Possible Implication of Red Blood Cells in the Prothrombotic Risk in Early Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune inflammatory disease that can be considered as a prothrombotic state1. A great number of studies have investigated the possible role of reactive oxygen species (ROS) in the etiology and pathogenesis of this disease. The presence of large amounts of superoxide radicals and hydrogen peroxide produced by activated neutrophils has been reported in the synovial fluid of patients with RA. This may cause lipid peroxidation that yields a wide variety of end products, including malondialdehyde (MDA), a known marker of oxidative stress. These products are therefore transported from the synovial fluid to the blood circulation system2. Considering that elevated levels of MDA have been observed in the blood plasma of patients with RA2, the aim of this pilot study was to investigate whether the elevated levels of plasmatic MDA could be associated with a modification of the total antioxidant capacity (TAC) of blood plasma that is usually indicative of a “systemic” oxidative imbalance3. In addition, in view of their activity as redox effectors or scavengers4, as well as determinants of thrombus formation5, we evaluated red blood cell (RBC) features in terms of their redox state and lifespan marker molecules

Pain in systemic connective tissue diseases

Pain is frequent in patients with connective tissue diseases (CTDs), particularly those affected by systemic sclerosis (SSc) and systemic lupus erythematosus (SLE) in which it is virtually ubiquitous and can have different causes. The SLE classi fi cation criteria include pain associated with musculoskeletal involve- ment, which are frequently the initial symptom of SLE and can include arthralgia, arthritis and/or myalgia. Chronic widespread pain, the cornerstone of fi bromyalgia (FM), is also frequently associated with CTDs. Chronic pain has a considerable impact on mental health, and the professional and family lives of patients. It can be due to many disorders, but there are few reports concerning its prevalence during the course of other diseases. It is essential to identify the origin of pain in CTDs in order to avoid dangerous over-treatment in patients with co-existing widespread pain. Effective pain management is a primary goal of patient care, although it has not been investigated in detail in patients with SSc

Building bridges between doctors and patients: the design and pilot evaluation of a training session in argumentation for chronic pain experts

Shared decision-making requires doctors to be competent in exchanging views with patients to identify the appropriate course of action. In this paper we focus on the potential of a course in argumentation as a promising way to empower doctors in presenting their viewpoints and addressing those of patients. Argumentation is the communication process in which the speaker, through the use of reasons, aims to convince the interlocutor of the acceptability of a viewpoint. The value of argumentation skills for doctors has been addressed in the literature. Yet, there is no research on what a course on argumentation might look like. In this paper, we present the content and format of a training session in argumentation for doctors and discuss some insights gained from a pilot study that examined doctors' perceived strengths and limitations vis-à-vis this training

Popular Magazines in Fascist Italy, 1934 - 1943

The dissertation examines the field of popular magazines in 1930s Italy, by first examining the broad field of magazine production under Fascism and then undertaking three case studies of individual magazines – L’Avventuroso (1934 – 1943), Omnibus (1937 – 1939), and Grazia (1938 –) – in order to build an in-depth analysis of the production, format and reception of the popular press in this period. In the interwar years, and in particular from 1934 onwards, innovative printing techniques and production methods transformed the periodical press worldwide. The emergence of new forms of illustrated magazines expanded the readership and started a process of standardisation and mass production of periodicals. The dissemination in Italy of the rotocalco, a new product aimed at the masses that was developed in the 1930s, offers a particularly interesting starting point for analysing the development of a modern Italian mass press and culture within the peculiar dynamics of a controlling Fascist regime and the mixed national and international forces that shaped it. Modern Italian magazines developed in dialogue with foreign industries, imitating models from abroad and adapting them to the Italian culture. The development of popular press in the 1930s represented a challenge for the Fascist regime, which approached it both as a threat and an opportunity to shape Italian popular culture. Through the analysis of three case studies, each from a key sector of popular press – comics, general cultural magazines, and women's magazines – and each produced by one of the three main publishing companies in the field – Nerbini, Rizzoli, and Mondadori – the dissertation aims to provide a detailed picture of the development of mass print culture in Italy during Fascism. The analysis provides examples of the impact of and cracks in Fascist censorship and cultural autarchy on the periodical press and argues that the Italian popular press developed in dialogue with European and American culture, which influenced both the form and content of rotocalchi, reinterpreting and adapting these models to Italian standards and to the constrictions of Fascist control

Pain biomarkers in fibromyalgia syndrome. current understanding and future directions

Fibromyalgia is a complex and heterogeneous clinical syndrome, mainly characterized by the presence of widespread pain, possibly associated with a variety of other symptoms. Fibromyalgia can have an extremely negative impact on the psychological, physical and social lives of people affected, sometimes causing patients to experience dramatically impaired quality of life. Nowadays, the diagnosis of fibromyalgia is still clinical, thus favoring diagnostic uncertainties and making its clear identification challenging to establish, especially in primary care centers. These difficulties lead patients to undergo innumerable clinical visits, investigations and specialist consultations, thus increasing their stress, frustration and even dissatisfaction. Unfortunately, research over the last 25 years regarding a specific biomarker for the diagnosis of fibromyalgia has been fruitless. The discovery of a reliable biomarker for fibromyalgia syndrome would be a critical step towards the early identification of this condition, not only reducing patient healthcare utilization and diagnostic test execution but also providing early intervention with guideline-based treatments. This narrative article reviews different metabolite alterations proposed as possible biomarkers for fibromyalgia, focusing on their associations with clinical evidence of pain, and highlights some new, promising areas of research in this context. Nevertheless, none of the analyzed metabolites emerge as sufficiently reliable to be validated as a diagnostic biomarker. Given the complexity of this syndrome, in the future, a panel of biomarkers, including subtype-specific biomarkers, could be considered as an interesting alternative research area

Mucosa-Environment Interactions in the Pathogenesis of Rheumatoid Arthritis

Mucosal surfaces play a central role in the pathogenesis of rheumatoid arthritis (RA). Several risk factors, such as cigarette smoking, environmental pollution, and periodontitis interact with the host at the mucosal level, triggering immune system activation. Moreover, the alteration of microbiota homeostasis is gaining increased attention for its involvement in the disease pathogenesis, modulating the immune cell response at a local and subsequently at a systemic level. Currently, the onset of the clinical manifest arthritis is thought to be the last step of a series of pathogenic events lasting years. The positivity for anti-citrullinated protein antibodies (ACPAs) and rheumatoid factor (RF), in absence of symptoms, characterizes a preclinical phase of RA namely systemic autoimmune phase- which is at high risk for disease progression. Several immune abnormalities, such as local ACPA production, increased T cell polarization towards a pro-inflammatory phenotype, and innate immune cell activation can be documented in at-risk subjects. Many of these abnormalities are direct consequences of the interaction between the environment and the host, which takes place at the mucosal level. The purpose of this review is to describe the humoral and cellular immune abnormalities detected in subjects at risk of RA, highlighting their origin from the mucosa environment interaction

Response to 'Is there a future for hydroxychloroquine/chloroquine in prevention of SARS-CoV-2 infection (COVID-19)?' by Moiseev <i>et al</i>

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Hypovitaminosis D in recent onset rheumatoid arthritis is predictive of reduced response to treatment and increased disease activity: a 12 month follow-up study.

BACKGROUND: Vitamin D displays immunomodulatory activities and has been proposed as a potential player in the pathogenesis of rheumatoid arthritis (RA). A negative association between serum 25(OH) vitamin D levels and RA activity was demonstrated but longitudinal studies investigating the role of vitamin D levels in predicting RA activity and response to treatment are lacking. Therefore, this study was designed to test the hypothesis of an association between serum 25(OH) vitamin D levels at RA diagnosis and disease activity evaluated by clinimetric, laboratory and ultrasound (US) parameters and to detect the prevalence of remission and response to treatment after 12 months follow-up. METHODS: This is a longitudinal, retrospective study on data obtained from thirty-seven patients with early RA treatment-naïve. Serum inflammatory markers, auto-antibodies and 25(OH) vitamin D levels were obtained at baseline. Hypovitaminosis D was diagnosed for 25(OH) vitamin D levels < 20 ng/ml. Tender joint count (TJCs), swollen joint count (SJCs), Visual Analog Scales (VAS), Disease Activity Score (DAS) 28 score were assessed at baseline and 12 months after diagnosis. Joints synovitis and power-Doppler were evaluated at baseline and 12 months later. RESULTS: At baseline mean 25(OH) vitamin D levels were 24.4 ± 11.9 ng/ml; 35% of study subjects had hypovitaminosis D which strongly associated with higher RA activity and lower prevalence of remission and response to treatment (all p-values < 0.001). The percentage of patients not presenting a reduction of the US synovitis score after 12 months from diagnosis was significantly higher among patients with hypovitaminosis D than in those with normal serum 25(OH) vitamin D at baseline. CONCLUSIONS: In patients with early RA and basal hypovitaminosis D after 12 months follow-up reduction of disease activity and percentage of remission and response to treatment were significantly lower than those observed in patients with normal vitamin D levels. These results provide further support to the immunomodulatory action of vitamin D in RA and suggest a role of basal vitamin D status in the prediction of disease evolution. Vitamin D measurement and possibly vitamin D supplementation should be considered an additional option in the management of early RA patients

Association between antibodies to carbamylated proteins and subclinical atherosclerosis in rheumatoid arthritis patients

BACKGROUND: Rheumatoid arthritis (RA) patients carry a high risk of cardiovascular morbidity and mortality. The excess of cardiovascular disease cannot be entirely explained by traditional risk factors and the immune system contributes to the development of atherosclerosis. Moreover, post-translational modifications such as citrullination and carbamylation have been linked to inflammation and atherosclerosis. Anti-carbamylated proteins antibodies (anti-CarP) are a new subset of autoantibodies identified in RA patients. This study aimed to investigate a possible association between anti-CarP and subclinical atherosclerosis in RA patients. METHODS: We enrolled RA patients and normal healthy controls (NHS) without known cardiovascular risk factors or heart disease. Cardiovascular risk was assessed using the Modified Systemic Coronary Risk Evaluation (mSCORE). Anti-CarP were investigated by a solid phase "home-made" ELISA. Anti-citrullinated protein antibodies (ACPA) and Rheumatoid Factor (RF) were investigated by ELISA assays. Subclinical atherosclerosis was evaluated by brachial artery Flow-Mediated Dilatation (FMD) and Carotid Intima-Media Thickness (c-IMT) while arterial stiffness by Ankle-Brachial Index (ABI) and Cardio-Ankle Vascular Index (CAVI). RESULTS: We enrolled 50 RA patients (34 F and 16 M, mean age 58.4 ± 13.1 years, mean disease duration 127 ± 96.7 months) and 30 age and sex matched NHS. According to the mSCORE, 58% of patients had a low risk, 32% a moderate and 8% a high risk for cardiovascular disease. FMD was significantly lower in RA patients than in NHS (5.6 ± 3.2 vs 10.7 ± 8.1%; p < 0.004) and CAVIs significantly higher in a RA patients compared to NHS (left CAVI 8.9 ± 1.7 vs 8.1 ± 1.5; p < 0.04 for and right CAVI 8.8 ± 1.6 vs 8.0 ± 1.4; p < 0.04 for the). ABI and c-IMT did not differ between the two populations. The multivariate regression analysis showed a significant association of anti-CarP antibodies with FMD, left and right CAVI and both c-IMT (r = 1.6 and p = 0.05; r = 1.7 and p = 0.04; r = 2.9 and p = 0.05; r = 1.5 and p = 0.03; r = 1.1 and p = 0.03 respectively). CONCLUSIONS: This study confirms that RA patients, without evidence of cardiovascular disease or traditional risk factors, have an impaired endothelial function. Moreover, we found an association with anti-CarP antibodies suggesting a possible contribution of these autoantibodies to endothelial dysfunction, the earliest stage of atherosclerosis. Besides ultrasound assessment, anti-CarP should be assessed in RA patients and considered an additional cardiovascular risk factor