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Background: Systemic sclerosis (SSc) is a chronic autoimmune disease, with impaired immune response, increased fibrosis and endothelial dysfunction. Regulatory T cells (Tregs), which are essential to control inflammation, tissue repair and autoimmunity, have a decreased frequency and impaired function in SSc patients. Low-dose interleukin-2 (IL-2 LD ) can expand and activate Tregs and has, therefore, a therapeutic potential in SSc., Objective: We aimed to assess the safety and biological efficacy of IL-2 LD in patients with SSc., Methods: As part of the TRANSREG open-label phase IIa basket trial in multiple autoimmune diseases, we studied nine patients with SSc without severe organ involvement. Patients received 1 million international units (MIU)/day of IL-2 for 5 days, followed by fortnightly injections for 6 months. Laboratory and clinical evaluations were performed between baseline and month 6., Results: At day 8, the primary endpoint (Treg frequency) was reached with a 1.8±0.5-fold increase of Treg levels among CD4 + T lymphocytes (p=0.0015). There were no significant changes in effector T cells nor in B cells. IL-2 LD was well tolerated, and no serious adverse events related to treatment occurred. There was a globally stable measurement in the modified Rodnan skin score and Valentini score at month 6. Disease activity and severity measures, the quality of life evaluated by EuroQL-5D-5L and pulmonary function test parameters remained stable during the study period., Conclusion: IL-2 LD at a dosage of 1 MIU/day safely and selectively activates and expands Tregs. Clinical signs remain stable during the study period. This opens the door to properly powered phase II efficacy trials investigating IL-2 LD therapeutic efficacy in SSc., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: We aimed to analyse the association between infections and the subsequent risk of giant cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) by a systematic review and a meta-analysis of observational studies., Methods: Two databases (Medline and Embase) were systematically reviewed. Epidemiological studies studying the association between any prior infection and the onset of GCA/PMR were eligible. Risk of bias was assessed using the Newcastle-Ottawa quality assessment scale. Outcomes and pooled statistics were reported as OR and their 95% CI., Results: Eleven studies (10 case-control studies and one cohort study) were analysed, seven of them were included in the meta-analysis. Eight were at low risk of bias. A positive and significant association was found between prior overall infections and prior Herpes Zoster (HZ) infections with pooled OR (95% CI) of 1.27 (1.18 to 1.37) and 1.20 (1.08 to 1.21), respectively. When analysed separately, hospital-treated and community-treated infections, were still significantly associated with the risk of GCA, but only when infections occurring within the year prior to diagnosis were considered (pooled OR (95% CI) 1.92 (1.67 to 2.21); 1.67 (1.54 to 1.82), respectively). This association was no longer found when infections occurring within the year prior to diagnosis were excluded., Conclusion: Our study showed a positive association between the risk of GCA and prior overall infections (occurring in the year before), and prior HZ infections. Infections might be the reflect of an altered immunity of GCA patients or trigger the disease. However, reverse causation cannot be excluded.CRD42023404089., Competing Interests: Competing interests: LP, FB and YN declare no competing interests. RS received consulting fees from GSK, Bristol Myer Squib, Boerhinger and Janssen; honoraria from GSK, Bristol Myer Squib, Boehringer, Amgen, Pfizer and Roche; travel fees from Amgen and GSK; none of this links are related to the topic of this study., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objectives: To assess the relationship between consumption of largely consumed beverages (coffee, tea, alcohol and soft drinks) and the risk of RA., Material and Methods: The E3N Study (Étude Épidémiologique auprès des femmes de la Mutuelle Générale de l'Éducation Nationale) is a French prospective cohort including 98 995 women since 1990. Food and beverage consumption was assessed using a validated food-frequency questionnaire. Hazard ratios (HR) and their 95% CI for incident RA were estimated by Cox proportional hazards model., Results: Among 62 631 women, 481 incident RA cases were identified. Consumptions of tea, alcohol and sugar-sweetened soft drinks were not associated with RA risk. We observed a linear association between coffee consumption and RA risk [≥4 cups/day vs ≤1cup/day, HR  =  1.24; 95% CI (0.94, 1.64), Ptrend  =  0.04], and a higher risk of RA with artificially sweetened soft drinks consumption [consumers vs not, HR  =  1.66; 95% CI (1.12, 2.45)], particularly in never-smokers. Among ever-smokers, moderate liquor intake was associated with a reduced risk of RA [1-3 glasses/week vs non-consumers, HR  =  0.63; 95% CI (0.43, 0.91)] and moderate wine consumption with a reduced risk of seropositive RA., Conclusions: In a large cohort of women, tea, alcohol and sugar-sweetened soft drinks consumption was not associated with RA risk, whereas consumption of coffee (especially caffeinated coffee), and artificially sweetened soft drinks was associated with higher RA risk, particularly among never-smokers. If further confirmed, these results could lead to novel mechanistic hypotheses and to simple prevention measures., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Posaconazole diffusion has been documented in various organs, which contrasts with the scarce data available for the human central nervous system (CNS). We analyzed posaconazole concentrations in plasma and multiple CNS specimens taken from a patient who received posaconazole because of cerebral phaeohyphomycosis. Low posaconazole concentrations were obtained in CNS specimens, with sample-to-plasma ratios between 5% and 22%. This case highlights the role of neurosurgery during cerebral phaeohyphomycoses, even those caused by posaconazole-susceptible black fungi., (Copyright © 2019 American Society for Microbiology.)

Batteries based on Ca hold the promise to leapfrog ahead regarding increases in energy densities and are especially attractive as Ca is the 5th most abundant element in the Earth's crust. The viability of Ca metal anodes has recently been shown by approaches that either use wide potential window electrolytes at moderately elevated temperatures or THF-based electrolytes at room temperature. This paper provides realistic estimates of the practical energy densities for Ca-based rechargeable batteries at the cell level, calculated using open source models for several concepts. The results from the Ca metal anode batteries indicate that doubled or even tripled energy density as compared to the state-of-the-art Li-ion batteries is viable if a practical proof-of-concept can be achieved.