Laurent Arnaud

Aix-Marseille Université, Marsiglia, Provence-Alpes-Côte d'Azur, France

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Publications (159)691.76 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: The clinical benefit of ticagrelor compared to clopidogrel in ACS patients suggested off-target property. Such pleiotropic effect could be mediated by circulating endothelial progenitor cells (EPC) which are critical for vascular healing. We aimed to investigate the impact of ticagrelor on EPC in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). We prospectively randomized 106 ACS patients to ticagrelor or clopidogrel. Sub-populations of CD34+ circulating progenitor cells (PC) were analyzed by flow cytometry allowing one to determine the levels of CD34+ PC, CD34+CD45+ Hematopoietic PC, CD34+133+ immature PC and CD34+KDR+ EPC on admission and at 1month. Changes in PC level were calculated as the difference between 1month and baseline value. The 2 groups were similar regarding baseline characteristics including PC numbers on admission. The 2 groups had similar change in overall CD34+ PC and hematopoietic CD34+45+ PC level (p=0.2). On the contrary, when considering CD34+133+ PC and CD34+KDR+ EPC, we observed that patients treated by ticagrelor had a significantly higher increase in levels of these PC subtypes compared to those treated by clopidogrel (0.23 (-0.33; 0.79) vs 0.00 (-0.5; 0.34); p=0.04 and 0.01 (-0.04; 0.05) vs -0.01 (-0.06; 0.03); p=0.02). Changes in the level of CD34+CD133+ PC correlated with platelet activity measured by the VASP index (r=-0.30; p=0.008). By contrast the increase in the level of CD34+KDR+ EPC in the ticagrelor group was independent of platelet activity. Ticagrelor increases the number of EPC in ACS patients suggesting a benefit on endothelial regeneration that may participate in the pleiotropic property of the drug. Copyright © 2015. Published by Elsevier Ireland Ltd.
    International journal of cardiology 03/2015; 187:502-507. DOI:10.1016/j.ijcard.2015.03.414 · 6.18 Impact Factor
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    ABSTRACT: Interaction between smoking and efficacy of antimalarials, the mainstay of treatment for cutaneous lupus erythematosus (CLE), remains controversial. We systematically reviewed the evidence for such an interaction and performed a meta-analysis to compare the efficacy of antimalarials among smoker versus nonsmoker patients with CLE. Observational studies published up to March 2014 in the MEDLINE, Embase, and Cochrane databases were selected if they reported on the efficacy of antimalarials for treatment of CLE, according to smoking status. The strength of association between smoking and cutaneous response rate was expressed using the odds ratio. Individual study odds ratios were combined in the meta-analysis using a random effects model. Of 240 citations retrieved, 10 studies met inclusion criteria, for a total of 1398 patients. The pooled odds ratio for the response to antimalarials in smoker patients with CLE (n = 797) was 0.53 (95% confidence interval 0.29-0.98) compared with nonsmokers (n = 601). Subgroup analyses for the response to antimalarials considering CLE subtypes, type, and dosage of antimalarials could not be performed because of the lack of available data. Smoking is associated with a 2-fold decrease in the proportion of patients with CLE achieving cutaneous improvement with antimalarials. Smoking cessation should be considered in patients with CLE and refractory cutaneous involvement. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
    Journal of the American Academy of Dermatology 01/2015; 72(4). DOI:10.1016/j.jaad.2014.12.025 · 5.00 Impact Factor
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    ABSTRACT: The capillary leak syndrome (CLS) is a rare condition characterized by the onset of hypotension, edema, hemoconcentration and hypoalbuminemia. CLS can be idiopathic (Clarkson's disease) or secondary to various conditions and treatments. Here, we review the clinical and biological features, pathophysiology, causes and treatment of this rare condition.
    La Revue de Médecine Interne 01/2015; 36(6). DOI:10.1016/j.revmed.2014.11.005 · 1.32 Impact Factor
  • Annales de Dermatologie et de Vénéréologie 12/2014; 141(12). DOI:10.1016/j.annder.2014.09.063 · 0.67 Impact Factor
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    ABSTRACT: Histiocytoses are rare disorders with heterogeneous prognosis. BRAF(V600E) mutations have been observed in half of patients with Langerhans cell histiocytosis (LCH) and in 50% to 100% of patients with Erdheim-Chester disease (ECD) patients. We recently reported short-term efficacy of a BRAF inhibitor (vemurafenib) in three patients with multisystemic ECD. Vemurafenib was given to eight patients with multisystemic ECD with CNS and/or cardiac involvement. All patients were refractory to first-line treatment and harbored a BRAF(V600E) mutation. Four patients also had LCH lesions. Positron emission tomography (PET) scan response at month 6 was used as the main evaluation criterion. Secondary evaluation criteria were comparison at baseline and at last visit of PET and of cardiovascular and cerebral infiltrations (computed tomography scan and magnetic resonance imaging [MRI]). All patients were partial metabolic responders at 6 months of vemurafenib, and the median reduction in maximum standardized uptake value was 63.5% (range, 41.3% to 86.9%). Evaluation of cardiac and aortic infiltrations showed that seven patients had a partial response and one patient had stable disease according to surface measurements derived from RECIST criteria. The four patients with infratentorial CNS infiltration had an objective decrease of the lesions on MRI. All patients had an improvement of general symptoms and a persistent response to vemurafenib, with a median follow-up time of 10.5 months (range, 6 to 16 months). Skin adverse effects were frequent and severe. Vemurafenib has an objective and sustained efficacy in BRAF(V600E)-mutated ECD as second-line therapy. In contrast to melanoma, no resistance has emerged to date after 6 to 16 months. © 2014 by American Society of Clinical Oncology.
    Journal of Clinical Oncology 11/2014; 33(5). DOI:10.1200/JCO.2014.57.1950 · 17.88 Impact Factor
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    ABSTRACT: To develop French recommendations about screening and management of cardiovascular risk factors in systemic lupus erythematosus (SLE). Thirty-nine experts qualified in internal medicine, rheumatology and nephrology have selected recommendations from a list developed based on evidence from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified. Experts recommended an annual screening of cardiovascular risk factors in SLE. Statins should be prescribed for primary prevention in SLE patients based on the level of LDL-cholesterol and the number of cardiovascular risk factors, considering SLE as an additional risk factor. For secondary prevention, experts have agreed on an LDL-cholesterol target of <0.7 g/L. Hypertension should be managed according to the 2013 European guidelines, using renin-angiotensin system blockers as first line agents in case of renal involvement. Aspirin can be prescribed in patients with high cardiovascular risk or with antiphospholipid antibodies. These recommendations about the screening and management of cardiovascular risk factors in SLE can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients. Copyright © 2014. Published by Elsevier SAS.
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    ABSTRACT: Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.
    La Revue de Médecine Interne 11/2014; DOI:10.1016/j.revmed.2014.07.005 · 1.32 Impact Factor
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    ABSTRACT: To date, only a small number of studies have examined the epidemiology of systemic lupus erythematosus (SLE) on a nation-wide basis. We used French national administrative databases to analyze the nation-wide prevalence and incidence rates of SLE within the largest French health insurance scheme, which covers 86% of the population (almost 58,200,000 individuals). Patients with SLE were identified if they had full coverage for a chronic disease with a code (ICD-10th M32) in the health insurance information system, or if they had a SLE code in the hospital discharge database as a primary or secondary diagnosis in 2010. We defined incident cases as patients who had a new long-term disease diagnosis of SLE in 2010. Overall, 27,369 individuals were identified as having SLE, 88% were female. The crude 2010 prevalence of identified SLE was 47.0/100,000, and the WHO age-standardized rate 40.8/100,000. The crude 2010 annual incidence of SLE was 3.32 cases per 100,000 with peaks in females aged 30-39yo (9.11/100,000) and in males aged 50-59yo (1.78/100,000). Major differences in regional age-standardized prevalence rates were observed, with highest rates in the Caribbean overseas areas (up to 126.7/100,000), and lowest rates in north-western metropolitan territories (down to 29.6/100,000). This is the largest nation-wide population-based study of SLE patients to date, based on more than 58 million beneficiaries of the French health insurance system. These data and subsequent analyses provide guidance to both clinicians and policymakers for improving care of SLE.
    Autoimmunity Reviews 11/2014; 13(11). DOI:10.1016/j.autrev.2014.08.034 · 7.10 Impact Factor
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    ABSTRACT: Objectives. This study aimed to estimate the responsiveness to change of a generic [the 36-item Short Form Health Survey (SF-36)] and a specific health-related quality of life questionnaire [the Lupus Quality if Life questionnaire (LupusQoL)] according to SLE patients’ self-reported changes in health status. Methods. In a cohort of 185 SLE patients, quality of life (QoL) was measured three times at 3 month intervals by the LupusQoL and SF-36 questionnaires. Anchors for responsiveness were defined by patients’ global assessment of disease impact according to changes in a visual analogue scale (VAS), a 7-point Likert scale and a 0-3 scale of five patient-reported symptoms. Mean change and s.d. in worsening and improving patients according to anchors were estimated using mixed models for repeated measures. Standardized response means (SRMs) were calculated in each group. Results. Patients [mean age 39.6 years (s.d. 10.5), mean Safety of Estrogen in Lupus Erythematosus National Assessment-SLEDAI score 2.6 (s.d. 3.5)] answered a total of 515 questionnaires. For the VAS and Likert global anchors, worsening patients showed a significant decrease in all LupusQoL domains except for burden to others, body image and fatigue and all SF-36 domains with low to moderate responsiveness. Improving patients had a significant increase in all LupusQoL domains except for intimate relationship and all SF-36 domains except for physical functioning and global health with low to moderate responsiveness. Regarding similar domains in the SF-36 and LupusQoL, SRMs were higher in LupusQoL domains in improving patients, while SF-36 domains had larger SRMs in worsening patients. Conclusion. Both the SF-36 and LupusQoL were responsive to changes in QoL in SLE patients over a 3 month interval. LupusQoL seems to be more appropriate to measure improvements in QoL.
    Rheumatology (Oxford, England) 10/2014; 54(5). DOI:10.1093/rheumatology/keu410 · 4.44 Impact Factor
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    ABSTRACT: We performed an individual patient meta-analysis to determine whether aspirin has a significant protective effect on the risk of first thrombosis among patients with antiphospholipid antibodies (aPL). Five international cohort studies with available individual patient-level data, reporting on primary prophylaxis with continuous treatment with low-dose aspirin in patients with aPL were included. The main outcome was the occurrence of a first thrombotic in patients with aPL treated with low-dose aspirin compared to those not treated with low-dose aspirin. Pooled Hazard Ratios (HRs) and 95%CIs were calculated using frailty models. We pooled data from 497 subjects and 79 first thrombotic events (3469 patient-years of follow-up). After adjustment on cardiovascular risk factors, aPL profiles, and treatment with hydroxychloroquine, the HR for the risk of a first thrombosis of any type in aPL carriers treated with low-dose aspirin versus those not treated with aspirin was 0.43 (95%CI 0.25–0.75). Subgroup analysis showed a protective effect of aspirin against arterial (HR: 0.43 [95%CI: 0.20–0.93]) but not venous (HR: 0.49 [95%CI: 0.22–1.11]) thrombosis. Subgroup analysis according to underlying disease revealed a protective effect of aspirin against arterial thrombosis for systemic lupus erythematosus (SLE) (HR: 0.43 [95%CI: 0.20–0.94]) and asymptomatic aPL carriers (HR: 0.43 [95%CI 0.20–0.93]). We found no independent protective effect of hydroxychloroquine. This individual patient data meta-analysis shows that the risk of first thrombotic event as well of first arterial thrombotic event is significantly decreased among SLE patients and asymptomatic aPL individuals treated by low-dose aspirin.
    Autoimmunity Reviews 10/2014; 14(3). DOI:10.1016/j.autrev.2014.10.019 · 7.10 Impact Factor
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    ABSTRACT: Multiple factors contribute to the increased cardiovascular risk observed in patients with systemic lupus erythematosus (SLE). Among these are the so-called classical cardiovascular risk factors, the disease itself through its activity, treatments, and complications, and the thrombotic risk due to antiphospholipid antibodies (aPL). Observational studies suggest that most classical cardiovascular risk factors are observed more frequently in SLE patients than in the general population, and that these are insufficient to explain the increased cardiovascular risk observed in most studies. Given this high risk, adequate management of cardiovascular risk factors should be recommended in SLE patients. Paradoxically, the benefit due to the anti-inflammatory properties of treatments such as corticosteroids may exceed, in certain cases, their pro-atherogenic effect. Importantly, the tools that were developed for the estimation of cardiovascular risk at the individual level among the general population cannot be used reliably in SLE patients, as these tools appear to underestimate the true cardiovascular risk. The adequate indications and targets of cardiovascular treatments are therefore not fully known in SLE. A better understanding of the determinants of the cardiovascular risk in SLE will allow the identification and more tailored management of these high-risk patients.
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    ABSTRACT: In patients with systemic sclerosis (scleroderma, SSc), impaired hand function greatly contributes to disability and reduced quality of life, and is insufficiently relieved by currently available therapies. Adipose tissue-derived stromal vascular fraction (SVF) is increasingly recognised as an easily accessible source of regenerative cells with therapeutic potential in ischaemic or autoimmune diseases. We aimed to measure for the first time the safety, tolerability and potential efficacy of autologous SVF cells local injections in patients with SSc with hand disability.
    Annals of the Rheumatic Diseases 08/2014; DOI:10.1136/annrheumdis-2014-205681 · 9.27 Impact Factor
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    ABSTRACT: Background Autoimmune thrombotic thrombocytopenic purpura (AI-TTP) is characterized by an excess of circulating ultra-large von Willebrand Factor (vWF) due to anti-ADAMTS13 auto-antibodies. Animal studies however have shown that endothelial cell activation may also be an important trigger of AI-TTP.Objectives To prospectively study circulating biomarkers of endothelial lesion and activation such as circulating endothelial cells (CEC), soluble (s)P-selectin or vWF and of endothelial repair such as circulating progenitor cells (CPC) and endothelial progenitor cells (EPC) in AI-TTP, in correlation with disease severity and prognosis.Results22 patients were included in this study. CEC (p<0.01), vWF (p<0.05) and sP-selectin (p<0,01) were significantly increased during crisis and returned to baseline levels during remission. Both CEC (p<0.05) and sP-selectin (p<0.05) were significantly higher in patients who died or developed neurological sequelae. CPC counts were highly increased during the acute phase of the disease (p<0.001) and returned to baseline levels during remission. Among CPC, EPC were also increased during crisis (p<0.05) and significantly decreased during remission. Patients who received less than 16 plasma exchange (PE) therapy had significantly higher EPC counts (p<0.05) than those who needed more numerous PE to obtain remission, suggesting that initial EPC counts may be associated with faster endothelial repair.Conclusion The profile of circulating endothelial markers shows massive endothelial activation and repair/remodeling during AI-TTP, and suggests that CEC and EPC may be promising prognosis biomarkers of the disease.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 08/2014; 12(10). DOI:10.1111/jth.12681 · 5.55 Impact Factor
  • Source
    A. Mathian, L. Arnaud, Z. Amoura
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    ABSTRACT: Systemic lupus erythematous is a chronic autoimmune disease characterized by the inflammation of several tissues and the production of auto-antibodies directed against nuclear antigens. Complex genetic disorders and environmental factors are at the origin of the disease but the precise cause of the auto-immune process is still unknown. Both innate and adaptive immune systems are involved. Apoptosis seems to be the main source of auto-antigens. The interactions between apoptotic cells, dendritic cells and lymphocytes activate the production of pathogenic antibodies and T lymphocytes. Amplification loops sustain the auto-immune process and the chronic inflammation. Several data point out B-lymphocytes and several cytokines involved in their homeostasis as new promising therapeutic targets.
    La Revue de Médecine Interne 08/2014; 35(8):503–511. DOI:10.1016/j.revmed.2013.10.334 · 1.32 Impact Factor
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    ABSTRACT: Distinction between infection and febrile disease flare in patients with systemic lupus erythematosus (SLE) is fundamental but often difficult to make, because clinical presentation can be similar. A systematic review of all articles indexed in PubMed through October 2013 was performed, in order to examine the potential role of procalcitonin (PCT) for the discrimination between SLE flare and infection. Among the 12 papers identified, 5 articles reported on PCT levels in SLE patients without infection, 6 compared PCT levels between SLE patients with flare versus those with infection, and 1 analyzed PCT levels in active patients with and without bacterial infection. These data suggest the absence of correlation between PCT levels and SLE disease activity. Furthermore, PCT levels detected during disease flares are lower than those observed during bacterial infections. PCT can therefore be used accurately in the early differentiation between bacterial infection and flare in febrile SLE patients. Raised PCT levels ≥0.5 μg/L should strongly suggest bacterial infection in the context of SLE, keeping in mind the limited data available in case of hemophagocytic syndrome. Elevated PCT levels in SLE patients should always prompt a thorough search for sources of potential infection.
    Clinical Rheumatology 07/2014; 33(9). DOI:10.1007/s10067-014-2738-4 · 1.77 Impact Factor
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    ABSTRACT: Histiocytoses are a group of heterogeneous diseases that mostly comprise Langerhans cell histiocytosis (LCH) and non-LCH. The association of LCH with non-LCH is exceptional. We report 23 patients with biopsy proven LCH associated with Erdheim-Chester disease (ECD) (mixed histiocytosis) and discuss the significance of this association. We compare the clinical phenotype of these patients with that of 56 patients with isolated LCH and 53 patients with isolated ECD. The average age at diagnosis was 43. ECD followed (n=12), or was diagnosed simultaneously (n=11), but never preceded LCH. Although heterogeneous, the phenotype of patients with mixed histiocytosis was closer to that of isolated ECD than to that of isolated LCH (principal component analysis). LCH and ECD improved in response to interferon-α-2a treatment in only 50% (8/16) of cases. We found the BRAF(V600E) mutation in 11/16 LCH lesions (69%) and in 9/11 ECD lesions (82%). Eight patients were mutated in both ECD and LCH biopsies. Our findings indicate that the association of LCH and ECD is not fortuitous and suggest a link between these diseases involving the BRAF(V600E) mutation.
    Blood 06/2014; 124(7). DOI:10.1182/blood-2013-12-543793 · 10.43 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A43–A44. DOI:10.1016/j.revmed.2014.03.037 · 1.32 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A44. DOI:10.1016/j.revmed.2014.03.038 · 1.32 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A65-A66. DOI:10.1016/j.revmed.2014.03.077 · 1.32 Impact Factor
  • La Revue de Médecine Interne 06/2014; 35:A50. DOI:10.1016/j.revmed.2014.03.048 · 1.32 Impact Factor

Publication Stats

1k Citations
691.76 Total Impact Points

Institutions

  • 2009–2015
    • Aix-Marseille Université
      • • Faculté de Pharmacie
      • • Département de biologie
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Université Paris 13 Nord
      Île-de-France, France
  • 2014
    • Université Paris-Sorbonne - Paris IV
      Lutetia Parisorum, Île-de-France, France
    • UPMC
      Pittsburgh, Pennsylvania, United States
  • 2012–2014
    • Polytech Paris-UPMC
      Lutetia Parisorum, Île-de-France, France
  • 2006–2014
    • Hôpital La Pitié Salpêtrière (Groupe Hospitalier "La Pitié Salpêtrière - Charles Foix")
      • Service de Médecine Interne 1
      Lutetia Parisorum, Île-de-France, France
    • Hôpital Foch
      Lutetia Parisorum, Île-de-France, France
  • 2013
    • Assistance Publique Hôpitaux de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Laboratoire d’Informatique Fondamentale de Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
    • Hôpital Européen, Marseille
      Marsiglia, Provence-Alpes-Côte d'Azur, France
  • 2011–2013
    • Hôpitaux Universitaires La Pitié salpêtrière - Charles Foix
      Lutetia Parisorum, Île-de-France, France
    • Pierre and Marie Curie University - Paris 6
      • Immunologie, immunopathologie, immunothérapie UMR 7211
      Lutetia Parisorum, Île-de-France, France
    • Azienda Ospedaliera Ospedali Riuniti Villa Sofia Cervello
      Palermo, Sicily, Italy
  • 2009–2013
    • Assistance Publique – Hôpitaux de Paris
      Lutetia Parisorum, Île-de-France, France
  • 2011–2012
    • Unité Inserm U1077
      Caen, Lower Normandy, France
  • 2010–2012
    • French Institute of Health and Medical Research
      • Unit of Immunity and Infection
      Lutetia Parisorum, Île-de-France, France