Should we be Afraid of Immune Check Point Inhibitors in Cancer Patients with Pre-Existing Rheumatic Diseases? Immunotherapy in Pre-Existing Rheumatic Diseases

Background: Cancer immunotherapy is rapidly expanding but its clinical efficacy is hampered by immune related adverse events (ir-AE). There is a concern regarding patients with pre-existing autoimmune diseases (PAD) undergoing immunotherapy. Methods: An electronic search was performed (Medline) to identify cases of patients with PAD treated with immune checkpoint inhibitors (ICI). Results: Published data are rather limited but continue to emerge. Patients with PAD exhibit a high risk of PAD flare and/or de novo ir-AE. In most cases PAD flares and de novo irAEs were not severe and could be managed effectively with standard treatment. Conclusions: This risk in patients with PAD appears acceptable, and therefore, these patients could receive immunotherapy under close monitoring. Collaboration of oncologists and rheumatologists for the management of these patients is crucial. © 202

Pathogenetic Aspects of Systemic Sclerosis: A View Through the Prism of B Cells

Systemic sclerosis (SSc) is a rare fibrotic rheumatic disease, associated with psychological distress and increased morbidity and mortality due to skin involvement and internal organ damage. The current understanding of the complex pathogenesis is yet incomplete and disease therapeutic algorithms are far from optimal. Immunologic aberrations are considered key factors for the disease, along with vascular involvement and excess fibrosis. Adaptive immunity and its specialized responses are an attractive research target and both T and B cells have been extensively studied in recent years. In the present review, the focus is placed on B cells in SSc. B cell homeostasis is deranged and B cell subsets exhibit an activated phenotype and abnormal receptor signaling. Autoantibodies are a hallmark of the disease and the current perception of their diagnostic and pathogenetic role is analyzed. In addition, B cell cytokine release and its effect on immunity and fibrosis are examined, together with B cell tissue infiltration of the skin and lung. These data support the concept of targeting B cells as part of the therapeutic plan for SSc through well designed clinical trials. Copyright © 2022 Melissaropoulos, Iliopoulos, Sakkas and Daoussis

Targeting very early systemic sclerosis: a case-based review

It is unknown whether treatment in very early/early systemic sclerosis (SSc) can affect long-term outcomes. A case-based review was conducted (i) to assess the effect of rituximab (RTX) in very early SSc and (ii) to explore how many clinical trials in SSc targeted early disease and whether treatment of these patients led to better clinical outcomes. We identified cases of very early SSc from our department and performed a search in MEDLINE and Scopus databases for clinical trials in SSc during 2005–2018. Two cases are reported where RTX was administered within 24 months from the appearance of Raynaud’s. In the first case, there was an improvement in interstitial lung disease as indicated by the improvement in pulmonary function tests and the regression of changes in high-resolution chest computed tomography. In the second case, a good clinical response in skin fibrosis was observed. The review revealed the following: (i) only one-third of the studies were specifically designed to target early disease, (ii) there is confusion related to disease duration definition across SSc clinical trials but an obvious trend towards improvement was evident during the past years, (iii) the question of whether early implementation of therapy may lead to better clinical outcomes cannot be definitely answered based on existing data and (iv) there is still a very low level of incorporation of the new classification criteria in SSc trials. This review suggests that there may be a window of opportunity in SSc and highlights the need for clinical trials targeting very early/early disease. © 2019, Springer-Verlag GmbH Germany, part of Springer Nature

Primary sjögren’s syndrome and cardiovascular disease

Sjögren’s syndrome is a rheumatic autoimmune disease that primarily affects middle-aged women and runs a slowly progressing course with sicca symptoms being the prevalent manifestation. Premature atherosclerosis and increased cardiovascular (CV) morbidity and mortality are frequently encountered in rheumatic diseases characterized by significant systemic inflammation, such as the inflammatory arthritides, systemic vasculitides and systemic lupus erythematosus. In the same context, chronic inflammation and immune aberrations underlying Sjögren’s syndrome are also reported to be associated with augmented risk of atherosclerosis. Increased CV disease (CVD) frequency has been found in recent meta-analyses. The involvement of the CV system is not a common feature of Sjögren’s0 syndrome; however, specific manifestations, such as autoantibody-mediated heart block, pericarditis, pulmonary arterial hypertension and dysautonomia, have been described. This review focuses on studies addressing CV morbidity in Sjögren’s syndrome and presents current data regarding distinct CV fea-tures of the disease. © 2020 Bentham Science Publishers

A multicenter, open-label, comparative study of B-cell depletion therapy with Rituximab for systemic sclerosis-associated interstitial lung disease

Objectives Rituximab (RTX) may favorably affect lung function and skin fibrosis in patients with systemic sclerosis (SSc). We aimed to assess long-term efficacy and safety of RTX in SSc compared to standard treatment. Methods A total of 51 patients with SSc-associated interstitial lung disease were recruited and treated with RTX (n = 33) or conventional treatment (n = 18). Median follow-up was 4 years (range: 1–7). Conventional treatment consisted of azathioprine (n = 2), methotrexate (n = 6), and mycophenolate mofetil (n = 10). Results Patients in the RTX group showed an increase in FVC at 2 years (mean ± SD of FVC: 80.60 ± 21.21 vs 86.90 ± 20.56 at baseline vs 2 years, respectively, p = 0.041 compared to baseline). In sharp contrast, patients in the control group had no change in FVC during the first 2 years of follow-up. At the 7 year time point the remaining patients in the RTX group (n = 5) had higher FVC compared to baseline (mean ± SD of FVC: 91.60 ± 14.81, p = 0.158 compared to baseline) in contrast to patients in the control group (n = 9) where FVC deteriorated (p < 0.01, compared to baseline). Direct comparison between the 2 groups showed a significant benefit for the RTX group in FVC (p = 0.013). Improvement of skin thickening was found in both the RTX and the standard treatment group; however, direct comparison between groups strongly favored RTX at all-time points. Adverse events were comparable between groups. Conclusions Our data indicate that RTX has a beneficial effect on lung function and skin fibrosis in patients with SSc. Randomized controlled studies are highly needed. © 2017 Elsevier Inc

On the response of Y3Al5O12 : Ce (YAG : Ce) powder scintillating screens to medical imaging X-rays

The aim of this study was to examine Y3Al5O12:Ce (also known as YAG:Ce) powder scintillator under X-ray imaging conditions. This material shows a very fast scintillation decay time and it has never been used in X-ray medical imaging. In the present study various scintillator layers (screens) with coating thickness ranging from 13 to 166 mg/cm(2) were prepared in our laboratory by sedimentation of Y3Al5O12: Ce powder. Optical emission spectra and light emission efficiency (spectrum area over X-ray exposure) of the layers were measured under X-ray excitation using X-ray tube voltages (80-120 kVp) often employed in general medical radiography and fluoroscopy. Spectral compatibility with various optical photon detectors (photodiodes, photocathodes, charge coupled devices, films) and intrinsic conversion efficiency values were determined using emission spectrum data. In addition, parameters related to X-ray detection, energy absorption efficiency and K-fluorescence characteristic emission were calculated. A theoretical model describing radiation and light transfer through scattering media was used to fit experimental data. Intrinsic conversion efficiency (eta(C) approximate to 0.03-0.05) and light attenuation coefficients (sigma approximate to 26.5 cm(2)/g) were derived through this fitting. Y3Al5O12:Ce showed peak emission in the wavelength range 530-550 nm. The light emission efficiency was found to be maximum for the 107 mg/cm(2) layer. Due to its “green” emission spectrum, Y3Al5O12:Ce showed excellent compatibility (of the order of 0.9) with the sensitivity of many currently used photodetectors. Taking into account its very fast response Y3Al5O12:Ce could be considered for application in X-ray imaging especially in various digital detectors. (C) 2004 Published by Elsevier B.V

Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients

Background: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. Methods: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. Results: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR&lt;3.2) while 43% did not (34%: moderate disease activity: DAS28ESR ⩾3.2 to &lt;5.1, 9%: high disease activity, DAS28ESR ⩾5.1). By multivariate analysis, male sex was positively associated with LDA [odds ratio (OR) = 2.29 p &lt; 0.001] whereas advanced age (OR = 0.98, p = 0.005), high Health Assessment Questionnaire (HAQ) score (OR = 0.57, p &lt; 0.001), use of GCs (OR = 0.75, p = 0.037) or ⩾2 bDMARDs (OR = 0.61, p = 0.002), high co-morbidity index (OR = 0.86, p = 0.011) and obesity (OR = 0.62, p = 0.002) were negative predictors of LDA. During follow-up, among active patients (DAS28ESR &gt;3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. Conclusion: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors. © The Author(s), 2020

Treatment patterns and achievement of the treat-to-target goals in a real-life rheumatoid arthritis patient cohort: data from 1317 patients

Background: Data regarding the real-life predictors of low disease activity (LDA) in rheumatoid arthritis (RA) patients are limited. Our aim was to evaluate the rate and predictors of LDA and treatment patterns in RA. Methods: This was a multicenter, prospective, RA cohort study where patients were evaluated in two different time points approximately 12 months apart. Statistical analysis was performed in order to identify predictors of LDA while patterns of disease-modifying anti-rheumatic drug [DMARDs; conventional synthetic (csDMARD) or biologic (bDMARD)] and glucocorticoid (GC) use were also recorded. Results: The total number of patients included was 1317 (79% females, mean age: 62.9 years, mean disease duration: 10.3 years). After 1 year, 57% had achieved LDA (DAS28ESR3.2), 21% initiated (among csDMARDs users) and 22% switched (among bDMARDs users) their bDMARDs. Conclusion: In a real-life RA cohort, during 1 year of follow-up, 43% of patients do not reach treatment targets while only ~20% of those with active RA started or switched their bDMARDs. Male sex, younger age, lower HAQ, body mass index and co-morbidity index were independent factors associated with LDA while use of GCs or ⩾2 bDMARDs were negative predictors. © The Author(s), 2020