Constraining dust properties in circumstellar envelopes of C-stars in the Small Magellanic Cloud: optical constants and grain size of carbon dust

We present a new approach aimed at constraining the typical size and optical properties of carbon dust grains in circumstellar envelopes (CSEs) of carbon-rich stars (C-stars) in the Small Magellanic Cloud (SMC). To achieve this goal, we apply our recent dust growth description, coupled with a radiative transfer code to the CSEs of C-stars evolving along the thermally pulsing asymptotic giant branch, for which we compute spectra and colours. Then, we compare our modelled colours in the near- and mid-infrared (NIR and MIR) bands with the observed ones, testing different assumptions in our dust scheme and employing several data sets of optical constants for carbon dust available in the literature. Different assumptions adopted in our dust scheme change the typical size of the carbon grains produced. We constrain carbon dust properties by selecting the combination of grain size and optical constants which best reproduce several colours in the NIR and MIR at the same time. The different choices of optical properties and grain size lead to differences in the NIR and MIR colours greater than 2 mag in some cases. We conclude that the complete set of observed NIR and MIR colours are best reproduced by small grains, with sizes between ~0.035 and ~0.12 μm, rather than by large grains between ~0.2 and 0.7 μm. The inability of large grains to reproduce NIR and MIR colours seems independent of the adopted optical data set. We also find a possible trend of the grain size with mass-loss and/or carbon excess in the CSEs of these stars. © 2016 The Authors

The mass-loss, expansion velocities, and dust production rates of carbon stars in the Magellanic Clouds

The properties of carbon stars in the Magellanic Clouds (MCs) and their total dust production rates are predicted by fitting their spectral energy distributions (SED) over pre-computed grids of spectra reprocessed by dust. The grids are calculated as a function of the stellar parameters by consistently following the growth for several dust species in their circumstellar envelopes, coupled with a stationary wind. Dust radiative transfer is computed taking as input the results of the dust growth calculations. The optical constants for amorphous carbon are selected in order to reproduce different observations in the infrared and optical bands of Gaia Data Release 2. We find a tail of extreme mass-losing carbon stars in the Large Magellanic Cloud (LMC) with low gas-to-dust ratios that is not present in the Small Magellanic Cloud (SMC). Typical gas-to-dust ratios are around 700 for the extreme stars, but they can be down to similar to 160-200 and similar to 100 for a few sources in the SMC and in the LMC, respectively. The total dust production rate for the carbon star population is similar to 1.77 +/- 0.45 x 10(-5) M-circle dot yr(-1), for the LMC, and similar to 2.52 +/- 0.96 x 10(-6) M-circle dot yr(-1), for the SMC. The extreme carbon stars observed with the Atacama Large Millimeter Array and their wind speed are studied in detail. For the most dust-obscured star in this sample the estimated mass-loss rate is similar to 6.3 x 10(-5) M-circle dot yr(-1). The grids of spectra are available at:(1) and included in the SED-fitting python package for fitting evolved stars.(2

Long-term effect of tocilizumab in patients with giant cell arteritis:open-label extension phase of the Giant Cell Arteritis Actemra (GiACTA) trial

Background: The combination of tocilizumab plus a glucocorticoid taper is effective in maintaining clinical remission without requiring additional glucocorticoid therapy in patients with giant cell arteritis, as shown in part one of the Giant Cell Arteritis Actemra (GiACTA) trial. However, the duration of the tocilizumab effect after discontinuation is unknown. Here, we explored the maintenance of efficacy 1 year after discontinuation of tocilizumab treatment, the effectiveness of retreatment with tocilizumab after relapse, and the long-term glucocorticoid-sparing effect of tocilizumab. Methods: In part one of the GiACTA trial, 251 patients were randomly assigned (2:1:1:1) to receive subcutaneous tocilizumab (162 mg) once a week or every other week, combined with a 26-week prednisone taper, or placebo combined with a prednisone taper over a period of either 26 weeks or 52 weeks. Patients in clinical remission stopped masked injections at 1 year (the conclusion of part one). In part two, treatment was at the investigators' discretion and could consist of no treatment, tocilizumab, glucocorticoids, methotrexate, or combinations of these, for two years. Maintenance of efficacy as assessed by clinical remission (defined as absence of relapse determined by the investigator), cumulative glucocorticoid dose, and long-term safety were exploratory objectives in part two of the trial. This trial is registered at ClinicalTrials.gov, NCT01791153. Findings: 215 patients participated in part two of the trial; 81 patients who were randomly assigned to tocilizumab once a week in part one were in clinical remission after 1 year, of whom 59 started part two on no treatment. 25 of these 59 patients (42%) maintained tocilizumab-free and glucocorticoid-free clinical remission throughout part two. Median (95% CI) cumulative glucocorticoid doses over 3 years were 2647 mg (1987\u20133507) for tocilizumab once a week, 3948 mg (2352\u20135186) for tocilizumab-every-other-week, 5277 mg (3944\u20136685) for placebo with a 26-week prednisone taper, and 5323 mg (3900\u20136951) for placebo with a 52-week prednisone taper (van Elteren p 640\ub7001, tocilizumab once a week vs placebo groups; p<0\ub705, tocilizumab-every-other-week vs placebo groups). Tocilizumab-based regimens restored clinical remission among patients who experienced relapse in part two and were treated (median time to remission: 15 days for tocilizumab alone [n=17]; 16 days for tocilizumab plus glucocorticoids [n=36]; and 54 days for glucocorticoids alone [n=27]). No new or unexpected safety findings were reported over the full 3 years of the study. Interpretation: Giant cell arteritis remains a chronic disease that entails ongoing management and careful vigilance for disease relapse, but continuous indefinite treatment with immunosuppressive drugs is not required for all patients. A substantial proportion of patients treated with tocilizumab for one year maintain drug-free remission during the two years after tocilizumab cessation. For patients who experience relapse, tocilizumab can be used to manage relapses, but it remains prudent to include prednisone for patients who experience relapse because of the risk for vision loss. Funding: F Hoffmann-La Roche

Effects of nintedanib in patients with limited cutaneous systemic sclerosis and interstitial lung disease

OBJECTIVES: To investigate the course of interstitial lung disease (ILD) and the effects of nintedanib in patients with limited cutaneous systemic sclerosis (lcSSc). METHODS: In the SENSCIS trial, patients with SSc-ILD were randomised to receive nintedanib or placebo. Patients who completed the SENSCIS trial were eligible to enter SENSCIS-ON, in which all patients received open-label nintedanib. RESULTS: Among 277 patients with lcSSc treated in the SENSCIS trial, the rate (SE) of decline in FVC (mL/year) over 52 weeks was -74.5 (19.2) in the placebo group and -49.1 (19.8) in the nintedanib group (difference: 25.3 [95% CI -28.9, 79.6]). Among 249 patients with data at week 52, mean (SE) changes in FVC at week 52 were -86.4 (21.1) mL in the placebo group and -39.1 (22.2) mL in the nintedanib group. Among 183 patients with lcSSc who participated in SENSCIS-ON and had data at week 52, mean (SE) changes in FVC from baseline to week 52 of SENSCIS-ON were -41.5 (24.0) mL in patients who took placebo in the SENSCIS trial and initiated nintedanib in SENSCIS-ON and -45.1 (19.1) mL in patients who took nintedanib in the SENSCIS trial and continued it in SENSCIS-ON. CONCLUSION: Patients with lcSSc may develop progressive fibrosing ILD. By targeting pulmonary fibrosis, nintedanib slows decline in lung function in patients with lcSSc and ILD. TRIAL REGISTRATION: ClinicalTrials.gov (https://www.clinicaltrials.gov), NCT02597933 and NCT03313180

New-onset versus relapsing giant cell arteritis treated with tocilizumab:3-year results from a randomized controlled trial and extension

OBJECTIVE: Tocilizumab plus prednisone induces sustained glucocorticoid-free remission in patients with giant cell arteritis (GCA). However, its long-term benefits in new-onset vs relapsing disease are uncertain and the value of weekly vs every-other-week dosing has not been evaluated. METHODS: In GiACTA part 1, patients with new-onset or relapsing GCA received blinded tocilizumab weekly (TCZ QW), tocilizumab every-other-week (TCZ Q2W), or placebo for 52 weeks with a prednisone taper. In part 2 (open-label), patients were treated at investigator discretion for 104 weeks. In this analysis, patients were evaluated according to their original treatment assignments and outcomes beyond 52 weeks were assessed. Outcomes of interest included time to first flare and cumulative glucocorticoid exposure over 3 years according to baseline disease status. RESULTS: Part 1 enrolled 250 patients; 215 entered part 2. At baseline, 48% had new-onset disease and 52% had relapsing disease. In patients with new-onset and relapsing disease, median time to first flare in the TCZ QW group was 577 and 575 days, respectively, vs 479 and 428 days with TCZ Q2W and 179 and 224 days with placebo; median cumulative glucocorticoid dose was 3068 mg and 2191 mg with TCZ QW, 4080 mg and 2353 mg with TCZ Q2W, and 4639 mg and 6178 mg with placebo. CONCLUSIONS: TCZ QW delays the time to flare and reduces cumulative glucocorticoid dose in patients with relapsing GCA and new-onset GCA. These data support initiating TCZ QW as part of first-line therapy in all patients with active GCA. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT01791153

Case Report: Response of cutaneous lupus lesions in SLE to interferon receptor blockade parallels reduction of interferon score in blood

Cutaneous lupus erythematosus (CLE), the main manifestation of systemic lupus erythematosus (SLE), is driven by type I interferons (IFNs) and often only partially responds to conventional therapies. Treatment of seven SLE patients with the monoclonal antibody anifrolumab induced fast and sustained remission of previously refractory CLE lesions, beginning within the first weeks of treatment. Decline in CLASI-A score was paralleled by a reduction in IFN score determined by mRNA expression of seven IFN-stimulated genes (ISGs) in blood. These data suggest that a subset of ISGs could be a valuable biomarker in CLE

EULAR recommendations for the management of systemic lupus erythematosus : 2023 update

To update the EULAR recommendations for the management of systemic lupus erythematosus (SLE) based on emerging new evidence.An international Task Force formed the questions for the systematic literature reviews (January 2018-December 2022), followed by formulation and finalisation of the statements after a series of meetings. A predefined voting process was applied to each overarching principle and recommendation. Levels of evidence and strengths of recommendation were assigned, and participants finally provided their level of agreement with each item.The Task Force agreed on 5 overarching principles and 13 recommendations, concerning the use of hydroxychloroquine (HCQ), glucocorticoids (GC), immunosuppressive drugs (ISDs) (including methotrexate, mycophenolate, azathioprine, cyclophosphamide (CYC)), calcineurin inhibitors (CNIs, cyclosporine, tacrolimus, voclosporin) and biologics (belimumab, anifrolumab, rituximab). Advice is also provided on treatment strategies and targets of therapy, assessment of response, combination and sequential therapies, and tapering of therapy. HCQ is recommended for all patients with lupus at a target dose 5 mg/kg real body weight/day, considering the individual's risk for flares and retinal toxicity. GC are used as 'bridging therapy' during periods of disease activity; for maintenance treatment, they should be minimised to equal or less than 5 mg/day (prednisone equivalent) and, when possible, withdrawn. Prompt initiation of ISDs (methotrexate, azathioprine, mycophenolate) and/or biological agents (anifrolumab, belimumab) should be considered to control the disease and facilitate GC tapering/discontinuation. CYC and rituximab should be considered in organ-threatening and refractory disease, respectively. For active lupus nephritis, GC, mycophenolate or low-dose intravenous CYC are recommended as anchor drugs, and add-on therapy with belimumab or CNIs (voclosporin or tacrolimus) should be considered. Updated specific recommendations are also provided for cutaneous, neuropsychiatric and haematological disease, SLE-associated antiphospholipid syndrome, kidney protection, as well as preventative measures for infections, osteoporosis, cardiovascular disease.The updated recommendations provide consensus guidance on the management of SLE, combining evidence and expert opinion