Effectiveness of Repetitive Transcranial Magnetic Stimulation on Fibromyalgia Patients Responding to a First Repetitive Transcranial Magnetic Stimulation Induction Course After Six Months of Maintenance Treatment: A Randomized Pilot-Controlled Study.

BACKGROUND: Fibromyalgia is a chronic painful condition without real, effective treatment. The administration of repetitive transcranial magnetic stimulation (rTMS) has been shown to have a therapeutic effect on pain, but there are still questions about the maintenance of its effect over time. Continuation of the treatment upon clinical response through maintenance sessions is promising and merits further exploration. MATERIALS AND METHODS: We conducted a randomized, parallel-group, controlled study involving 78 patients to evaluate the effect of rTMS vs sham stimulation after a three-week induction treatment and six months of maintenance treatment (three-week periodicity) on 22 patients who presented a clinical response to the induction treatment. The clinical response was defined as a ≥30% decrease of the baseline visual analog scale (VAS) for pain and a score for the Patient Global Impression of Change (PGIC) >5. The clinic global impression, fibromyalgia impact questionnaire, symptom severity score, and Beck's depression inventory were also studied. RESULTS: A significant clinical response to treatment with rTMS was observed after the induction phase and maintained over six months, particularly as measured by the PGIC parameter of pain, as well as of the intensity of fatigue and depression, with an absence of adverse effects induced by this method. CONCLUSION: A three-week rTMS treatment, characterized by a reduction in pain, as evaluated by VAS, should be continued with the administration of rTMS maintenance sessions for an additional six months to maintain the best possible long-term effects.

Use of eHealth by Patients With Rheumatoid Arthritis: Observational, Cross-sectional, Multicenter Study.

BACKGROUND: The use of eHealth tools (eg, the internet, mobile apps, and connected devices) in the management of chronic diseases and for rheumatoid arthritis is growing. eHealth may improve the overall quality of care provided to patients with chronic diseases. OBJECTIVE: The primary objective of this study was to describe eHealth use by patients with rheumatoid arthritis in France. The secondary objectives were to identify associations between patient demographics and disease characteristics and the use of eHealth tools, and assess their expectations of eHealth. METHODS: In this cross-sectional, multicenter study, patients with rheumatoid arthritis, according to the 2010 ACR/EULAR classification criteria, were recruited from 5 university hospitals (Bordeaux, Clermont-Ferrand, Limoges, Montpellier, and Toulouse). Patients completed an anonymous self-questionnaire, including demographic data, evaluating their eHealth use (ie, access, support, frequency of use, type of use, and reason for use). The rheumatologist in charge of each patient completed an independent medical questionnaire on disease characteristics, activity of rheumatoid arthritis, and treatments. Data were collected between December 2018 and July 2019. RESULTS: Questionnaires were completed by 575 participants, with a mean age of 62 (SD 13) years, 447 (77.7%) of whom were female. Overall, 82.2% (473/575) of the participants had access to eHealth through a computer (402/467, 86.1%), tablet (188/467, 40.2%), or smartphone (221/467, 47.3%). Of these, 36.4% (170/467) of the participants used the internet for health in general, and 28.7% (134/467) used it specifically for rheumatoid arthritis-related reasons. All these 134 patients used eHealth to learn about disease pathology, and 66.4% (89/134) of them used it as a tool to help monitor rheumatoid arthritis. Most patients (87/125, 69.6%) had a paper file, 19.2% (24/125) used a digital tool (spreadsheets, 10/125, 8%; mobile app, 9/125, 7.2%; or website, 5/125, 4%), and 24.8% (31/125) did not use any tools for monitoring. Few patients (16/125, 12.8%) used tools for treatment reminders. About 21.6% (27/125) of the patients using eHealth used a specific app for rheumatoid arthritis. Univariate analysis showed that age, education level, employment status, treatment, comorbidities, membership of a patient association, and patient education program were associated with eHealth use for rheumatoid arthritis. Multivariate analysis showed that membership of a patient association (odds ratio [OR] 5.8, 95% CI 3.0-11.2), use of biologic disease-modifying antirheumatic drugs (OR 0.6, 95% CI 0.4-1.0), and comorbidities (OR 0.7, 95% CI 0.6-0.8) remained associated with eHealth use for rheumatoid arthritis. Recommendation by a doctor (225/330, 68.2%), ease of use (105/330, 31.8%), and data security (69/330, 20.9%) were factors favoring the use of eHealth. CONCLUSIONS: To date, few patients have used eHealth for disease management. The use of a reliable and validated eHealth tool for rheumatoid arthritis could therefore be promoted by rheumatologists and could optimize therapeutic adherence.

Systemic Scleroderma Induced by Nivolumab in Malignant Melanoma.

BACKGROUND: Immunotherapy using immune checkpoint inhibitors is not devoid of immune-related adverse events (irAEs) including rheumatological conditions. CASE REPORT: We report a rare case of a 47-year-old woman with metastatic melanoma who developed systemic scleroderma after initiating nivolumab. The patient displayed inflammatory arthralgias, morning stiffness, and classical cutaneous manifestations of the disease. Clinical evaluations also revealed carpal tunnel syndrome, cardiac involvement, and dyspnea. RNA-Polymerase III antibodies were positive. Nivolumab, an anti-PD-1 antibody, was considered as a potential trigger for this condition. CONCLUSION: To our knowledge, this is the first case of nivolumab-induced systemic scleroderma in the context of melanoma described in the literature that fulfills the classification criteria of the disease. This case underscores the need for increased awareness of immune-related adverse events in patients receiving immune checkpoint inhibitors, emphasizing timely intervention and further research.

[ACACIAS 3: Learning about announcement consultations in the second cycle of medical studies]. / ACACIAS 3 : Apprentissage des consultations d'annonce dans le deuxième cycle d'études médicales.

INTRODUCTION: The second cycle of medical studies is a key time for developing interpersonal skills and the doctor-patient relationship. High-fidelity simulation is an initial learning option that enables learners to confront situations involving empathy. METHODS: This is a feedback report from May 2023 on the implementation of simulation as a training tool for 2nd cycle medical students in the announcement consultation. The training consists of two parts: theoretical teaching via a digital platform with an assessment of theoretical knowledge and a practical part with a simulation session with an actress playing a standardized patient. The acquisition of skills and the reflexivity of learners are assessed by means of a pre- and post-test. RESULTS: Twenty-nine externs took part in this project. Student satisfaction was 96 %. The feedback was very positive, both in terms of the quality of the sessions and the briefings/debriefings. Almost all the students wanted to repeat the experience. The simulation exercise was beneficial for the students in terms of the development (before vs. after) of their skills (verbal, emotional and relational) (1.05±0.25 vs. 1.22±0.19, P=0.047) and appeared to be relevant to the development of reflexivity (3.29±0.72 vs. 3.48±0.9, P=0.134). CONCLUSION: This first published French study demonstrates the feasibility and value of training in announcing a diagnosis, combining teaching via a digital platform and high-fidelity simulation for second cycle medical students.

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.

Ruthenium-based assemblies incorporating tetrapyridylporphyrin panels: a photosensitizer delivery strategy for the treatment of rheumatoid arthritis by photodynamic therapy.

Ruthenium-based assemblies containing tetrapyridylporphyrins (TPyP) in their structure have been evaluated as photosensitizers (PS) to treat rheumatoid arthritis (RA) by photodynamic therapy (PDT). TPyP is useless by itself as a PS due to its low solubility in biological media, however, incorporated in metallacages it can be internalized in cells. The study shows a cellular antiproliferative activity in fibroblast-like synoviocyte (FLS) in the lower nanomolar range in the presence of light, and no dark toxicity at 1 µM concentration, thus having an excellent photoactivity index. The presence of diamagnetic (Zn2+) and paramagnetic (Co2+) metals in the center of TPyP impairs the effectiveness of PDT, showing no (Co) or reduced (Zn) photoactivity. A total of five metallacages with different structural characteristics have been evaluated, and our results suggest that the incorporation of PS in metalla-assemblies is not only an elegant method to increase solubility in biological media for TPyP but also appears to be an efficient hybrid system to treat RA by PDT.

Diet and Disease Activity in Patients with Axial Spondyloarthritis: SpondyloArthritis and NUTrition Study (SANUT).

Axial Spondyloarthritis (axSpA) patients with inflamed intestines have higher SpA activity. Diets that modulate microbiota may influence inflammation and SpA activity. Today, data concerning the impact of diet on SpA activity are scarce. SANUT was a single-center, noninterventional, cohort study that assessed dietetic profiles associated with SpA activity in axSpA. Demographic, clinical, SpA-related, quality of life (QoL), fatigue, physical activity, and dietary data were collected. SpA activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and by Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). We assessed whether high SpA activity was associated with nutriment consumption. Between 12 February 2018 and 12 February 2020, 278 patients participated. High SpA activity, as measured by ASDAS and BASDAI, was significantly associated with higher body mass index and waist circumference, negative HLA-B27, lower QoL, higher fatigue, and higher digestive-symptom scores. Furthermore, high SpA activity, as measured by BASDAI, was associated with female sex, smoking status, patients who were not actively employed, reduced physical activity, and high intake of ultra-transformed foods, while high SpA activity, as measured by ASDAS, was associated with low intake of omega-3 PUFAs and fiber. Therefore, low intakes of omega-3 PUFAs and fiber, and high intake of ultra-transformed foods, are associated with high SpA activity.

eDOL mHealth App and Web Platform for Self-monitoring and Medical Follow-up of Patients With Chronic Pain: Observational Feasibility Study.

BACKGROUND: Chronic pain affects approximately 30% of the general population, severely degrades quality of life (especially in older adults) and professional life (inability or reduction in the ability to work and loss of employment), and leads to billions in additional health care costs. Moreover, available painkillers are old, with limited efficacy and can cause significant adverse effects. Thus, there is a need for innovation in the management of chronic pain. Better characterization of patients could help to identify the predictors of successful treatments, and thus, guide physicians in the initial choice of treatment and in the follow-up of their patients. Nevertheless, current assessments of patients with chronic pain provide only fragmentary data on painful daily experiences. Real-life monitoring of subjective and objective markers of chronic pain using mobile health (mHealth) programs can address this issue. OBJECTIVE: We hypothesized that regular patient self-monitoring using an mHealth app would lead physicians to obtain deeper understanding and new insight into patients with chronic pain and that, for patients, regular self-monitoring using an mHealth app would play a positive therapeutic role and improve adherence to treatment. We aimed to evaluate the feasibility and acceptability of a new mHealth app called eDOL. METHODS: We conducted an observational study to assess the feasibility and acceptability of the eDOL tool. Patients completed several questionnaires using the tool over a period of 2 weeks and repeated assessments weekly over a period of 3 months. Physicians saw their patients at a follow-up visit that took place at least 3 months after the inclusion visit. A composite criterion of the acceptability and feasibility of the eDOL tool was calculated after the completion of study using satisfaction surveys from both patients and physicians. RESULTS: Data from 105 patients (of 133 who were included) were analyzed. The rate of adherence was 61.9% (65/105) after 3 months. The median acceptability score was 7 (out of 10) for both patients and physicians. There was a high rate of completion of the baseline questionnaires and assessments (mean 89.3%), and a low rate of completion of the follow-up questionnaires and assessments (63.8% (67/105) and 61.9% (65/105) respectively). We were also able to characterize subgroups of patients and determine a profile of those who adhered to eDOL. We obtained 4 clusters that differ from each other in their biopsychosocial characteristics. Cluster 4 corresponds to patients with more disabling chronic pain (daily impact and comorbidities) and vice versa for cluster 1. CONCLUSIONS: This work demonstrates that eDOL is highly feasible and acceptable for both patients with chronic pain and their physicians. It also shows that such a tool can integrate many parameters to ensure the detailed characterization of patients for future research works and pain management. TRIAL REGISTRATION: ClinicalTrial.gov NCT03931694; http://clinicaltrials.gov/ct2/show/NCT03931694.

Ketamine in chronic pain: A Delphi survey.

BACKGROUND: There is no recommendation in Europe for the use of ketamine in patients with chronic pain. The heterogeneity of practice highlights the need to seek the advice of experts in order to establish a national consensus. This Delphi survey aimed to reach a national consensus on the use of ketamine in chronic pain in Pain clinics. METHODS: A collaborative four-round internet-based questionnaire was used. It was created after literature search on ketamine administration in chronic pain and included about 96 items. It discussed utility and advantages, adverse events and deleterious aspects, methods of administration, concomitant treatments and assessment of results. RESULTS: Twenty-eight experts completed all rounds of the survey with a total of 81.3% items reaching a consensual answer. Neuropathic pain represents the first indication to use ketamine, followed, with a good to moderate utility, by other situations (fibromyalgia, complex regional pain syndrome, central neuropathic pain, peripheral neuropathic pain, nociceptive pain, sensitization, opioid withdrawal, palliative care, depression). Experts agreed on the rare occurrence of adverse events. Concerning routes of administration, intravenous infusion with doses of 0.5-0.9 mg/kg/d for 4 days of treatment is preferred. Place of care is hospital, as in- or out-patient, with a quarterly administration of ketamine. Finally, ketamine effectiveness is assessed 1 month after infusion, and experts encourage combination with non-pharmacological treatment. CONCLUSIONS: This Delphi survey established a consensus of pain specialists on the use of ketamine in refractory chronic pain, thus providing a basis for future comparative trials. SIGNIFICANCE: This Delphi survey in chronic pain reached agreement on four main aspects: (1) Priority to treat neuropathic pain with evaluation of effectiveness at 1 month; (2) No deleterious effects in the majority of listed diseases/situations with the absence or <3% of suggested adverse events; (3) 0.5-0.9 mg/kg/d IV infusion; (4) Combination with non-pharmacological treatment.

Chronic pain and neuroinflammation.

In rheumatology, chronic pain most often sets in after a musculoskeletal injury. Its persistence is not always due to the progression of the initial injury, but in some cases to the onset of central sensitization. Much scientific data suggests that this central sensitization is caused by multiple complex interactions between the nervous system and immune system. Afferent nerve fibers carrying pain information are responsible for peripheral sensitization partly linked to inflammation molecules. These afferent fibers release neurotransmitters in the dorsal root ganglion and dorsal horn of the spinal cord, capable of activating microglia, which are the local immune cells. The activated microglia will produce pro-inflammatory cytokines, chemokines and neuropeptides capable of interacting with the second-order neuron, but also segmental and descending inhibitory neurons. This is referred to as neuroinflammation, which will amplify the hypersensitivity of second-order neurons, otherwise called central sensitization. This neuroinflammation will be able to reach the higher brain structures, which are involved in pain modulation and the emotional and cognitive aspects of pain. The aim of this update is to describe the pathophysiology of chronic pain, incorporating the latest scientific data on neuroplasticity and neuroinflammation.

Evaluation of Ruthenium-Based Assemblies as Carriers of Photosensitizers to Treat Rheumatoid Arthritis by Photodynamic Therapy.

For the first time, ruthenium-based assemblies have been used as carriers for photosensitizers in the treatment of rheumatoid arthritis by photodynamic therapy (PDT). These metallacages are totally soluble in physiological media and can transport photosensitizers (PS) in their cavity. After an incubation period, the PS is released in the cytoplasm and irradiation can take place. This strategy allows photosensitizers with low or null solubility in biological media to be evaluated as PDT agents in rheumatoid arthritis. The systems in which 21H,23H-porphine and 29H,31H-phthalocyanine are encapsulated show excellent photocytotoxicity and no toxicity in the dark. On the other hand, systems in which metalated derivatives such as Mg(II)-porphine and Zn(II)-phthalocyanine are used show good photocytotoxicity, but to a lesser extent than the previous two. Furthermore, the presence of Zn(II)-phthalocyanine significantly increases the toxicity of the system. Overall, fifteen different host-guest systems have been evaluated, and based on the results obtained, they show high potential for treating rheumatoid arthritis by PDT.

Opioid epidemic: Does rheumatological practice favors risk for patients? National survey on rheumatologists' opioid prescriptions and compliance to guidelines for strong opioid prescription.

OBJECTIVES: Given the scope of rheumatology and its prevalence of pain, it seems needed that a study should focus on prescription habits, in the midst of the international opioid epidemic and given the moderate efficacy of strong opioids in chronic musculoskeletal conditions. We compared rheumatologists' opioid prescribing patterns in non-cancer pain with recommended practice. METHODS: We performed a cross-sectional study of the French health insurance database, including all patients aged 16 years or over reimbursed for at least one strong opioid prescription from a rheumatologist in 2015. A nationwide survey of all registered rheumatologists in France was performed with a 47-item questionnaire in June 2015. RESULTS: Only 2.4% of the patients receiving a strong opioid in 2015 (n=700,946) had at least one prescription from a rheumatologist. Rheumatologists prescribed mostly morphine, and significantly less oxycodone and fentanyl (P<0.00001) than other specialists. Rheumatologists prescribed a mean of 35.8mg morphine equivalent/day. A response rate of 33.7% was obtained to the questionnaire. Acute musculoskeletal pain was the principal condition for strong opioids prescription, with 94.5% re-evaluating opioid treatment within two weeks of initiation. For efficacy, 80% said that they stopped treatment if no benefit was observed after a test period (mean=1.2 months). Rheumatologists with pain management training were significantly more likely to evaluate pain before prescribing strong opioids (P=0.001), evaluate efficacy within three months (P=0.01) and screen for risk factors for misuse at initiation (P<0.0001). CONCLUSIONS: For non-cancer pain, rheumatologists generally prescribe opioids for short periods, at low doses, mostly according to national recommendations. Pain education strongly affected opioid prescription by rheumatologists.

The burden of pain in rheumatoid arthritis: Impact of disease activity and psychological factors.

BACKGROUND: Pain remains a prevalent symptom for rheumatoid arthritis (RA) patients despite a wide therapeutic choice. The objective of this study was to provide a multidimensional evaluation of pain. METHODS: A total of 295 RA patients from 7 French rheumatology centres were enrolled in a cross-sectional study. Patients completed a chronic pain assessment questionnaire approved by the French National Authority for Health, the health assessment questionnaire (HAQ) as well as depression and anxiety scales (HAD, Beck Depression Inventory, STAI). Disease activity (DAS28) and ESR were recorded. A multivariate descriptive analysis was undertaken using principal component analysis (PCA). RESULTS: 38.4% of patients had a pain score > 40 mm/100, although 83% were on biological treatment and 38.7% were in remission based on the RA activity score. The PCA analysis found four axes representing 70% of total variance. The axes, per cent of variance and variables represented were as follows: (a) axis 1, 41% variance, anxiety and depression scores, sensory and affective qualifier score, HAQ and pain impact on daily life; (b) axis 2, 13% variance, disease activity score (DAS28) and pain relief with current treatment; (c) axis 3, 9% of variance, RA duration and radiographic score and (d) axis 4, 6% of variance, DAS28 and ESR. Moderate to severe pain was significantly associated with axes 1 and 2. CONCLUSIONS: Despite a high proportion of patients on biological treatments, 38.4% of patients continue to experience moderate to severe pain. Pain is associated with the RA activity score, but also with the depression and anxiety scores. SIGNIFICANCE: Substantial proportion of rheumatoid arthritis (RA) patients still experiences relevant pain, although more than 80% on biological treatment. Pain is primarily associated with anxiety and depression scores and with disease activity score. These findings highlight the need to assess patients' mental well-being alongside. Clinical measures of disease activity to better manage pain and guide treatment decisions.

Factors influencing the choice of biologic therapy following Rituximab in patients with rheumatoid arthritis: A retrospective study using propensity score.

OBJECTIVES: To assess factors influencing the choice and effectiveness of biological disease-modifying antirheumatic drugs (DMARDs) following failure of rituximab (RTX) in rheumatoid arthritis (RA), taking patient profile into account. METHODS: In a retrospective, multicenter study, data about RA patients starting a new biologic during the year after RTX discontinuation were collected at baseline (when the biologic was introduced after RTX), and during follow-up (3, 6, and 12 months). Characteristics of patients receiving tocilizumab (TCZ), abatacept (ABA), or a TNFα inhibitor (TNFi), EULAR response, and retention rate were compared using multidimensional factorial analysis for patient profiles and multivariate analysis including propensity score built on the patient profile. RESULTS: Among 152 patients analyzed (37.5% TCZ, 31.6% ABA, 30.9% TNFi), sex, disease characteristics and activity, concomitant DMARDs or glucocorticoids, and previous use of RTX and TNFi were similar at baseline. Patients receiving ABA were slightly older. Multimorbidity index was higher but not significantly different. Multidimensional factorial analysis showed a distinct profile of patients receiving ABA, characterized by older age, more men, more smokers, more comorbidities, and higher anti-cyclic citrullinated peptide antibody. At 1 year, drug retention was higher for ABA than TNFi after adjustment for disease duration, concomitant DMARDs, glucocorticoids, and propensity score (P=0.04). Tolerance and serious infections were similar among groups. CONCLUSIONS: The profile of patients receiving ABA following failure of RTX differed from TNFi and TCZ using multidimensional factorial analysis. After adjustment for propensity score, drug retention rate remained higher with ABA than TNFi.

MAP kinase subtypes and Akt regulate diosgenin-induced apoptosis of rheumatoid synovial cells in association with COX-2 expression and prostanoid production.

In the present study, we investigated the signalling pathways involved in diosgenin-induced apoptosis in human rheumatoid arthritis (RA) fibroblast-like synoviocytes (FLS) in vitro with particular interest on Akt and MAPKs activation in relation to arachidonic acid metabolism via COX-2 pathway. MAPK activation was measured by ELISA quantification in diosgenin-treated human RA FLS. Expression of Akt and phospho-Akt was analyzed by Western blot analysis. Nuclear factor-kappaB (NF-kappaB) translocation was evaluated by electromobility shift assay. The prostanoid production (COX-2 activity) was measured by quantitative ELISA. Diosgenin-induced apoptosis in the presence of MAPK or Akt inhibitors was detected by a quantitative determination of DNA fragmentation. Treatment of human RA FLS with 40 microM diosgenin caused an activation of p38 and JNK and an inhibition of ERK phosphorylation. Akt and NF-kappaB are potentially required for diosgenin-induced apoptosis in human RA FLS because 40 microM diosgenin abrogated Akt phosphorylation which correlated with an inhibition of NF-kappaB nuclear translocation. SB203580 and SP600125 (p38 and JNK inhibitors) reduced diosgenin-induced DNA fragmentation whereas U0126 and LY294002 (MEK and PI3 kinase/Akt inhibitors) caused an amplification of proapoptotic effect of diosgenin. Diosgenin increased COX-2 activity resulting in PGE2 and 6-keto-PGF1alpha overproduction in human RA FLS. All MAPK inhibitors markedly reduced diosgenin-induced PGE2 and 6-keto-PGF1alpha synthesis except for SP600125 on 6-keto-PGF1alpha production. These results provide, for the first time, strong evidence that a combined association implicating a MEK inhibitor (U0126) and diosgenin is the most effective in inducing very strong apoptosis with down-regulation of COX-2 expression and activity in human RA FLS.

Inhibition of human rheumatoid arthritis synovial cell survival by hecogenin and tigogenin is associated with increased apoptosis, p38 mitogen-activated protein kinase activity and upregulation of cyclooxygenase-2.

We conducted our study to assess the antiproliferative and proapoptotic potential of hecogenin and tigogenin, two saponins which are structurally similar to diosgenin. We particularly focused our attention on mitogen-activated protein kinase (MAPK) activation in relation to apoptosis but also with the COX-2 expression and activity. Rheumatoid arthritis (RA) synoviocytes were isolated from fresh synovial biopsies obtained from five RA patients undergoing hip arthroplasty. Measurement of cell proliferation was determined using the MTT assay. Apoptosis was evaluated by studying caspase-8, caspase-9 and caspase-3 activities but also by quantification of DNA fragmentation. Quantification of human phospho-MAPKs was realized by ELISA. COX-2 expression was demonstrated by Western blot analysis and COX-2 activity by assay of endogenous prostaglandin E2 (PGE2) production. Tigogenin was more effective than hecogenin in inducing apoptosis in human RA fibroblast-like synoviocytes (FLS) which was caspase dependent but poly(ADP-ribose) polymerase independent and characterized by DNA fragmentation. Our results demonstrated hecogenin- and tigogenin-induced apoptosis through activation of p38 without affecting the JNK and ERK pathways. Indeed, pretreatment with a p38 inhibitor decreased saponin-induced apoptosis with a significant decrease in DNA fragmentation. Furthermore, the rate of apoptosis induced by hecogenin or tigogenin was associated with overexpression of COX-2 correlated with overproduction of endogenous PGE2. These new results provide strong evidence that a family of structurally similar plant steroids is capable of inducing apoptosis in human RA FLS with different rates and different signalling pathways. This study also confirms the discussed appearance of the downregulation or upregulation of COX-2 in cell apoptosis as a function of cell type.

Is restless legs syndrome underrecognized? Current management.

Restless legs syndrome (RLS) is a poorly understood sensory-motor neurological disorder whose prevalence in Caucasian populations ranges from 10% to 15%. The patient reports unpleasant sensations in the lower limbs with dysesthesia resulting in an urge to move the legs. The symptoms occur during periods of inactivity, increasing in the evening and at night. Moving the legs provides relief. In 80% of cases, polysomnography shows periodic leg movements during sleep. Patients with idiopathic RLS often report similar symptoms in family members. Secondary RLS may be due to medications, diabetes mellitus, renal failure, iron deficiency, neurological disorders, or rheumatoid arthritis. In secondary RLS, the management rests on treatment of the cause. Symptomatic treatment is warranted in patients with moderate-to-severe symptoms that adversely affect the quality of life. Dopaminergic agents are tried first. When they fail or induce adverse effects, weak opioids, benzodiazepines, anticonvulsants or, if needed, strong opioids, may be used.

[Contribution of sacroiliac magnetic resonance imaging (MRI) to the evaluation of infliximab efficacy in spondyloarthropathy (a prospective study of 34 patients)]. / Contribution de l'IRM des sacro-iliaques dans l'evaluation des spondylarthropathies sous infliximab (etude prospective sur 34 patients).

Thirty-four patients who met ESSG criteria for spondylarthropathy and were eligible for anti-TNFalpha treatment (infliximab) were enrolled in this open-label study lasting 14 weeks. The aims were to evaluate the progression of sacroiliitis by means of MRI, and to determine the positive predictive value of this exam for the treatment response. Patients underwent MRI of the sacroiliac region at baseline (W0), and also at 14 weeks if the baseline MRI showed sacroiliitis. Two blinded readers reviewed all imaging studies. The patients also had a physical examination and ESR and CRP assays at W0 and W14. Sacroiliitis was found in 22 patients (65%) at W0, but only 18 of these patients had a second MRI at W14, for technical reasons. After 14 weeks of therapy, MRI signs of sacroiliac inflammation diminished by 77.7% on average. Clinical and biological parameters also improved. However, MRI was not predictive of the treatment response. Sacroiliac MRI seems to be interesting for objective therapeutic evaluation and monitoring of patients with spondyloarthropathy.