing treatments (anti-IL-6). CONCLUSION: These recommendations take account of current data on PMR, with the aim of reducing exposure to corticosteroid therapy and its side effects in a fragile population. They are intended to be practical, to help practitioners in the day-to-day management of patients with PMR.

Diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease: Data from the French Tw-IRD registry.

OBJECTIVES: Tropheryma whipplei infection can manifest as inflammatory joint symptoms, which can lead to misdiagnosis of inflammatory rheumatic disease and the use of disease-modifying antirheumatic drugs. We investigated the impact of diagnosis and treatment of Tropheryma whipplei infection in patients with inflammatory rheumatic disease. METHODS: We initiated a registry including patients with disease-modifying antirheumatic drugs-treated inflammatory rheumatic disease who were subsequently diagnosed with Tropheryma whipplei infection. We collected clinical, biological, treatment data of the inflammatory rheumatic disease, of Tropheryma whipplei infection, and impact of antibiotics on the evolution of inflammatory rheumatic disease. RESULTS: Among 73 inflammatory rheumatic disease patients, disease-modifying antirheumatic drugs initiation triggered extra-articular manifestations in 27% and resulted in stabilisation (51%), worsening (34%), or improvement (15%) of inflammatory rheumatic disease. At the diagnosis of Tropheryma whipplei infection, all patients had rheumatological symptoms (mean age 58 years, median inflammatory rheumatic disease duration 79 months), 84% had extra-rheumatological manifestations, 93% had elevated C-reactive protein, and 86% had hypoalbuminemia. Treatment of Tropheryma whipplei infection consisted mainly of doxycycline plus hydroxychloroquine, leading to remission of Tropheryma whipplei infection in 79% of cases. Antibiotic treatment of Tropheryma whipplei infection was associated with remission of inflammatory rheumatic disease in 93% of cases and enabled disease-modifying antirheumatic drugs and glucocorticoid discontinuation in most cases. CONCLUSIONS: Tropheryma whipplei infection should be considered in inflammatory rheumatic disease patients with extra-articular manifestations, elevated C-reactive protein, and/or hypoalbuminemia before disease-modifying antirheumatic drugs initiation or in inflammatory rheumatic disease patients with an inadequate response to one or more disease-modifying antirheumatic drugs. Positive results of screening and diagnostic tests for Tropheryma whipplei infection involve antibiotic treatment, which is associated with complete recovery of Tropheryma whipplei infection and rapid remission of inflammatory rheumatic disease, allowing disease-modifying antirheumatic drugs and glucocorticoid discontinuation.

Espondilodiscitis infecciosa primaria en 51 pacientes mayores de 75 años: estudio comparativo / Primary infectious spondylodiscitis in 51 patients over 75 years old: A comparative study

Antecedentes y objetivo: Se ha demostrado que la incidencia de la espondilodiscitis infecciosa se incrementa con la edad; sin embargo, esto no ha sido investigado ampliamente en los mayores. Material y métodos: Estudio retrospectivo, en un único centro, que incluyó a los pacientes hospitalizados en nuestro Departamento de Reumatología debido a espondilodiscitis infecciosa entre 2000 y 2015, y comparación de los pacientes mayores de 75 con los pacientes más jóvenes. Resultados: De los 152 pacientes, 51 (33,6%) eran≥75 años, 59 de entre 61 y 74, y 42≤60. Los pacientes≥75 estaban frecuentemente institucionalizados (7,8 frente a 0; p=0,02), estuvieron menos sujetos a los factores de riesgo de infección (27,5 frente a 54,5%; p=0,02), pero no difirieron del resto en cuanto a la frecuencia de diabetes y cáncer. El tiempo de diagnóstico fue menor para los pacientes menores de 60 años (23 frente a 30 frente a 30 días para cada grupo de edad, respectivamente; p<0,05). No se produjeron diferencias entre los grupos de edad en términos de localización de la espondilodiscitis, frecuencia de síntomas neurológicos y fiebre, frecuencia o intensidad del síndrome inflamatorio, toma de imágenes, frecuencia de identificación de microorganismos, positividad del hemocultivo, o uso o eficacia de la biopsia discovertebral. La distribución de los microorganismos fue comparable entre los grupos, exceptuando los bacilos gramnegativos, siendo Escherichia coli el más común en los pacientes mayores de 75 años (7/8 frente a 414; p=0,02). La duración del tratamiento antibiótico y la hospitalización fueron comparables entre los grupos de edad. Cinco pacientes fallecieron, todos ellos mayores de 75 años (5/51 frente a 0/101; p=0,001). Conclusión: La edad es un factor de riesgo para la espondilodiscitis primaria, que se asocia a una mortalidad significativa en los pacientes mayores de 75 años (10%). Para estos pacientes mayores, la espondilodiscitis no comporta otras características distintivas

Background and objetive: The incidence of infectious spondylodiscitis has been shown to rise with age; however, they had not been extensively investigated in the very elderly. Material and methods: This retrospective, monocentric study included patients hospitalized in our department of rheumatology for primary infectious spondylodiscitis between 2000 and 2015, and compared over 75-year-olds with younger patients. Results: Of the 152 patients, 51 (33.6%) were≥75 years old, 59 were 61-74, and 42 were≤60. Patients≥75 years old were more often institutionalized (7.8 vs. 0; P=.02), were less often subject to infection risk factors (27.5 vs. 54.5%; P=.02), but did not differ from the others as regards the frequency of diabetes and cancer. Time to diagnosis was shorter for the under 60-year-olds (23 vs. 30 vs. 30 day for each age group, respectively; P<.05). There were no differences among the age groups in terms of spondylodiscitis localization, frequency of neurological symptoms and fever, frequency or intensity of inflammatory syndrome, imaging use, frequency of microorganism identification, blood culture positivity, or use and efficacy of disco-vertebral biopsy. Microorganism distribution was comparable among the groups, except for Gram-negative bacilli, with Escherichia coli more common in over 75-year-olds (7/8 vs. 4/14; P=.02). Duration of antibiotherapy and hospitalization was comparable across the age groups. Five patients died, all over 75 years old (5/51 vs. 0/101; P=.001). Conclusion: Age is a risk factor for primary spondylodiscitis, associated with significant mortality in over 75-year-olds (10%). For these elderly patients, spondylodiscitis does not bear any other distinguishing features