Publications by authors named "Hervé Lévesque"

81 Publications

TRIM33 gene somatic mutations identified by next generation sequencing in neoplasms of patients with anti-TIF1γ positive cancer-associated dermatomyositis.

Rheumatology (Oxford) 2021 Mar 25. Epub 2021 Mar 25.

Normandie University, UNIROUEN, IRIB, Inserm, U1234, Rouen, France.

Objective: To deep sequence the TRIM33 gene in tumours from patients with cancer-associated anti-TIF1γ autoantibody-positive dermatomyositis (DM) since TRIM33 somatic mutations in tumours may trigger this auto-immune disease.

Methods: Next generation sequencing of tumour DNA samples from patients with cancer-associated anti-TIF1γ autoantibody-positive DM. Fourteen tumours from 13 anti-TIF1γ autoantibody-positive DM individuals were sequenced along with 2 control tumours from non-DM individuals.

Results: Fourteen probable somatic variants from 4 tumours were identified in the TRIM33 gene.

Conclusion: These results are in accordance with the previous report of Pinal-Fernandez et al. and support the hypothesis of a role of TRIM33 gene mutations in the pathophysiology of anti-TIF1γ autoantibody-positive DM.
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http://dx.doi.org/10.1093/rheumatology/keab260DOI Listing
March 2021

Association between familial Mediterranean fever and multiple sclerosis: A case series from the JIR cohort and systematic literature review.

Mult Scler Relat Disord 2021 May 10;50:102834. Epub 2021 Feb 10.

Sorbonne University; Internal Medicine Department; AP-HP; Hôpital Tenon; Paris; France; Centre de Référence des Maladies Auto-Inflammatoires et des Amyloses Inflammatoire (CEREMAIA)-JIR Cohort; France. Electronic address:

Introduction: Familial Mediterranean fever (FMF) is the most frequent monogenic autoinflammatory disorder; and leads to the uncontrolled production of interleukin (IL)-1β. Multiple sclerosis (MS) is an inflammatory disease of the central nervous system; and its development seems to be partly correlated with IL-1β levels. It is hypothesized that FMF could be associated with MS. We aim to describe the features of patients displaying both diseases and to investigate the MEFV mutation rate in MS patients.

Methods: Patients with definite MS were retrieved from the cohort of FMF patients in the Reference Center for Rare Auto-inflammatory Diseases and Amyloidosis (CEREMAIA). We also performed a systematic literature review of articles from PubMed that were published from 1990 to 2020.

Results: Twenty-four patients were included in the case series: five patients (1.3%) from our cohort of 364 and 19 patients from the literature. The sex ratio was 2:1. The mean age at diagnosis of FMF was 19 years old; and that for MS was 29 years old. Seven studies investigating the MEFV mutation rate in MS patients were included. Three studies found a higher mutation rate in MS patients than in the control group.

Conclusion: FMF and MS features were comparable to those of patients with unrelated diseases; and MEFV mutation carriage was not positively correlated with MS. However; MS prevalence in FMF patients was higher than was expected in a healthy population. To a lesser extent; FMF prevalence in MS patients was higher than expected in a healthy population and the difference might not be significant. These data suggest that FMF could be associated with MS; and further studies are needed to investigate a potential causal association.
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http://dx.doi.org/10.1016/j.msard.2021.102834DOI Listing
May 2021

Cardiac involvement in adult-onset Still's disease: Manifestations, treatments and outcomes in a retrospective study of 28 patients.

J Autoimmun 2021 01 15;116:102541. Epub 2020 Sep 15.

Department of Internal Medicine, Rouen University Hospital, 76000, Rouen, France; INSERM U 905, University of Rouen IFRMP, Institute for Biochemical Research, Rouen University Hospital, 76000, Rouen, France.

Objective: Adult-onset Still's disease (AOSD) is a rare inflammatory disease that may be life-threatening if complicated by cardiac problems. We performed a retrospective multicenter study to describe the manifestations, treatments and outcomes of cardiac involvement in AOSD.

Methods: We reviewed the medical databases of eight centers. All AOSD patients identified as fulfilling Yamagushi's or Fautrel's criteria were included in the study. Cardiac involvement, clinical manifestations, laboratory features, the course of the disease and treatments were evaluated.

Results: We included 96 AOSD patients in this study: 28 (29%) had documented cardiac involvement (AOSD + C group) and 68 (71%) had no cardiac involvement (control group). Cardiac complications were observed at diagnosis in 89% of cases. It were pericarditis (n = 17), tamponade (n = 5), myocarditis (n = 5) and non-infectious endocarditis (n = 1). Levels of leukocytes, neutrophils and C-reactive protein were significantly higher (p = 0.02, p = 0.02 and p = 0.002, respectively in the AOSD + C group than in the control group. Admission to intensive care, and the use of biotherapy were more frequent during follow-up in the AOSD + C group than the control group (p = 0.0001 and p = 0.03 respectively). Cardiac involvement was associated with refractory form in multivariate analyzed (p = 0.01). Corticosteroids were effective with or without methotrexate in 71% of patients but not in severe involvement as myocarditis or tamponade.

Conclusion: Cardiac complications are frequent, inaugural, can be life-threatening and predictive of a refractory course in patients with AOSD. Systematic cardiac screening should be proposed at diagnosis and biotherapy early use should be considered especially in myocarditis.
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http://dx.doi.org/10.1016/j.jaut.2020.102541DOI Listing
January 2021

[Toward the use of direct oral anticoagulants as a first line therapy in cancer-associated venous thromboembolism].

Rev Med Interne 2020 09 25;41(9):575-577. Epub 2020 Jul 25.

Normandie Université, UNIROUEN, Service de Médecine Interne, F 76031 Rouen, France; Normandie Université, UNIROUEN, INSERM U1096, FHU REMOD-VHF, Rouen, France.

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http://dx.doi.org/10.1016/j.revmed.2020.06.001DOI Listing
September 2020

Comparison of conventional immunosuppressive drugs versus anti-TNF-α agents in non-infectious non-anterior uveitis.

J Autoimmun 2020 09 23;113:102481. Epub 2020 Jun 23.

Ophthalmology Department, Hospital Charles Nicolle, Rouen, France; EA7510, UFR Santé, Rouen University, Rouen, France.

Objective: To compare the efficacy and safety of Disease-modifying antirheumatic drugs (DMARDs) and anti-TNF-α agents in patients with non-infectious non-anterior uveitis.

Methods: Single center retrospective study including adult patients with non-infectious intermediate, posterior or pan-uveitis. Outcomes were compared between patients treated with DMARDs or anti-TNF-α agents. The primary outcome was treatment failure or occurrence of serious adverse events. Treatment failure was determined by ophthalmologic criteria.

Results: Seventy-three patients were included, mostly female (52%). Among them, 39 were treated with DMARDs and 34 with anti-TNF-α agents. The main uveitis causes were idiopathic (30%), birdshot chorio-retinopathy (25%), sarcoidosis (16%) and Behçet's disease (14%). The primary outcome was observed in 56% of patients treated with anti-TNF-α agents versus 59% of patients treated with DMARDs (p = 0.82). Median time to observe the primary outcome was 16 months (anti-TNF-α group) versus 21 months (p = 0.52). There was no significant difference between the two groups in terms of treatment failure, corticosteroid sparing effect, visual acuity improvement or adverse events. Earlier control of ocular inflammation was achieved with anti-TNF-α agents than with DMARDs (p = 0.006). In relapsing patients, anti-TNF-α agents allowed better corticosteroid sparing (p = 0.06).

Conclusion: DMARDs could still be used as first-line therapy for non-infectious non-anterior uveitis after corticosteroid therapy. However, anti-TNF-α agents could be proposed as an alternative in cases of severe inflammation or initial high level of steroid dependency.
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http://dx.doi.org/10.1016/j.jaut.2020.102481DOI Listing
September 2020

Systemic lupus erythematosus associated with thymoma: A fifteen-year observational study in France.

Autoimmun Rev 2020 Mar 7;19(3):102464. Epub 2020 Jan 7.

Assistance Publique - Hôpitaux de Paris, Hopital Bicêtre, Service de Médecine Interne et Immunologie Clinique, F-94275 Le Kremlin-Bicêtre, France; Université Paris Sud, UMR 1184, F-94276 Le Kremlin-Bicêtre, France; INSERM, U1184, Immunologie des Maladies Virales et Autoimmunes, F-94276 Le Kremlin-Bicêtre, France; CEA, DSV/iMETI, Département d'Immunovirologie, IDMIT, F-92265 Fontenay-aux-Roses, France. Electronic address:

Objective: To describe the clinical, biological and pathological characteristics of patients with the association of SLE and thymic epithelial tumors (TET) in a retrospective multicenter series.

Methods: Cases diagnosed in France between 2000 and 2015 were collected after a call for observations from the French network for thymic epithelial tumors (RYTHMIC database) and the French National Society of Internal Medicine (SNFMI).

Results: Fourteen patients were identified, the majority were women (93%). The median age at diagnosis of lupus was 43.5 [range: 30-66] years and 43.5 [range: 26-73] years at diagnosis of thymoma. TET required chemotherapy and/or radiotherapy complementary to surgery in >90% cases. Lupus was diagnosed before, simultaneously, or after diagnosis of thymoma in 6, 3 and 5 cases, respectively. Among the lupus manifestations, joint involvement was predominant (78.6%), followed by autoimmune cytopenia (35.7%), cutaneous affections (28.6%), serositis (28.6%) and renal involvement (21.4%). SLE was associated with one or more AID in 5/14 patients. These characteristics were compared with those from 17 patients identified in the literature. Among them, joint and skin involvement as well as pleural/pericardial effusions occurred in >50%. SLE was controlled by prednisone and hydroxychloroquine in the majority of cases, but 7 out of 31 patients had an immunosuppressant.

Conclusion: The association of SLE and TET is rare, and its clinical profile seems to be distinguished by the frequency of cytopenias. The management of these patients is complicated by the need to treat cancer, lupus and/or associated autoimmune diseases.
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http://dx.doi.org/10.1016/j.autrev.2020.102464DOI Listing
March 2020

Workload, well-being and career satisfaction among French internal medicine physicians and residents in 2018.

Postgrad Med J 2020 Jan 29;96(1131):21-27. Epub 2019 Aug 29.

Hôpital Cochin, Service de Médecine Interne, Université Paris Descartes, Paris, France.

Objectives: This work aimed to study the prevalence and risk factors associated with well-being and career satisfaction among French internal medicine physicians and residents.

Methods: A total of 1689 French internal medicine physicians or trainees were surveyed to evaluate their workload, well-being and career satisfaction during February 2018.

Results: The response rate was 620/1689 (37%). The mean age of the participants was 37 years (±12); 49% of the participants were female, 27% worked in the Paris area, 74% worked in a university hospital and 49% were residents. Sixty-six per cent of the responders were satisfied with their work, and 66% would choose the internal medicine specialty again. However, 71% of the responders worked more than 50 hours a week, 21% worked more than 60 hours a week and 70% believed that they did not have enough time for personal/family activities. Twenty-five per cent of the responders had at least one sign of burnout (19% of the physicians in practice and 32% of the residents). Compared with the graduate physicians in practice, the residents worked more hours a week, had more activities at night, spent more time on administrative tasks, had a worse global appreciation of their work and felt that their work was less meaningful. In multivariate analysis, the factors associated with global satisfaction at work were autonomy and meaningful work.

Conclusions: French internal medicine physicians have a high rate of career satisfaction. However, residents have a higher workload, less time for personal/family activities and feel that their work is less meaningful.
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http://dx.doi.org/10.1136/postgradmedj-2019-136657DOI Listing
January 2020

Hydroxychloroquine reverses the prothrombotic state in a mouse model of antiphospholipid syndrome: Role of reduced inflammation and endothelial dysfunction.

PLoS One 2019 14;14(3):e0212614. Epub 2019 Mar 14.

Rouen University Hospital, Department of Internal Medicine, Rouen, France.

Antiphospholipid antibodies (aPL) promote endothelial dysfunction, inflammation and procoagulant state. We investigated the effect of hydroxychloroquine (HCQ) on prothrombotic state and endothelial function in mice and in human aortic endothelial cells (HAEC). Human aPL were injected to C57BL/6 mice treated or not with HCQ. Vascular endothelial function and eNOS were assessed in isolated mesenteric arteries. Thrombosis was assessed both in vitro by measuring thrombin generation time (TGT) and tissue factor (TF) expression and in vivo by the measurement of the time to occlusion in carotid and the total thrombosis area in mesenteric arteries. TGT, TF, and VCAM1 expression were evaluated in HAEC. aPL increased VCAM-1 expression and reduced endothelium dependent relaxation to acetylcholine. In parallel, aPL shortened the time to occlusion and extended thrombus area in mice. This was associated with an overexpression of TF and an increased TGT in mice and in HAEC. HCQ reduced clot formation as well as TGT, and improved endothelial-dependent relaxations. Finally, HCQ increased the p-eNOS/eNOS ratio. This study provides new evidence that HCQ improves procoagulant status and vascular function in APS by modulating eNOS, leading to an improvement in the production of NO.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0212614PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417644PMC
November 2019

Intravenous Immunoglobulins Improve Survival in Monoclonal Gammopathy-Associated Systemic Capillary-Leak Syndrome.

Am J Med 2017 10 9;130(10):1219.e19-1219.e27. Epub 2017 Jun 9.

Service de médecine interne 2, CHU La Pitié-Salpêtrière, APHP, Université Paris 6, France. Electronic address:

Background: Monoclonal gammopathy-associated systemic capillary-leak syndrome, also known as Clarkson disease, is a rare condition characterized by recurrent life-threatening episodes of capillary hyperpermeability in the context of a monoclonal gammopathy. This study was conducted to better describe the clinical characteristics, natural history, and long-term outcome of monoclonal gammopathy-associated systemic capillary-leak syndrome.

Methods: We conducted a cohort analysis of all patients included in the European Clarkson disease (EurêClark) registry between January 1997 and March 2016. From diagnosis to last follow-up, studied outcomes (eg, the frequency and severity of attacks, death, and evolution toward multiple myeloma) and the type of preventive treatments administered were monitored every 6 months.

Results: Sixty-nine patients (M/F sex ratio 1:1; mean ± SD age at disease onset 52 ± 12 years) were included in the study. All patients had monoclonal gammopathy of immunoglobulin G type, with kappa light chains in 47 (68%). Median (interquartile range) follow-up duration was 5.1 (2.5-9.7) years. Twenty-four patients (35%) died after 3.3 (0.9-8) years. Fifty-seven (86%) patients received at least one preventive treatment, including intravenous immunoglobulins (IVIg) n = 48 (73.8%), theophylline n = 22 (33.8%), terbutaline n = 22 (33.8%), and thalidomide n = 5 (7.7%). In the 65 patients with follow-up, 5- and 10-year survival rates were 78% (n = 35) and 69% (n = 17), respectively. Multivariate analysis found preventive treatment with IVIg (hazard ratio 0.27; 95% confidence interval, 0.10-0.70; P = .007) and terbutaline (hazard ratio 0.35; 95% confidence interval, 0.13-0.96; P = .041) to be independent predictors of mortality.

Conclusions: We describe the largest cohort to date of patients with well-defined monoclonal gammopathy-associated systemic capillary-leak syndrome. Preventive treatment with IVIg was the strongest factor associated with survival, suggesting the use of IVIg as the first line in prevention therapy.
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http://dx.doi.org/10.1016/j.amjmed.2017.05.023DOI Listing
October 2017

Aortic involvement in relapsing polychondritis.

Joint Bone Spine 2018 05 17;85(3):345-351. Epub 2017 May 17.

Department of Internal Medicine, Rouen University Hospital, 1, rue de Germont, 76000 Rouen, France; INSERM U 905, University of Rouen IFRMP, Institute for Biochemical Research, Rouen University Hospital, 76000 Rouen, France. Electronic address:

Objective: To assess prevalence of aortic involvement in relapsing polychondritis (RP) patients; to evaluate clinical features and long-term outcome of RP patients exhibiting aortitis, aortic ectasia and/or aneurysm.

Methods: One hundred and seventy-two RP patients underwent aortic computed tomography (CT)-scan; they were seen in 3 medical centers.

Results: Eleven patients (6.4%) had aortic involvement, occurring within a median time of 2 years after RP diagnosis. CT-scan showed isolated aortitis (n=2); the 9 other patients exhibited: aortitis and aortic aneurysm (n=2) or ectasia (n=1), isolated aortic aneurysm (n=4) or ectasia (n=2); aortic localizations were as follows: thoracic (n=6), abdominal (n=2), thoracic and abdominal (n=4) aorta. Patients exhibited: resolution (n=3) improvement (n=3), stabilization (n=4) or deterioration (n=1) of aortic localization. Five patients experienced recurrence of aortic localization; one patient died of aortic abdominal aneurysm rupture. Predictive factors of death related to aortic complications were: aortitis on CT-scan, higher median levels of erythrocyte sedimentation rate. Predictive parameters of aortic relapses were: aortitis on CT-scan and involvement of the abdominal aorta.

Conclusions: This study underlines that aortic involvement is severe in RP. Furthermore, we suggest that RP patients exhibiting poor prognostic factors, including panaortitis and higher values of ESR, may require more aggressive therapy.
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http://dx.doi.org/10.1016/j.jbspin.2017.05.009DOI Listing
May 2018

Adjusted value of thromboprophylaxis in hospitalized obese patients: A comparative study of two regimens of enoxaparin: The ITOHENOX study.

Thromb Res 2017 Jul 12;155:1-5. Epub 2017 Apr 12.

Department of internal medicine, vascular and thrombosis unit, Rouen University Hospital, Rouen, France. Electronic address:

Thromboprophylaxis is a mainstay of hospital care in patients at high risk of thrombosis. Fixed doses of low-molecular-weight heparin (LMWH) are recommended for thromboprophylaxis in patients admitted to hospital for an acute medical condition. However, the distribution of LMWH is weight-based, and the efficacy of standard doses in obese patients may be decreased. Data for obese patients are mainly available in bariatric surgery with extremely obese patients who are at greater risk of venous thromboembolism than those hospitalized for a medical condition. We conducted a randomized control trial in medically obese inpatients (BMI≥30kg/m) assessing two regimens of enoxaparin (40mg and 60mg SQ daily) in order to determine whether a stronger dosage would achieve higher anti-Xa level suitable for thromboprophylaxis. Between September 2013 and April 2015, 91 patients were included in the study (mean (±standard deviation) age was 70.4±10.7years, average BMI 37.8±6.4kg/m). Main indications of thromboprophylaxis were mainly acute infection (50%), acute respiratory failure (10%), acute congestive heart failure (9%) and acute rheumatic disorders (18%). Average anti-Xa activity, measured 4h after the third administration of enoxaparin was 0.25±0.09IU/mL in group 1 (enoxaparin 40mg) and 0.35±0.13IU/mL in group 2 (enoxaparin 60mg) (P<10). The proportions of patients with normal anti-Xa activity (between 0.32 and 0.54IU/mL) were 31% (n=11) and 69% (n=24) in group 1 and 2 respectively (P=0.007). The proportions of anti-Xa activity measurement below the normal range were 64% and 36% in group 1 and 2 (P<10) respectively. Subgroup analysis focusing on high weight patients (above 100kg, n=45) showed a marked difference in the proportion of patients with normal anti-Xa activity between group 1 (9%) and 2 (44%) (P=0.009). No venous thromboembolism occurred during the study and one patient in group 1 died because of hemorrhagic shock due to a gastric ulcer. Incidence of adverse events was not different between the two groups (P=0.52). In conclusion, the ITOHENOX study shows in medically obese inpatients that thromboprophylaxis with enoxaparin 60mg provides higher control of anti-Xa activity, without more bleeding complications than the standard enoxaparin regimen. This trial is registered with ClinicalTrials.gov, number NCT01707732.
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http://dx.doi.org/10.1016/j.thromres.2017.04.011DOI Listing
July 2017

Nail involvement in systemic sclerosis.

J Am Acad Dermatol 2017 Jun 20;76(6):1115-1123. Epub 2016 Dec 20.

Department of Internal Medicine, Rouen University Hospital, Rouen, France; Institut National de la Santé et de la Recherche Médicale U 905, University of Rouen Institut Fédératif Multidisciplinaire sur les Peptides, Institute for Biochemical Research, Rouen, France.

Background: Nail involvement has rarely been recognized in systemic sclerosis (SSc). Indeed, only a few small series have assessed nail changes in SSc, most of which are case reports.

Objective: The aims of the current case-control study were to: (1) determine the prevalence of fingernail changes in SSc; and (2) evaluate the correlation between fingernail changes and other features of SSc.

Methods: In all, 129 patients with SSc and 80 healthy control subjects underwent routine fingernail examination.

Results: The prevalence of fingernail changes was 80.6% in SSc. Patients with SSc more frequently exhibited: trachyonychia (P = .006), scleronychia (P < .0001), thickened nails (P < .0001), brachyonychia (P = .0004), parrot beaking (P < .0001), pterygium inversum unguis (P < .0001), splinter hemorrhages (P < .0001), and cuticle abnormalities (P < .0001) than healthy control subjects. The presence of fingernail changes was associated with digital ulcers (P < .0001), calcinosis cutis (P = .004), and higher values of mean nailfold videocapillaroscopy score (P = .0009).

Limitations: The cohort originated from a single center.

Conclusion: This study underlines that fingernail changes are correlated with more severe forms of SSc characterized by digital microangiopathy, including digital ulcers and calcinosis cutis. Nail changes should be systematically checked in all patients with SSc, and may be included in the American College of Rheumatology/European League Against Rheumatism classification criteria for SSc.
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http://dx.doi.org/10.1016/j.jaad.2016.11.024DOI Listing
June 2017

[Association of progressive multifocal leukoencephalopathy and sarcoidosis].

Presse Med 2016 Jul-Aug;45(7-8 Pt 1):707-10. Epub 2016 May 17.

CHU de Rouen, département de médecine interne, 1, rue de Germont, 76031 Rouen cedex, France.

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http://dx.doi.org/10.1016/j.lpm.2016.04.015DOI Listing
February 2017

Antineutrophil Cytoplasmic Antibodies Associated With Infective Endocarditis.

Medicine (Baltimore) 2016 Jan;95(3):e2564

From the Department of Internal Medicine, Institute for Biochemical Research, IFRMP, University of Rouen (VL, AL, NG, HL, IM); Department of Infectious diseases (FC); and Department of Biostatistics (J-F M), CHU Rouen, France.

To determine the prevalence of antineutrophil cytoplasmic antibodies (ANCA) in patients with infective endocarditis (IE) in internal medicine; and to compare clinical and biochemical features and outcome between patients exhibiting IE with and without ANCA.Fifty consecutive patients with IE underwent ANCA testing. The medical records of these patients were reviewed.Of the 50 patients with IE, 12 exhibited ANCA (24%). ANCA-positive patients with IE exhibited: longer duration between the onset of first symptoms and IE diagnosis (P = 0.02); and more frequently: weight loss (P = 0.017) and renal impairment (P = 0.08), lower levels of C-reactive protein (P = 0.0009) and serum albumin (P = 0.0032), involvement of both aortic and mitral valves (P = 0.009), and longer hospital stay (P = 0.016). Under multivariate analysis, significant factors for ANCA-associated IE were: longer hospital stay (P = 0.004), lower level of serum albumin (P = 0.02), and multiple valve involvement (P = 0.04). Mortality rate was 25% in ANCA patients; death was because of IE complications in all these patients.Our study identifies a high prevalence of ANCA in unselected patients with IE in internal medicine (24%). Our findings further underscore that ANCA may be associated with a subacute form of IE leading to multiple valve involvement and more frequent renal impairment. Because death was due to IE complications in all patients, our data suggest that aggressive therapy may be required to improve such patients' outcome.
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http://dx.doi.org/10.1097/MD.0000000000002564DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4998285PMC
January 2016

Angioedema Triggered by Medication Blocking the Renin/Angiotensin System: Retrospective Study Using the French National Pharmacovigilance Database.

J Clin Immunol 2016 Jan 28;36(1):95-102. Epub 2015 Dec 28.

Internal Medicine Department, Rouen University Hospital, Rouen, France.

Introduction: Bradykinin-mediated angioedema (AE) is a rare side effect of some medications, including angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). In France, side-effects to treatments are reported to the national pharmacovigilance database.

Methods: The national MedDRA database was searched using the term "angioedema". Patients were included if they met the clinical criteria corresponding to bradykinin-mediated AE, if their C1-inhibitor levels were normal, and if they were treated with an ACEi or an ARB.

Results: 7998 cases of AE were reported between 1994 and 2013. Among these, 112 met the criteria for bradykinin-mediated AE with normal C1-inhibitor levels. On the 112 drug-AE, patients were treated with an ARB in 21% of cases (24 patients), or an ACEi in 77% of cases (88 patients), in combination with another treatment in 17 cases (mTORi for 3 patients, iDPP-4 for 1 patient, hormonal treatment for 7 patients). ENT involvement was reported in 90% of cases (tongue: 48.2%, larynx: 23.2%). The median duration of treatment before the first attack was 720 days, and the mean duration of attacks was 36.6 h. Forty-one percent (19/46) of patients relapsed after discontinuing treatment.

Conclusion: Angioedema triggered by medication blocking the renin/angiotensin system is rare but potentially severe, with a high risk of recurrence despite cessation of the causative drug.
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http://dx.doi.org/10.1007/s10875-015-0228-3DOI Listing
January 2016

Fructose Malabsorption in Systemic Sclerosis.

Medicine (Baltimore) 2015 Sep;94(39):e1601

From the Department of Internal Medicine, CHU Rouen, and INSERM U 905 (IM, HL); Department of Digestive Physiology, CHU Rouen, and INSERM UMR 1073, University of Rouen IFRMP, Institute for Biochemical Research (A-ML, GG); Department of Biostatistics, CHU Rouen (J-FM); and Department of Gastroenterology, CHU Rouen, and INSERM UMR 1073, University of Rouen IFRMP, Institute for Biochemical Research, Rouen, France (PD).

The deleterious effect of fructose, which is increasingly incorporated in many beverages, dairy products, and processed foods, has been described; fructose malabsorption has thus been reported in up to 2.4% of healthy subjects, leading to digestive clinical symptoms (eg, pain, distension, diarrhea). Because digestive involvement is frequent in patients with systemic sclerosis (SSc), we hypothesized that fructose malabsorption could be responsible for intestinal manifestations in these patients. The aims of this prospective study were to: determine the prevalence of fructose malabsorption, in SSc; predict which SSc patients are at risk of developing fructose malabsorption; and assess the outcome of digestive symptoms in SSc patients after initiation of standardized low-fructose diet. Eighty consecutive patients with SSc underwent fructose breath test. All SSc patients also completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated. The prevalence of fructose malabsorption was as high as 40% in SSc patients. We also observed a marked correlation between the presence of fructose malabsorption and: higher values of GSS score of digestive symptoms (P = 0.000004); and absence of delayed gastric emptying (P = 0.007). Furthermore, in SSc patients with fructose malabsorption, the median value of GSS score of digestive symptoms was lower after initiation of standardized low-fructose diet (4 before vs. 1 after; P = 0.0009). Our study underscores that fructose malabsorption often occurs in SSc patients. Our findings are thus relevant for clinical practice, highlighting that fructose breath test is a helpful, noninvasive method by: demonstrating fructose intolerance in patients with SSc; and identifying the group of SSc patients with fructose intolerance who may benefit from low-fructose diet. Interestingly, because the present series also shows that low-fructose diet resulted in a marked decrease of gastrointestinal clinical manifestations in SSc patients with fructose malabsorption, our findings underscore that fructose malabsorption may play a significant role in the onset of gastrointestinal symptoms in these patients. Finally, we suggest that fructose malabsorption may be due to reduced fructose absorption by enterocytes, impaired enteric microbiome, and decreased intestinal permeability.
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http://dx.doi.org/10.1097/MD.0000000000001601DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616824PMC
September 2015

Reply to the comment of Brinster et al. "Acquired hemophilia, rheumatoid arthritis, and TNFα antagonists".

Joint Bone Spine 2015 Oct 7;82(5):385-6. Epub 2015 Jul 7.

Inserm U1096, IRIB, service de médecine interne, CHU-Hôpitaux de Rouen, université de Rouen, 76031 Rouen cedex, France.

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http://dx.doi.org/10.1016/j.jbspin.2015.05.003DOI Listing
October 2015

Infliximab improves endothelial dysfunction in a mouse model of antiphospholipid syndrome: Role of reduced oxidative stress.

Vascul Pharmacol 2015 Aug 11;71:93-101. Epub 2015 Apr 11.

Rouen University Hospital, Department of Internal Medicine, Rouen France; University of Rouen, Institute for Research and Innovation in Biomedicine, Rouen, France.

Antiphospholipid syndrome (APS), induces endothelial dysfunction, oxidative stress and systemic inflammation that may be mediated by TNFα. Thus, we investigated the possible protective effect of the anti-TNFα antibody infliximab (5μg/g) on endothelial function in a mouse APS model (induced by injection of purified human anti-β2GP1-IgG). Seven days after anti-β2GPI-IgG injection, we observed an increase in plasma sVCAM-1 and sE-selectin levels and in aortic mRNA expression of VCAM-1 and E-selectin. This was associated with a decreased endothelium-dependent relaxation of isolated mesenteric arteries to acetylcholine, together with decreased mesenteric eNOS mRNA expression and increased eNOS uncoupling, accompanied by increased iNOS and gp91phox mRNA and increased left ventricular GSH/GSSH ratio. Infliximab significantly improved the NO-mediated relaxing responses to acetylcholine, and induced a decrease in iNOS and gp91phox mRNA expression. The õpro-adhesive and pro-coagulant phenotypes induced by the anti-β2GP1-IgG were also reversed. This study provides the first evidence that TNFα antagonism improves endothelial dysfunction in APS and suggests that endothelial dysfunction is mediated by TNFα and oxidative stress. Therefore, infliximab may be of special relevance in clinical practice.
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http://dx.doi.org/10.1016/j.vph.2015.03.014DOI Listing
August 2015

Acquired hemophilia possibly induced by etanercept in a patient with rheumatoid arthritis.

Joint Bone Spine 2015 May 20;82(3):200-2. Epub 2015 Jan 20.

Service de rhumatologie, CHU-Hôpitaux de Rouen, Inserm U905, CRB CIC 1404, IRIB, Université de Rouen, 76031 Rouen Cedex, France.

A 47-year-old woman with rheumatoid arthritis (RA) treated successively with infliximab, abatacept, and etanercept spontaneously developed subcutaneous bruises and a noncompressive hematoma 11 months after starting etanercept therapy (50mg/week). Her prothrombin time was normal but her activated partial thromboplastin time was increased to 2.48 (normal range, 0.85-1.17). She had a circulating anticoagulant (Rosner index, 45; normal,<13) due to an anti-factor VIII antibody in a titer of 45 Bethesda units. Her factor VIII level was less than 1% (normal range, 55-150). The etanercept and leflunomide were stopped and prednisone was given in a daily dosage of 1mg/kg, in combination with rituximab, two 1-g doses at an interval of 2 weeks. After 5 months, persistence of the anti-factor VIII antibody prompted the initiation of azathioprine therapy, 2mg/kg/d. A remission was achieved 9 months after the diagnosis of acquired hemophilia and was sustained at last follow-up after 3 years. This new case of acquired hemophilia in a patient with RA may reflect a simple association or an inducing role of etanercept.
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http://dx.doi.org/10.1016/j.jbspin.2014.12.003DOI Listing
May 2015

Association of occupational exposure with features of systemic sclerosis.

J Am Acad Dermatol 2015 Mar 10;72(3):456-64. Epub 2015 Jan 10.

Department of Internal Medicine, Centre Hospitalier Universitaire (CHU) Rouen, and Institut National de la Santé et de la Recherche Biomédicale (INSERM) Unit 905, University of Rouen Institut Fédératif Multidisciplinaire sur les Peptides (IFRMP), Institute for Biochemical Research, Rouen, France.

Background: Occupational exposure is reported as playing a substantial causative role in systemic sclerosis (SSc).

Objective: We sought to compare the characteristics of SSc in patients with and without occupational exposure to crystalline silica/solvents.

Methods: In all, 142 patients with SSc were enrolled in this prospective study. An expert committee performed blind evaluation of occupational exposure to crystalline silica/solvents.

Results: Patients exposed to crystalline silica more often exhibited: diffuse cutaneous SSc (P = .02), digital ulcers (P = .05), interstitial lung disease (P = .0004), myocardial dysfunction (P = .006), and cancer (P = .06). Patients exposed to solvents more frequently developed: diffuse cutaneous SSc (P = .001), digital ulcers (P = .01), interstitial lung disease (P = .02), myocardial dysfunction (P = .04), and cancer (P = .003); in addition, these patients were more frequently anti-Scl 70 positive and anticentromere negative. Under multivariate analysis, significant factors for SSc associated with exposure to silica/solvents were: male gender (odds ratio 19.31, 95% confidence interval 15.34-69.86), cancer (odds ratio 5.97, 95% confidence interval 1.55-23.01), and digital ulcers (odds ratio 2.42, 95% confidence interval 1.05-5.56).

Limitations: The cohort originated from a single geographic region.

Conclusion: Occupational exposure to crystalline silica/solvents is correlated with more severe forms of SSc characterized by: diffuse cutaneous involvement, interstitial lung disease, general microangiopathy (digital ulcers and myocardial dysfunction), and association with cancer. Occupational exposure should be systematically checked in all patients with SSc, as exposed patients seem to develop more severe forms of SSc.
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http://dx.doi.org/10.1016/j.jaad.2014.11.027DOI Listing
March 2015

Digital ischemia associated with cancer: results from a cohort study.

Medicine (Baltimore) 2014 Aug;93(10):e47

Department of Internal Medicine (MLB, SM, NC, NG, IM, HL, YB), Rouen University Hospital, 1 Rue de Germont and Inserm (National Institute for Health and Medical Research) U1096 (HL, YB), University of Rouen, Rouen, France.

Digital ischemia associated with cancer (DIAC) is increasing in frequency and recent reports have suggested the concept of paraneoplastic manifestation. The aims of this study were to characterize the clinical presentation of DIAC and identify clinical features that could lead physicians to diagnose underlying cancer.From January 2004 to December 2011, 100 patients were hospitalized in the Department of Internal Medicine at Rouen University Hospital, France for a first episode of DI. Fifteen (15%) exhibited symptomatic or asymptomatic cancer during the year preceding or following vascular episode and constituted the DIAC group. Other patients without cancer made up the digital ischemia (DI) group.Median time between diagnosis of cancer and episode of digital necrosis was 2 months [0.25-9]. Diagnosis of DI and concomitant cancer was made in 7 of the 15 patients, while DI preceded the malignant disorder in 2 cases and followed it in 6 cases. Histological types were adenocarcinoma for 7 (46.7%), squamous cell carcinoma for 4 (26.7%), and lymphoid neoplasia for 3 patients (20%). Six patients (40%) had extensive cancer. Three patients were lost to follow-up and 5 patients died <1 year after diagnosis of cancer. Cancer treatment improved vascular symptoms in 6 patients (40%). Patients with DIAC, compared to patients with DI, were significantly older (56 years [33-79] vs 46 [17-83] P =0.005), and had significantly lower hemoglobin and hematocrit levels (12.7 g/dl vs 13.9 g/dl; P =0.003 and 38% vs 42%; P =0.003, respectively). Patients with DIAC had a higher platelet rate (420 vs 300 G/L P =0.01), and 6 patients with DIAC (40%) had thrombocytosis. There was no difference between groups either in C-reactive protein level (12 mg/L vs 5 mg/L; P =0.08) or regarding cardiovascular risk factors, presence of autoimmunity, or monoclonal protein.This retrospective study suggests that DIAC may be more prevalent than previously reported. Outcomes of the 2 diseases were not strictly chronologically parallel. However, in the majority of cases, treatment of the tumor resolved vascular involvement. Our findings suggest that age >50 years and thrombocytosis should alert physicians to consider a possible occult malignancy when digital necrosis occurs.
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http://dx.doi.org/10.1097/MD.0000000000000047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616330PMC
August 2014

Role of Toll-like receptors 2 and 4 in mediating endothelial dysfunction and arterial remodeling in primary arterial antiphospholipid syndrome.

Arthritis Rheumatol 2014 Nov;66(11):3210-20

Rouen University Hospital, INSERM U1096, University of Rouen, and Centre d'Investigation Clinique, INSERM 1404, Rouen, France.

Objective: To assess the role of Toll-like receptors (TLRs) in antiphospholipid antibody (aPL)-mediated vascular abnormalities in patients with primary arterial antiphospholipid syndrome (APS).

Methods: Forty-eight subjects participated in the study. Arterial function and structure and TLR pathway activation were determined in patients with primary arterial APS and matched controls. The pathogenic effects of aPL isolated from patients were assessed in wild-type (WT) and TLR-knockout mice.

Results: APS patients had endothelial dysfunction, arterial stiffening, and hypertrophy, as evidenced by decreased brachial artery endothelium-dependent flow-mediated dilation (FMD) and increased aortic pulse wave velocity and carotid intima-media thickness (IMT), as compared with controls. Plasma samples from APS patients revealed decreased nitric oxide (NO) availability and a pro-oxidative, proinflammatory, and prothrombotic state illustrated by a decrease in nitrite and an increase in lipid peroxidation, tumor necrosis factor α levels, and tissue factor (TF) levels. Furthermore, TLR pathway activation was found in APS patients with increased TLR-2 and TLR-4 messenger RNA expression and increased protein levels of the activated TLR transduction protein interleukin-1 receptor-associated kinase 1 in peripheral blood mononuclear cells. Moreover, agonist-stimulated cell-surface expression of TLR-2 and TLR-4 in circulating monocytes was higher in APS patients than in controls. These changes were positively associated with IMT and negatively associated with FMD. Finally, aPL injection decreased mesenteric endothelium-dependent relaxation and increased TF expression in WT mice but not in TLR-2- or TLR-4-knockout mice.

Conclusion: This translational study supports the notion that TLR-2 and TLR-4 play a role in mediating vascular abnormalities in patients with primary arterial APS. TLRs thus constitute a promising pharmacologic target for preventing cardiovascular complications in APS.
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http://dx.doi.org/10.1002/art.38785DOI Listing
November 2014

[Hearing loss revealing sarcoidosis].

Presse Med 2014 May 25;43(5):609-11. Epub 2014 Feb 25.

Département de médecine interne, CHU de Rouen, 1, rue de Germont, 76031 Rouen cedex, France. Electronic address:

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http://dx.doi.org/10.1016/j.lpm.2013.09.012DOI Listing
May 2014

Detection of microcirculatory impairment by transcutaneous oxymetry monitoring during hemodialysis: an observational study.

BMC Nephrol 2014 Jan 8;15. Epub 2014 Jan 8.

Department of Internal Medicine, Rouen University Hospital, 1 Rue de Germont, 76031 Rouen, France.

Background: Little is known about the effects of intermittent hemodialysis on microcirculatory perfusion. The aim of this study is to assess the effects of hemodialysis on microvascular perfusion using transcutaneous oxymetry (TCPO2).

Methods: In this observational study, hourly TCPO2 measurements were performed during hemodialysis sessions. Ankle brachial index (ABI) was carried out to classify patients according their vascular condition.

Results: 50 patients (mean age 70 ± 8 years old) were enrolled. Mean TCPO2 decreased significantly on average 23.9% between start and finish of hemodialysis. Severe ischemia (TCPO2 < 30 mmHg) and critical ischemia (TCPO2 < 10 mmHg) occurred during dialysis in 47.1% and 15.5% respectively. Critical ischemia occurred only in limbs with ABI < 0.9 (8.3%) or > 1.3 (28%). Patients with critical ischemia experienced a significantly larger decline in mean blood pressure (32.4 ± 26.1 mmHg vs 12.7 ± 10.7 mmHg; P = 0.007) and a more pronounced ultrafiltration (45.55 ± 16.9 ml/kg vs 35.17 ± 18.2 ml/kg; P = 0.04) compared to patients without ischemia. Clinical outcomes (death or vascular procedures) were five times more frequent in patients who had developed critical ischemia (55.7% vs 10.1% P = 0.01). The elevated age of patients, the low basal value of TCPO2, and the occurrence of critical ischemia were more frequently associated with clinical outcome (P = 0.03, P = 0.048, P = 0.01 respectively).

Conclusions: This study demonstrates that hemodialysis induces microcirculatory injury, dependent on blood pressure reduction, peripheral vascular state and ultrafiltration. The occurrence of critical ischemia is associated to pejorative patient outcome and therefore, TCPO2 seems to be useful to avoid potential distal tissue damage during hemodialysis.
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http://dx.doi.org/10.1186/1471-2369-15-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3906095PMC
January 2014

Reactive macrophage activation syndrome possibly triggered by canakinumab in a patient with adult-onset Still's disease.

Joint Bone Spine 2013 Dec 7;80(6):653-5. Epub 2013 Jun 7.

Service de Rhumatologie, Inserm U905, CIC-CRB0204, Institute for Research and Innovation in Biomedicine (IRIB), CHU-Hôpitaux de Rouen, Université de Rouen, 76031 Rouen cedex, France. Electronic address:

Macrophage activation syndrome (MAS) is a rare and serious complication of adult-onset Still's disease. We describe a case in a 49-year-old woman with Still's disease refractory to glucocorticoids, methotrexate, and infliximab. Anakinra provided satisfactory disease control for 1 year, after which escape phenomenon occurred. After four tocilizumab injections, cutaneous melanoma developed. The persistent systemic manifestations prompted treatment with two canakinumab injections. Ten days later, she had a spiking fever, dyspnea, low back pain, abdominal pain, odynophagia, and hepatomegaly. Laboratory tests showed liver cytolysis (180 IU/L; N: 10-35), acute renal failure (creatinine, 407 μmol/L; N:50-100), thrombocytopenia (60 G/L; N: 150-400), leukocytosis (12,200/mm(3); N: 4000-10,000), hypertriglyceridemia (5070 mmol/L; N: 0.4-1.6), lactate dehydrogenase elevation (4824 IU/L; N: 135-250), and hyperferritinemia (97 761 μg/L; N:15-150). Examination of a bone marrow biopsy showed phagocytosis. Tests were negative for viruses and other infectious agents. Glucocorticoid therapy (1.5 mg/Kg/d) and intravenous polyvalent immunoglobulins (0.5 g/Kg/d) were given. Her condition improved despite the many factors of adverse prognostic significance (thrombocytopenia, absence of lymphadenopathy, and glucocorticoid therapy at diagnosis). This is the first reported case of MAS after canakinumab therapy in a patient with adult-onset Still's disease.
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http://dx.doi.org/10.1016/j.jbspin.2013.04.011DOI Listing
December 2013

Severe aplastic anemia associated with eosinophilic fasciitis: report of 4 cases and review of the literature.

Medicine (Baltimore) 2013 Mar;92(2):69-81

From Université Paris Diderot, Sorbonne Paris Cité; AP-HP; Service de Dermatologie (AdM, JDB, MR, MB) and Service de Greffe de Moëlle et Centre de Référence Maladies Rares des Aplasies Médullaires (RPdL, DM, GS), Hôpital Saint Louis, Paris; Service de Médecine Interne (YB, HL) and Service d'Anatomopathologie (AL), Hôpital Charles-Nicolle, Rouen; Service d'Hématologie (CMC, JOB), Hôpital Estaing, Clermont-Ferrand; Service d'Anatomopathologie (JMP) and Service d'Hématologie (FJ), Centre Henri Becquerel, Rouen; and Service de Médecine Interne et Immunologie Clinique (VLS, BB), Hôpital Le Bocage, Dijon; France.

Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 18-71 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1).
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http://dx.doi.org/10.1097/MD.0b013e3182899e78DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4553982PMC
March 2013

Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry.

Blood 2012 Jul 22;120(1):39-46. Epub 2012 May 22.

Thrombosis and Hemostasis Unit, Ospedale Niguarda, Milan, Italy.

Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).
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http://dx.doi.org/10.1182/blood-2012-02-408930DOI Listing
July 2012

Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2).

Blood 2012 Jul 18;120(1):47-55. Epub 2012 Apr 18.

Arthur Bloom Haemophilia Centre, University Hospital of Wales, School of Medicine, Cardiff University, Cardiff, UK.

Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.
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http://dx.doi.org/10.1182/blood-2012-02-409185DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3390961PMC
July 2012

Delayed gastric emptying determined using the 13C-octanoic acid breath test in patients with systemic sclerosis.

Arthritis Rheum 2012 Jul;64(7):2346-55

Department of Internal Medicine, Rouen University Hospital, Rouen, France.

Objective: To determine the prevalence of delayed gastric emptying using the 13C-octanoic acid breath test in unselected patients with systemic sclerosis (SSc), to evaluate whether findings of the 13C-octanoic acid breath test are associated with clinical digestive manifestations, gastric mucosal abnormalities detected by gastroscopy, motor activity dysfunction detected by antroduodenal manometry, and esophageal motor impairment and extradigestive manifestations of SSc, and to develop a risk prediction score of gastric emptying in SSc.

Methods: Consecutive patients with SSc (n=57) underwent the 13C-octanoic acid breath test. All of the patients with SSc completed a questionnaire on digestive symptoms, and a global symptom score (GSS) was calculated.

Results: The prevalence of delayed gastric emptying was 47.4% in patients with SSc. A marked correlation was observed between a GSS of digestive symptoms≥5 and the presence of delayed gastric emptying (P<0.00001). The sensitivity of a GSS≥5 for predicting delayed gastric emptying was as high as 0.93, while the specificity was 0.73. Moreover, a GSS≥5, mucosal gastric abnormalities, severe esophageal motor impairment, and interstitial lung disease were factors that were independently associated with the presence of delayed gastric emptying, and these variables were used to create a risk prediction score. The area under the receiver operating characteristic curve for the risk prediction score was 0.90; the sensitivity of this score for the prediction of delayed gastric emptying was 0.93, while the specificity was 0.77.

Conclusion: The results indicate that delayed gastric emptying occurs often in patients with SSc. Interestingly, using risk models with routine clinical characteristics, a simple risk prediction score can be calculated, allowing prediction of the occurrence of delayed gastric emptying in patients with SSc.
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http://dx.doi.org/10.1002/art.34374DOI Listing
July 2012

Arterial stiffness and stroke in sickle cell disease.

Stroke 2012 Apr 22;43(4):1129-30. Epub 2011 Dec 22.

Internal Medicine, University Hospital, 4 rue Larrey, 49000 Angers, France.

Background And Purpose: Large vessels are also affected in sickle cell disease. The aim of this study was to assess several parameters in adult patients with sickle cell disease compared with control subjects and in patients with sickle cell disease with stroke.

Methods: Carotid arterial stiffness, intima-media thickness, and transcranial Doppler ultrasonography were measured.

Results: Arterial stiffness and transcranial Doppler velocity were significantly increased in 49 patients with sickle cell disease compared with 47 control subjects (P<0.05) and especially in patients with stroke (P<0.05).

Conclusions: These data suggest that transcranial Doppler and arterial stiffness might be associated to stroke in adult patients with sickle cell disease.
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http://dx.doi.org/10.1161/STROKEAHA.111.635383DOI Listing
April 2012