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Systemic lupus erythematosus (SLE), primary Sjögren's syndrome (pSS), systemic sclerosis (SSc), idiopathic inflammatory myopathies (IIM) and rheumatoid arthritis (RA) are connective tissue diseases (CTD) whose complications can lead to management in the intensive care unit (ICU).To estimate by meta-analysis ICU mortality rates for CTD.A systematic literature review was performed to identify articles studying critically ill CTD patients. A random-effects model was chosen for analysis. Pooled proportion mortality was calculated using aggregated-data meta-analysis with a random-effects model and assessment of heterogeneity with the IOf the 5694 individual publications, a sample of 31 independent cohorts was used for the meta-analysis totalling 5007 patients. The main cause for admission was sepsis (43%) followed by "flare-ups" (40%). The overall pooled proportion of mortality of CTD patients across all 31 studies was 33% (95%CI: 28-38%). In the IIM subgroup and that of SSc, mortality was 70% (95%CI: 46-86%) and 40% (95%CI: 25-47%), respectively. In the SLE subgroup, mortality was similar to the overall pooled mortality of 35% (95%CI: 29-42%). Subgroup mortality for RA and pSS patients was respectively 20% (95%CI: 11-33%) and 17% (95%CI: 6-41%); lower than the overall pooled mortality. Heterogeneity in each subgroup remained high.The overall pooled proportion of mortality of ICU patients with CTD was 33% (95%CI: 28-38%), with a high heterogeneity (I

Sustained response off-treatment (SROT) after thrombopoietin receptor agonist (TPO-RA) discontinuation has been reported in ITP. This prospective multicenter interventional study enrolled adults with persistent or chronic primary ITP and complete response on TPO-RAs. The primary endpoint was the proportion of patients achieving SROT (platelet count > 30x109/L and no bleeding) at W24 with no other ITP-specific medications. Secondary endpoints included the proportion of sustained complete response off-treatment (SCROT, platelet count > 100x109/L and no bleeding) and SROT at W52, bleeding events, and pattern of response to a new course of TPO-RAs. We included 48 patients with median (IQR) age 58.5 years (41-73.5); 30/48 (63%) had chronic ITP at TPO-RA initiation. In the intention-to-treat analysis, 27/48 (56.2%, 95% CI, 41.2-70.5) achieved SROT; 15/48 (31.3%; 95% CI, 18.9-44.5) achieved SCROT at W24, and 25/48 (52.1%; 95% CI, 37.2-66.7) achieved respectively SROT and 14/48 (29.2%; 95% CI, 17.2-42.3) SCROT at W52. No severe bleeding episode occurred in patients who relapsed. Among patients re-challenged with TPO-RA, 11/12 achieved CR. We found no significant clinical predictors of SROT at W24. Single-cell RNA-seq revealed enrichment of a "TNFα signaling via NF-κB" signature in CD8+ T cells of patients with no sustained response after TPO-RA discontinuation, which was further confirmed by a significant overexpression of CD69 on CD8+ T cells at baseline in these patients as compared with those achieving SCROT/SROT. Our results strongly support a strategy based of progressive tapering and discontinuation of TPO-RAs for patients with chronic ITP who achieved a stable CR on treatment. Clinical trial number: NCT03119974

Takayasu arteritis (TAK) is a large vessel vasculitis affecting young women of childbearing age. The outcome of pregnancies in TAK patients, factors associated with maternal and foetal complications and adverse outcomes were analysed.All pregnancies in women with a TAK diagnosis were retrospectively included from 20 French hospitals providing care for TAK, until August 2015.The study consisted of 43 pregnancies in 33 women, including 29 with a pre-existing TAK diagnosis and 4 diagnosed during pregnancy. Complications were observed in 20 pregnancies (47%), including 35% with arterial hypertension (n = 15), 9% with pre-eclampsia (n = 4), 2% with HELLP syndrome (n = 1) and 14% with intrauterine growth restriction (IUGR, n = 6, leading in one case to a medically indicated termination of pregnancy). There were 42 live births (98%) at a median term of 38 [27-42] weeks gestation including 9 before 37 weeks (21%). The median birth weight was 2940 [610-4310] grams. Five children (12%) required transfer to a neonatal intensive care unit. One premature boy (27 weeks gestation) died after 2 days. Treatment during pregnancy included steroids (n = 25/43; 58%), azathioprine (n = 9/43; 21%) and infliximab (n = 1/43; 2%). The risk of developing arterial hypertension during pregnancy was associated with previous chronic arterial hypertension and with an infra-diaphragmatic vasculitis injury (P = 0.01 and P = 0.04, respectively). No correlation was reported between TAK activity and any of the obstetrical complications described in the study.This study showed a high rate of adverse obstetrical complications without significant impact on live birth rates. Pregnancy did not appear to influence TAK disease activity. Key Points • We observed a high rate of adverse obstetrical complications in women with Takayasu arteritis; however, the rate of live births was high. Pregnancy did not appear to influence TA disease activity.

To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM). Patients with DM (n = 24) who met the European Neuro-Muscular Centre diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUVPROX) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUVMLT), whereas mean SUV was measured for the liver (SUVLIV). Muscle-to-liver SUV ratios for either muscle group were compared and a SUVPROX/SUVMLT ratio was calculated. SUVPROX/SUVMLT of DM patients were compared with age- and sex-matched control subjects (n = 24) with melanoma who had received FDG-PET scans. DM patients presented with proximal and symmetrical muscle uptake. Differences in SUVPROX/SUVLIV and SUVMLT/SUVLIV ratios in DM subjects were significant (p

Context The management of systemic auto-immune diseases (SAID) -associated thrombotic microangiopathies (TMA) [SAID-TMA] remains debated. Objectives To provide a demographic, clinical and therapeutic picture of SAID-TMA. Methods A cross-sectional analysis was conducted on adult patients presenting with SAID and TMA from the French National TMA Registry over a 20-year period. Clinical features were extracted and compared to those from a historical cohort of atypical haemolytic and uremic syndrome (aHUS) patients. Results Forty-one patients with SAID-TMA were compared to 78 patients with aHUS from a historical cohort. Connective tissue diseases (CTD) were systemic lupus erythematosus (n=18), primary Sjogren's syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2) and 2 cases of vasculitides, including 7 overlapping forms and 8 cases of primary antiphospholipid syndromes (APLS). Patients with SAID-TMA generally had pre-existing chronic kidney failure (OR= 3.17, 95%CI: 1.204 to 7.923; p= 0.016) compared to aHUS patients, though creatinine levels were significantly lower (216 [IQR, 108-334] µmol/L vs. 368 [IQR, 170-722] µmol/L; p= 0.002). Patients were less likely to recover if renal replacement therapy was needed at onset (OR= 0.07; 0.02 to 0.34; p 0.05). Conclusion The management of SAID-TMA implies an early initiation of immunosuppressive drugs for flares of the associated SAID, whereas TPE seem ineffective. Key messages • Systemic auto-immune diseases (SAID) in thrombotic microangiopathies (TMA) [SAID-TMA] include mainly systemic lupus erythematosus, systemic sclerosis and primary Sjogren's syndrome. • SAID-TMA improves with the treatment of the underlying SAID • Therapeutic plasma exchange does not seem to have an early effect on TMA features at Day-7 nor Day-15

International audience; Objectives: Myelodysplastic syndromes (MDS) and chronic myelomonocytic leukaemia (CMML) are associated with systemic inflammatory and autoimmune diseases (SIADs) in 10-30% of cases. The aims of this study were (i) to evaluate the prevalence of venous thromboembolism VTE in patients presenting with both MDS/CMML and SIADs, (ii) to describe risk factors associated with thrombosis, and (iii) to analyse the impact of VTE on overall survival and transformation to acute myeloid leukaemia in comparison to patients with MDS/CMML-associated SIADs without VTE.Methods: This retrospective multicentre case-control study was conducted among patients with MDS/CMML and dysimmune disorders and featured in the French retrospective database of the French Network of Dysimmune Disorders Associated with Hemopathies (MINHEMON), diagnosed with MDS/CMML and dysimmune disorders.Results: During a median follow-up of 16 months (5-48) VTE occurred in 35 patients (21.6 %) whereas 127 patients did not. Among those with VTE, 8 patients (22.9%) experienced two or more VTE. Common prothrombotic risk factors were not significantly different in patients with or without VTE. CMML was more frequent in patients without VTE (37 % vs. 14.3%, p=0.01), whereas myelodysplasic/myeloproliferative neoplasm (MDS/MPN) was higher in VTE patients (20 % vs. 5.5 %, p=0.01). In a multivariate analysis, only MDS/CMML progression at the time of VTE (odds ratio 28.82, 95 % CI (5.52-530.70) was significantly associated with VTE. When treated with an anticoagulation therapy, bleeding occurred in 19.4% of cases (6/31). Overall survival was not significantly different between patients with and without VTE (p=0.68). Leukaemia-free survival between groups was not significantly different (p=0.83).Conclusions: VTE is a common complication in MDS/CMML-associated SIADSs with an increased risk of bleeding when treated by anticoagulants. In the MDS/CMML subgroup, SIADS flares and MDS/CMML progression seem to be prothrombotic risk factors.

The anti–von Willebrand factor nanobody caplacizumab was licensed for adults with immune-mediated thrombotic thrombocytopenic purpura (iTTP) based on prospective controlled trials. However, few data are available on postmarketing surveillance. We treated 90 iTTP patients with a compassionate frontline triplet regimen associating therapeutic plasma exchange (TPE), immunosuppression with corticosteroids and rituximab, and caplacizumab. Outcomes were compared with 180 historical patients treated with the standard frontline treatment (TPE and corticosteroids, with rituximab as salvage therapy). The primary outcome was a composite of refractoriness and death within 30 days since diagnosis. Key secondary outcomes were exacerbations, time to platelet count recovery, the number of TPE, and the volume of plasma required to achieve durable remission. The percentage of patients in the triplet regimen with the composite primary outcome was 2.2% vs 12.2% in historical patients (P = .01). One elderly patient in the triplet regimen died of pulmonary embolism. Patients from this cohort experienced less exacerbations (3.4% vs 44%, P < .01); they recovered durable platelet count 1.8 times faster than historical patients (95% confidence interval, 1.41-2.36; P < .01), with fewer TPE sessions and lower plasma volumes (P < .01 both). The number of days in hospital was 41% lower in the triplet regimen than in the historical cohort (13 vs 22 days; P < .01). Caplacizumab-related adverse events occurred in 46 patients (51%), including 13 major or clinically relevant nonmajor hemorrhagic events. Associating caplacizumab to TPE and immunosuppression, by addressing the 3 processes of iTTP pathophysiology, prevents unfavorable outcomes and alleviates the burden of care.

To determine the prevalence of the V617F Janus Kinase 2 (JAK2) mutation in patients with thrombosis without other biological signs of underlying myeloproliferative neoplasm (MPN) and identify associated risk factors for thrombosis. Over a 10-year period, data were collected from patients with thrombotic events and who had also been screened for the V617F JAK2 mutation. Patients with signs of underlying MPN, such as haematocrit levels ≥ 50% and/or platelet counts ≥ 450 × 109/L and/or splanchnic thrombosis were excluded from the study. Of 340 patients fulfilling inclusion criteria, JAK2 mutation was found in 9 (2.65%), the allele burden being at least 2% in 4 (1.1%). Upon follow-up, MPN was diagnosed in the latter 4. Univariate analysis of the whole cohort showed that age (54 ± 15 vs. 64 ± 13, p = 0.027), platelet count (317 ± 111 vs. 255 ± 75, p = 0.017), C-reactive protein level > 5 mg/L (OR 7.29, p = 0.014), and splenomegaly (OR 54.5, p = 0.0002) were significantly associated with JAK2 mutation. There was also a trend for an increased risk of cerebral venous thrombosis (OR 6.54, p = 0.064). Logistic regression confirmed a significant association between splenomegaly and JAK2 mutation (OR 43.15 [95%CI, 3.05–610.95], p = 0.0054). The V617F JAK2 mutation is rarely found in patients with thrombotic events without overt MPN. Splenomegaly, however, is a statistically and clinically relevant indicator of a potential JAK2 mutation in patients with non-splanchnic thrombotic events. Such patients should require further assessment and a close follow-up.

Introduction La sclerodermie systemique [ScS] est une maladie rare du tissu conjonctif dont la pneumopathie interstitielle diffuse [PID] dans sa forme progressive est la principale cause de deces. La prise en charge de la PID-ScS repose sur une approche multimodale. Il n’y a pas de recommandation consensuelle concernant la validation de cette progression de la PID-ScS ni de sa therapeutique. Nous proposons par une enquete nationale de dresser un panorama national des pratiques diagnostiques, therapeutiques et de suivi de ces patients. Materiels et methodes Une enquete en ligne, en francais, a ete soumise par l’intermediaires des Societes Savantes et Groupes de Recherche, a des praticiens prenant en charge les PID-ScS. L’enquete comprenait 79 questions a choix multiples et 9 questions ouvertes etudiant les caracteristiques demographiques des participants, le depistage de la PID au diagnostic de ScS, le suivi des patients atteints de PID-ScS et la prise en charge therapeutique de la PID-ScS. A la fin du questionnaire, 14 vignettes cliniques, facultatives, explorant un phenotype specifique de PID-ScS a differents stades de progression, etaient soumises aux participants en vue de recueillir leur decision therapeutique. Resultats Les reponses ont ete recueillies de mai 2018 a juin 2020, avec 93 participants eligibles dont 72 medecins internistes et 18 pneumologues. La PID etait recherchee systematiquement avec un recours au scanner thoracique par 89 % des participants et une prescription d’explorations fonctionnelles respiratoires [EFR] par 94 %. La quasi-totalite des participants (97 %) placait les EFR comme un marqueur de progression de la PID-ScS, et 31 % y associait systematiquement un scanner pulmonaire. Les valeurs-seuil retenues par les participants pour une CVF et une DLCO pathologique etaient respectivement de 80 % et 70 % des valeurs predites. Par ordre de frequence decroissante, l’initiation d’un traitement specifique de la PID-ScS etait decidee en fonction des resultats des EFR (95 %), du scanner thoracique (89 %), de la presence d’une dyspnee (72 %), d’une desaturation en oxygene pendant le test de marche de 6 minutes [TM6] (66 %), d’une hypertension pulmonaire associee (48 %), de la distance parcourue au TM6 (45 %), des parametres gazometriques arteriels (45 %) et d’une pression partielle d’oxygene arterielle (PaO2) anormale (24 %). Les 3 traitements de premiere ligne les plus cites, en monotherapie ou en combinaison, etaient le cyclophosphamide [CYC] (89 %), le mycophenolate mofetil [MMF] (83 %) et la prednisone (73 %). Le rituximab etait retenu comme un traitement immunosuppresseur de deuxie recours (41 %) alors que les antifibrosants n’etaient cites que par 19 % et 10 % des participants pour, respectivement, le nintedanib et la pirfenidone. La corticotherapie etait associee (41 %) a 10 mg/j de prednisone. Dans les vignettes cliniques, 45 participants (66 %) envisageaient un autre traitement immunosuppresseur dans le contexte d’une PID extensive de ScS de forme cutanee limitee (ScS-l) de moins de 5 ans d’evolution en privilegiant le MMF au CYC (27 vs. 13 ; p = 0,006) parmi d’autres traitements proposes. A contrario, le MMF ou le CYC etaient indifferemment utilises pour la meme situation au-dela de 5 ans d’evolution de la maladie. Dans le cas de PID extensive de ScS-l et d’aggravation des EFR sur 6 mois, un traitement immunosuppresseur etait initie par 66 participants (97 %) en privilegiant CYC par rapport au MMF (48 vs. 15 ; p Conclusion Dans ce premier panorama des pratiques sur la PID-ScS, nous faisons le constat d’une homogeneite des pratiques diagnostiques et de suivi, refletant les consensus nationaux et europeens. Toutefois, la complexite des phenotypes cliniques de la ScS amene a constater des divergences dans les approches therapeutiques et un recours encore exceptionnel aux nouveaux traitements anti-fibrosants dans cette etude faite avant la mise a disposition notamment du nintedanib. Il sera important de renouveler cette enquete maintenant que cette option est labelisee.

Background: Thrombopoietin receptor agonists(TPO-RAs) have been thought to play only a supporting role in ITP management. Several retrospective studies and a recent prospective study have reported unexpected cases of durable remission after TPO-RAs discontinuation in adult ITP in up to 30%. However, newly diagnosed ITP cases for which spontaneous remission may occur have been included in most of these studies. Thus, the main purpose of this study was to determine the proportion of patients with either persistent or chronic phase and no recent exposure to any potentially curative therapy (i.e., splenectomy or rituximab) achieving long-term remission off-treatment at 24 and 52 months after at least 3 months of TPO-RAs exposure with a complete response (CR). Patients/methods: We conducted a nationwide prospective multicenter interventional study (NCT03119974). Inclusion criteria were: 1) Patients aged > 18 years, with persistent or chronic primary ITP, 2) A stable CR defined by a platelet count > 100 x 10 9/L for more than 2 months on TPO-RA therapy, 3) Treatment with TPO-RA for at least 3 months. Main exclusion criteria were: 1) Anticoagulation or anti-platelet treatment, 2) Previous failure of TPO-RA discontinuation, 3) Concomitant treatment with corticosteroids ± intravenous immunoglobulin 4) Rituximab or splenectomy within the 2 months preceding or after TPO-RA initiation. After inclusion, the decrease and wean of either eltrombopag or romiplostim was initiated according to a standardized protocol (respectively tapering of 25 mg every 2 weeks or tapering of 1 ug/kg every week). In any case TPO-RAs had to be stopped at week 10. In case of relapse after TPO-RA discontinuation, the decision to start a new therapy was left at every investigator discretion. The primary endpoint was the proportion of patients achieving an overall response (CR + R) at week 24 (6 months) after TPO-RAs discontinuation. Secondary outcomes were overall response rate over the study period (W52), bleeding events, and to identify predictive factors, for overall prolonged response (W24 and W52). Results: Forty-nine patients (30 females, 61%), with persistent (n=2) or chronic (n=47, 96%) chronic ITP, with a median age of 58.5 years IQR (41 to 73) fulfilling the eligibility criteria were included over 2 year-period in 22 centers from the French reference network for adult' ITP. Forty patients received eltrombopag and 9 romiplostim at the time of inclusion. One patient was excluded since she was diagnosed pregnant one day after inclusion. In intention to treat 27/48 (56.2%; 95% CI, 29.5 to 58.8) patients achieved the primary-endpoint and maintained an overall response at week 24 after TPO-RAS discontinuation with a complete response for 15/27 (55%). During the full follow-up period of 52 weeks after TPO-RAs discontinuation, overall response was observed in 25/48 (52.1%; 95% CI, 37.2 to 66.2) patients (Figure 1). Bleeding events occurred in 13/21 (61.9%) and 15/23 (65.2%) patients relapsing respectively at 24 and 52 months with a median platelet count of 31´10 9/L(26 to 39) and 31 ´10 9/L(23 to 39). No severe bleeding episode (French bleeding score > 8) occurred. Median time of relapse after tapering initiation was 8 weeks. Among 21 patients with a relapse ( Conclusion: These results showed an unexpectedly high rate of sustained off-treatment remission after TPO-RAs discontinuation in chronic ITP among patients who initially achieve a stable CR. When they occur, relapses are mainly observed within the first weeks after discontinuation, very rarely afterwards and with no severe bleeding. While no predictive factor of lasting remission has been yet identified, our study strongly supports a progressive tapering of the dose of TPO-RAs in patients achieving a stable CR on treatment. Figure 1: Relapse at 52 weeks after TPO-RAs discontinuation Figure 1 Figure 1. Disclosures Mahevas: GSK: Research Funding; Amgen: Honoraria. Viallard: Novartis: Consultancy; Grifols: Consultancy; LFB: Consultancy; Amgen: Consultancy. Moulis: Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Argenx: Membership on an entity's Board of Directors or advisory committees; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sobi: Membership on an entity's Board of Directors or advisory committees. Terriou: Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Michel: Novartis: Consultancy; Amgen: Consultancy; UCB: Honoraria; Argenx: Honoraria; Rigel: Honoraria; Alexion: Honoraria. Godeau: Sobi: Consultancy; Novartis: Consultancy; Amgen: Consultancy; Grifols: Consultancy.

Methods: Data on clinical characteristics, histologic features, and treatment response from 260 patients with IgAV included in a French multicenter retrospective survey were analyzed. Efficacy data were compared using different statistical models. Results: The mean ± SD age of the patients with IgAV at diagnosis was 50.1 ± 18 years, and 63% of patients were male. Baseline manifestations included purpura (100%), arthralgias/arthritis/myalgia (61%), glomerulonephritis (70%), and/or gastrointestinal involvement (53%). Thirty percent of patients showed renal failure at baseline. In univariate analysis, the response to therapy was 80% (64 of 80) in patients treated with corticosteroids (CS) alone, compared to 77% (23 of 30) in patients treated with CS plus cyclophosphamide (CYC) and 59% (10 of 17) in patients treated with colchicine (P = 0.17). Multivariable analysis showed that treatment with CS or CS plus CYC was more effective than colchicine in achieving a response. Efficacy differences were demonstrated using different statistical models: in the multivariable logistic regression model, odds ratio (OR) 3.68, 95% confidence interval (95% CI) 1.10–12.33 (P = 0.03); in the inverse probability weighting on propensity score model, OR 3.75, 95% CI 1.28–10.99 (P = 0.02). The efficacy of CS plus CYC as compared to CS alone was discordant according to the analytic method used. Analysis with the multivariable logistic regression model did not demonstrate a difference between CS plus CYC and CS alone (OR 0.88, 95% CI 0.29–2.67; P = 0.82). In contrast, inverse probability weighting on propensity score showed that CS plus CYC was more effective than CS alone (OR 1.79, 95% CI 1.00–3.20; P = 0.049). Conclusion: This series constitutes the largest series of adults with IgAV reported in the literature so far. It provides data on clinical and histologic presentation and therapeutic efficacy, suggesting that CS alone appears to be a reasonable first‐line therapy in patients with IgAV, while the benefit of adding CYC to CS remains uncertain.

Introduction L’internat, et en particulier son debut, associe aux premieres gardes, est une periode source de stress et d’anxiete importante. La simulation en sante est un outil pedagogique reconnu comme efficace pour l’amelioration des competences techniques mais egalement non techniques dans de nombreux domaines. Cependant, elle est encore peu utilisee dans le co- Diplome d’Etudes Specialisees (DES) de Medecine Interne Immunologie Clinique, Maladies Infectieuses et Tropicales, et Allergologie (MIIC-MIT-A). Son utilisation a par ailleurs montre un benefice sur le stress, l’anxiete et le sentiment d’auto-efficacite chez les etudiants infirmiers. L’objectif de cette etude etait d’evaluer le benefice d’une seance de simulation immersive sur le vecu des premieres gardes des internes du co-DES de MIIC-MIT-A. Materiels et methodes Nous avons realise une etude prospective, controlee, multicentrique, dans laquelle deux groupes d’internes ont ete constitues. Le groupe simulation comprenait les internes qui ont beneficie de la seance de simulation immersive pour la preparation aux premieres gardes lors du premier semestre d’internat, comportant 4 scenarios mettant en jeu des situations critiques (choc hypovolemique sur hemorragie digestive, detresse respiratoire aigue avec arret cardiorespiratoire, choc septique sur pyelonephrite obstructive, choc anaphylactique). Il etait constitue des internes des DES de MIIC-MIT-A de Montpellier, Bordeaux et Nice, qui ont passe les Epreuves Classantes Nationales Informatisees (ECNi) en 2019. Le groupe controle, qui n’a pas beneficie des seances de simulation, etait constitue des internes du meme co-DES de Montpellier et Nice, qui ont passe les ECNi en 2018. L’objectif principal etait d’explorer l’impact de la seance de simulation immersive realisee au premier semestre d’internat, sur le stress, l’anxiete, et le sentiment d’auto efficacite lors des premieres gardes, evalues au second semestre. Les objectifs secondaires etaient la comparaison du stress et de la confiance en soi auto estimes entre le debut et la fin de la seance, et leur association avec le stress, l’anxiete, et l’auto-efficacite au second semestre. Le niveau de stress et de confiance en soi etaient evalues par autoquestionnaire anonymise en debut et fin de seance (echelles de Likert de 0 a 5). Au cours du second semestre, les niveaux de stress, d’anxiete et de sentiment d’auto-efficacite ont ete evalues dans les deux groupes d’internes, a l’aide d’echelles validees : Perceived Stress Scale (PSS), Generalized Anxiety Disorder -7 (GAD-7) scale et General Self-efficacy Scale (GSES). Nous avons enfin evalue la satisfaction des apprenants et leur avis concernant la pertinence de cet outil dans leur formation dans le cadre du co-DES de MIIC-MIT-A. Resultats Les groupes simulation et controle comprenaient respectivement 19 et 9 internes. Au second semestre, les scores PSS, GSES et GAD-7 etaient de 20.71 ± 8,15 et 22,44 ± 5,68 (p = 0,40) ; 26,88 ± 6,30 et 27,11 ± 3,95 (p = 0,87) ; 6,94 ± 5,25 et 8,89 ± 4,78 (p = 0,22) dans les groupes simulation et controle, respectivement. A noter qu’en utilisant le seuil de 8 pour le GAD-7, a partir duquel on considere que l’interroge est anxieux, on retrouve 35,3 % d’internes anxieux dans le groupe simulation contre 55,6 % dans le groupe controle (p = 0,32). Dans le groupe simulation, le niveau de confiance en soi s’est significativement ameliore apres la seance (1,82/5 avant versus 2,29/5 apres, p = 0,05). De maniere interessante, cette amelioration de la confiance en soi est significativement correlee au niveau d’anxiete (GAD-7 ; p = 0,014) et de stress (PSS ; p = 0,05) au second semestre, et tendait a l’etre avec le GSES (p = 0,09). Le niveau de satisfaction des internes concernant la seance etait excellent, ainsi que leur volonte d’integration de la simulation dans le co-DES (4,8/5 ± 0,5). Conclusion Notre etude a mis en evidence une amelioration significative de la confiance en soi entre avant et apres la seance de simulation. Les internes qui tirent un benefice immediat de la seance de simulation, avec une amelioration de leur confiance en eux, voient leur niveau de stress et d’anxiete diminuer a moyen terme au second semestre. A notre connaissance, il s’agit de la premiere etude controlee montrant l’interet de la simulation immersive sur le vecu du debut d’internat et des premieres gardes en MIIC-MIT-A. La simulation semble etre une methode d’interet pour l’amelioration des competences et du vecu des internes dans le co-DES de MIIC-MIT-A.

INTRODUCTION In France, the National Ranking Examination (ECNi) evaluates medical students based on their clinical reasoning. Simulation-based education on ECNi preparation has not been assessed. Our objective is to establish the added value of high-fidelity (HF) simulation-based learning in ECNi preparation compared with the current standard. METHODS We performed a controlled, prospective study. Fifth-year medical students from Nancy and Nice participated in a 3-phase process. In phase 1, students were tested on 6 themes (A-F) that were each presented as an ECNi clinical case and were randomized into 2 groups (#1 and #2). A 20-point grading scale was used. In phase 2, group #1 carried out HF simulation on themes A, B, and C, whereas group #2 did so on themes D, E, and F. Students were tested, in phase 3, with a new set of clinical cases on the same 6 themes. Progression in scores between phases 1 and 3 was analyzed. RESULTS One hundred sixty-six medical students randomized into 2 groups partook in the study. In phase 1, there was no significant difference in scores between groups. In phase 3, group #1 had significantly higher scores than group #2 for cases A, B, and C. Scores were significantly higher in group #2 for cases D, E, and F. Average scoring significantly improved between phases 1 and 3 with a 1.4-point gain for cases A, B, and C in group #1 and a 2.10-point gain for cases D, E, and F in group #2. CONCLUSIONS Our study shows that HF simulation learning significantly increases ECNi-like test results when compared with traditional forms.

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Objectives To describe the clinical presentation, treatments and prognosis of gastrointestinal (GI) involvement in adult IgA vasculitis (IgAV). Methods Data from 260 adults with IgAV included in a French multicentre retrospective survey were analysed. Presentation and outcomes of patients with (GI+) and without (GI-) GI involvement were compared. Results One hundred and thirty-seven (53%) patients had GI involvement. Initial manifestations were abdominal pain in 99%, intestinal bleeding in 31%, diarrhoea in 26% and acute surgical abdomen in only 4%. Abdominal imaging revealed thickening of intestinal wall in 61%, and endoscopies revealed abnormalities in 87%, mostly mucosal ulcerations. GI+ vs GI- patients were younger (46 ± 18 vs 54 ± 18 years; P = 0.0004), had more constitutional symptoms (43% vs 23%; P = 0.0005) and joint involvement (72 vs 50%; P = 0.0002), and higher CRP levels (3.7 vs 1.9 mg/dl; P = 0.001). Clinical response and relapse rates were comparable between groups, and all causes mortality (2 vs 4%) and IgAV-related mortality (1% vs 2%) as well. GI-related deaths were due to intestinal perforation and mesenteric ischaemia. Conclusion GI involvement is frequent in adult IgAV. GI involvement is frequent in adult IgAV. Mortality is not uncommon but does not seem to be specifically related to GI. Immunosuppressants should not be preferred as first-line therapy for GI+ patients but may be required in case of acute surgical abdomen.

Rationale: Given the paucity of effective treatments for idiopathic pulmonary fibrosis (IPF), new insights into the deleterious mechanisms controlling lung fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. TGF-β (transforming growth factor-β) is the main profibrotic factor, but its inhibition is associated with severe side effects because of its pleiotropic role. Objectives: To determine if downstream noncoding effectors of TGF-β in fibroblasts may represent new effective therapeutic targets whose modulation may be well tolerated. Methods: We investigated the whole noncoding fraction of TGF-β-stimulated lung fibroblast transcriptome to identify new genomic determinants of lung fibroblast differentiation into myofibroblasts. Differential expression of the long noncoding RNA (lncRNA) DNM3OS (dynamin 3 opposite strand) and its associated microRNAs (miRNAs) was validated in a murine model of pulmonary fibrosis and in IPF tissue samples. Distinct and complementary antisense oligonucleotide-based strategies aiming at interfering with DNM3OS were used to elucidate the role of DNM3OS and its associated miRNAs in IPF pathogenesis. Measurements and Main Results: We identified DNM3OS as a fibroblast-specific critical downstream effector of TGF-β-induced lung myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to three distinct profibrotic mature miRNAs (i.e., miR-199a-5p/3p and miR-214-3p), which influence SMAD and non-SMAD components of TGF-β signaling in a multifaceted way. In vivo, we showed that interfering with DNM3OS function not only prevents lung fibrosis but also improves established pulmonary fibrosis. Conclusions: Pharmacological approaches aiming at interfering with the lncRNA DNM3OS may represent new effective therapeutic strategies in IPF.

Background Myositis is recognized as a manifestation of primary Sjogren’s syndrome (pSS). Grading muscle involvement using the EULAR Sjogren Syndrome Disease Activity index (ESSDAI) does not require biopsy-proven active myositis or extensive immunological investigations. However, several studies have reported that a high proportion of pSS-associated myositis is either inclusion body myositis (IBM) or an overlap with idiopathic inflammatory myopathies. Objectives The objective of our study was to investigate the nature of inflammatory muscle involvement in a large sample of patients with pSS and concurrent myositis. Methods We conducted a French nation-wide survey among reference centers known for their experience in the field of systemic auto-immune diseases. Patients with physician-based diagnosis of pSS and inflammatory muscle involvement were included. They were categorized and subsequently described and compared according to the identification of an associated condition likely to explain inflammatory muscle involvement. Results 60 cases of myositis in patients with pSS were identified. Patients were mostly female (52/60) and pSS classification criteria were met in 43/60. Muscle biopsy was performed in 50/60 patients and showed inflammatory lesions in 80% of cases. An associated condition likely to explain myositis was identified in 31 patients: typical dermatomyositis rash (n=8), MCTD-specific antibodies (n=11), myositis specific antibodies (n=10), and systemic lupus erythematosus, scleroderma or ANCA associated vasculitis specific antibodies in favor of an overlap syndrome (n=7). Among the 29 patients without associated condition likely to explain myositis, 17 had a biopsy proven inflammatory muscle disease, showing histopathologic features consistent with IBM in 5 cases. 4 of the 5 patients with IBM histological features received corticosteroids and/or other immunosuppressive agents to treat muscle disease. Worsening of muscular involvement despite treatment was reported in these 4 patients. Comparative analysis showed a lower ESSDAI (p = 0.001) among patients without identified associated condition likely to explain myositis. Conclusion In most cases of concurrent pSS and myositis, inflammatory muscle involvement is explained by a context of overlap syndrome or has a histological pattern consistent with IBM. Extensive immunological investigations and muscle biopsy appear to be necessary in pSS patients with suspected inflammatory muscle involvement, in order to avoid misclassification and/or overtreatment. Disclosure of Interests Camille Houssais: None declared, Jean-baptiste Noury: None declared, Yves Allenbach: None declared, Laure Gallay: None declared, Florence Assan: None declared, Olivier Benveniste: None declared, Jonathan Broner: None declared, Pierre Duffau: None declared, Alexandra Espitia-Thibault: None declared, Anne Grasland: None declared, Sebastien SANGES: None declared, Gilles Hayem: None declared, Veronique LE GUERN: None declared, Nihal Martis: None declared, Kuberaka Marianpillai: None declared, Denis Mulleman Speakers bureau: Pfizer, Novartis, Grifols, Gaetane Nocturne: None declared, alain meyer: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Divi Cornec: None declared, Dewi Guellec: None declared

ObjectiveMeningeal involvement in Immunoglobulin G (IgG)-4-related disease is rare and only described in case reports and series. Because a review into the disease is lacking, we present 2 cases followed by a literature review of IgG4-related hypertrophic pachymeningitis (IgG4-HP).MethodsTwo IgG4-HP cases were reported, one involving the spinal cord and responding to surgical management and a second involving the brain and responding to Rituximab therapy. We then review clinical cases and case-series of histologically proven IgG4-HP that were published in the PubMed-NCBI database.ResultsForty-two case reports and 5 case-series were studied (60 patients, 20 women). The median age was 53. Eighteen patients had systemic involvement and 24 had single-organ IgG4-HP. Fifty-five percent of patients had an elevated serum IgG4. Treatment was surgical in 20/53 cases. Steroid therapy and immunosuppressors were effective in 85% and more than 90% of the cases, respectively. The rate of disease relapse was 42.1% after steroid therapy was discontinued.Discussion/conclusionIgG4-HP is characterized by the lack of extra-neurologic organ-involvement and systemic signs. Histopathologic studies should be performed as it is crucial for diagnosis because serum markers are rarely informative. 18F-FDG positon tomography can be useful to characterize systemic forms. There is no specific CSF marker for IgG4-HP and the diagnostic value of CSF IgG4 levels needs to be studied with larger samples. We provide a treatment algorithm for IgG4-HP. Such treatment strategies rely on early surgery, steroids, and early immunosuppressive therapy to prevent neurologic complications.

Background Takayasu arteritis (TA) is a large-vessel vasculitis that affects young women of childbearing age. Several small case-series described the pregnancy outcome in TA patients with lack of study determining risk factors associated with adverse pregnancy outcome. Objectives We performed a French retrospective study, to determine the risk factors associated with obstetrical adverse outcome; and the relation between pregnancy outcome and TA disease activity. Methods French nationwide retrospective study of pregnancies that lasted at least 12 weeks of gestation (WG) in TA patients. Results Forty-three pregnancies occurred in 33 patients. The diagnosis of TA was preexisting in 29 patients, and done during pregnancy in 4. For the 39 pregnancies in the 29 patients with a preexisting diagnosis of TA: steroids were maintained throughout pregnancy in 23/39 (59%) with a median dose of 5 mg/day2–40 immunosuppressive treatment during pregnancy included azathioprine (n=9, 21%) or infliximab (TNF-α antagonist) (n=1, 2%). For the 4 pregnancies with TA diagnosis during, only one was treated by steroids. Aspirin (100 mg/day) was used in 27/43 pregnancies (63%) and antihypertensive drugs were used in 10 pregnancies (23%). Before pregnancy, immunosuppressive treatment had been used in 16 patients: azathioprine (n=10, 30%), methotrexate (n=7, 21%), TNF-α antagonist (infliximab in 3 and adalimumab in 1; n=4, 12%) and cyclophosphamide (n=2, 6%). Maternal adverse events were noted in 20 pregnancies (47%). The most frequent adverse event was arterial hypertension (n=12; 28%): 10 worsening of previous arterial hypertension and 2 de novo arterial hypertension. Other adverse events included pre-eclampsia (n=3; 7%), HELLP syndrome (n=1; 2%) and post-partum haemorrhage (n=2; 5%). No maternal death was observed. There were 42 live births (98%) delivered at a median term of 3827–42 WG with 9 (21%) before 37 WG and one medical termination of pregnancy for major IUGR at 21WG. IUGR was observed in 6 pregnancies (14%) associated with hypertension and pre-eclampsia or HELLP syndrome in 2 cases. The median birth weight was 2940 [610–4310] grams. Five children (12%) required intensive care units hospitalisation. One premature boy (27 WG) died after 2 days. Treatment during pregnancy included steroids (n=25/43, 58%), azathioprine (n=9/43; 21%) and infliximab (n=1/43; 2%). Pre-eclampsia were less frequent in patients treated with steroids during pregnancy (p=0.02). The risk of developing arterial hypertension was associated with previous chronic arterial hypertension, and an infra-diaphragmatic vasculitis injury (p=0.01 and p=0.04). Activity of TA was observed in the course of 12/43 pregnancies (28%). Conclusions We observed both a high rate of obstetrical complications and of live birth. A preexisting chronic arterial hypertension, the infra-diaphragmatic location of vasculitis and/or an active disease in the 6 months preceding the pregnancy were associated with an impaired pregnancy outcome. TA disease activity did not seem to be influenced by pregnancy. Disclosure of Interest None declared

Introduction Les vascularites associees aux ANCA (VAA) sont une cause frequente de glomerulonephrite rapidement progressive (GNRP). Au decours d’une poussee, le pronostic est domine par le risque d’evolution vers une insuffisance renale terminale (IRT) ou le deces. L’etude prospective multicentrique PEXIVAS, incluant des patients en poussee severe de VAA avec hemorragie alveolaire et/ou insuffisance renale (avec un DFGe Materiels et methodes Nous avons inclus dans cette etude retrospective multicentrique des patients avec granulomatose avec polyangeite (GPA), polyangeite microscopique (PAM) ou vascularite limitee au rein, traites par EP pour une GNRP et ayant eu une biopsie renale initiale. Deux classifications histologiques ont ete utilisees : celle de Berden distinguant 4 classes (focale, a croissants, mixte, sclereuse), et celle de Brix distinguant 3 groupes a risque (faible, intermediaire, eleve) et utilisant le pourcentage de glomerules normaux, le pourcentage de fibrose interstitielle et atrophie tubulaire et le DFGe initial. Le critere de jugement principal etait l’independance de la dialyse et la survie a 12 mois. Les criteres secondaires etaient un DFGe > 30 mL/min/1,73 m2 a 12 mois et un gain de DFGe > 15 mL/min/1,73 m2 a 12 mois par rapport au debut de la poussee. Resultats Nous avons inclus 163 patients : 99 (60 %) hommes, 92 (56 %) avec ANCA-MPO, 65 (40 %) avec ANCA-PR3 ; creatininemie initiale 555 ± 274 μmol/L, 62 (38 %) avec hemorragie alveolaire ; 139 (85 %) ont recu du cyclophosphamide et 30 (18 %) du rituximab ; 74 (45 %) ont necessite initialement le recours a l’epuration extra-renale. Le nombre moyen d’EP etait de 7,0 ± 2,3. Les classes de Berden etaient focales dans 19 %, a croissants dans 39 %, mixtes dans 20 % et sclereuses dans 21 %. Selon la classification de Brix, 11 % des patients avait un risque bas, 48 % un risque intermediaire et 41 % un risque eleve. Les classifications de Berden et de Brix etaient toutes les deux fortement associees a la survenue du critere de jugement principal : independance de la dialyse et survie a 12 mois (respectivement c224,9, p Concernant les criteres secondaires : un DFGe > 30 mL/min/1,73 m2 a 12 mois etait associe a la classification de Berden (c214,0, p = 0,003) et de Brix (c217,3, p = 0,0002) ; et un gain de DFGe > 15 mL/min/1,73 m2 etait egalement associe avec la classification de Berden (c218,1, p = 0,0004) et de Brix (c217,7, p = 0,0001). Conclusion Dans cette cohorte de patients traitees par EP pour poussee renale de VAA, nos resultats suggerent que les resultats de la biopsie renale initiale sont fortement associes au devenir de la fonction renale a 12 mois. La biopsie renale doit etre realisee chez les patients avec poussee renale de VAA pour aider les cliniciens a identifier les patients qui pourraient beneficier le plus des EP.

Introduction La vascularite a IgA (V-IgA) est une vascularite systemique des petits vaisseaux a depots predominant d’IgA1. L’atteinte articulaire au cours de la V-IgA chez l’adulte, manifestation frequente mais non constante, reste jusqu’ici peu etudiee. L’objectif de cette etude duale est de decrire les caracteristiques longitudinales distinctives, cliniques et cytokiniques, des V-IgA avec et sans atteinte articulaire chez l’adulte. Materiels et methodes Les donnees cliniques de la cohorte retrospective multicentrique francaise de 260 patients adultes atteints d’une V-IgA prouvee histologiquement ont ete analysees (cohorte IGAVAS). Une analyse de 13 cytokines plasmatiques (GM-CSF, IFN-γ, IL-1β, IL-4, IL-6, IL-12p70, IL-17A, IL-21, IL-22, IL-23, IL-27, IL-33, et TNF-α ; technique multiplex) a parallelement ete realisee chez 37 patients adultes de la cohorte prospective multicentrique francaise de V-IgA (cohorte HSPrognosis) et chez des patients sains. Resultats Cent soixante patients (62 %) avaient une atteinte oligo-articulaire des grosses articulations au diagnostic de la V-IgA. Il s’agissait principalement d’arthralgies pures, seuls 16 % de ces patients presentaient de reelles arthrites. Les articulations les plus touchees etaient les genoux (68 %) et les chevilles (68 %). Apres 6 mois de suivi, la tres grande majorite (96 %) des patients ne presentait plus de manifestation articulaire active, qu’ils aient recu ou non un traitement specifique de la maladie. En analyse multivariee au diagnostic, les patients qui presentaient des manifestations articulaires montraient, en comparaison a ceux depourvus d’atteintes articulaires, un plus jeune âge (OR = 0,87 ; p = 0,0021) et une atteinte digestive plus frequente (OR = 2,08 ; p = 0,0116). Il n’y avait pas de difference significative en termes d’atteinte renale, de reponse au traitement, de rechutes ou de survie entre les deux groupes. Concernant l’etude du profil cytokinique plasmatique, les patients presentant une atteinte articulaire montraient, comparativement a ceux n’en ayant pas, des taux seriques d’interleukine-1β (IL-1β) plus eleve au diagnostic (p = 0,0415) ; par contre pour les 12 autres cytokines testees, aucune difference de taux n’etait observee. Conclusion L’atteinte articulaire est frequente au cours de la V-IgA de l’adulte. Il s’agit principalement d’arthralgies des genoux et des chevilles, d’evolution favorable dans la majorite des cas. Les patients presentant une atteinte articulaire semblent etre plus jeunes et ont plus frequemment une atteinte digestive. L’IL-1β plasmatique des patients ayant une atteinte articulaire est aussi plus elevee et pourrait orchestrer la reponse inflammatoire articulaire, comme au cours de nombreux rhumatismes inflammatoires.

In 2012, a 51-year-old woman presented with a 2-year history of painful hepatomegaly, chronic asthenia and recurrent fevers. Her medical history comprised augmentation mammoplasty 6 years prior to the onset of her symptoms and she received fenofibrate as a treatment for dyslipidaemia. Physical examination found an increased liver span and splenomegaly, cervical lymphadenopathy, and peritoneal and pleural effusion outbreaks. There was neither rash nor joint pain. Plasma inflammatory markers were constantly raised with C reactive protein (CRP) levels of 80–100 mg/L, increasing when fever and effusions occurred. Subsequently, in the course of the disease, biochemical analysis found hypercalcaemia peaking at 3.81 mmol/L with hypercalciuria. The blood cells count, serum angiotensin conversion enzyme, parathormone (PTH), PTH-rp and plasma protein electrophoresis were constantly unremarkable. Fludeoxyglucose F18 positron-emission tomography (FDG-PET) showed heterogeneous hypermetabolism of the liver, spleen, entire bone frame and several mediastinal, thoracic and abdominal lymph nodes (figure 1). Repetitive pleural …

The Diffuse Infiltrative Lymphocytosis Syndrome (DILS) is a rare multisystemic syndrome described in HIV-infected patients. It is characterised by CD8 + T-cell lymphocytosis associated with a CD8 + T-cell infiltration of multiple organs. DILS is usually seen in uncontrolled or untreated HIV infection but can also manifest itself independently of CD4 + T-cell counts. The syndrome may present as a Sjogren-like disease that generally associates sicca signs with bilateral parotiditis, lymphadenopathy, and extraglandular organ involvement. The latter may affect the lungs, nervous system, liver, kidneys, and digestive tract. Anomalies of the respiratory system are often identified as lymphocytic interstitial pneumonia. Facial nerve palsy, aseptic meningitis or polyneuropathy are among the more frequent neurological features. Hepatic lymphocytic infiltration, lymphocytic interstitial nephropathy and digestive tract lymphocytic infiltration account for more rarely noted complications. Sicca syndrome, organomegaly and/or organ dysfunction associated with polyclonal CD8 + T-cell organ-infiltration are greatly suggestive of DILS in people living with HIV. Labial salivary gland biopsy is therefore helpful when the focus score is equal or greater than 1 (or Chisholm Score ≥ 3). Primary Sjogren syndrome, chronic HCV or HTLV1 infection, graft versus host disease, IgG4-related disease, and immune reconstitution inflammatory syndrome are among the differential diagnoses that need to be considered. Treatment consists in highly active anti-retroviral therapy (HAART), which is usually effective in resolving clinical signs and symptoms. Steroids, however, may also be occasionally required when organ infiltration does not respond to HAART. This review should provide an insight into this rare entity complicating the course of HIV infection.

Given the paucity of effective treatments for fibrotic disorders, new insights into the deleterious mechanisms controlling fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies. Here, we identified the long non-coding RNA DNM3OS as a critical downstream effector of TGF-β-induced myofibroblast activation. Mechanistically, DNM3OS regulates this process in trans by giving rise to 3 distinct profibrotic mature miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which influence both SMAD and non-SMAD components of TGF-β signaling in a multifaceted way, through two modes of action consisting of either signal amplification or mediation. Finally, we provide preclinical evidence that interfering with DNM3OS function using distinct strategies not only prevents lung and kidney fibrosis but also improves established lung fibrosis, providing thus a novel paradigm for the treatment of refractory fibrotic diseases such as idiopathic pulmonary fibrosis.One Sentence SummaryThe DNM3OS lncRNA is a reservoir of fibromiRs with major functions in fibroblast response to TGF-β and represents a valuable therapeutic target for refractory fibrotic diseases such as idiopathic pulmonary fibrosis (IPF).

Non-coding RNAs have recently gained widespread attention given their broad implication in the initiation and progression of various complex diseases. Whereas previous studies on fibrotic lung disorders, especially the idiopathic form (IPF), have mainly focused on miRNAs, the precise contribution of other class of non-coding RNAs in lung fibrogenesis is unclear. Given the paucity of effective treatment in IPF, new insights into the deleterious mechanisms controlling lung fibroblast activation, the key cell type driving the fibrogenic process, are essential to develop new therapeutic strategies for this devastating disease. Here we identify a long non-coding RNA, termed DNM3OS, which tightly controls the various cellular and molecular phenotypic changes occurring during lung fibroblast activation in response to TGF-β. Notably, DNM3OS regulates these processes in trans by giving rise to 3 distinct profibrotic miRNAs (i.e. miR-199a-5p/3p and miR-214-3p), which repress distinct but functionally related targets within TGF-β signaling cascade. Finally, we provide in vivo evidence that interfering with DNM3OS function may be a promising strategy for the treatment of lethal fibrotic diseases such as IPF.

Objective.Exercise limitation in patients with systemic sclerosis (SSc) is often multifactorial and related to complications such as interstitial lung disease (ILD), pulmonary vasculopathy (PV), left ventricular dysfunction (LVD), and/or peripheral/muscular limitation (PML). We hypothesized that cardiopulmonary exercise testing (CPET) could not only suggest and rank competing etiologies, but also highlight peripheral impairment.Methods.Clinical, resting pulmonary function testing, and CPET data from patients with SSc referred for exercise limitation between October 2009 and November 2015 were retrospectively analyzed in this bi-center study. Patients were categorized as having ILD, PV, LVD, and/or PML based on CPET response patterns and the diagnoses were matched with results from the reference investigations. The latter consisted of transthoracic echocardiography, chest computed tomography scan, and right heart catheterization (RHC).Results.Twenty-seven patients presented with CPET profiles consistent with ILD (n = 16), PV (n = 15), LVD (n = 5), and PML (n = 19). None of the subjects had a normal CPET profile. There was a statistically significant negative correlation between resting DLCO, on the one hand, and dead space to tidal volume ratio and alveolar–arterial gradient [P(Ai-a)O2] on the other (p < 0.005). CPET identified 90% of patients with a mean pulmonary arterial pressure at rest ≥ 21 mmHg measured by RHC (n = 10). Peak P(Ai-a)O2, taken independently from other variables, was crucial in distinguishing subjects with ILD from those without ILD (p < 0.05).Conclusion.CPET is useful for the characterization of multifactorial exercise limitation in patients with SSc and in identifying SSc-related complications such as ILD and PV. This study also identifies PML as an underestimated cause of exercise limitation.

Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.

Diffuse alveolar haemorrhage (DAH) complicating primary catastrophic anti-phospholipid syndrome (CAPS) was diagnosed in a 50-year-old female patient. Treatment strategies are limited for this often life-threatening autoimmune disease that requires aggressive immunosuppression. In the absence of clinically validated treatment strategies, high-dose steroids associated with plasma exchange and eventually intravenous immunoglobulins were used to manage the disease. Its severity prompted the initiation of rituximab that was administered weekly for four consecutive weeks. Anticoagulation therapy, on the other hand, needed to be discontinued due to the major haemorrhagic episodes. This combination treatment provided an effective control of the CAPS-associated DAH and helped achieve clinical remission.

La Presse Medicale - In Press.Proof corrected by the author Available online since mardi 11 fevrier 2014

Joint Bone Spine - In Press.Proof corrected by the author Available online since lundi 20 juin 2016

Leishmaniasis caused by Leishmania infantum is endemic in the Mediterranean region. Its visceral form can present a diagnostic challenge owing to the disease's wide spectrum of clinical presentations. We describe the very atypical case of a 66-year-old male Caucasian patient with hepatopulmonary syndrome and an exceptionally rare expression of visceral leishmaniasis in a disseminated form with mucocutaneous involvement presenting as an autoimmune systemic disease.

Antimicrobial resistance to Pseudomonas aeruginosa is on the rise. In the absence of new anti-pseudomonal drugs, clinicians have had to resort to older antimicrobials such as colistin for the treatment of multi-drug resistant (MDR) strains. This polymyxin compound acts on the outer membrane of the bacteria resulting in its permeability and cell-death. Its bactericidal action is concentration-dependant. This antibiotic is mainly used as salvage therapy in the treatment of often life-threatening infections due to MDR P. aeruginosa blood-stream infections (BSI). Its potential nephrotoxicity and neurotoxicity have been overestimated and have limited the use in its intravenous form. A better understanding of its pharmacokinetics and pharmacodynamics, has facilitated more appropriate dosing strategies with a standard 9 million-unit daily-dose that should be adapted to kidney function. Combination treatment that involves the association of colistin with classical anti-pseudomonal treatment has rarely been clinically tested. In vitro synergy has been reported for certain combinations that could be used to prevent or limit the risk of induced resistance in MDR strains. Positioning colistin in antimicrobial strategies especially as a first-line treatment remains to be properly assessed.

Hodgkin lymphoma (HL) is one of the most common types of non-AIDS-defining tumors in the HIV-infected. Its incidence however seems to have increased under highly active anti-retroviral therapy (HAART). HIV-HL is a different entity from HL in HIV-negative subjects with a poorer prognosis that is associated with tumor-subtype, EBV-infection, and “B” symptoms. Despite the aggressive nature of the disease, clinical outcome has improved with combination therapies including appropriately timed antiretroviral strategies and the quality of supportive care—notably the use of hematopoietic growth factors. More intensive chemotherapy regimens with or without autologous stem cell transplantation appear to improve survival. Functional imaging such as positron emission tomography and computed tomography (FDG-PET) may help guide treatment strategy and minimize long-term toxicity.

Clinical outcome for B-cell non-Hodgkin’s lymphoma has been greatly improved through the combination of new treatment options, in particular noncytotoxic drugs that specifically target disease mechanisms. Furthermore, in many cases, lymphoma survivors have to cope with long-term toxicity. Therefore, as with survival and remission length, the assessment of quality of life (QoL) is a major consideration when judging therapeutic benefit in patients. The aim of this article is to discuss the impact of widespread treatments on QoL and the relevance of QoL assessment in B-cell non-Hodgkin’s lymphoma in day-to-day clinical practice. Additional studies of QoL in the general population, the associations between QoL and treatment strategy, QoL and specific situations (i.e., stem-cell transplantation and aging population) are also considered.