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Background: Conflicting data exist regarding the benefit of urgent coronary angiogram and percutaneous coronary intervention (PCI) after sudden cardiac arrest, particularly in the absence of ST-segment elevation. We hypothesized that the type of lesions treated (stable versus unstable) influences the benefit derived from PCI. Methods: Data were taken between May 2011 and 2014 from a prospective registry enrolling all sudden cardiac arrest in Paris and suburbs (6.7 million inhabitants). Patients undergoing emergent coronary angiogram were included. Decision to perform PCI was left to the discretion of local teams. We assessed the impact of emergent PCI on survival at discharge according to whether the treated lesion was angiographically unstable or stable, and we investigated the predictive factors for unstable coronary lesions. Results: Among 9265 sudden cardiac arrests occurring during the study period, 1078 underwent emergent coronary angiogram (median age: 59.6 years, 78.3% males): 463 (42.9%) had an unstable lesion, 253 (23.5%) only stable lesions, and 362 (33.6%) no significant lesions. Emergent PCI was performed in 478 patients (91.4% of unstable and 21.7% of stable lesions). At discharge, PCI of unstable lesions was associated with twice-higher survival rate compared with untreated unstable lesions (47.9% versus 25.6%, P =0.013), while stable lesions PCI did not improve survival (25.5% versus 26.3%, P =1.00). After adjustment, PCI of unstable coronary lesions was independently associated with improved survival (odds ratio, 2.09 [95% CI, 1.42–3.09], P P =0.824). Angina, initial shockable rhythm, ST-segment elevation, and absence of known coronary artery disease were independent predictors of unstable lesions. Conclusions: Emergent PCI of unstable lesions is associated with improved survival after sudden cardiac arrest, contrary to PCI of stable lesions. Accordingly, early PCI should only be performed in patients with unstable lesions. Four factors (chest pain, ST-elevation, absence of coronary artery disease history, and shockable initial rhythm) could help identify patients with unstable lesions who would, therefore, benefit from emergent coronary angiogram.

Additional file 4. Summary of reporting of LVDF items.

Additional file 6. Summary of reporting of AET items.

Additional file 1. Search strategies.

Additional file 2. Summary of reporting of LVSF items.

Additional file 5. Summary of reporting of FM items

Additional file 3. Summary of reporting of RVF items.

Introduction La chirurgie pancreatique majeure est associee a une importante morbidite, principalement infectieuse, conduisant certains auteurs a proposer une antibiotherapie postoperatoire systematique. Cette attitude n’est neanmoins pas consensuelle et les pratiques antibiotiques varient significativement d’un centre a l’autre. Ces prescriptions exposent en outre les patients aux complications potentielles de l’antibiotherapie et aux risques d’emergence de resistance bacterienne. L’objectif de ce travail etait d’etudier les pratiques de l’antibiotherapie postoperatoire de chirurgie pancreatique majeure et d’identifier des facteurs associes a la survenue d’une infection qui pourraient aider a en preciser les indications. Materiels et methodes Nous avons mene une etude retrospective monocentrique dans un centre hospitalo-universitaire. De janvier 2007 a novembre 2018, les patients ayant subi une chirurgie pancreatique majeure reglee ont ete inclus dans l’etude. Le critere principal de jugement concernait la prescription systematique postoperatoire d’antibiotique (ATB) et la survenue d’une infection du site operatoire (ISO). L’objectif secondaire etait d’etudier les facteurs associes aux infections postoperatoires (ISO, pneumonie, bacteriemie) afin d’identifier les criteres cliniques et/ou biologiques pouvant influencer la prescription d’antibiotiques. Resultats Cent quarante-neuf patients (115 duodeno-pancreatectomies cephaliques, 34 spleno-pancreatectomies caudales) ont ete inclus. Trente patients (20,1 %) ont presente une ISO et 72 (28,2 %) ont recu une antibiotherapie systematique. La prescription d’une antibiotherapie postoperatoire etait similaire entre les groupes de patients ISO+ et ISO− (26,7 versus 28,6 %, p = 0,9). Quatre-vingt-quatre patients (57 %) appartenant au groupe ATB− n’ont pas developpe d’ISO, alors que 22 (14,8 %) du meme groupe ont developpe une ISO. Ces derniers presentaient une mortalite hospitaliere significativement plus elevee que les patients du groupe ATB−/ISO− (18,2 versus 0 %, p = 0,002), mais identique aux patients du groupe ATB+/ISO+. La presence d’une prothese biliaire etait similaire dans les groupes ATB−/ISO− et ATB−/ISO+. Une fievre etait plus frequemment notee dans le groupe ATB−/ISO+ (72,7 versus 33,3 %, p = 0,001). En analyse multivariee, la fievre etait independamment associee a la survenue d’une ISO (odds ratio 6,24 [2,4–18,57], p Conclusion Dans cette serie monocentrique, l’antibiotherapie postoperatoire systematique apres chirurgie pancreatique majeure a ete evitee sans consequence sur la survenue d’une ISO chez plus de la moitie des patients. Cette attitude d’epargne est a mettre en balance avec la survenue d’une ISO responsable d’une surmortalite, mais la fievre postoperatoire semble etre un parametre clinique pertinent pour traiter sans delai une telle complication.

Objective Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK. Methods T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behcet's disease (disease controls), and 20 age- and sex-matched healthy control subjects. Results We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon-γ (IFNγ) and interleukin-17A (IL-17A). We demonstrated the presence of IFNγ-, IL-6–, and IL-17A–producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid-free patients with TAK (for IL-2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL-1 receptor, IL-17, and IL-23). Conclusion The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.

La frequenza degli aneurismi aortici (AA), particolarmente di quelli dell’aorta addominale (AAA), aumenta costantemente nei paesi industrializzati. I risultati della chirurgia in urgenza degli aneurismi aortici per complicanze restano deludenti e rappresentano il migliore argomento a favore di una chirurgia elettiva precoce.

Le syndrome post-arret cardiaque (AC) regroupe l’ensemble des phenomenes survenant apres la restauration d’une activite cardiaque efficace par la reanimation cardiopulmonaire. Schematiquement, il se compose d’une defaillance d’organes precoce d’une part et d’un dommage neurologique anoxique d’autre part. Les defaillances d’organe peuvent etre multiples, mais la defaillance hemodynamique (vasoplegique et/ou cardiogenique) est la plus frequente. L’intensite de ces defaillances est extremement variable, difficile a prevoir, et peut conduire rapidement a un etat de defaillance multiviscerale refractaire. Le dommage neurologique anoxique s’exprime lui aussi de maniere variable, mais peut aboutir a la constitution d’un etat vegetatif ou paucirelationnel et parfois a la mort encephalique. Le support d’organes non specifique est la regle, tant que le pronostic neurologique ne peut pas etre formellement evalue. La recherche et le traitement du facteur declenchant (et notamment d’une occlusion coronaire) sont essentiels. Concernant la neuroprotection, le controle cible de la temperature est a ce jour le seul traitement valide, tous les autres restant du domaine de la recherche clinique. Malgre des progres recents, le taux de mortalite du syndrome post-AC reste tres eleve et s’echelonne entre 60 et 90 %.

Objective.Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by alterations of the B cell subset, global regulatory T cell (Treg) depletion, and an increase in Th17 cells. Interleukin 21 (IL-21) plays a critical role in T cell and B cell homeostasis. Our objective was to determine the implication of IL-21 and IL-21-producing CD4+ T cells in the pathogenesis of SLE.Methods.Twenty-five patients with SLE and 25 healthy donor controls were included. Analysis of CD4+ T cells producing IL-21, Th1, Th2, Th17, Treg, follicular helper T (TFH) cells, and B cells was performed in peripheral blood, and levels of cytokines were measured in culture supernatants.Results.Circulating CD4+ T cells producing IL-21 were markedly expanded in patients with SLE compared to controls and were correlated with increased Th17, decreased Treg, and increased memory B cells. CD4+ T cells producing IL-21 were composed of CXCR5+ and CXCR5–CD4+ T cell subsets. Both IL-21-producing CXCR5+CD4+ T cells and CXCR5–CD4+ T cells were increased in patients with SLE, the CXCR5–CD4+ subset correlating with Th17 cells and Treg, while the CXCR5+CD4+ subset was correlated with alterations of the B cell subset. The CXCR5+CD4+ subset comprised mainly circulating Bcl6+CXCR5+CD4+ TFH cells that were markedly expanded in patients with SLE and were correlated with increased circulating Bcl6+CXCR5+ germinal center B cells.Conclusion.These findings suggest that IL-21, produced by distinct cellular CD4+ T cells, correlates with alterations of T cell and B cell subsets in SLE, and that targeting IL-21 could provide beneficial effects on both T cell and B cell alterations.

In recent years, a surge of interest in biodiversity conservation have led to the development of new approaches to facilitate ecologically-based conservation policies and management plans. In particular, image classification and predictive distribution modeling applied to forest habitats, constitute a crucial issue as forests constitute the most widespread vegetation type and play a key role for ecosystem functioning. Then, the general purpose of this study is to develop a framework that in the absence of large amounts of field data for large areas may allow to select the most appropriate classification. In some cases, a hard division of classes is required, especially as support to environmental policies; despite this it is necessary to take into account problems which derive from a crisp view of ecological entities being mapped, since habitats are expected to be structurally complex and continuously vary within a landscape. In this paper, a niche model (MaxEnt), generally used to estimate species/habitat distribution, has been applied to classify forest cover in a complex Mediterranean area and to estimate the probability distribution of four forest types, producing continuous maps of forest cover. The use of the obtained models as validation of model for crisp classifications, highlighted that crisp classification, which is being continuously used in landscape research and planning, is not free from drawbacks as it is showing a high degree of inner variability. The modeling approach followed by this study, taking into account the uncertainty proper of the natural ecosystems and the use of environmental variables in land cover classification, may represent an useful approach to making more efficient and effective field inventories and to developing effective forest conservation policies.

Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count.

Resume Les pericardites recidivantes sont frequentes et complexes a prendre en charge. Leur physiopathologie est mal connue et implique l’ensemble des acteurs des immunites innee et adaptative. Un bilan etiologique exhaustif devant un premier episode de pericardite aigue ne semble pas necessaire, mais celui-ci s’impose devant une pericardite recidivante. Cependant, environ 80 % des pericardites recidivantes restent idiopathiques. La colchicine associee aux anti-inflammatoires non steroidiens est le traitement de choix dans cette situation et le recours a des agents immunosuppresseurs reste exceptionnel.

Key points Cardiac involvement is unfrequent in antiphospholipid syndrome (APS) but its prognosis is poor. It may involve all the cardiac structures. Endocardial involvement is the most frequent feature. Prognosis of coronary arteries involvement is poor. Catastrophic APS may be revealed by cardiac symptoms. Except for the catastrophic APS, there is no specific treatment as anticoagulation remains the gold standard.

Takayasu arteritis (TAK) is a large-vessel vasculitis that induces damage to the aorta and its branches. Glucocorticoids remain the gold standard of therapy for TAK. The nature of the T cells driving vascular inflammation and the effects of glucocorticoids on the systemic components of TAK are not understood. The aim of this study was to analyze T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta in patients with TAK.T cell homeostasis and cytokine production in peripheral blood and inflammatory lesions of the aorta were analyzed using Luminex analysis, flow cytometry, and immunohistochemical analysis. The study included 41 patients fulfilling the American College of Rheumatology 1990 criteria for the classification of TAK (17 patients with active TAK and 24 patients with disease in remission), 30 patients with giant cell arteritis and 39 patients with Behçet's disease (disease controls), and 20 age- and sex-matched healthy control subjects.We observed a marked increase in the expression of Th1 and Th17 cells, which correlated with TAK disease activity. The addition of serum from patients with active TAK to sorted CD4+ T cells from healthy donors in culture medium induced significant production of interferon-γ (IFNγ) and interleukin-17A (IL-17A). We demonstrated the presence of IFNγ-, IL-6-, and IL-17A-producing T cells in vascular inflammatory infiltrates in patients with TAK. Corticosteroid therapy was associated with decreased levels of circulating Th1 cytokines in corticosteroid-treated patients with TAK compared with steroid-free patients with TAK (for IL-2, mean ± SD 5,079 ± 5,300 versus 7,359 ± 3,197 pg/ml; for IFNγ, 2,592 ± 3,072 versus 8,393 ± 3,392 pg/ml; for tumor necrosis factor α, 847 ± 724 versus 1,491 ± 392 pg/ml). However, glucocorticoids had essentially no effect on the frequency of Th17 cytokines (IL-1 receptor, IL-17, and IL-23).The Th17 and Th1 pathways contribute to the systemic and vascular manifestations of TAK. Glucocorticoid treatment suppresses Th1 cytokines but spares Th17 cytokines in patients with TAK.

This review aims at providing an update on post-cardiac arrest syndrome, from pathophysiology to treatment.Medline database.All data on pathophysiology, clinical manifestations and therapeutic management, with focus on the publications of the 5 last years.Care of the patients after cardiac arrest is a medical challenge, in face of "post-cardiac arrest syndrome", which culminates into multi-organ failure. This syndrome mimics sepsis-related dysfunctions, with all clinical and biological manifestations related to the phenomenon of global ischemia-reperfusion. Acute cardiocirculatory dysfunction is usually controlled through pharmacological and mechanical support. Meanwhile, as a majority of cardiac arrest is related to myocardial infarction, early angiographic exploration should then be discussed when there is no obvious extracardiac cause, percutaneous coronary revascularization being associated with improved short and long-term prognosis. Therapeutic hypothermia is the cornerstone of neuroprotective armamentarium, beyond hemodynamic stabilization and metabolic maintenance.If ongoing evaluations should shed light on potential efficiency of new therapeutic drugs, a multidisciplinary approach of the post-cardiac arrest syndrome in expertise centre is essential.

Homogeneous η5-cyclopentadienyl nickel catalysts have been applied to ethylene oligomerization. Their activity, enhanced by the presence of Al(OEt)Et 2 as co-catalyst, resulted the highest up to now reported for this type of complexes. The same catalytic systems were also able to oligomerize propylene as well as ethylene/propylene mixtures. In particular propylene was converted into branched dimers, mostly 2,3-dimethylbutenes. Heterogenization of the above system, carried out by anchoring the nickel derivative to a styrene/divinylbenzene resin properly functionalized with the cyclopentadienyl group, caused a drastic change of the selectivity of the process, ethylene polymerization to HDPE taking place instead of oligomerization.

To investigate body traits and muscle chemical composition in common carp as influenced by age and rearing environment, 2000 fry were stocked in two earthen ponds (300 m2): warm (W), with warm water (refluent from a thermal power station) at about 10 °C above natural temperature, and natural (N), with water from Lake Trasimeno. Because of the different growth rate, W subjects were sampled 3 times (at 12, 15 and 18 months of age) while N-subjects were sampled only once (at 15 months of age). The W 12-month-old fish weighed on average 102 g while N-fish did not reach this weight even at 15 months. At this age, the W subjects showed, in comparison with N-subjects, higher body weight (143 vs. 85 g), component weights, linear measurements (20.94 vs. 17.8 cm), fins (1.80 vs. 1.63g) and filleting remnants (12.80 vs. 11.25%) and lower incidence of skin and head index; no differences resulted in proximate analysis, but muscles of W-fish were richer in saturated fatty acid and in n − 3 PUFA content and showed a higher n-3n-6 PUFA ratio. By comparison with the 15-month-old subjects collected in October 1992, the 12-month-old W-subjects, collected in July 1992, showed lower fin (0.59 vs. 1.8%), viscera (7.6 vs. 10.2 %) and head (20.36 vs. 22.92%) percentages but higher gill (4.27 vs. 3.24%), filleting remnant (14.99 vs. 12.80%), skin (3.92 vs. 3.37%) and dressing (92.4 vs. 89.79%) percentages. The 18-month-old W-subjects, collected in January 1993, did not differ significantly from the 15-month-old subjects either in body weight (154 vs. 143 g) or in the other traits studied, excluding the incidence of viscera (12.01 vs. 10.21%) and gills (2.69 vs. 3.34%), respectively, in the older subjects. Intramuscular lipid content decreased from July according to a seasonal trend. Allometric coefficient showed tachyauxesis for viscera, pectoral and pelvic fins, skin and total muscle and bradyauxesis for filleting remnants and head.

Objective. Chronic HCV infection is associated with extra-hepatic manifestations. Recent studies have suggested an immunomodulatory role for vitamin D during HCV infection. We investigated the association between serum vitamin D status and the presence of HCV extra-hepatic manifestations. Methods. 25(OH)D serum levels were assessed in 94 HCV + RNA + patients [including 48 patients with mixed cryoglobulinaemia (MC) vasculitis]. Correlations between serum 25(OH)D levels and the presence of extra-hepatic manifestations of HCV infection were analysed. Results. Overall, 84 of 94 patients (89%) had hypovitaminosis D (430 ng/ml). Patients with vitamin D deficiency vs insufficiency vs sufficiency more frequently had systemic vasculitis (P=0.02), in particular purpura (P=0.006), detectable MC (P=0.008) and low C4 serum levels (P=0.006). Serum levels of 25(OH)D were also correlated with cryoglobulin and C4 levels and with marginal zone B cells and regulatory T cells. In multivariate analysis, the presence of MC and systemic vasculitis remained independently associated with low 25(OH)D levels. Conclusion. In chronic HCV infection, low 25(OH)D levels correlate with the presence of mixed cryoglobulinaemia and systemic vasculitis in chronic HCV infection. These findings suggest the potential multifaceted benefits of vitamin D supplementation in HCV-infected patients with extra-hepatic manifestations, but interventional studies are needed to confirm these data.

Therapeutic options in hepatitis C virus (HCV)-related vasculitis may target the viral trigger using antiviral therapy [pegylated interferon plus ribavirin (PEG-IFN/RBV)], and/or the downstream B-cell arm of autoimmunity with rituximab (RTX). To date, no study has compared the efficacy of RTX combined with PEG-IFN/RBV on biomarkers of liver insufficiency in patients with severe liver fibrosis. Twenty-eight untreated HCV-related vasculitis patients with severe liver fibrosis (Metavir F3-F4) were included: 14 patients received RTX plus PEG-IFN/RBV and 14 patients PEG-IFN/RBV. The main clinical and biological data were recorded and compared at baseline, month 3 (M3), M12 and M24 of follow-up. Baseline epidemiological, clinical, virological and immunological features were similar between the groups. The virological response did not differ between cases and controls. The alanine aminotransferase (ALT) level and HCV viral load did not increase in patients treated with RTX. Serum albumin levels increased in patients treated with RTX at M3 and M6 (108% and 111% of baseline value; P = 0.06 and P = 0.13), whereas it was stable in patients treated without RTX. FibroTest values decreased from 0.70 at baseline to 0.59 at M3 (P = 0.5) and returned to 0.69 at M24 in the RTX-PEG-IFN/RBV group, whereas they were stable in the PEG-IFN/RBV group. RTX is safe in patients with severe HCV liver fibrosis and vasculitis. No beneficial effects of RTX were evidenced on liver fibrosis progression, but we found interesting correlations with the serum albumin level, FibroTest values and B-cell count.

Cardiac abnormalities in patients with Behcet disease (BD) include pericarditis, myocarditis, endocarditis with valvular regurgitation, intracardiac thrombosis, endomyocardial fibrosis, coronary arteritis with or without myocardial infarction, and aneurysms of the coronary arteries or sinus of Valsalva. Data regarding the clinical spectrum, prevalence, and outcome of cardiac lesions in BD are lacking. In this study, we report the main characteristics, treatment, and long-term outcomes of 52 patients with cardiac lesions from a cohort of 807 (6%) BD patients. Forty-five (86.5%) patients were male, with a mean (±SD) age at BD diagnosis of 29.3 ± 10.3 years.Cardiac involvement was the first feature of BD in 17 (32.7%) patients. Cardiac lesions included pericarditis (n = 20; 38.5%), endocarditis (mostly aortic insufficiency) (n = 14; 26.9%), intracardiac thrombosis (n = 10; 19.2%), myocardial infarction (n = 9; 17.3%), endomyocardial fibrosis (n = 4; 7.7%) and myocardial aneurysm (n = 1; 1.9%). Patients with cardiac involvement were more frequently male (86.5% vs. 64.9%; p < 0.01) and had more arterial (42.3% vs. 11.1%; p < 0.01) and venous lesions (59.6% vs. 35.8%; p < 0.01) compared to those without cardiac manifestations. Factors associated with complete remission of cardiac involvement were treatment regimens with oral anticoagulants, immunosuppressants, and colchicine. The 5-year survival rate was 83.6% and 95.8% (p = 0.03) in BD patients with and without cardiac involvement, respectively. After a median (Q1-Q3) follow-up of 3.0 (1.75-4.2) years, 8 patients had died, in 3 cases directly related to cardiac involvement.In conclusion, cardiac lesions affected 6% of our large cohort of BD patients. The prognosis of cardiac involvement in BD is poor and improves with oral anticoagulation, immunosuppressive therapy, and colchicine.

Objective Giant cell arteritis (GCA) is a large-vessel vasculitis of unknown origin. Recent findings indicate that at least 2 separate lineages of CD4+ T cells, Th1 and Th17 cells, participate in vascular inflammation. The pathways driving these T cell differentiations are incompletely understood, but may provide novel therapeutic targets. This study was undertaken to identify cytokines involved in the pathogenesis of GCA. Methods Thirty GCA patients fulfilling the American College of Rheumatology criteria, with active disease or disease in remission, and 30 age-matched controls were included. Levels of 27 cytokines were determined in culture supernatants, and flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) and immunohistochemical analysis of temporal artery samples were performed. Results Multiparametric analysis of cytokines produced by PBMCs associated with GCA disease activity identified a signature involving interleukin-2 receptor (IL-2R), IL-12, interferon-γ (IFNγ), IL-17A, IL-21, and granulocyte–macrophage colony-stimulating factor (GM-CSF). An expansion of Th1 and Th17 cells and a decrease in Treg cells were observed in the peripheral blood of patients with active GCA. An expansion of IL-21–producing CD4+ T cells was also observed in patients with active GCA and correlated positively with Th17 and Th1 cell expansion. Immunohistochemical analysis revealed IFNγ, IL-17A, and IL-21 expression within inflammatory infiltrates. Stimulation of purified CD4+ T cells with IL-21 increased Th1 and Th17 cell frequencies and decreased FoxP3 expression. In contrast, blockade of IL-21 using IL-21R-Fc markedly decreased the production of IL-17A and IFNγ and increased FoxP3 expression. Conclusion Our findings indicate that IL-21 plays a critical role in modulating Th1 and Th17 responses and Treg cells in GCA, and might represent a potential target for novel therapy.

Behcet's disease (BD) is a recurrent systemic inflammatory disorder of unknown origin characterized by oral and genital mucous ulcer, uveitis, and skin lesions. Involvement of large vessels, central nervous system (CNS), gastrointestinal tract and thrombotic events are less frequent but can be life threatening. The aim of this review is to provide new insights into the pathogenesis of BD. Over the past year substantial advances have been done in the understanding of the genetic [1,2] and immunology [3] of BD. BD is at the crossroad between autoimmune and autoinflammatory syndromes. In common with autoimmune diseases BD shares class I MHC association. However, in contrast to autoimmune disorders, BD has clinical features that seem to be mostly autoinflammatory. The pathogenesis of BD is still unknown, but major determinants of the genetic and immune system abnormalities have been reported recently. Triggering infectious factors are supposed to participate in the outbreak of BD in genetically predisposed patients. Two recent large genome-wide association study (GWAS) conducted in Turkey and Japan reported association between single nucleotide polymorphism (SNP) of interleukin (IL)-10 and IL-23R/IL-12RB2 genes and BD. New insights into the perturbations of T cell homeostasis of BD recently emerged. We have recently demonstrated the promotion of Th17 responses and the suppression of regulatory T cells (Tregs) that were driven by interleukin (IL)-21 production and that correlates with BD activity. Inflammatory cells within BD inflammatory lesions included mostly neutrophils, Th1 and Th17 cells, and cytotoxic CD8+ and γδ T cells. Altogether, the recent progresses in the knowledge of BD pathogenesis pave the way for innovative therapy.

Background Behcet disease (BD) is a chronic systemic inflammatory disorder of unknown etiology. Objective To determine the nature of T cells driving inflammatory lesions in BD. Methods T cell homeostasis and cytokines production were analyzed in peripheral blood and brain inflammatory lesions from 45 adult patients with BD (active and untreated BD [n = 25] and patients in remission [n = 20]) and 20 healthy donors, using Luminex, flow cytometry, immunohistochemistry, and immunofluorescence analysis. Results We found a marked increase in T H 17 cells and a decrease in the frequency of CD4 + forkhead box P3 + regulatory T cells (Tregs) in peripheral blood that were induced by IL-21 production and that correlate with BD activity. The addition of serum from patients with active BD in a sorted CD4 + T cells culture of healthy donors induced a significant and dose-dependent production of IL-17A and a decrease in forkhead box P3 expression. We demonstrated the presence of IL-21– and IL-17A–producing T cells within the cerebrospinal fluid, brain parenchyma inflammatory infiltrates, and intracerebral blood vessels from patients with active BD and central nervous system involvement. The stimulation of CD4 + T cells with IL-21 increased T H 17 and T H 1 differentiation and decreased the frequency of Treg cells. Conversely, IL-21 blockade with an IL-21R-Fc restored the T H 17 and Treg homeostasis in patients with BD. Conclusion We provided here the first evidence of the critical role of IL-21 in driving inflammatory lesions in BD by promoting T H 17 effectors and suppressing Treg cells. IL-21 represents a promising target for novel therapy in BD.

Introduction – objectifs La cefoxitine a une activite in vitro sur les E-BLSE mais son efficacite clinique et microbiologique n’a pas ete evaluee a ce jour. Materiels et methodes Etude observationnelle incluant tous les patients de l’hopital (830 lits) ayant recu un traitement par cefoxitine a visee curative pour une infection documentee a E-BLSE entre janvier 2012 et octobre 2013. L’evolution clinique et microbiologique a ete evaluee 48-72H apres le debut et 14 jours ou plus apres la fin du traitement. Resultats Trente deux patients ont ete inclus, principalement des hommes (n = 26), âges de 71 ans (mediane, min : 23, max : 93), avec un score de Charlson median de 2 (de 0 a 10). Onze patients etaient hospitalises en reanimation, dont 4 avaient un score APACHE > 15. L’infection a E-BLSE est survenue en moyenne 6 jours apres l’admission (1 a 93). La porte d’entree etait urinaire (n = 23), une bacteriemie sur catheter central (n = 4), respiratoire (n = 3) ou digestive (n = 2). Escherichia coli ou Klebsiella pneumoniae ont ete isoles respectivement chez 19 et 13 patients. La duree mediane de traitement par cefoxitine etait de 9 jours, en association avec des aminosides (duree moyenne 48H) chez 13 patients. L’evolution clinique etait favorable chez 29 sujets a 48-72H. Chez 2 patients, l’evolution defavorable a conduit au remplacement de la cefoxitine par un carbapeneme. A la fin du suivi (mediane 14 jours apres la fin du traitement, de 0 a 164), l’evolution etait favorable au plan clinique et microbiologique pour respectivement 17/22 et 11/16 patients. Une resistance a la cefoxitine est apparue chez deux souches de K. pneumoniae chez des patients consideres en echec clinique. Conclusion La cefoxitine pourrait etre une alternative aux carbapenemes dans les infections a E-BLSE, en particulier a E. coli . Ces resultats meritent d’etre confirmes sur des etudes de plus grand effectif.

Background & Aims Recent findings in hepatitis C virus (HCV)-monoinfected patients have shown a correlation between low serum levels of 25-OH vitamin D3 [25(OH)D3] and severe liver fibrosis and low sustained virologic response to therapy. Data are lacking in HIV-HCV coinfected patients. Methods One hundred and eighty nine HIV-HCV coinfected patients, who received ⩾80% of interferon (IFN) plus ribavirin therapy, were analyzed for baseline serum 25(OH)D3 levels. Correlations between serum 25(OH)D3 levels, chronic hepatitis C features, HCV virologic response to antiviral therapy, and HIV infection characteristics were analyzed. Results Mean serum 25(OH)D3 level was 18.5±9.8ng/ml, including 162 (85%) patients with level ⩽30ng/ml. Serum 25(OH)D3 levels were significantly correlated with the histological Metavir fibrosis score ( r =−0.16; p =0.027). Patients with severe fibrosis (Metavir F3/F4) had lower serum 25(OH)D3 levels compared to F2 and F1 patients (16.2±10.0 vs. 18.9±8.5 and 20.9±11.1ng/ml, respectively; p =0.06). In multivariate analysis, low serum 25(OH)D levels were independently associated with severe liver fibrosis ( p =0.04) and cold season ( p =0.0002). Serum levels of 25(OH)D3 were also significantly correlated with liver fibrosis as assessed by FibroTest® ( r =−0.22; p =0.008) and serum α2-macroglobulin levels ( r =−0.23; p =0.006). In contrast, no correlation was found between 25(OH)D3 levels and HCV sustained virologic response to IFN-based therapy [OR 0.98 (0.95–1.01); p =0.22]. No association was found between 25(OH)D3 levels and markers of HIV-related immunodeficiency. Conclusions In HIV-HCV coinfected patients, low serum 25(OH)D3 levels correlate with severe liver fibrosis. In contrast, serum 25(OH)D3 levels are not linked to HCV virologic response to therapy or severity of immunodeficiency.

Recurrent pericarditis are common and their management remains a matter of debate. Their precise pathophysiology is unclear, and both innate and adaptative immunity seem involved. An extensive work-up seeking for etiology seems to be unnecessary during the first episode of acute pericarditis, whereas it is mandatory in recurrent pericarditis. Despite extensive investigations, up to 80 % of recurrent pericarditis remains of unknown origin. Colchicin associated to non steroidal antiinflammatory drugs is the first line treatment whereas immunosuppressive drugs are exceptionally required.

Liver granulomas are histopathologically defined and associated with various liver and non-livers disorders. There are five main causes of liver granulomatosis: primary biliary cirrhosis, tuberculosis, sarcoidosis, B and C viral hepatitis, and drug related. In the other cases, not associated with an underlying systemic granulomatous disease, a systematic diagnostic approach should be used to identify less common etiologies. After a careful diagnostic work-up, a long-term follow-up of patients with undetermined liver granulomatosis is mandatory as it may be a presenting feature of liver lymphoma.

Liver involvement is common in connective tissue disorders and usually asymptomatic. However, it may be symptomatic and cases of fulminant hepatitis have been reported. A diagnosis of specific hepatic involvement needs to rule out drug toxicity, viral hepatitis, or auto-immune liver disease. The large panel of auto-antibodies that is now available to the clinician is helpful to differentiate auto-immune hepatitis and specific liver involvement associated with connective tissue disease. In the latter, the outcome is generally favourable with immunosuppressive treatment.

Purulent pneumoccocal pericarditis are extremely rare since the introduction of antibiotics.A 59-year-old woman presented to the emergency room with a seven-day history of dyspnea and fever. No signs of heart failure or cardiac friction rub were evidenced. Laboratory tests disclosed elevated acute phase reactants and elevated white blood cells with a high neutrophil count. Chest radiograph showed cardiomegaly and a bilateral pleural effusion. Chest-computed tomography confirmed the pleural effusion and evidenced a large pericardial effusion. Streptoccocus pneumoniae grew up form pericardial fluid and blood cultures. In addition to the pericardial drainage, the patient received intravenous amoxicillin therapy. Outcome was favourable. There was no evidence of immunodeficiency.Although exceptional, diagnosis of purulent pneumococcal pericarditis should not be missed as it may compromise vital prognosis. Therapy should combine pericardial drainage and antibiotics.