ChatGPT: when artificial intelligence replaces the rheumatologist in medical writing.

In this editorial we discuss the place of artificial intelligence (AI) in the writing of scientific articles and especially editorials. We asked chatGPT « to write an editorial for Annals of Rheumatic Diseases about how AI may replace the rheumatologist in editorial writing ¼. chatGPT's response is diplomatic and describes AI as a tool to help the rheumatologist but not replace him. AI is already used in medicine, especially in image analysis, but the domains are infinite and it is possible that AI could quickly help or replace rheumatologists in the writing of scientific articles. We discuss the ethical aspects and the future role of rheumatologists.

Impact of NSAIDs on 8-year cumulative incidence of major cardiovascular events in patients with ankylosing spondylitis: a nationwide study.

OBJECTIVES: The objectives of this study were to describe the incidence of major adverse cardiovascular events (MACEs) in French patients newly benefiting from the French Long-term Illness scheme (LTI) for AS and to evaluate the effect of various treatments on the risk of MACE occurrence. METHODS: This national cohort study was based on the French national medico-administrative database SNDS containing data on hospitalization, the LTI, and outpatient care consumption. All French patients newly receiving LTI benefits for AS from 2010 to 2013 were included. The final follow-up date was 31 December 2018. The occurrences of MACEs [stroke and myocardial infarction (MI)] and comorbidities were identified from algorithms previously described in the literature. Competitive risk analysis using propensity score and inverse weighting was performed to calculate cumulative incidence functions and to determine subhazard ratios (SHRs) for the various treatments of interest. RESULTS: Between 2010 and 2013, 22 929 patients were included [mean age 43.0 (s.d. 13.9) years, 44.9% mal]. The 8-year cumulative incidences of MACE, stroke, and MI were 1.81% (1.61-2.05), 0.97% (0.83-1.14), and 0.85% (0.71-1.04), respectively. NSAIDs [SHR: 0.39 (0.32-0.50), P < 0.001] and anti-TNF [SHR 0.61 (0.46-0.80), P < 0.001], but not anti-IL17 [2.10 (0.79-5.57)] were associated with a lower risk of MACE occurrence. CONCLUSION: MACE incidence rates at 8 years are low in patients newly benefiting from LTI for AS. Our results support the hypothesis of a protective role of NSAIDs and anti-TNF in cardiovascular risk in these patients.

Reactive Arthritis: Treatment Challenges and Future Perspectives.

PURPOSE OF THE REVIEW: Reactive arthritis is synovitis related to an infection away from the joint. The evolution is variable, frequently self-limited, but with the possible evolution to a prolonged form, generating functional incapacity and sequelae. RECENT FINDINGS: New microbiological families have been incriminated and pathophysiological links have been clarified, highlighting the role of the mucous membranes (gut in particular), specific cell populations, and the production of pro-inflammatory cytokines. First-line pharmacological treatment is based on NSAIDs. In case of failure, synthetic and more recently biological DMARDs are indicated. Only open data are available for biological DMARDs but suggest good efficacy and safety. Reactive arthritis has not disappeared. The diagnosis must be mentioned by the clinic and history to allow the rapid introduction of an appropriate treatment.

Structural efficacy of NSAIDs, COX-2 inhibitor and glucocorticoid compared with TNFα blocker: a study in adjuvant-induced arthritis rats.

OBJECTIVE: To evaluate radiographic outcomes after an early treatment for 21 days with etanercept, naproxen, celecoxib, prednisone or methotrexate in adjuvant-induced arthritis in rats. METHODS: At the onset of arthritis, rats were daily treated with naproxen (10 mg/kg/day i.p.), celecoxib (3 mg/kg/day), prednisolone (10 mg/kg/day), etanercept (10 mg/kg/3 days), methotrexate (2 mg/kg/3 days) or saline solution (vehicle) for 21 days. The arthritis score was daily monitored. At the end of treatment, a hind paw radiographic examination was performed with a BMA high-resolution digital X-ray system (40 mV, 10 mA). A score of 0-20 was determined for each paw. Plasma levels of TNFα were measured. RESULTS: Compared with vehicle, all treatments reduced (P < 0.001) the arthritis score. All treatments, except methotrexate, slowed radiographic destruction (P < 0.001). All treatments, except etanercept, reduced the plasma level of TNFα. Naproxen, glucocorticoid and celecoxib were more effective than etanercept on the radiographic score (P < 0.01). Naproxen was the only treatment to be more effective on all different radiographic subscores than etanercept. CONCLUSION: Our study demonstrated for the first time that an early treatment with NSAIDs, excluding cyclooxygenase-2 selective inhibitor, is more beneficial than a TNFα blocker in preventing structural damage in adjuvant-induced arthritis.

Methotrexate did not improve endothelial function in rheumatoid arthritis: a study in rats with adjuvant-induced arthritis.

OBJECTIVES: Rheumatoid arthritis is associated with an increased cardiovascular risk, secondary to endothelial dysfunction. There is accumulating evidence that methotrexate reduces cardiovascular risk in rheumatoid arthritis, but the mechanisms involved are still unknown. In this study, we aimed to determine the effect of methotrexate on endothelial function and traditional cardiovascular risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS: On the first signs of arthritis, methotrexate (1 mg/kg/week, s.c.) or saline (Vehicle) was administered to AIA for 3 weeks. Endothelial function was studied in aortic rings relaxed with acetylcholine in the presence or not of inhibitors of nitric oxide synthase, cyclooxygenase-2, arginase, EDHF and superoxide anions production. Arthritis and radiological scores, blood pressure and blood levels of cytokines, triglycerides, cholesterol, homocysteine and BMP-4 were measured. RESULTS: Although methotrexate significantly reduced the arthritis score, it had no effect on Ach-induced relaxation. As regards mechanisms, methotrexate increased nitric oxide synthase activity and reduced the superoxide anions production but did not change arginase, cyclooxygenase-2 and EDHF pathways. Methotrexate did not change the radiological score or blood pressure, lipid, glucose and homocysteine levels. By contrast, methotrexate significantly reduced plasma IL-1ß and TNF-α levels and increased serum BMP-4 level. CONCLUSIONS: Despite a reduction of clinical and biological inflammation, methotrexate did not improve endothelial function in AIA rats. Overall data suggest that mechanisms other than the ED reduction are likely involved, and remain to be elucidated to better understand the cardiovascular benefits of methotrexate in rheumatoid arthritis.

Utility of 18F-fluoro-dexoxyglucose positron emission tomography for the diagnosis of polymyalgia rheumatica: a controlled study.

OBJECTIVES: To compare (18)F-fluoro-dexoxyglucose PET/CT (FDG-PET/CT) findings in patients with polymyalgia rheumatica (PMR) and controls without rheumatologic disease. METHODS: We retrospectively included 50 patients with a diagnosis of PMR as well as 53 patients with a neoplasm as a control group. All patients underwent FDG-PET/CT. Seventeen hotspots were analysed. We performed a semi-quantitative analysis of FDG uptake (4-point score from 0 to 3). The cut-offs for the number of sites with high activity and for FDG uptake score were assessed using receiver operating characteristics curves and odds ratios (ORs). RESULTS: The two groups were comparable for the median patient age (69.3 years for PMR vs 68.1 for controls). Significant differences between the two groups were found for FDG uptake score (1.12 vs 0.34, P < 0.00001) and for the number of sites with significant uptake (score ⩾ 2): 6.36 sites vs 1.49 sites (P < 0.00001). The presence of three or more sites with significant uptake was correlated with the diagnosis of PMR with 74% sensitivity and 79% specificity (OR = 10.8). For the FDG uptake score, the cut-off was 0.53 (sensitivity 80%, specificity 77%, OR = 13.6). We found significant differences in all sites for FDG uptake score and the number of sites with significant uptake, particularly marked for shoulders, ischial tuberosities and interspinous bursitis (P < 0.00001 for FDG uptake score). CONCLUSION: Our results suggest that the number of sites with significant FDG uptake and the uptake score could be relevant criteria for the diagnosis of PMR.

Etanercept improves endothelial function via pleiotropic effects in rat adjuvant-induced arthritis.

OBJECTIVES: To determine the effect of etanercept on endothelial dysfunction and on traditional cardiovascular (CV) risk factors in the adjuvant-induced arthritis (AIA) rat model. METHODS: At the first signs of arthritis, etanercept (10 mg/kg/3 days, s.c.) or saline was administered for 3 weeks in AIA rats. Body weights and arthritis scores were monitored daily. Endothelial function was studied in aortic rings relaxed with acetylcholine (Ach) with or without inhibitors of nitric oxide synthase (NOS), cyclo-oxygenase (COX-2), arginase, endothelium-derived hyperpolarizing factor and superoxide anions (O2 (-)°) production. Aortic expression of endothelial nitic oxide synthase (eNOS), Ser1177-phospho-eNOS, COX-2, arginase-2, p22(phox) and p47(phox) was evaluated by western blotting analysis. Blood pressure, heart rate and blood levels of triglycerides, cholesterol and glucose were measured. RESULTS: Etanercept significantly reduced arthritis score (P < 0.001). It improved Ach-induced relaxation (P < 0.05) as a result of increased NOS activity, decreased COX-2/arginase activities and decreased O2 (-)° production. These functional effects relied on increased eNOS expression and phosphorylation, and decreased COX-2, arginase-2 and p22(phox) expressions. No correlation was found between arthritis score and Ach-induced relaxation. The treatment did not change triglycerides, cholesterol and glucose levels, but significantly increased systolic blood pressure and heart rate (P < 0.05). CONCLUSION: Our data demonstrated that efficient dosage of etanercept on inflammatory symptoms improved endothelial function in AIA. This beneficial effect on endothelial function is disconnected from its impact on CV risk factors and relates to pleiotropic effects of etanercept on endothelial pathways. These results suggest that etanercept could be a good choice for patients with rheumatoid arthritis at high risk of CV events.

Effects of disease-modifying anti-rheumatic drugs on sacroiliac MRI score in axial spondyloarthritis: a systematic review and meta-analysis.

INTRODUCTION: Sacroiliac bone marrow edema is an important factor in the diagnosis and management of axial spondyloarthritis (axSpA). The aim of this meta-analysis is to assess the effect of the different bDMARDs and tsDMARDs on the SPARCC score at 12-16 and 48-52 weeks. METHODS: A systematic review, performed on PubMed (including Medline), Cochrane (CENTRAL) and DOAJ databases, included randomized controlled studies evaluating the sacroiliac joint (SIJ) SPARCC score at 12-16 or 48-52 weeks in patients with axSpA meeting the ASAS 2009 criteria or the modified New York criteria. We included studies evaluating the effects of the different treatments on the SPARCC score of SIJ in axial spondyloarthritis in comparison to a control group. RESULTS: Eighteen studies were included in the meta-analysis. Nine studies evaluated the effect of TNFα inhibitors (TNFi), three for IL-17 inhibitors, and four for JAK inhibitors. At 12 and 16 weeks, SIJ SPARCC score was significantly improved by TNFi (WMD: - 3.29 [95% CI - 4.25; - 2, 34]), by IL-17 inhibitors (WMD: - 4.66 [95% CI - 6.22; - 3.09]), and by JAK inhibitors (JAKi) (WMD: - 3.06 [95% CI - 3.24; - 2.89]). There was no difference between the molecule subgroups. At 48-52 weeks, TNFα inhibitors reduced more SIJ SPARCC, but not significantly (WMD: - 2.26 [95% CI - 4.94; 0.42]), than placebo groups who began a TNFi treatment with delay. CONCLUSION: Our meta-analysis shows a comparable improvement of the SIJ SPARCC score regarding TNFi, JAKi, and IL-17 inhibitors at three months and suggests the presence of an opportunity window. Key Points • Anti-TNF Ab, anti-IL17 Ab, and JAK inhibitor treatments reduce the sacroiliac joint SPARCC scores. • There is no difference between the different treatments in the reduction of the sacroiliac joint SPARCC score after 3 months in axial spondyloarthritis.

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.

Fluorescence-enabled evaluation of nasal tract deposition and coverage of pharmaceutical formulations in a silicone nasal cast using an innovative spray device.

INTRODUCTION: The characterisation of nasal formulations is a critical point. However, there are still no recommendations or guidelines in terms of standard approaches for evaluating the formulation's nasal deposition and/or coverage profile. This study optimises a method for quantifying silicone nasal cast deposition and coverage of liquid formulations using different nasal devices. OBJECTIVES: The present work investigates the nasal deposition and coverage patterns of innovative nasal spray nozzles producing slow velocity soft mists, using a nasal cavity replica and a fluorescent dye. METHODS: The study of the deposition pattern of a fluorescent liquid formulation in a transparent nasal cast was carried out in both the presence and absence of a simulated inhalation flow. The extent of the deposition pattern was investigated using ImageJ and fluorescence in the nasal cast, quantified by fluorometric analysis. The particle size distribution and initial droplet velocity were determined using a laser diffractometer and a high-speed camera with a frame rate of 1000 fps. RESULTS: A uniform intranasal coverage was obtained with droplets of a volume median particle size (Dv50) between 15 and 25 µm in airflow between 10 and 30 L/min. In these conditions, aerosol formulations can be uniformly deposited in the vestibule and turbinate cavity nasal regions, with less than 10 % passing beyond the nasopharyngeal region. CONCLUSION: The method applied allowed for the determination of the coverage of the nasal cast in different regions using images analysis and fluorometric analysis. Droplet velocity is a critical parameter in the deposition in the nasal cavity. With standard swirl nozzles, many droplets are found on the surface of the nasal vestibule. Soft mist nozzles produce smaller droplets at a much lower initial velocity (<1 m/s), resulting in a more uniform coverage.

Cytokines and intestinal epithelial permeability: A systematic review.

BACKGROUND: The intestinal mucosa is composed of a well-organized epithelium, acting as a physical barrier to harmful luminal contents, while simultaneously ensuring absorption of physiological nutrients and solutes. Increased intestinal permeability has been described in various chronic diseases, leading to abnormal activation of subepithelial immune cells and overproduction of inflammatory mediators. This review aimed to summarize and evaluate the effects of cytokines on intestinal permeability. METHODS: A systematic review of the literature was performed in the Medline, Cochrane and Embase databases, up to 01/04/2022, to identify published studies assessing the direct effect of cytokines on intestinal permeability. We collected data on the study design, the method of assessment of intestinal permeability, the type of intervention and the subsequent effect on gut permeability. RESULTS: A total of 120 publications were included, describing a total of 89 in vitro and 44 in vivo studies. TNFα, IFNγ or IL-1ß were the most frequently studied cytokines, inducing an increase in intestinal permeability through a myosin light-chain-mediated mechanism. In situations associated with intestinal barrier disruption, such as inflammatory bowel diseases, in vivo studies showed that anti-TNFα treatment decreased intestinal permeability while achieving clinical recovery. In contrast to TNFα, IL-10 decreased permeability in conditions associated with intestinal hyperpermeability. For some cytokines (e.g. IL-17, IL-23), results are conflicting, with both an increase and a decrease in gut permeability reported, depending on the study model, methodology, or the studied conditions (e.g. burn injury, colitis, ischemia, sepsis). CONCLUSION: This systematic review provides evidence that intestinal permeability can be directly influenced by cytokines in numerous conditions. The immune environment probably plays an important role, given the variability of their effect, according to different conditions. A better understanding of these mechanisms could open new therapeutic perspectives for disorders associated with gut barrier dysfunction.

Difficult-to-treat axial spondyloarthritis is associated with psoriasis, peripheral involvement and comorbidities: results of an observational nationwide study.

OBJECTIVES: To determine the cumulative incidence and identify the factors associated with difficult-to-treat axial spondyloarthritis (D2T-axSpA) in French patients newly benefiting from the French 'long-term illness' (LTI) social security scheme for axial spondyloarthritis (axSpA). METHODS: This national cohort study was based on the French National Medico-Administrative Database, SNDS, which contains data on hospitalisation, LTI and outpatient care consumption. All French patients newly receiving LTI benefits for ankylosing spondylitis (AS) between 2010 and 2013 were included in the study. In France, LTI is required to access biological/targeted synthetic DMARDs (b/tsDMARDs). The follow-up period ended on 31 December 2018. So-called D2T-axSpA was defined as the failure of three b/tsDMARDs or of two b/tsDMARDs with different modes of action. Comorbidities and extra-musculoskeletal manifestations were identified using previously described algorithms. Characteristics were compared between patients with D2T-axSpA and patients with non-D2T-axSpA who had received at least one b/tsDMARD with bivariate and multivariate analysis using logistic regression. Incidence rates of major cardiovascular event (MACE) and death were compared using competitive risk analysis. RESULTS: 22 932 patients were included. 10 798 (47.08%) patients received at least one bDMARD. None received tsDMARD. During follow-up, 2115 patients were classified as having D2T-axSpA, representing 19.59% of patients who received at least one bDMARD. In multivariate analysis, D2T-axSpA was significantly associated with female gender, peripheral involvement, psoriasis, hypertension and depression (p<0.001 for each case). There was no difference in the incidence of MACE (p=0.92) or death (p=0.87). CONCLUSION: D2T-axSpA affects one in five patients exposed to bDMARDs in this national cohort. D2T-axSpA is more common in women and patients with peripheral involvement and/or comorbidities.