Research Interests: Medicine and Gynecology
L’immunothérapie représente désormais un des piliers de la prise en charge du cancer, notamment avec l’arrivée des inhibiteurs de points de contrôle (checkpoint) immunitaire (ICI, immune checkpoint inhibitors). Ces anticorps... more
L’immunothérapie représente désormais un des piliers de la prise en charge du cancer, notamment avec l’arrivée des inhibiteurs de points de contrôle (checkpoint) immunitaire (ICI, immune checkpoint inhibitors). Ces anticorps thérapeutiques ciblent ces co-signaux inhibiteurs entre cellules tumorales ou cellules présentatrices d’antigènes et lymphocytes T, activant ou réactivant ainsi une immunité cellulaire T anti-tumorale. Mais la survenue d’une toxicité immunologique, qui peut concerner tous les organes, représente le facteur limitant dans le développement clinique de ces anticorps. La gestion de cette toxicité nécessite une collaboration étroite entre oncologues et spécialistes d’organe, et repose sur l’utilisation de corticoïdes et/ou d’autres immunosuppresseurs, avec l’objectif de contrôler la dysimmunité induite sans perdre l’efficacité anti-tumorale.
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Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active rheumatoid arthritis (RA) who start (new)... more
Objectives To investigate whether meticulously following a treat-to-target (T2T)-strategy in daily clinical practice will lead to less radiographic progression in patients with active rheumatoid arthritis (RA) who start (new) DMARD-therapy. Methods Patients with RA from 10 countries starting/changing conventional synthetic or biologic DMARDs because of active RA, and in whom treatment intensification according to the T2T principle was pursued, were assessed for disease activity every 3 months for 2 years (RA-BIODAM cohort). The primary outcome was the change in Sharp-van der Heijde (SvdH) score, assessed every 6 months. Per 3-month interval DAS44-T2T could be followed zero, one or two times (in a total of 2 visits). The relation between T2T intensity and change in SvdH-score was modelled by generalised estimating equations. Results In total, 511 patients were included (mean (SD) age: 56 (13) years; 76% female). Mean 2-year SvdH progression was 2.2 (4.1) units (median : 1 unit). A st...
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Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell... more
Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by a loss of tolerance toward self-nucleic acids, autoantibody production, interferon expression and signaling, and a defect in the regulatory T (Treg) cell compartment. In this work, we identified that platelets from patients with active SLE preferentially interacted with Treg cells via the P-selectin/P-selectin glycoprotein ligand-1 (PSGL-1) axis. Selectin interaction with PSGL-1 blocked the regulatory and suppressive properties of Treg cells and particularly follicular Treg cells by triggering Syk phosphorylation and an increase in intracytosolic calcium. Mechanistically, P-selectin engagement on Treg cells induced a down-regulation of the transforming growth factor–β axis, altering the phenotype of Treg cells and limiting their immunosuppressive responses. In patients with SLE, we found an up-regulation of P- and E-selectin both on microparticles and in their soluble forms that correlated with dise...
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OBJECTIVES To analyse the worldwide occurrence of sicca/Sjögren's (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer. METHODS The ImmunoCancer International Registry (ICIR) is a Big... more
OBJECTIVES To analyse the worldwide occurrence of sicca/Sjögren's (SS) syndrome associated with the use of immune checkpoint inhibitors (ICI) in patients with cancer. METHODS The ImmunoCancer International Registry (ICIR) is a Big Data-Sharing multidisciplinary network composed by 40 specialists in Rheumatology, Internal Medicine, Immunology and Oncology from 18 countries focused on the clinical and basic research of the immune-related adverse events (irAEs) related to cancer immunotherapies. For this study, patients who were investigated for a clinical suspicion of SS after being exposed to ICI were included. RESULTS We identified 26 patients (11 women and 15 men, with a mean age at diagnosis of 63.57 years). Underlying cancer included lung (n=12), renal (n=7), melanoma (n=4), and other (n=3) neoplasia. Cancer immunotherapies consisted of monotherapy (77%) and combined regimens (23%). In those patients receiving monotherapy, all patients were treated with PD-1/PD-L1 inhibitors ...
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ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries... more
ObjectivesTo investigate whether following a treat-to-target (T2T)-strategy in daily clinical practice leads to more patients with rheumatoid arthritis (RA) meeting the remission target.MethodsRA patients from 10 countries starting/changing conventional synthetic or biological disease-modifying anti-rheumatic drugs were assessed for disease activity every 3 months for 2 years (RA BIODAM (BIOmarkers of joint DAMage) cohort). Per visit was decided whether a patient was treated according to a T2T-strategy with 44-joint disease activity score (DAS44) remission (DAS44 <1.6) as the target. Sustained T2T was defined as T2T followed in ≥2 consecutive visits. The main outcome was the achievement of DAS44 remission at the subsequent 3-month visit. Other outcomes were remission according to 28-joint disease activity score-erythrocyte sedimentation rate (DAS28-ESR), Clinical Disease Activity Index (CDAI), Simplified Disease Activity Index (SDAI) and American College of Rheumatology/European ...
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Research Interests: Medicine and Gynecology
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Resume L’anticorps anti-Jo-1 est associe a un syndrome de chevauchement caracterise par l’association d’une fibrose pulmonaire, d’une myopathie inflammatoire idiopathique et d’une polyarthrite. Nous rapportons trois observations... more
Resume L’anticorps anti-Jo-1 est associe a un syndrome de chevauchement caracterise par l’association d’une fibrose pulmonaire, d’une myopathie inflammatoire idiopathique et d’une polyarthrite. Nous rapportons trois observations illustrant differents aspects des manifestations articulaires associees a la presence de l’anticorps anti-Jo-1. Deux patientes avaient une polyarthrite erosive et deformante des mains associee a des calcifications periarticulaires et a une luxation de l’interphalangienne du pouce. La troisieme patiente, pour qui le recul est moins important, avait simplement une polyarthrite non erosive des mains associee a des calcifications periarticulaires. Les trois patientes avaient une fibrose pulmonaire et seulement deux une atteinte musculaire. Une arthropathie caracterisee par une arthrite erosive des doigts, avec une dislocation de l’interphalangienne du pouce et des calcifications periarticulaires semble etre specifiquement associee a la presence de l’anticorps anti-Jo-1.
Research Interests: Medicine and Gynecology
The CRI Fact Sheets will soon celebrate their tenth anniversary. Their considerable popularity is ascribable to their practical focus on the issues raised by biotherapy use in adults and children seen in the real-life setting. The CRI... more
The CRI Fact Sheets will soon celebrate their tenth anniversary. Their considerable popularity is ascribable to their practical focus on the issues raised by biotherapy use in adults and children seen in the real-life setting. The CRI Fact Sheets present recommendations developed by experts in various medical fields, based both on published scientific evidence and, in the absence thereof, on expert opinion.
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We performed a genotypic characterization of seven strains ofMycoplasma fermentans which have been isolated from the synovial fluid of patients with rheumatoid arthritis (n = 2), spondyloarthropathy (n = 1), and unclassified arthritis (n... more
We performed a genotypic characterization of seven strains ofMycoplasma fermentans which have been isolated from the synovial fluid of patients with rheumatoid arthritis (n = 2), spondyloarthropathy (n = 1), and unclassified arthritis (n = 4). We compared them to three reference strains (strains PG18 and K7 and incognitus strain) and to a clinical isolate from the urethra of a patient with nongonococcal urethritis. The characterization methods included electrophoresis of native DNA, arbitrarily primed PCR, and restriction fragment length polymorphism analysis following conventional and pulsed-field gel electrophoresis. Southern blot analysis with a probe internal to an insertion sequence was performed with the restriction products produced by the last two techniques. No extrachromosomal DNA sequences were detected. The M. fermentans strains identified by these methods did not present a unique profile, but they could be separated into two main categories: four articular isolates were...
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Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut... more
Cystic fibrosis (CF) is a systemic genetic disease that leads to pulmonary and digestive disorders. In the majority of CF patients, the intestine is the site of chronic inflammation and microbiota disturbances. The link between gut inflammation and microbiota dysbiosis is still poorly understood. The main objective of this study was to assess gut microbiota composition in CF children depending on their intestinal inflammation. We collected fecal samples from 20 children with CF. Fecal calprotectin levels were measured and fecal microbiota was analyzed by 16S rRNA sequencing. We observed intestinal inflammation was associated with microbiota disturbances characterized mainly by increased abundances of Staphylococcus, Streptococcus, and Veillonella dispar, along with decreased abundances of Bacteroides, Bifidobacterium adolescentis, and Faecalibacterium prausnitzii. Those changes exhibited similarities with that of Crohn’s disease (CD), as evidenced by the elevated CD Microbial-Dysbio...
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Five clinical isolates of Mycoplasma hominis from three different patients were examined for resistance to fluoroquinolones; some of these isolates were probably identical. All five isolates harbored amino acid substitutions in the... more
Five clinical isolates of Mycoplasma hominis from three different patients were examined for resistance to fluoroquinolones; some of these isolates were probably identical. All five isolates harbored amino acid substitutions in the quinolone resistance-determining regions of both DNA gyrase (GyrA) and topoisomerase IV (ParC or ParE). Furthermore, the novobiocin MIC for three isolates showed a significant increase. This is the first characterization of fluoroquinolone-resistant clinical mycoplasma isolates from humans.
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To study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease. Patients with a well-controlled rheumatic disease... more
To study acceptance rate and factors influencing acceptance of the switch from originator etanercept (Enbrel©) to biosimilar etanercept (SB4, Bénépali©) in patients with rheumatic disease. Patients with a well-controlled rheumatic disease consulting in our rheumatology department were offered the switch for SB4. After oral and written information concerning biosimilar, free choice to accept the switch was left to the patients. The main outcome was primary switch acceptance rate defined by switch acceptance during the initial consult. Real switch adherence, socio-cultural factors and beliefs influencing switch acceptance rate were retrieved during a telephonic interview at distance from the consultation. Fifty-two patients were eligible for the switch: 32 (62%) with spondyloarthritis and 20 (38%) with rheumatoid arthritis. The primary acceptance rate was 92% (48/52). Patients refusing the switch were more likely to report a bad opinion on generic drugs (100% vs 11%, p < 0.001). Ot...
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Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the... more
Spondyloarthritis (SpA) pathophysiology remains largely unknown. While the association with genetic factors has been established for decades, the influence of gut microbiota is only an emerging direction of research. Despite the remarkable efficacy of anti-TNF-α treatments, non-responders are frequent and no predictive factors of patient outcome have been identified. Our objective was to investigate the modifications of intestinal microbiota composition in patients suffering from SpA three months after an anti-TNF-α treatment. We performed 16S rDNA sequencing of 38 stool samples from 19 spondyloarthritis patients before and three months after anti-TNF-α treatment onset. SpA activity was assessed at each time using ASDAS and BASDAI scores. Some modifications of the microbiota composition were observed after three months of anti-TNF-α treatment, but no specific taxon was modified, whatever the clinical response. We identified a particular taxonomic node before anti-TNF-α treatment tha...
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Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4-5 chronic kidney disease (CKD) patients. However, efficacy and... more
Interleukin (IL)-1β blocking is effective for the treatment of gout flares and is recommended in patients with contraindications to the standard of care, such as stage 4-5 chronic kidney disease (CKD) patients. However, efficacy and safety data regarding these agents are lacking in this population. We aimed to investigate the efficacy and safety of anakinra for the treatment of gout flares in patients with stage 4-5 CKD or renal transplantation. This retrospective study encompassing 3 academic centres included consecutive patients with stage 4-5 CKD or kidney transplantation who received anakinra for the treatment of acute gouty arthritis and completed at least one follow-up visit. Efficacy, occurrence of infection, and renal function variations were recorded. Of the 31 included patients (24 men, mean age 72 ± 11 years), 25 were non-transplant subjects with stage 4-5 CKD (mean estimated glomerular filtration rate, MDRD formula (eGFR) 22.7 ± 6.5mL/min/1.73 m), and 6 had undergone kid...
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To determine whether subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE) compared to healthy individuals, using carotid intima-media thickness (CIMT), carotid plaque (CP) presence or flow-mediated... more
To determine whether subclinical atherosclerosis is increased in patients with systemic lupus erythematosus (SLE) compared to healthy individuals, using carotid intima-media thickness (CIMT), carotid plaque (CP) presence or flow-mediated dilatation (FMD). A systematic literature search was performed using MedLine, Embase and Cochrane databases. Two reviewers independently screened the articles to identify studies that compared the rates of atherosclerosis in SLE patients versus healthy controls. The results were pooled in a meta-analysis. Factors influencing the CIMT, CP or FMD results were collected. Of the 203 articles initially identified, 68 were selected for the meta-analysis. Compared to healthy controls, SLE patients had a significantly increased CIMT (mean difference [MD] of 0.08mm, 95% CI [0.06-0.09], P<0.05), more CP (odds ratio 2.01, 95% CI [1.63-2.47], P<0.05) and decreased FMD (MD -3.96%, 95% CI [-5.37 to -2.54)], P<0.05). There was marked heterogeneity among t...
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Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on... more
Resident microbiota do not just shape host immunity, they can also contribute to host protection against pathogens and infectious diseases. Previous reviews of the protective roles of the microbiota have focused exclusively on colonization resistance localized within a microenvironment. This review shows that the protection against pathogens also involves the mitigation of pathogenic impact without eliminating the pathogens (i.e., "disease tolerance") and the containment of microorganisms to prevent pathogenic spread. Protective microorganisms can have an impact beyond their niche, interfering with the entry, establishment, growth, and spread of pathogenic microorganisms. More fundamentally, we propose a series of conceptual clarifications in support of the idea of a "co-immunity," where an organism is protected by both its own immune system and components of its microbiota.
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Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18... more
Adult-onset Still's disease (AOSD) is a rare systemic autoinflammatory disease; its management is largely empirical. This is the first clinical study to determine if interleukin (IL)-18 inhibition, using the recombinant human IL-18 binding protein, tadekinig alfa, is a therapeutic option in AOSD. In this phase II, open-label study, patients were ≥18 years with active AOSD plus fever or C reactive protein (CRP) levels ≥10 mg/L despite treatment with prednisone and/or conventional synthetic disease-modifying antirheumatic drugs (DMARDs). Previous biological DMARD treatment was permitted. Patients received tadekinig alfa 80 mg or 160 mg subcutaneously three times per week for 12 weeks; those receiving 80 mg not achieving early predicted response criteria (reduction of ≥50% CRP values from baseline and fever resolution) were up-titrated to 160 mg for a further 12 weeks. The primary endpoint was the occurrence of adverse events (AEs) throughout the study. Ten patients were assigned t...
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To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. This was a single-centre prospective... more
To evaluate the prevalence and type of rheumatic immune-related adverse events (irAEs) in patients receiving immune checkpoint inhibitors (ICIs), as well as the correlation with tumour response. This was a single-centre prospective observational study including all cancer patients receiving ICIs. The occurrence of irAEs and tumour response was assessed on a regular basis. Patients who experienced musculoskeletal symptoms were referred to the department of rheumatology for clinical evaluation and management. From September 2015 to May 2017, 524 patients received ICIs and 35 were referred to the department of rheumatology (6.6%). All but one of the rheumatic irAEs occurred with anti-programmed cell death protein 1(PD-1)/PD-1 ligand 1(PD-L1) antibodies, with a median exposure time of 70 days. There were two distinct clinical presentations: (1) inflammatory arthritis (3.8%) mimicking either rheumatoid arthritis (n=7), polymyalgia rheumatica (n=11) or psoriatic arthritis (n=2) and (2) no...
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The impact of gender on the response and tolerance to abatacept was assessed in a large prospective cohort during 2 years of follow-up. From the 1017 patients included in the Orencia and Rheumatoid Arthritis registry, disease activity was... more
The impact of gender on the response and tolerance to abatacept was assessed in a large prospective cohort during 2 years of follow-up. From the 1017 patients included in the Orencia and Rheumatoid Arthritis registry, disease activity was assessed at baseline, 6, 12 and 24 months. The relationship between the European League Against Rheumatism (EULAR) response, Disease Activity Score 28 (DAS28) remission, rate of adverse events and gender was explored in multivariate analysis. 990 patients, 79.3%female, with at least one follow-up visit were analysed. At baseline, women had longer disease duration, higher disease activity and more often received antitumour necrosis factor (TNF) drugs. The remission was not different between men and women during the follow-up after adjustment on age, disease duration and activity, rheumatoid factor and anti-cyclic citrullinated pyeptide (CCP) positivity, and current disease-modifying antirheumatic drugs (DMARDs), previous TNF blockers and corticoster...
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Resume L'etiologie de la sclerodermie systemique demeure mysterieuse. Parallelement a l'intervention de facteurs de predisposition genetique, le role de divers facteurs environnementaux et d'elements iatrogenes a ete discute.... more
Resume L'etiologie de la sclerodermie systemique demeure mysterieuse. Parallelement a l'intervention de facteurs de predisposition genetique, le role de divers facteurs environnementaux et d'elements iatrogenes a ete discute. Ainsi, de nombreux produits « toxiquesnaturels ou synthetiques seraient susceptibles d'induire par leur contact repete avec l'organisme (par inhalation, penetration percutanee, injection, ingestion ou implantation chirurgicale) une sclerodermie typique ou un tableau pseudosclerodermique. Certains de ces toxiques appartiennent exclusivement au milieu professionnel alors que d'autres entrent dans la composition de produits manipules couramment lors de travaux menagers ou de bricolage. Nous nous proposons de resumer l'etat des connaissances sur le sujet.
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... Hôpital Pellegrin, place Amélie-Raba-Léon -F-33076 Bordeaux Cedex, France. **** Hôpital Haut-Levêque, av. Magellan - F-33604 Pessac, France. ... JM Blasco and R. Diaz, Brucella melitensis Rev-1 vaccine as a cause of human brucellosis,... more
... Hôpital Pellegrin, place Amélie-Raba-Léon -F-33076 Bordeaux Cedex, France. **** Hôpital Haut-Levêque, av. Magellan - F-33604 Pessac, France. ... JM Blasco and R. Diaz, Brucella melitensis Rev-1 vaccine as a cause of human brucellosis, Lancet 342 (1993), p. 805. ...
Resume Objectif Les doses maximales de l’allopurinol sont limitees en cas d’insuffisance renale chronique, particulierement aux stades 4/5. Le febuxostat possede un metabolisme hepatique et son utilisation a ete autorisee sans... more
Resume Objectif Les doses maximales de l’allopurinol sont limitees en cas d’insuffisance renale chronique, particulierement aux stades 4/5. Le febuxostat possede un metabolisme hepatique et son utilisation a ete autorisee sans modification posologique chez les patients insuffisants renaux stades 1 a 3. Notre objectif etait d’etudier la tolerance et l’efficacite du febuxostat chez les patients insuffisants renaux chroniques stades 4/5. Methodes Dans cette etude retrospective, nous avons inclus les patients presentant (1) un diagnostic de goutte, (2) un traitement par febuxostat, (3) un debit de filtration glomerulaire ≤ 30 mL/min/1,73m 2 (formule MDRD) lors de l’initiation du febuxostat et (4) un suivi d’au moins 3 mois apres le debut du traitement par febuxostat. L’efficacite, la tolerance et la variation de la fonction renale ont ete analysees. Resultats Nous avons inclus 73 patients goutteux (âge moyen 70,2 ± 11,8 ans, 61 hommes, 31 patients avec nephrangiosclerose et 18 patients transplantes renaux) provenant de 10 centres universitaires. L’uricemie a l’initiation etait de 9,86 ± 2,85 mg/dL, la duree devolution moyenne de la goutte etait de 6,2 ± 7,0 ans. Les comorbidites etaient constituees d’insuffisance cardiaque (17,8 %), d’hypertension arterielle (98,6 %), de diabete (30,1 %), de dyslipidemie (64,8 %) et d’antecedents d’evenements thromboemboliques (38,4 %). Lors de la derniere visite (suivi moyen de 68,5 ± 64,8 semaines), la dose de febuxostat etait de 40 mg/j pour 7 patients (10,5 %), 80 mg/j pour 50 (74,6 %) et 120 mg/j pour 10 patients (14,9 %). L’uricemie etait Conclusion Le febuxostat semble etre efficace chez les patients goutteux insuffisants renaux chroniques stades 4/5. Cependant, la tolerance concernant la fonction renale n’est pas certaine. De plus grandes etudes sont necessaires pour la determiner.
Resume Objectifs Dans la polyarthrite rhumatoide (PR), patients et medecins peuvent avoir des perceptions differentes. L’objectif de ce travail etait de definir la notion de « poussees » du point de vue du patient. Methodes Analyse... more
Resume Objectifs Dans la polyarthrite rhumatoide (PR), patients et medecins peuvent avoir des perceptions differentes. L’objectif de ce travail etait de definir la notion de « poussees » du point de vue du patient. Methodes Analyse post-hoc d’un essai comparatif randomise consacre a une strategie de diminution progressive des anti-TNF chez des patients atteints de PR, ayant un score DAS 28 de remission depuis au moins six mois et randomises dans deux groupes : « espacement » (E) ou « maintien » (M) du traitement. La survenue de poussees rapportees par le patient (PRP) a ete evaluee tous les trois mois sur une periode de 18 mois par la question suivante : « Au cours des trois derniers mois, avez-vous ressenti des symptomes evoquant une exacerbation de la maladie ? » Les visites avec et sans PRP ont ete comparees a l’aide d’un modele lineaire a effets mixtes pour les symptomes, l’invalidite mesuree par le questionnaire d’evaluation de l’etat de sante HAQ (Health Assessment Questionnaire), la qualite de vie evaluee par le questionnaire SF-36 (Short Form-36) et les rechutes definies par le score DAS 28 (RDD), c’est-a-dire une augmentation du score DAS 28 de plus de 0,6 et une valeur absolue superieure a 2,6. L’accord entre PRP et RDD a ete mesure par le coefficient kappa sur les donnees repetees. Resultats Ont ete analyses au total 137 patients d’âge moyen 55 ± 11 ans, dont 78 % de femmes, atteints de PR depuis en moyenne 9,5 ± 8 ans. Au cours des 18 mois de l’etude, des PRP etaient rapportees par 95 patients (70,9%) et concernaient 27,2% des 940 visites disponibles sur 18 mois de suivi. Tous les criteres d'activite etaient associes aux PRP avec une ampleur d’effet standardisee comprise entre –0,58 (PCS SF-36) et 0,87 (DAS 28). L’agrement entre PRP et RDD etait modere (κ = 0,44). Conclusion La notion de poussees englobe d’autres dimensions que la seule activite de la PR.
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To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO). A... more
To assess the efficacy of bisphosphonate therapy on bone pain in patients with osteoid osteoma (OO) (main objective), and to describe bisphosphonate-induced changes in nidus mineralisation and regional bone-marrow oedema (BMO). A prospective, observational study was conducted from 2011 to 2014. Patients with risk factors for complications of percutaneous or surgical ablation or recurrence after ablation, were offered once monthly intravenous bisphosphonate treatment until significant pain alleviation was achieved. We included 23 patients. The first two patients received pamidronate and the next 21 zoledronic acid (mean, 2.95 infusions per patient). Bisphosphonate therapy was successful in 19 patients (83%), whose mean pain visual analogue scale score decreased by 76.7%; this pain-relieving effect persisted in 17 patients (74%) with a mean follow-up time of 36 months. Computed tomography (CT) demonstrated a mean nidus density increase of 177.7% (p = 0.001). By magnetic resonance imaging (MRI), mean decreases were 38.4% for BMO surface area and 30.3% for signal intensity (p = 0.001 and p = 0.000, respectively). In 17/23 patients with painful OO managed conservatively with bisphosphonates, long-term final success was achieved. Bisphosphonates may accelerate the spontaneous healing of OO. • 19/23 patients with OO managed with bisphosphonates experienced significant pain relief • Pain relief was sustained in 17/23 patients, mean follow-up of 36 months • CT demonstrated a significant increase in nidus mineralisation • MRI demonstrated a significant decrease in bone marrow oedema • Bisphosphonate therapy may accelerate the spontaneous healing of OO.
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although the outcome for patients with rheumatoid arthritis (ra) has improved in the past decades, adequate disease control cannot be achieved in a substantial proportion of patients. new drugs with a novel mechanism of action, may... more
although the outcome for patients with rheumatoid arthritis (ra) has improved in the past decades, adequate disease control cannot be achieved in a substantial proportion of patients. new drugs with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Areas covered: This review focuses on the pharmacodynamics and pharmacokinetics of baricitinib. Furthermore, the article summarizes and comments the drug&amp;amp;amp;amp;#39;s efficacy and safety profile in RA patients. Expert opinion: Baricitinib is an oral targeted synthetic (ts) disease-modifying antirheumatic drug (DMARD) that mainly inhibits JAK1 and JAK2. Baricitinib monotherapy, or in combination with conventional synthetic (cs) DMARDs, has demonstrated its efficacy while having an acceptable safety profile in early active RA naive to DMARDs, and active RA with an inadequate response to csDMARDs and/or biologic (b)DMARDs. The future place of baricitinib in the management of RA patients will depend on several factors. However, baricitinib offer few advantages: oral administration, rapidity of action, efficacy in monotherapy and over adalimumab in one study and non-immunization. However, pending further safety data, current practice would be to start a bDMARD when the treatment target is not achieved with csDMARDs. Availability of additional long-term safety data may influence prescribing decisions.
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Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual... more
Despite its high prevalence and mortality, little is known about the pathogenesis of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Given that familial pulmonary fibrosis (FPF) and RA-ILD frequently share the usual pattern of interstitial pneumonia and common environmental risk factors, we hypothesised that the two diseases might share additional risk factors, including FPF-linked genes. Our aim was to identify coding mutations of FPF-risk genes associated with RA-ILD.We used whole exome sequencing (WES), followed by restricted analysis of a discrete number of FPF-linked genes and performed a burden test to assess the excess number of mutations in RA-ILD patients compared to controls.Among the 101 RA-ILD patients included, 12 (11.9%) had 13 WES-identified heterozygous mutations in the TERT, RTEL1, PARN or SFTPC coding regions. The burden test, based on 81 RA-ILD patients and 1010 controls of European ancestry, revealed an excess of TERT, RTEL1, PARN or SFTPC mut...
Research Interests: Medicine, Software, Humans, Interstitial Lung Disease, Pulmonary fibrosis, and 15 moreMutation, Europe, Female, Male, Genetic Association Studies, Risk factors, Phenotype, Aged, Middle Aged, Adult, Risk Factors, Idiopathic Pulmonary Fibrosis, Exome, Case Control Studies, and Medical and Health Sciences
Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand... more
Mitochondrial DNA (mtDNA) contains sequestered damage-associated molecular patterns that might be involved in osteoimmunological pathogenesis of RA. Here, we aimed to investigate the cellular source of mtDNA and its role in RANK ligand (RANKL) expression by RA SF neutrophils. The gene expression signature of SF neutrophils was examined by proteomic quantitative analysis. Levels of mtDNA in circulating and SF neutrophils from RA patients and OA control subjects were assessed by real-time PCR. Purified neutrophils were challenged in vitro with Toll-like receptor agonists as well as mtDNA. RANKL expression by neutrophils was studied by flow cytometry. . SF neutrophils from RA patients displayed a gene expression signature of oxidative stress. This stress signature was associated with the release of mtDNA in SF as observed by a significant increase of mtDNA in the SF of RA patients compared with OA patients. mtDNA in RA SF was correlated with systemic inflammation as assessed by CRP con...
Research Interests: Rheumatology, Immunology, Flow Cytometry, Oxidative Stress, Medicine, and 15 moreSignal Transduction, Humans, Female, Male, Clinical Sciences, Aged, Middle Aged, Neutrophils, Adult, Retrospective Studies, Reference Values, Enzyme Linked Immunosorbent Assay, Gene Expression Regulation, Case Control Studies, and real time polymerase chain reaction
Mucopolysaccharidoses are a group of rare lysosomal storage diseases including a great number of polymorph syndromes, each being related to a particular mutation responsible for a deficiency of glycosaminoglycan degrading enzymes, leading... more
Mucopolysaccharidoses are a group of rare lysosomal storage diseases including a great number of polymorph syndromes, each being related to a particular mutation responsible for a deficiency of glycosaminoglycan degrading enzymes, leading to an accumulation of glycosaminoglycans in tissues. Many of them are diagnosed in children or teenagers and have a severe prognosis because of organ failure, and are consequently usually not seen by the adult rheumatologist. However, some of them have a more progressive presentation, with musculoskeletal symptoms at the forefront and a lifespan that nearly reaches that of the general population. These milder forms are more likely to be diagnosed in adults, in patients who have suffered for years and sometimes even decades with unrecognized mucopolysaccharidosis. Indeed, they can sometimes mimic inflammatory rheumatic disorders, and therefore be misdiagnosed for a long time. Recognition and diagnosis of these attenuated forms can be a real challeng...
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Joint Bone Spine - In Press.Proof corrected by the author Available online since samedi 21 janvier 2017