Endogenous and environmental variables are fundamental in explaining variations in fish condition. Based on more than 20 yr of fish weight and length data, relative condition indices were computed ...for anchovy and sardine caught in the Gulf of Lions. Classification and regression trees (CART) were used to identify endogenous factors affecting fish condition, and to group years of similar condition. Both species showed a similar annual cycle with condition being minimal in February and maximal in July. CART identified 3 groups of years where the fish populations generally showed poor, average and good condition and within which condition differed between age classes but not according to sex. In particular, during the period of poor condition (mostly recent years), sardines older than 1 yr appeared to be more strongly affected than younger individuals. Time-series were analyzed using generalized linear models (GLMs) to examine the effects of oceanographic abiotic (temperature, Western Mediterranean Oscillation WeMO and Rhône outflow) and biotic (chlorophyll a and 6 plankton classes) factors on fish condition. The selected models explained 48 and 35% of the variance of anchovy and sardine condition, respectively. Sardine condition was negatively related to temperature but positively related to the WeMO and mesozooplankton and diatom concentrations. A positive effect of mesozooplankton and Rhône runoff on anchovy condition was detected. The importance of increasing temperatures and reduced water mixing in the NW Mediterranean Sea, affecting planktonic productivity and thus fish condition by bottom-up control processes, was highlighted by these results. Changes in plankton quality, quantity and phenology could lead to insufficient or inadequate food supply for both species.
Increasing abundance of non-commercial sprats and decreasing biomass and landings of commercial anchovies and sardines justify the need to study the feeding ecology and trophic niche overlap of these ...planktivorous species in the Gulf of Lions. Their diet has been investigated on the basis of stomach content and stable isotope analyses in 2011 and 2012 according to different depths and regions in the study area. The main prey were Corycaeidae copepods, Clauso/Paracalanus, Euterpina acutifrons and Microsetella, for sprats and small copepods, such as Microsetella, Oncaea and Corycaeidae, for anchovies and sardines. This is the first time that the diet of sprats is described in the Gulf of Lions. Sprats fed on a larger size spectrum of prey and seem to be more generalist feeders compared to anchovies and sardines. Ontogenetic changes as well as spatial and temporal variations of the diet occurred in the three species. Stable isotope analysis revealed mobility of sardines and sprats among feeding areas while anchovies exhibited preferred feeding areas. Sprats showed a higher relative condition assessed by C/N ratios than sardines and anchovies. Our results showed an overlap of the trophic niches for the three species, indicating a potential trophic competition in the Gulf of Lions.
•Sprats' diet was described for the first time in the NW Mediterranean Sea.•There was a high trophic overlap for sardines, anchovies and sprats.•Spatio-temporal and ontogenetic variations of their diet were described.•Sprats were more generalist than sardines and anchovies and fed on larger prey.•Diet particularities may explain the better relative condition of sprats.
Objective
Findings from the WEGENT trial and other short‐term studies have suggested that azathioprine (AZA) or methotrexate (MTX) could effectively maintain remission of granulomatosis with ...polyangiitis (Wegener's) (GPA) or microscopic polyangiitis (MPA). This study was undertaken to examine whether differences in rates of relapse or adverse events would appear after discontinuation of these 2 maintenance regimens, when assessed over a longer followup period.
Methods
Long‐term outcomes in patients enrolled in the WEGENT trial were analyzed according to their randomized treatment group (AZA or MTX). Parameters at trial entry were evaluated as potential prognostic factors for death, relapse, or damage in multivariate models.
Results
Data from 10 years of followup were available for 112 (88.8%) of the 126 original trial participants. The median followup time was 11.9 years (95% confidence interval 95% CI 11.3–12.5 years). In patients receiving AZA and those receiving MTX, the 10‐year overall survival rates were 75.1% (95% CI 64.8–86.9%) and 79.9% (95% CI 70.3–90.8%) (P = 0.56), respectively, and relapse‐free survival rates were 26.3% (95% CI 17.3–40.1%) and 33.5% (95% CI 23.5–47.7%) (P = 0.29), respectively. No between‐treatment differences were observed with regard to rates of relapse, adverse events, damage, survival without severe side effects, and survival without relapse and severe side effects. In analyses limited to the 97 patients with GPA, no between‐treatment differences in survival rates were observed. The 10‐year relapse‐free survival rate was lower in patients with GPA than in patients with MPA. However, in the multivariate analysis, anti–proteinase 3 antineutrophil cytoplasmic antibody (ANCA) positivity, and not GPA, was retained as being independently associated with the relapse rate.
Conclusion
The results of this long‐term analysis confirm that AZA and MTX are comparable treatment options for maintaining remission of GPA or MPA. Despite achieving good overall survival with these treatments, relapse rates, adverse events, and damage remain matters of concern and further studies are needed to reduce their frequency in these ANCA‐associated vasculitides.
Summary
Viral infections are thought to play a part in some cutaneous drug reactions. Human herpesvirus 6 (HHV6), which is the agent of exanthema subitum (sixth disease), has never been implicated in ...a drug reaction. We report a patient with severe phenobarbital‐induced anticonvulsant hypersensitivity syndrome in whom a fulminant haemophagocytic syndrome was associated with HHV6 infection. We discuss the possible role of HHV6 in this reactive condition.
Objective: We conducted this study to determine whether alcohol consumption influences radiological progression in early rheumatoid arthritis (RA).
Method: Patients fulfilling the European League ...Against Rheumatism/American College of Rheumatology 2010 criteria in the early arthritis cohort ESPOIR (Étude et Suivi des Polyarthrites Indifférenciées Récentes) were included in this study. Alcohol consumption was collected at baseline and at each visit. We classified alcohol consumption into three groups: abstinent (0 g/day), moderate (≤ 20 g/day for women, ≤ 30 g/day for men), and abuse (> 20 g/day for women, > 30 g/day for men). The primary outcome was the occurrence of radiological progression, defined as an increase ≥ 5 points in the total Sharp/van der Heijde score. We investigated whether alcohol consumption is predictive of radiological progression at 1, 3, and 5 years by univariate and multivariate analysis adjusted for age, baseline erosion, rheumatoid factor, anti-citrullinated peptide antibody, smoking status, body mass index, and treatment with leflunomide or methotrexate and biologics.
Results: The study included 596 patients. When considering the influence of gender on the interaction between alcohol consumption and radiological progression, we showed a deleterious effect of moderate consumption in women odds ratio (OR) = 1.73, 95% confidence interval (CI) 1.01; 2.96, p = 0.045 and a trend towards a protective effect of moderate consumption in men (OR = 0.50, 95% CI 0.21; 1.16, p = 0.106) in multivariate analysis.
Conclusion: Our data suggest a deleterious effect of moderate consumption of alcohol on radiological progression in women, but not in men, with early RA.
Objective
The effector T cell and B cell cytokine networks have been implicated in the pathogenesis of systemic autoimmune diseases, but the association of these cytokine networks with the ...heterogeneity of clinical manifestations and immune profiles has not been carefully examined. This study was undertaken to examine whether cytokine profiles can delineate distinct groups of patients in 4 systemic autoimmune diseases (systemic lupus erythematosus, Sjögren’s syndrome, rheumatoid arthritis, and systemic sclerosis).
Methods
A total of 179 patients and 48 healthy volunteers were enrolled in the multicenter cross‐sectional PRECISE Systemic Autoimmune Diseases (PRECISESADS) study. Multi‐low‐dimensional omics data (cytokines, autoantibodies, circulating immune cells) were examined. Coculture experiments were performed to test the impact of the cytokine microenvironment on T cell/B cell cross‐talk.
Results
A proinflammatory cytokine profile defined by high levels of CXCL10, interleukin‐6 (IL‐6), IL‐2, and tumor necrosis factor characterized a distinct group of patients in the 4 systemic autoimmune diseases. In each disease, this proinflammatory cluster was associated with a specific circulating immune cell signature, more severe disease, and higher levels of autoantibodies, suggesting an uncontrolled proinflammatory Th1 immune response. We observed in vitro that B cells reinforce Th1 differentiation and naive T cell proliferation, leading to the induction of type 1 effector B cells and IgG production. This process was associated with an increase in CXCL10, IL‐6, IL‐2, and interferon‐γ production.
Conclusion
This composite analysis brings new insights into human B cell functional heterogeneity based on T cell/B cell cross‐talk, and proposes a better stratification of patients with systemic autoimmune diseases, suggesting that combined biomarkers would be of great value for the design of personalized treatments.
Progressive fibrosing interstitial lung disease (ILD) is rarely associated with antineutrophil cytoplasm antibody (ANCA)-associated vasculitis (AAV). This study focused on the outcomes of ILD ...patients with associated AAV (AAV–ILD).
AAV–ILD (cases: microscopic polyangiitis (MPA) or granulomatosis with polyangiitis (GPA) with ILD) were compared to AAV patients without ILD (controls). ILD was defined as a usual interstitial pneumonia (UIP) or non-specific interstitial pneumonia (NSIP) pattern. Two controls were matched to each case for age (>or ≤65 years), ANCA status (PR3-or MPO-positive) and creatininemia (≥or <150 μmol/L).
Sixty-two cases (89% MPO-ANCA+) were included. Median age at AAV diagnosis was 66 years. ILD (63% UIP), was diagnosed before (52%) or simultaneously (39%) with AAV. Cases versus 124 controls less frequently had systemic vasculitis symptoms. One-, 3- and 5-year overall survival rates, respectively, were: 96.7%, 80% and 66% for cases versus 93.5%, 89.6% and 83.8% for controls (p = 0.008). Multivariate analyses retained age >65 years (hazard ratio (HR) 4.54; p < 0.001), alveolar haemorrhage (HR 2.25; p = 0.019) and UIP (HR 2.73; p = 0.002), but not immunosuppressant use, as factors independently associated with shorter survival.
For AAV–ILD patients, only UIP was associated with poorer prognosis. Immunosuppressants did not improve the AAV–ILD prognosis. But in analogy to idiopathic pulmonary fibrosis, anti-fibrosing agents might be useful and should be assessed in AAV–ILD patients with a UIP pattern.
•Progressive fibrosing interstitial lung disease is a rare comorbidity of MPO-vasculitis.•This condition is associated with shorter survival when it has a CT-scan UIP pattern.•Immunosuppressants did not improve the prognosis of these patients.•Our results support the evaluation of anti-fibrotic drugs in this condition.
This study, developed within the Innovative Medicines Initiative Joint Undertaking project PRECISESADS framework, aimed at functionally characterize the monocyte subsets in RA patients, and analyze ...their involvement in the increased CV risk associated with RA.
The frequencies of monocyte subpopulations in the peripheral blood of 140 RA patients and 145 healthy donors (HDs) included in the PRECISESADS study were determined by flow cytometry. A second cohort of 50 RA patients and 30 HDs was included, of which CD14
and CD16
monocyte subpopulations were isolated using immuno-magnetic selection. Their transcriptomic profiles (mRNA and microRNA), proinflammatory patterns and activated pathways were evaluated and related to clinical features and CV risk. Mechanistic
analyses were further performed.
CD14
CD16
intermediate monocytes were extended in both cohorts of RA patients. Their increased frequency was associated with the positivity for autoantibodies, disease duration, inflammation, endothelial dysfunction and the presence of atheroma plaques, as well as with the CV risk score. CD14
and CD16
monocyte subsets showed distinctive and specific mRNA and microRNA profiles, along with specific intracellular signaling activation, indicating different functionalities. Moreover, that specific molecular profiles were interrelated and associated to atherosclerosis development and increased CV risk in RA patients.
, RA serum promoted differentiation of CD14
CD16
to CD14
CD16
monocytes. Co-culture with RA-isolated monocyte subsets induced differential activation of endothelial cells.
Our overall data suggest that the generation of inflammatory monocytes is associated to the autoimmune/inflammatory response that mediates RA. These monocyte subsets, -which display specific and distinctive molecular signatures- might promote endothelial dysfunction and in turn, the progression of atherosclerosis through a finely regulated process driving CVD development in RA.
In most patients with nonsevere systemic necrotizing vasculitides (SNVs), remission is achieved with glucocorticoids alone, but one-third experience a relapse within 2 years. This study was ...undertaken to determine whether the addition of azathioprine (AZA) to glucocorticoids could achieve a higher sustained remission rate of newly diagnosed nonsevere eosinophilic granulomatosis with polyangiitis (Churg-Strauss) (EGPA), microscopic polyangiitis (MPA), or polyarteritis nodosa (PAN).
All patients included in this double-blind trial received glucocorticoids, gradually tapered over 12 months, and were randomized to receive AZA or placebo for 12 months, with stratification according to SNV (EGPA or MPA/PAN). The primary end point was the combined rate of remission induction failures and minor or major relapses at month 24.
Ninety-five patients (51 with EGPA, 25 with MPA, and 19 with PAN) met the inclusion criteria, were randomized, and received at least 1 dose of AZA (n = 46) or placebo (n = 49). At month 24, 47.8% of the patients receiving AZA versus 49% of the patients receiving placebo had remission induction failures or relapses (P = 0.86). Secondary end points were comparable between the AZA and placebo arms. These included initial remission rate (95.7% versus 87.8%), total relapse rate (44.2% versus 40.5%), and glucocorticoid use. Two patients in the placebo arm died; 22 patients in the AZA arm (47.8%) and 23 patients in the placebo arm (46.9%) experienced ≥1 severe adverse event. For EGPA patients, the primary end point (48% in the AZA arm versus 46.2% in the placebo arm) and the percent of patients who experienced asthma/rhinosinusitis exacerbations (24% in the AZA arm versus 19.2% in the placebo arm) were comparable between treatment arms.
Addition of AZA to glucocorticoids for the induction of remission of nonsevere SNVs does not improve remission rates, lower relapse risk, spare steroids, or diminish the EGPA asthma/rhinosinusitis exacerbation rate.
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