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

Unconventional monitoring methods. can BIS® predict airway obstruction?

Anaesthesia depth assessment is still under discussion despite several monitors available to this day (BIS®, Entropia®, SED-line®, NarcoTrend® etc). Since manufacturer introduced the BIS device in 1994, a huge debate raised about its real usefulness in monitoring anaesthesia depth and preventing awareness. Just to mention the main studies that have been published about BIS, in 2004 the "B-Aware Trial" showed better outcomes for adult patients at high risk of awareness1; in 2008 the "B-Unaware Trial" demonstrated no differences in awareness incidence when BIS is compared to end-tidal anaesthetic gas (ETAG) measurement2. In 2007, Manyam discussed the need to maintain BIS reading below 60, demonstrating how BIS values are minimally influenced by the addition of opioids to general anaesthetics3. In 2011, the BAG-RECALL Research Group was unable to prove superiority of BIS-guided anaesthesia versus ETAG-guided anaesthesia4. More recently, Mashour et al. found no differences in the incidence of awareness in a study with more than 21.000 patients5. A 2014 Cochrane review confirmed the previous trend, finding inconclusive evidence of intraoperative awareness protection6. In addition, in 2015, the BJA released a special issue about memory and awareness, from which two studies are worth mentioning: a study by Schuller, in which BIS monitor was used in awake volunteers receiving neuromuscular blocking agents, showing unreliable values7, and a review on "controversies and non-controversies" in intraoperative awareness

Decrease of Asymmetric Dimethyl Arginine After Anti-TNF Therapy in Patients with Rheumatoid Arthritis.

Postmarketing Phase IV Chronic inflammatory diseases such as rheumatoid arthritis (RA) are associated with accelerated atherosclerosis and increased morbidity and mortality for cardiovascular events. Asymmetric dimethyl arginine (ADMA), an endogenous inhibitor of nitric oxide synthase, contributes to the impairment of endothelial function, the earlier and reversible stage of atherosclerotic plaque formation. Since tumor necrosis factor (TNF) inhibits enzymatic degradation of ADMA, anti-TNF agents could restore its physiological level. The aim of this study was to investigate the effect of TNF inhibitors on ADMA serum levels in patients with RA. Our results suggest a possible effect of anti-TNF drugs on ADMA serum levels; longer studies would be necessary to confirm the role ADMA in assessing cardiovascular risk in RA

Gender differences in the revised fibromyalgia Impact questionnaire. a pilot study

Fibromyalgia (FM) is a chronic syndrome characterised by widespread musculoskeletal pain associated with symptoms such as fatigue, sleep disturbances and cognitive impairment. Prevalence is higher in females but the application of the 2010/2011 and 2016 revision of the American College of Rheumatology (ACR) criteria reduced prevalence differences and the actual female:male ratio is approximately 3:1. Even if lately some studies have been conducted regarding FM gender differences, disease severity is still assessed using questionnaires, such as the Revised Fibromyalgia Impact Questionnaire (FIQR), designed and validated through a predominantly female sample. The aim of this pilot study was to compare the 21 items of the FIQR among male and female patients in order to evaluate the possible existence of a gender bias. Methods In this case-control study, consecutive patients with a diagnosis of FM (2016 ACR criteria) were asked to answer an online survey, including demographic characteristics, disease variables and the Italian version of the FIQR. Among the 544 patients that compiled the questionnaire, 78 patients, 39 males and 39 females, matched for age and disease duration, were consecutively enrolled in order to compare their FIQR scores. Results The univariate analysis showed that total FIQR scores and physical function domain scores were significantly higher in females and, among the 21 items of the FIQR, the female group obtained significantly higher scores in 6 of them. Our results showed that female patients obtain significantly higher scores in the FIQR total score and physical function domain score, in particular in 5 out of the 9 sub-items of the FIQR physical function domain. Conclusion These preliminary results indicate that the use of the FIQR as a severity index in male patients probably underestimates the disease impact in this group

Gender influence on clinical manifestations, depressive symptoms and brain-derived neurotrophic factor (BDNF) serum levels in patients affected by fibromyalgia

Introduction: OBJECTIVES: Fibromyalgia (FM) is a common rheumatic disorder characterized by chronic, widespread pain associated with several not painful symptoms. The contribution of gender to the manifestation of the disease may influence the higher prevalence of FM among women. In spite of this, how patients' gender influences the clinical manifestation of FM is still not well understood. The frequent association with neuropsychiatric symptoms raised the attention on the role of neurotrophins, including the brain-derived neurotrophic factor (BDNF) as potential biomarkers of the condition. Aims of the study were to evaluate the influence of gender on clinical manifestations and to investigate BDNF serum levels as a potential biomarker of FM. Methods: We consecutively enrolled 201 adult patients of both sexes diagnosed with FM. For each patient, we collected clinical and clinimetric data and, in a subgroup of 40 patients, we measured serum BDNF levels. BDNF levels have been measured also in 40 matched healthy controls (HC). Results: Several symptoms were significantly higher in women compared with men, including pain, fatigue, memory problems, tenderness, balance problems and sensitivity to environmental stimuli. On the contrary, men reported a significant higher frequency of coexisting depressive symptoms. BDNF levels were significantly lower in FM patients compared with HC, discriminating with good accuracy the condition. Conclusion: Gender influences FM clinical manifestations, with a higher prevalence of pain, fatigue and other common FM symptoms among women while higher frequency of neuropsychiatric symptoms among men. BDNF offers promises as a potential biomarker of the disease. Key Points • Gender-related differences in the clinical manifestations of FM may contribute to the higher prevalence of FM among females. Indeed, women show higher levels of pain and symptoms traditionally associated to FM, which are evaluated to establish the diagnosis according to the clinical criteria. • The new insights into the pathogenesis of the disease raised the attention on the role of brain mediators in FM. Among these, BNDF shows potential as a diagnostic biomarker