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Pulmonary arterial hypertension (PAH) is a severe complication of connective tissue disease (CTD). Data on use of prostanoids in this particular subset of patients are lacking. We aimed to describe the characteristics of patients with PAH-CTD treated with prostanoids and the outcomes under treatment.In this multicenter retrospective study, all patients treated with prostanoids since 2006 were included. Data on PAH and CTD were collected at the time of prostanoid introduction and under treatment.Twenty-one patients were included, of whom 20 (95%) had limited cutaneous systemic sclerosis. Nineteen patients were treated with oral monotherapy or combination before addition of prostanoid. Treprostinil was the most used molecule (57% of patients). At the time of prostanoid introduction, 90% of patients were considered at high risk for death. Among patients who had right heart catheterization during follow-up, there was no significant difference in haemodynamics. No extrarespiratory worsening of the CTD was reported. The 1-year survival under prostanoid was 62%. In univariate analysis, NYHA functional class was associated with survival under treatment.This study provides original data on use of prostanoids in a cohort consisting mainly of systemic sclerosis. It underlines the difficulty to achieve a standardized assessment in this subset of patients. Safety profile was comparable with data reported in idiopathic PAH.

Pharmaceutical prescription in systemic sclerosis is guided by national and international recommendations. This study's primary objective was to describe and analyze these prescriptions among patients of our cohort. We also aimed to assess drug compliance among our patients.This is a monocentric observational study on two cohorts of patients with systemic sclerosis; a primary cohort comprising ambulatory patients, who were prospectively included, with exhaustive prescription's data collection; and a secondary cohort included patients asked to fill in a self-questionnaire on treatment compliance.The main cohort included 157 patients, including 31 cases of diffuse systemic sclerosis. A vasodilator drug for Raynaud's phenomenon was prescribed in 75 patients (47.9%) and a specific treatment for pulmonary arterial hypertension in 10 patients (6.4%). Immuno-modulators/immunosuppressants was prescribed in 62 patients (39.5%), who received prednisone (n=37, 23.6%), mycophenolate mofetil (n=14, 8.9%), hydroxychloroquine (n=12, 7.6%) and colchicine (n=22, 14%). Treatment for "gastro-intestinal tract involvement" was prescribed for 106 patients (67.5%) and treatment of a scleroderma renal crisis with an angiotensin-converting enzyme inhibitor for 6 patients (3.8%). Among the 42 patients in the secondary cohort, 21.4% reported a good compliance, mostly older patients (P=0.045) or those who had not experienced adverse events (P=0.009).This study provides original real-life data illustrating the heterogeneity of prescription habits in systemic sclerosis. As previously reported, treatment compliance was insufficient.

The InSight (Interior Exploration using Seismic Investigations, Geodesy and Heat Transport) mission landed in Elysium Planitia on Mars on 26 November 2018 and fully deployed its seismometer by the end of February 2019. The mission aims to detect, characterize and locate seismic activity on Mars, and to further constrain the internal structure, composition and dynamics of the planet. Here, we present seismometer data recorded until 30 September 2019, which reveal that Mars is seismically active. We identify 174 marsquakes, comprising two distinct populations: 150 small-magnitude, high-frequency events with waves propagating at crustal depths and 24 low-frequency, subcrustal events of magnitude Mw 3–4 with waves propagating at various depths in the mantle. These marsquakes have spectral characteristics similar to the seismicity observed on the Earth and Moon. We determine that two of the largest detected marsquakes were located near the Cerberus Fossae fracture system. From the recorded seismicity, we constrain attenuation in the crust and mantle, and find indications of a potential low-S-wave-velocity layer in the upper mantle. © 2020, The Author(s), under exclusive licence to Springer Nature Limited., We acknowledge NASA, CNES and its partner agencies and institutions (UKSA, SSO, DLR, JPL, IPGP-CNRS, ETHZ, IC and MPS-MPG) and the flight operations team at JPL, SISMOC, MSDS, IRIS-DMC and PDS for providing SEIS data. The Swiss co-authors were jointly funded by (1) the Swiss National Science Foundation and French Agence Nationale de la Recherche (SNF-ANR project 157133 ‘Seismology on Mars’), (2) the Swiss National Science Foundation (SNF project 172508 ‘Mapping the internal structure of Mars’), (3) the Swiss State Secretariat for Education, Research and Innovation (SEFRI project ‘MarsQuake Service-Preparatory Phase’) and (4) ETH Research grant no. ETH-06 17-02. Additional support came from the Swiss National Supercomputing Centre (CSCS) under project ID s922. The Swiss contribution in the implementation of the SEIS electronics was made possible by funding from the federal Swiss Space Office (SSO) and contractual and technical support from the ESA-PRODEX office. The French Team acknowledge the French Space Agency CNES, which has supported and funded all SEIS-related contracts and CNES employees, as well as CNRS and the French team universities for personal and infrastructure support. Additional support was provided by ANR (ANR-14-CE36-0012-02 and ANR-19-CE31-0008-08) and, for the IPGP team, by the UnivEarthS Labex programme (ANR-10-LABX-0023), IDEX Sorbonne Paris Cité (ANR-11-IDEX-0005-0). SEIS-SP development and delivery were funded by the UK Space Agency. A portion of the work was carried out at the InSight Project at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration. The MPS SEIS team acknowledges funding for development of the SEIS leveling system by the DLR German Space Agency. We thank gempa GmbH for software development related to the MQS tools. This paper is InSight contribution number 102.

Introduction Les formes rapidement progressives de PID (RP-PID) sont frequentes au cours des dermatomyosites (DM), en particulier associees a un anticorps (AC) anti-MDA5 (PID-MDA5). Les facteurs predictifs de survenue d’une RP-PID sont mal connus. L’objectif principal etait de determiner les elements facteurs predictifs de survenue des formes RP au cours de PID-MDA5. Methodes Il s’agit d’une etude retrospective multicentrique nationale de patients adultes ayant une PID-MDA5. La RP-PID, a ete definie par une deterioration respiratoire ou Resultats 92 patients ont ete inclus (29 (31 %) hommes, âge median 50,1 ans (38,7–58,6), 57,6 % afro-caribeens, 79,3 % non fumeurs) ( Fig. 1 ). CVF mediane: 68 % (52,2–86,8), DLCO mediane: 47 % (40,5–60,5). Des lesions ulcerations etaient notees chez 42.4 % des patients et 69.6 % etaient amyopathiques. L’extension de la PID etait > 20 % chez 34,8 % des patients. Le pattern initial etait le suivant: PINS (33,7 %), PINS-PO (29,3 %), PID indeterminee (19,6 %) et PIA (7,6 %). Le delai de suivi median etait de 36 mois (7.7-63). Douze patients ont presente un pneumomediastin au cours du suivi. Quarante et un patients (44,5 %) avaient une PID-RP. Les donnees demographiques, le tabac, les signes cutanes et musculaires etaient comparables mais les PID-RP avaient une fievre plus frequente (65.9 vs 29.4 % p = 0,001), et plus de condensations (75.6 vs 49 % p = 0,008). Vingt-neuf patients sont decedes dont 25 dans le groupe PID-RP et 3 ont ete greffes, tous dans le groupe PID-RP. L’extension de la PID, la fievre et la ferritinemie au diagnostic etaient associees a la survenue d’une PID-RP en analyse de regression logistique. La survenue d’une PID-RP etait associee a un pronostic defavorable avec 28 % de survie estimee a 5 ans (p Fig. 1 ). Les patients ayant une forme « limitee » avaient une meilleure survie que ceux ayant une forme « etendue » (p = 0,012). Enfin, en analyse multivariee, l’âge, l’extension de la PID, la ferritinemie etaient des facteurs pronostiques associes a la mortalite. Conclusion Dans cette serie francaise de PID-MDA5, la fievre, la ferritinemie et l’extension de la PID au diagnostic sont associes a la survenue d’une PID-RP.

Introduction Dans l’etude INBUILD, incluant 663 patients ayant une pneumopathie interstitielle diffuse fibrosante progressive (PID-FP) autre qu’une fibrose pulmonaire idiopathique (FPI), le nintedanib versus placebo a ralenti de maniere significative le taux de declin de la capacite vitale forcee (CVF) a 1 an, a la fois sur la population totale, mais egalement dans le sous-groupe des patients avec une PID-FP associee a une maladie auto-immune (MAI). Dans ce sous-groupe, nous avons evalue l’efficacite et la tolerance du nintedanib selon que les patients etaient ou n’etaient pas sous corticoides et/ou DMARD a l’inclusion. Patients et methodes Les donnees des patients PID-FP associees a une MAI, issues de l’etude INBUILD, ont ete comparees selon la prise d’un traitement par DMARD et/ou corticoides (toute dose ≤ 20 mg/j de prednisone) a l’inclusion. Les patients prenant des doses stables de medicaments pour traiter une PR ou une connectivite etaient eligibles. Les patients traites par azathioprine, ciclosporine, mycophenolate, tacrolimus, rituximab, cyclophosphamide ou corticoides oraux a une dose > 20 mg/jour etaient exclus. Les taux de declin annuel de la CVF et la survenue d’evenements indesirables ont ete mesures. Resultats Cent soixante-dix patients issus de l’etude INBUILD (82 sous nintedanib, 88 sous placebo) avaient une PID-FP associee a une MAI dont 89 patients avec une PR, 39 avec une sclerodermie systemique, 19 avec une connectivite mixte, et 23 « autres ». A l’inclusion, 131 patients prenaient des DMARD et/ou de corticoides et 39 patients ne prenaient pas de DMARD et/ou de corticoides. Le taux annuel moyen de declin de la CVF dans le groupe placebo etait plus important chez les patients traites par des DMARD et/ou des corticoides a l’inclusion (−202,2 mL/an). L’effet du nintedanib sur la reduction du declin de la CVF etait plus prononce chez les patients prenant des DMARD et/ou des corticoides a l’inclusion (−71,7 versus −202,2 mL/an ; difference 130,4 mL/an [IC a 95 % : 39,4 ; 221,5]). Toutefois, il n’y a pas de signe d’heterogeneite entre les sous-groupes (valeurs de p pour Interaction traitement/sous-groupe/temps). Chez les patients traites par nintedanib prenant versus ne prenant pas des DMARD et/ou des corticoides, une diarrhee etait rapportee chez respectivement 59,4 % et 77,8 % et respectivement 28,4 % et 23,8 % des patients recevant le placebo. Les EI graves ont ete plus frequents chez les patients prenant versus ne prenant pas de DMARD et/ou des corticoides dans les deux groupes nintedanib (39,1 % versus 16,7 %) et placebo (35,8 % versus 19,0 %). Conclusion Cette etude apporte de nouvelles donnees sur l’utilisation du nintedanib dans les PID-FP associees aux MAI. Dans cette population, le taux de declin de la CVF etait plus eleve chez les patients sous placebo qui prenaient des DMARD et/ou des corticoides a l’inclusion versus ceux qui n’en prenaient pas. Le declin annuel de la CVF etait ralenti chez les patients traites par le nintedanib versus placebo, aussi bien chez les patients qui prenaient versus ceux qui ne prenaient pas de DMARD et/ou des corticoides a l’inclusion. Le profil de tolerance du nintedanib etait acceptable aussi bien chez les patients qui a l’inclusion prenaient versus ceux qui ne prenaient pas de DMARD et/ou de corticoides. Donnees INBUILD initialement presentees a l’EULAR 2020.

Figure S1. Funnel plots, forest plots, and meta-regression for the meta-analysis of SMR. Figure S2. Funnel plots and forest plots of the risk factors related with mortality. (PDF 948 kb)

Table S1. Survival rates and survival curve for lcSSc and dcSSc. Table S2. Main characteristics of studies in the SMR meta-analysis. Table S3. Main characteristics of studies in the prognosis factors meta-analysis. (DOCX 51 kb)

Background Pleuroparenchymal fibroelastosis (PPFE) is a very rare interstitial lung disease (ILD) characterized by progressive fibrotic lesions of the visceral pleura and the sub-pleural parenchyma, affecting predominantly the upper lobes. PPFE may occur in different contextes like bone marrow or lung transplantations, but also in the context of telomeropathy with mutations of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC) or regulator of telomere elongation helicase 1 (RTEL1) genes. PPFE-like lesions have recently been described in patients with connective tissue disease (CTD)-related ILD. We report here the first detailed case of PPFE associated to systemic sclerosis (SSc) in a woman free of telomeropathy mutations. Case presentation A caucasian 46 year old woman was followed for SSc in a limited form with anti-centromere Ab since 1998, and seen in 2008 for a routine visit. Her SSc was stable, and she had no respiratory signs. Pulmonary function tests showed an isolated decreased cTLCO at 55.9% (of predicted value). Cardiac ultrasonography was normal. Thoracic CT-scan showed upper lobes predominant mild and focal pleural and subpleural thickenings, suggestive of PPFE, with a slight worsening at 8 years of follow-up. She remained clinically stable. Biology only found a moderate and stable peripheral thrombocytopenia, and sequencing analysis did not find any mutations in TERT and TERC genes. Conclusions ILD is frequent in SSc but isolated PPFE has never been described so far. In our case, PPFE is not related to telomeropathy, has indolent outcome and seems to have good prognosis. PPFE might be an extremely rare form of SSc-related ILD, although a fortuitous association remains possible.

Many factors can contribute to the risk of venous thrombosis observed in hemolytic diseases. Some mechanisms are related to hemolysis by itself, while others seem more specific to each disease. Despite recent advances in the quantification of this risk and in understanding its physiopathology, the association of hemolysis with venous thrombosis is often unknown. The purpose of this general review is to clarify the main pro-thrombotic mechanisms during hemolysis and to synthesize the clinical data currently available. We will focus on the main types of hemolytic pathologies encountered in current practice, namely paroxysmal nocturnal hemoglobinuria, hemoglobinopathies, auto-immune hemolytic anemia and thrombotic microangiopathies.

A large outbreak of OXA-48 carbapenemase-producing Klebsiella pneumoniae at Nantes University Hospital was investigated. The index case had no history of travel or hospitalization abroad and had been hospitalized in the internal medicine department for more than one month when the epidemic strain was isolated from a urine sample in June 2013. Seventy-two secondary cases were detected by weekly screening for gastrointestinal colonization during the two phases of the outbreak from June to October 2013 (33 cases) and from November 2013 to August 2014 (39 cases). Spread of the epidemic strain was attributed to the proximity of, and staff movement between, the infectious diseases (32 cases) and the internal medicine (26 cases) departments; 14 secondary cases were also observed in the renal transplant department following the transfer of an exposed patient from the infectious diseases department. Most of the patients (90%) were colonized and no death was linked to the epidemic strain. More than 3000 contact patients were reviewed and 6000 rectal swabs were performed. Initial control measures failed to control the outbreak owing to the late detection of the index case. The late implementation of three successive cohort units, the large number of transfers between wards, and the frequent readmission of cases contributed to the incomplete success of control measures.

We present here a 63-year old woman with a long history of immune thrombocytopenia. She was hospitalized for a traumatic intracranial hemorrhage with thrombocytopenia. Following inefficient treatment of four platelet transfusions, immunoglobulins, and corticosteroids, we initiated treatment with a thrombopoietin (TPO) receptor agonist (eltrombopag 25 mg/d) with a good efficacy. Her mother and sister also had chronic thrombocytopenia. Clinical history, hemostasis results, and gene analysis revealed von Willebrand disease (VWD) type 2B with the mutation (c.3946G>A; p.V1316M), which combines a von Willebrand factor defect with severe thrombocytopenia, as well as a thrombocytopathy. The efficacy of TPO receptor agonists appears to counterbalance, at least to some extent, the thrombocytopathy associated with this mutation. As such, the use of TPO receptor agonists could represent an alternative therapeutic approach in cases of VWD type 2B with severe thrombocytopenia.

The aim of this study was to describe special features of patients with systemic sclerosis (SSc) diagnosed after the age of 70.This is a retrospective study of patients aged above 70 years at the time of diagnosis of SSc and followed at an internal medicine unit between 2000 and 2015. Co-morbidities and clinical characteristics were analyzed, as well as survival at 1, 2 and 3 years.Of 246 patients, 27 (11%) were included (89% women, 96% Caucasians, age 78.3±4.5 years). Synchronous cancer was noted in 3 patients. SSc was mostly limited cutaneous only (24/27), with telangiectasia (63%), gastroesophageal reflux (59%) and digital ulcers (22%), and was associated with anti-centromere antibody (69%). Interstitial lung disease was not frequent (29%). Pulmonary arterial hypertension (PAH) was suspected at diagnosis of SSc in 14 cases (52%), but only 5 patients had undergone heart catheterization, with severe PAH in 3 cases. Survival at 1 and 3 years was 85.2% and 66.7%, and was worse in the case of suspected PAH, at 78.6% and 57.1% respectively.Cases of SSc diagnosed after 70 years are mostly limited cutaneous forms. Suspicion of PAH is frequent, and PAH may be the main initial sign of the disease for patients at this age. There may be association with synchronous cancer. Survival is poor.

Pulmonary hypertension (PH) is a serious complication of connective tissue diseases. The prevalence of PH in systemic lupus erythematosus (SLE) ranges from 0.5 to 17.5%, depending on whether echocardiography or right heart catheterization is used as the gold standard for diagnosis. The recent guidelines for the diagnosis and treatment of pulmonary hypertension include several potential causes of PH in SLE, including: a primary vasculopathy similar to idiopathic pulmonary arterial hypertension (PAH); left heart diseases; post-thromboembolic disease; hypoxia and fibrosis resulting from interstitial lung disease; and the infrequent SLE-associated pulmonary veno-occlusive disease. The pathogenesis of PAH associated with lupus is yet unclear, but likely includes a role for the genetic background, the presence of antiphospholipid antibodies, and some level of endothelial dysfunction. The evolution of SLE-associated PH is highly variable and difficult to elicit because the published series have used heterogeneous inclusion criteria. Optimal therapeutic management of PAH associated with lupus is unclear because no dedicated randomized controlled trial is yet available. Treatment usually includes arterial pulmonary vasodilators and immunosuppressive agents when the patients have NYHA functional class II, III or IV dyspnea.

Introduction Le syndrome HANAC (Hereditary Angiopathy with Nephropathy, Aneurysm and muscle Cramps) fait partie des maladies associees aux mutations du gene COL4A1. Il se manifeste sous la forme d’une angiopathie systemique, affectant les vaisseaux de grand et petit calibre, responsable d’AVC ischemiques ou hemorragiques, mais egalement de migraine, de leucomalacie, de syndrome de Raynaud (rarement), de nephropathie avec hematurie et de tortuosites arteriolaires retiniennes se compliquant d’hemorragies retiniennes. Concernant les atteintes extravasculaires, on retient principalement des crampes musculaires avec elevation permanente des CPK, des troubles du rythme cardiaque, une cataracte, un glaucome et syndrome d’Axenfeld-Rieger. Dans cette observation, nous rapportons le cas d’un patient de 70 ans avec un diagnostic recent de syndrome de Sjogren dont le suivi, notamment ophtalmologique, a permis d’identifier un syndrome HANAC avec mutation de l’exon 24 du gene COL4A1. Observation Un homme de 70 ans consultait son ophtalmologiste en 2017 en raison d’une baisse de l’acuite visuelle de l’œil droit d’apparition progressive depuis quelques semaines. Il etait suivi en medecine interne depuis 2014 pour un syndrome de Sjogren primaire (arthralgies, syndrome sec, sialadenite grade IV de Chisholm, avec AC antinucleaires a 1/2560, anti-SSA et − SSB + , et hyper-gammaglobulinemie polyclonale). Ses autres antecedents etaient : otospongiose, chondrocalcinose, HTA, insuffisance renale chronique stade 3a sur probable nephroangiosclerose, cataracte bilaterale, et hemorragie retinienne a l’âge de 22 ans. Sur le plan familial, son frere et sa sœur avaient tous deux fait un AVC avant l’age de 60 ans. L’examen du fond d’œil retrouvait une membrane epi-retinienne droite et des tortuosites arterielles bilaterales faisant evoquer une angiopathie dans le cadre d’un syndrome HANAC en tenant compte des antecedents familiaux d’AVC, de l’insuffisance renale, de la cataracte et de l’hemorragie retinienne ancienne. Une recherche de mutation genetique etait alors effectuee, permettant de retrouver effectivement une variation c.1501G > A de l’exon 24 du gene COL4A1 en faveur du diagnostic de syndrome HANAC. Discussion Le gene COL4A1 code pour la chaine alpha-1 du collagene IV, qui est le constituant majoritaire des membranes basales. Il est localise en 13q34 et il est en cause dans differentes maladies hereditaires comme la leucoencephalopathie vasculaire familiale, la microangiopathie cerebrale pontine autosomique dominante, la porencephalie familiale, la schizencephalie familiale, le syndrome de Walker-Warburg, le syndrome HANAC et la tortuosite arteriolaire retinienne. Il existe differentes mutations de ce gene qui se transmettent selon le mode autosomique dominant et les manifestations phenotypiques sont souvent correlees a l’exon atteint. La mutation du gene COL4A1 a ete mise en evidence en 2005 chez des nouveau-nes atteints de porencephalie. Sa prevalence est inconnue. L’association syndrome de Sjogren/Syndrome HANAC n’est pas decrite dans la litterature et semble etre fortuite dans notre cas. Le patient a ete diagnostique a l’âge de 70 ans principalement grâce a l’aspect de tortuosites arteriolaires retiniennes qui avaient probablement ete a l’origine de l’hemorragie retinienne alors qu’il n’avait que 22 ans. On constate finalement des disparites concernant le delai diagnostique dues a la diversite des symptomes et leur gravite allant des crampes jusqu’a l’AVC. Cette variation de phenotype clinique est aussi bien intrafamiliale qu’interfamiliale et cela suggere l’existence d’une modulation possible par des genes modificateurs et/ou des facteurs environnementaux. Des mutations du gene COL4A2 semblent etre egalement a l’origine de manifestations similaires et ses premieres mutations ont ete mises en evidence en 2012 dans des cas de porencephalie. Conclusion En conclusion, chez le patient adulte, le syndrome HANAC merite d’etre connu des medecins internistes notamment lorsqu’il existe une angiopathie cerebrale potentiellement responsable d’AVC. A l’heure actuelle, il n’existe pas de traitement curatif, mais des mesures preventives sont essentielles, reposant essentiellement sur l’eviction de facteurs favorisants (traumatismes crâniens, medicaments favorisants les saignements), et un controle strict de la pression arterielle.

Introduction Le syndrome de Gleich ou angioedeme avec hypereosinophilie est une entite rare associant des crises recurrentes d’angioedeme avec hypereosinophilie concomitante et elevation frequente d’immunoglobulines M seriques polyclonales. Patients et methodes Nous avons conduit une etude retrospective nationale multicentrique afin d’evaluer le spectre clinique et la prise en charge therapeutique des angiœdemes avec hypereosinophilie. Resultats Trente patients ont ete inclus avec un âge median au diagnostic de 41 ans [5–84]. La duree mediane de chaque crise d’angiœdeme etait de 5,5 jours [1–90] avec atteinte principale du visage et des membres superieurs. Le taux seriques d’immunoglobuline M etait eleve pour 20 patients (67 %). Un phenotype lymphocytaire T aberrant etait detecte chez 12 patients (40 %) avec mise en evidence d’un rearrangement clonal du TCR γ chez 5 de ces patients (17 %). Le suivi median etait de 53 mois [31-99]. Tous les patients ont recu une corticotherapie initialement efficace, mais 15 patients ont rechute apres cette premiere ligne (50 %) justifiant une deuxieme ou troisieme ligne de traitement par interferon-α (n = 8,27 %), mepolizumab (n = 2,7 %), ciclosporine A (n = 5,17 %), methotrexate (n = 4,13 %) ou hydroxycarbamide (n = 2,7 %). La presence d’un phenotype lymphocytaire aberrant etait le seul facteur associe aux rechutes (hazard ratio 4,15 [IC 95 % 1,18–14,66] ;p = 0,02). Lors du dernier suivi, 3 patients (10 %) etaient sevres de tout traitement et 11 patients (37 %) etaient en remission clinique et biologique sous moins de 10 mg d’equivalent prednisone par jour. Conclusion Le syndrome de Gleich ou angiœdeme avec hypereosinophilie est une entite heterogene au sein des syndromes hypereosinophiliques. Bien que les patients presentent une bonne reponse a la corticotherapie, les patients porteurs d’un phenotype lymphocytaire T aberrant ont un risque de rechute augmente.

Objectif Les ischemies digitales (ID) sont une entite rare et heterogene auxquelles est cependant, confronte le medecin vasculaire ; l’ischemie du membre superieur est quarante fois moins frequente que celle des membres inferieurs. L’objectif de cette etude etait d’evaluer les etiologies, les traitements, les pronostics et l’evolution a long terme des ID dans la plus grande cohorte jamais rapportee. Malades et methodes Nous avons inclus les patients presentant des ischemies digitales, avec ou sans necrose, limitees ou non aux doigts sur la periode de janvier 2000 a decembre 2016 au sein du CHU de Nantes. Nous avons recueilli les donnees retrospectives portant sur l’etiologie, la recidive d’ID, les amputations digitales et la survie globale. Resultats Les ischemies digitales d’origine cardio-emboliques (IDCE) etaient l’etiologie principale avec 59 patients (18,3 %), suivie des patients atteints de sclerodermie systemique (SSc) avec 52 patients (16 %), les ID idiopathiques representaient 38 patients (11,7 %), les maladies de Buerger avec 30 patients (9,3 %), les causes iatrogeniques avec 30 patients (9,3 %) et les neoplasies avec 20 patients (6,2 %). Les patients avec une IDCE etaient significativement plus vieux et presentaient plus d’hypertension arterielle alors que les maladies de Buerger consommaient plus de tabac et de cannabis. Sur le plan clinique, les patients avec une IDCE avaient plus de pâleur des doigts et de douleur a la fois nociceptive et neuropathique alors que les SSc presentaient plus de necrose digitale. Le suivi a long terme a montre des recidives significativement plus frequentes dans le groupe SSc par rapport a tous les autres groupes (p Conclusion Dans cette etude, les etiologies principales d’ID etaient les cardiopathies emboligenes, la SSc et les ID idiopathiques. Cette etude montre une augmentation de l’etiologie iatrogenique en comparaison aux series d’ID precedentes. Les ID de la SSc sont associees a un mauvais pronostic local alors que les IDCE sont associees a un mauvais pronostic general. Les ID dans la SSc et la maladie de Buerger sont associees a plus de recidive.

Background and purpose: Pulmonary arterial hypertension (PAH) is associated with increased contraction and proliferation of pulmonary vascular smooth muscle cells. The anti-diabetic drug metformin has been shown to have relaxant and anti-proliferation properties. We thus examined the effect of metformin in PAH. Experimental approach: Metformin effects were analysed in hypoxia- and monocrotaline-induced PAH in rats. Ex vivo and in vitro analyses were performed in lungs, pulmonary artery rings and cells. Key results: In hypoxia- and monocrotaline-induced PAH, the changes in mean pulmonary arterial pressure and right heart hypertrophy were nearly normalized by metformin treatment (100 mg·kg−1·day−1). Pulmonary arterial remodelling occurring in both experimental models of PAH was also inhibited by metformin treatment. In rats with monocrotaline-induced PAH, treatment with metformin significantly increased survival. Metformin increased endothelial nitric oxide synthase phosphorylation and decreased Rho kinase activity in pulmonary artery from rats with PAH. These effects are associated with an improvement of carbachol-induced relaxation and reduction of phenylephrine-induced contraction of pulmonary artery. In addition, metformin inhibited mitogen-activated protein kinase activation and strongly reduced pulmonary arterial cell proliferation during PAH. In vitro, metformin directly inhibited pulmonary artery smooth muscle cell growth. Conclusions and implications: Metformin protected against PAH, regardless of the initiating stimulus. This protective effect may be related to its anti-remodelling property involving improvement of endothelial function, vasodilatory and anti-proliferative actions. As metformin is currently prescribed to treat diabetic patients, assessment of its use as a therapy against PAH in humans should be easier.

Resume L’hypertension arterielle pulmonaire (HTAP) associee a la sclerodermie systemique est une maladie grave qui concerne environ 1000 patients en France. En 2008, tout patient sclerodermique doit beneficier d’un depistage annuel de l’HTAP par l’echographie Doppler cardiaque. La pathogenie de l’HTAP de la sclerodermie systemique reste mal connue mais il semble qu’en dehors des lesions arteriolaires habituelles de remodelage (hypertrophie de la media, epaississement intimal et proliferation endotheliale), on puisse egalement observer des lesions veinulaires evoquant une maladie veino-occlusive pulmonaire, ainsi que des lesions inflammatoires. Les traitements specifiques de l’HTAP comportent la prostacycline ou ses analogues, les inhibiteurs de phosphodiesterase-5 (sildenafil) et les antagonistes des recepteurs de l’endotheline-1. A la difference du bosentan, antagoniste non selectif inhibant les recepteurs ETA et ETB de l’endotheline-1, le sodium sitaxentan, recemment mis a disposition en France, a un effet selectif, inhibant les seuls recepteurs ETA, ce qui pourrait optimiser la vasodilatation pulmonaire.

Jaccoud's arthropathy (JA) is a chronic and non-erosive deforming arthropathy, usually affecting the hands. JA pathophysiology is poorly known but involves periarticular structures such as tendons and the joint capsule. JA is associated with various conditions including the connective tissue disease, especially systemic lupus erythematosis. JA has been rarely described and studied in systemic sclerosis.We report the clinical histories of 3 patients with systemic sclerosis (ScS) who developed JA. One patient had a systemic limited disease and the 2 others a cutaneous limited disease ; mean age of the patients was 79.3 years. Systemic sclerosis was diagnosed respectively 19, 1 and 21 years prior to the development of JA. One of the 3 patients had a past clinical history of discoid lupus. For 1 out of the 3 patients, JA appeared whereas the ScS was completely stable. The disease was still active in the 2 remaining patients, with concurrent pulmonary hypertension diagnosis. Deformities increased during years (Z thumbs, ulnar deviation), leading to mild to severe disability. No benefit from either prednisone (n=2) or a combination of prednisone and methotrexate (n=1) was obtained.We described 3 cases of Jaccoud's arthropathy among our scleroderma cohort of 296 patients (1%). This arthropathy worsens hand functional disability. Its pathophysiology is unknown and optimal therapeutic approach remains to establish.

To develop French recommendations about the management of vaccinations, the screening of cervical cancer and the prevention of pneumocystis pneumonia in systemic lupus erythematosus (SLE).Thirty-seven experts qualified in internal medicine, rheumatology, dermatology, nephrology and pediatrics have selected recommendations from a list of proposition based on available data from the literature. For each recommendation, the level of evidence and the level of agreement among the experts were specified.Inactivated vaccines do not cause significant harm in SLE patients. Experts recommend that lupus patient should receive vaccinations accordingly to the recommendations and the schedules for the general public. Pneumococcal vaccination is recommended for all SLE patients. Influenza vaccination is recommended for immunosuppressed SLE patients. Live attenuated vaccines should be avoided in immunosuppressed patients. Yet, recent works suggest that they can be considered in mildly immunosuppressed patients. Experts have recommended a cervical cytology every year for immunosuppressed patients. No consensus was obtained for the prevention of pneumocystis pneumonia.These recommendations can be expected to improve clinical practice uniformity and, in the longer term, to optimize the management of SLE patients.

Resume Introduction. – Cinq ans apres la mise en place des permanences d’acces aux soins de sante (PASS), il etait necessaire d’en analyser leurs fonctionnements et leurs activites. Materiel et methode. – Un systeme informatique de recueil et d’evaluation de l’activite medicosociale des PASS a ete mis en place dans 11 CHU et dix CHG. La saisie des donnees a ete effectuee du 1er janvier au 30 juin 2003. Resultats. – Les patients consultant sont jeunes (moyenne d’âge 35 ans) et cumulent plusieurs facteurs de precarite : precarite du logement, des liens sociaux et des ressources entre autres. Ils ne beneficient pour la plupart d’aucune couverture sociale. Le public des PASS est donc bien celui pour lequel le dispositif a ete mis en place. Les facteurs de risque de precarite varient en fonction de l’origine geographique : les Francais etant le plus souvent isoles, alors que les etrangers se retrouvent plus souvent sans ressources. La majeure partie des consultants est d’origine etrangere et plus d’un tiers d’entre eux ne parlent pas francais, ce qui constitue un facteur d’exclusion supplementaire. Les pathologies les plus souvent retrouvees sont les pathologies digestives, avec neanmoins des differences entre patients francais et patients etrangers : si les pathologies digestives et osteoarticulaires sont plus frequentes chez les etrangers, les troubles psychiques et les conduites addictives sont plus retrouves chez les Francais. Un certain nombre de patients sont orientes vers des medecins de ville (9 %) et vers des services sociaux exterieurs (39,5 %). Discussion. – Cette etude a permis, pour la premiere fois en France, de disposer de donnees homogenes concernant l’activite des PASS. L’utilite de l’outil informatique et son acceptabilite permettent d’en envisager les modalites de diffusion, avec des adaptations possibles a chacune, tout en gardant une base commune.