Smoking and response to rituximab in rheumatoid arthritis : results from an international European collaboration

Objectives: To investigate whether smoking habits predict response to rituximab (RTX) in rheumatoid arthritis (RA). Method: We included patients from the CERERRA international cohort receiving the first treatment cycle with available smoking status (n = 2481, smokers n = 528, non-current smokers n = 1953) and at least one follow-up visit. Outcome measures were change in Disease Activity Score based on 28-joint count (Delta DAS28) and European League Against Rheumatism (EULAR) good response at 6 months, with non-current smokers as the referent group. Results: Compared with non-smokers at baseline, smokers were more often rheumatoid factor (RF)/anti-citrullinated protein antibody (ACPA) positive and males, had shorter disease duration, lower DAS28 and Health Assessment Questionnaire (HAQ) score, a higher number of prior biological disease-modifying anti-rheumatic drugs, and were more likely to receive concomitant conventional synthetic disease-modifying anti-rheumatic drug (csDMARDs). Disease activity had decreased less in smokers at 6 months (Delta DAS28 = 1.5 vs 1.7, p = 0.006), although the difference was no longer significant after correction for baseline DAS28 (p = 0.41). EULAR good response rates did not differ between smokers and non-smokers overall or stratified by RF/ACPA status, although smokers had lower good response rates among seronegative patients (ACPA-negative: 6% vs 14%, RF-negative: 11% vs 18%). Smoking did not predict good response [odds ratio (OR) = 1.04, 95% confidence interval (CI) = 0.76-1.41], while ACPA, DAS28, HAQ, and concomitant csDMARDs were significant predictors for good response. However, when stratified by country, smokers were less likely to achieve good response in Sweden (unadjusted OR = 0.24, 95% CI = 0.07-0.89), and a trend was seen in the Czech Republic (OR = 0.45, 95% CI = 0.16-1.02). Conclusion: In this large, observational, multinational RA cohort, smokers starting RTX differed from non-smokers by having shorter disease duration and lower disease activity, but more previous treatments. The overall results do not support smoking as an important predictor for response to RTX in patients with RA.Peer reviewe

Strangeness enhancements at central rapidity in 40 A GeV/c Pb-Pb collisions

Results are presented on neutral kaon, hyperon and antihyperon production in Pb-Pb and p-Be interactions at 40 GeV/c per nucleon. The enhancement pattern follows the same hierarchy as seen in the higher energy data - the enhancement increases with the strangeness content of the hyperons and with the centrality of collision. The centrality dependence of the Pb-Pb yields and enhancements is steeper at 40 than at 158 A GeV/c. The energy dependence of strangeness enhancements at mid-rapidity is discussed.Comment: 15 pages, 10 figures and 3 tables. Presented at International Conference on Strangeness in Quark Matter (SQM2009), Buzios, Rio de Janeiro, Brazil, 27 Sept - 2 Oct 2009. Submitted to J.Phys.G: Nucl.Part.Phys, one reference adde

Rapidity distributions around mid-rapidity of strange particles in Pb-Pb collisions at 158 AA GeV/c

The production at central rapidity of K0s, Lambda, Xi and Omega particles in Pb-Pb collisions at 158 A GeV/c has been measured by the NA57 experiment over a centrality range corresponding to the most central 53% of the inelastic Pb-Pb cross section. In this paper we present the rapidity distribution of each particle in the central rapidity unit as a function of the event centrality. The distributions are analyzed based on hydrodynamical models of the collisions.Comment: 15 pages, 10 figure

Elevated NET, Calprotectin, and Neopterin Levels Discriminate between Disease Activity in COVID-19, as Evidenced by Need for Hospitalization among Patients in Northern Italy

Coronavirus disease 2019 (COVID-19) displays clinical heterogeneity, but little information is available for patients with mild or very early disease. We aimed to characterize biomarkers that are useful for discriminating the hospitalization risk in a COVID-19 cohort from Northern Italy during the first pandemic wave. We enrolled and followed for four weeks 76 symptomatic SARS-CoV-2 positive patients and age/sex-matched healthy controls. Patients with mild disease were discharged (n.42), and the remaining patients were hospitalized (n.34). Blood was collected before any anti-inflammatory/immunosuppressive therapy and assessed for soluble C5b-9/C5a, H3-neutrophil extracellular traps (NETs), calprotectin, and DNase plasma levels via ELISA and a panel of proinflammatory cytokines via ELLA. Calprotectin and NET levels discriminate between hospitalized and non-hospitalized patients, while DNase negatively correlates with NET levels; there are positive correlations between calprotectin and both NET and neopterin levels. Neopterin levels increase in patients at the beginning of the disease and do so more in hospitalized than non-hospitalized patients. C5a and sC5b-9, and other acute phase proteins, correlate with neopterin, calprotectin, and DNase. Both NET and neopterin levels negatively correlate with platelet count. We show that calprotectin, NETs, and neopterin are important proinflammatory parameters potentially useful for discriminating between COVID-19 patients at risk of hospitalization

New results from the NA57 experiment

We report results from the experiment NA57 at CERN SPS on hyperon production at midrapidity in Pb-Pb collisions at 158 $A$ GeV/$c$ and 40 $A$ GeV/$c$. $\Lambda$, $\Xi$ and $\Omega$ yields are compared with those from the STAR experiment at the higher energy of the BNL RHIC. $\Lambda$, $\Xi$, $\Omega$\ and preliminary $K_S^0$ transverse mass spectra are presented and interpreted within the framework of a hydro-dynamical blast wave model.Comment: 8 pages, 3 figures, contribution to the proceedings of The XXXVIIIth Rencontres de Moriond "QCD and High Energy Hadronic Interactions

Expansion dynamics of Pb-Pb collisions at 40 A GeV/c viewed by negatively charged hadrons

In this paper we present results on transverse mass spectra and Hanbury-Brown and Twiss correlation functions of negatively charged hadrons, which are expected to be mostly negative pions, measured in Pb-Pb collisions at 40 A GeV/c beam momentum. Based on these data, the collision dynamics and the space-time extent of the system at the thermal freeze-out are studied over a centrality range corresponding to the most central 53% of the Pb--Pb inelastic cross section. Comparisons with freeze-out conditions of strange particles and HBT results from other experiments are discussed.Comment: 29 pages, 18 figure

Results on hyperon production from the NA57 experiment

Recent results on hyperon production in Pb--Pb collisions from the NA57 experiment are reported. Strangeness enhancement and the transverse mass spectra properties at 158 GeV per nucleon are described.Comment: submitted to Acta Phys. Hung. A (Heavy Ion Physics

Strange particle production in 158 and 40 AA GeV/cc Pb-Pb and p-Be collisions

Results on strange particle production in Pb-Pb collisions at 158 and 40 $A$ GeV/$c$ beam momentum from the NA57 experiment at CERN SPS are presented. Particle yields and ratios are compared with those measured at RHIC. Strangeness enhancements with respect to p-Be reactions at the same beam momenta have been also measured: results about their dependence on centrality and collision energy are reported and discussed.Comment: Contribution to the proceedings of the "Hot Quarks 2004" Conference, July 18-24 2004, New Mexico, USA, submitted to Journal of Physics G 7 pages, 5 figure

Cartilage Oligomeric Matrix Protein Associates Differentially with Erosions and Synovitis and Has a Different Temporal Course in Cyclic Citrullinated Peptide Antibody (Anti-CCP)-positive versus Anti-CCP-negative Early Rheumatoid Arthritis

Objective.Cyclic citrullinated peptide antibody (anti-CCP)-positive and anti-CCP-negative rheumatoid arthritis (RA) have been suggested as 2 distinctive disease subsets with respect to disease activity and prognosis. Previously, we proposed that anti-CCP antibodies might have a chondrocyte-suppressive effect. We aimed to compare circulating cartilage oligomeric matrix protein (COMP), a marker of cartilage turnover, in untreated anti-CCP-positive and anti-CCP-negative RA, and to study the temporal pattern of COMP through 4 years of treatment, including the relationship to imaging and clinical findings.Methods.A total of 160 patients with newly diagnosed RA who were naive to disease-modifying antirheumatic drugs were included in the CIMESTRA trial. Ninety healthy blood donors served as controls. Demographic and disease measures including Disease Activity Score in 28 joints, IgM rheumatoid factor, anti-CCP, Health Assessment Questionnaire, visual analog scale scores for pain and global and physician assessment, and magnetic resonance imaging (MRI) of the nondominant hand were recorded at baseline. COMP in serum was measured by ELISA at inclusion and serially through 4 years.Results.Median baseline COMP was higher in patients with RA [9.8 U/l (interquartile range 8.96, 10.5)] compared with controls [8.3 U/l (IQR 7.84, 8.9); p &lt; 0.001] and remained elevated at 4 years [10.8 U/l (IQR 10.2, 11.7); p &lt; 0.001]. At baseline, anti-CCP-positive patients had lower COMP than anti-CCP-negative patients (p = 0.048). In anti-CCP-positive patients, COMP exhibited a parabolic course over 4 years, while COMP in anti-CCP-negative patients had an almost linear course. In anti-CCP-positive patients, COMP was associated with MRI edema and erosion score, while COMP was correlated with synovitis score in anti-CCP-negative individuals.Conclusion.Our study provides additional evidence for the existence of different disease pathways in anti-CCP-positive and anti-CCP-negative subsets of RA, and evidence that anti-CCP antibodies may be implicated in the disease process by modifying cartilage metabolism.</jats:sec

Dislocation Creep of Olivine: Backstress Evolution Controls Transient Creep at High Temperatures

Transient creep occurs during geodynamic processes that impose stress changes on rocks at high temperatures. The transient is manifested as evolution in the viscosity of the rocks until steady-state flow is achieved. Although several phenomenological models of transient creep in rocks have been proposed, the dominant microphysical processes that control such behavior remain poorly constrained. To identify the intragranular processes that contribute to transient creep of olivine, we performed stress-reduction tests on single crystals of olivine at temperatures of 1250–1300°C. In these experiments, samples undergo time‐dependent reverse strain after the stress reduction. The magnitude of reverse strain is ~10-3 and increases with increasing magnitude of the stress reduction. High-angular resolution electron backscatter diffraction analyses of deformed material reveal lattice curvature and heterogeneous stresses associated with the dominant slip system. The mechanical and microstructural data are consistent with transient creep of the single crystals arising from accumulation and release of backstresses among dislocations. These results allow the dislocation‐glide component of creep at high temperatures to be isolated, and we use these data to calibrate a flow law for olivine to describe the glide component of creep over a wide temperature range. We argue that this flow law can be used to estimate both transient creep and steady‐state viscosities of olivine, with the transient evolution controlled by the evolution of the backstress. This model is able to predict variability in the style of transient (normal versus inverse) and the load-relaxation response observed in previous work.LH and DW acknowledge support from the Natural Environment Research Council, grant NE/M000966/1, LH and CT acknowledge support from the Natural Environment Research Council, grant 1710DG008/JC4, and DW acknowledges support from the Netherlands Organisation for Scientific Research, User Support Programme Space Research, grant ALWGO.2018.038, and startup funds from Utrecht University. LH recognizes funds used to develop the uniaxial apparatus from the John Fell Fund at the University of Oxford