Tra sostenibilità sociale e benessere soggettivo. Lo spazio del lavoro dignitoso

Sustainability and Well-being. The Key of Decent Work as Cornerstone of Human Development. Sustainability is the mainstream issue of this century, while sustainable human development leans mainly on quality of life and subjective well-being for the entire mankind. This study introduces in synthesis the concept of sustainability It proceeds describing fundamental tools and methodologies, adopted in international contexts, to measure subjective well-being. The underlying idea is that subjective well-being is strictly connected to social relations and to social identity in particular. One of the domains in which the concept of identity and the goal of social sustainability are strongly related is decent work. Decent work is a multidimensional concept. This study describes some different sets of indicators and some data concerning work conditions in the world. Two operative chapters are devoted to subjective well-being indicators in official statistical surveys. The first describes the methodological approaches. The second presents the statistical analyses and some results. In particular there is an application of a synthesis methodology to ordinal variables based on discrete mathematics. The analyses explore available contents in the official statistics and investigate the presence of hidden information not yet exploited. The last chapter reaffirms the concept of identity and its link with the meaning of work and subjective and social well-being. It briefly introduces an experience of training and motivational intervention in a social cooperative

Dissecting the contribution of B cells in an experimental model of rheumatoid arthritis

Rheumatoid Arthritis (RA) is a chronic systemic autoimmune disease characterised by extensive synovitis resulting in cartilage and bone erosions. Both the innate and adaptive immune pathways contribute to the initiation and the maintenance of the disease. Understanding the role of these pathways is central to develop new therapeutics. We have developed a murine model of RA where ovalbumin (OVA) specific Th1 cells induced a breach of self-tolerance and a transient monoarthritis. This thesis aimed firstly to create a model of chronic autoimmune polyarthritis and then to investigate the contribution of B cells and innate inflammation to the induction of arthritis. Relapse of arthritis was associated with the nature of the antigen (OVA) employed and the route of administration. The analysis of collagen specific B cell response revealed that anti-type II collagen antibodies titres rise during the induction of the relapse of arthritis and that they were directed against the epitope U1. Although typical RA autoantibodies were detected in OVA-mediated arthritis, a mild arthritis could be elicited in absence of antigen presenting B cells and in complete absence of mature B cells. B cells were not necessary in the induction of pathology even though their presence was associated with a higher joint histology score. Finally, this thesis describes that an innate inflammatory stimulus, such as LPS, elicited joint pathology but was insufficient to breach B and T self-tolerance. On the contrary, antigen-specific T cell activation led to arthritis and the production of several autoantibodies typical of RA. The relapse and spread of arthritis developed in this thesis provides a useful tool to investigate the contribution of the innate and adaptive immune pathways in the development of autoreactive responses. A better understanding of these mechanisms will hopefully help to design new therapeutic intervention aiming to re-establish immunological tolerance

Overview on the Link Between the Complement System and Auto-Immune Articular and Pulmonary Disease

Complement system (CS) dysregulation is a key factor in the pathogenesis of different autoimmune diseases playing a central role in many immune innate and adaptive processes. Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by ta breach of self -tolerance leading to a synovitis and extra-articular manifestations. The CS is activated in RA and seems not only to mediate direct tissue damage but also play a role in the initiation of RA pathogenetic mechanisms through interactions with citrullinated proteins. Interstitial lung disease (ILD) represents the most common extra-articular manifestation that can lead to progressive fibrosis. In this review, we focused on the evidence of CS dysregulation in RA and in ILD, and highlighted the role of the CS in both the innate and adaptive immune responses in the development of diseases, by using idiopathic pulmonary fibrosis as a model of lung disease. As a proof of concept, we dissected the evidence that several treatments used to treat RA and ILD such as glucocorticoids, pirfenidone, disease modifying antirheumatic drugs, targeted biologics such as tumor necrosis factor (TNF)-inhibitors, rituximab, tocilizumab, and nintedanib may act indirectly on the CS, suggesting that the CS might represent a potential therapeutic target in these complex diseases

Identification of the Minimal Disease Activity Domains Achieved Based on Different Treatments in Psoriatic Arthritis

Introductionthe aim of this work is to characterize which minimal disease activity (MDA) domains are mainly achieved, based on different treatments, in psoriatic arthritis (PsA) patients. Moreover, the association between MDA achievement and the different treatment groups was assessed.MethodsWe conducted a cross-sectional analysis of two longitudinal PsA groups. Inclusion criteria were: age & GE; 18 years, PsA diagnosis, stable treatment for at least 6 months. patients were grouped depending on the therapy: group 1: non-steroidal anti-inflammatory drugs (NSAIDs)/cyclooxygenase 2 inhibitors (COX2i)/steroids, group 2: conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), group 3: tumor necrosisfFactor & alpha; inhibitors (TNFi), group 4: interleukin inhibitors (IL)12-23i or IL-23i, group 5: IL-17i, group 6: phosphodiesterase 4 inhibitors (PD4i). For each group, the achieved domains based on therapy were assessed. Multivariate logistic regression analysis was performed to assess the association between the treatment groups and the MDA achievement.resultsA total of 220 patients were enrolled, and MDA was achieved in 45.8% of them. In all treatment groups, the first MDA domains achieved were: body surface area & LE; 3, swollen joint count & LE; 1 and Leeds Enthesitis Index & LE; 1, while MDA domains less frequently achieved were Patient Global Assessment (PtgA) & LE; 2 cm and pain on visual analogue scale & LE; 1.5 cm. The logistic regression analysis showed higher odds ratios for the achievement of the MDA in those patients in groups 3 and 4.ConclusionsIn each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need.Due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA.ConclusionsIn each treatment group, MDA domains less frequently achieved were PtGA and pain, suggesting that "patient-driven domains" are still an unmet need.due to the study design and the low number of patients in some groups, it is not possible to clearly define which MDA domain was achieved or not based on treatment; however, it seems that some differences could be present. If larger and prospective studies confirm our preliminary results, we could move toward a personalized/domain treatment approach in PsA

Failure and multiple failure for disease modifying antirheumatic drugs in rheumatoid arthritis: Real-life evidence from a tertiary referral center in Italy

Background rheumatoid arthritis (RA) is a chronic inflammatory disease with a heterogeneous treatments' clinical response. goals of treatment are remission and low disease activity, which are not achieved in all patients despite the introduction of early treatment and the treat to target strategy. ObjectiveTo investigate the causes of disease-modifying antirheumatic drugs (DMARDs) discontinuation and treatment failure and multiple failure for inefficacy, and to identify possible failure predictors' according to RA patient characteristics in a real-world setting. methods718 RA patients were retrospectively evaluated. Conventional synthetic (cs) and biologic (b)DMARDs treatments line/s, effectiveness, and reasons of discontinuations were evaluated. patients failing to at least two csDMARDs or bDMARDs' drug for inefficacy were defined "csDMARDs multifailure" and "bDMARDs multifailure", respectively. Discontinuation of at least two cs- and bDMARDs was termed "global multifailure". ResultsIn total, 1422 csDMARDs and 714 bDMARDs treatment were analysed. Causes of csDMARDs discontinuation were intolerance (21.8%), inefficacy (20.2%), acute adverse reactions (5.3%) and severe infections (0.6%) while csDMARDs multifailure for inefficacy was observed in 5.7% of cases. reasons of bDMARDs withdrawal were inefficacy (29%), intolerance (10.0%), acute adverse reaction (6.3%) and severe infections (1.5%). Altogether, 8.4% of patients were bDMARDs multifailure for inefficacy while 16.6% were global multifailure. longstanding disease (>= 12 months) and smoke habit, resulted as positive predictor of csDMARDs failure (OR 2.6 and OR 2.7, respectively). thyreopathy was associated with both csDMARDs failure and global multifailure (OR 2.4 and OR 1.8, respectively). Higher prevalence of failure to at least one bDMARDs and global multifailure was detected in female than male (OR 2.3 and OR 2, respectively). conclusionsdifferent causes of drug discontinuation were observed on DMARDs treatments. demographic and clinical features were identified as possible predictors of both cs- and bDMARDs treatment failure and multiple failure, underlining the need of a more personalized therapeutic approach to achieve treatment targets

What's new and what's next for biological and targeted synthetic treatments in psoriatic arthritis?

introductionpsoriatic arthritis (PsA) is a chronic arthritis typically associated with cutaneous psoriasis (PsO). Its pathogenesis is connected to an innate and acquired immune response, as well as genetic risk alleles. the extent of immunopathogenic mechanisms and the heterogenicity of clinical manifestation make the identification of patient-targeted therapies a critical issue, and the treatment decision challenging in patients' management.areas coveredThis review includes a brief overview of biological and small-molecule therapies, focusing on evidence from clinical trials and real-world data that support their use in PsA. We summarize novel and future possible therapeutic strategies, the importance that comorbidities have on selection of therapy and discuss the adverse event of each drug. relevant papers for up to 1 august 2022 (trials, real-life studies, and reviews) regarding biologics and/or small molecules were summarized.Expert opinionIn recent years, the treatment of PsA has been revolutionized by new targeted therapies, which offer the opportunity to perform a tailored-tail management, considering risk factors, comorbidities, and the different PsA phenotypes. growing experience with these new agents allows novel treatment approaches that may improve clinical outcomes for PsA patients, in terms of remission/low disease activity and quality of life

Rheumatologist's Perspective on Non-Infectious Uveitis: Patterns from Tertiary Referral Rheumatologic Clinics in Italy

Non-infectious uveitis (NIU) can be an early or even the first extra-articular manifestation of systemic rheumatic diseases, or the first one; thus, rheumatologists are often involved in the diagnostic and therapeutic assessment of NIU. We evaluated 130 patients with a diagnosis of NIU who were admitted to two Italian rheumatologic clinics (Tor Vergata University Hospital in Rome, and Federico II University in Naples) from January 2018 to December 2021. Anterior uveitis (AU) occurred in 75.4% of patients, followed by posterior uveitis (PU, 21.5%); acute (54.6%) and recurrent (35.4%) NIU were more documented than chronic NIU (10%), and a bilateral involvement was observed in 38.7% of cases. Half of NIU cases were associated with spondyloarthritis (SpA); the remaining were affected by Behcet disease (BD)-related uveitis (13.9%) and idiopathic NIU (9.2%). HLA-B27(+) patients (34.8%) had a higher prevalence of anterior and unilateral NIU (p = 0.005) with acute course (p = 0.04) than HLA-B27(-) patients. On the contrary, HLA-B51(+) patients (19.6%) had mostly PU and bilateral NIU (p < 0.0001) and recurrent course (p = 0.04) than HLA-B51(-) patients. At the first rheumatologic referral, 117 patients (90%) received systemic treatments. Findings from this study demonstrate that rheumatologic referral has a pivotal role in the diagnostic work-up of NIU and may dramatically influence NIU-treatment strategies

Increased circulating levels and salivary gland expression of interleukin-18 in patients with Sjögren's syndrome: relationship with autoantibody production and lymphoid organization of the periductal inflammatory infiltrate

IL-18, an immunoregulatory and proinflammatory cytokine, has been shown to play an important pathogenic role in Th1-driven autoimmune disorders. In this study, we evaluated the circulating levels and salivary-gland expression of IL-18 in patients with Sjögren's syndrome (SS), a mainly Th1-mediated disease. IL-18 serum levels were measured by ELISA in 37 patients with primary SS, 42 with rheumatoid arthritis, and 21 normal controls. We demonstrated high IL-18 serum levels in SS, similar to those in rheumatoid arthritis patients and significantly higher than in controls (P < 0.01). In addition, IL-18 serum concentrations were significantly higher in anti-SSA/Ro(+ )and anti-SSB/La(+ )than in anti-SSA/Ro(- )and anti-SSB/La(- )SS patients (respectively, P = 0.01, P < 0.01). Serum IL-18 correlated strongly with anti-SSA/Ro (P = 0.004) and anti-SSB/La (P = 0.01) titers. Salivary gland IL-18 expression was investigated by single/double immunohistochemistry in 13 patients with primary SS and in 10 with chronic sialoadenitis, used as controls. The expression of IL-18 was also examined in periductal inflammatory foci in relation to the acquisition of features of secondary lymphoid organs such as T–B compartmentalization, formation of follicular dendritic cell networks, and presence of germinal-center-like structures. IL-18 expression in SS salivary glands was detected in 28 of 32 periductal foci of mononuclear cells (87.5%), while no IL-18 production by infiltrating cells was detected in patients with chronic sialoadenitis. Within the inflammatory foci, IL-18 immunoreactivity co-localized almost exclusively with CD68(+ )macrophages. In addition, IL-18 was found in 15 of 19 foci (78.9%) with no evidence of T–B cell compartmentalization (nonsegregated) but in 100% of the segregated aggregates, both in T- and B-cell-rich areas. Strikingly, IL-18 was strongly expressed by CD68(+ )tingible body macrophages in germinal-centre-like structures both in SS salivary glands and in normal lymph nodes. IL-18 expression was observed in the ducts of all SS biopsies but in only 4 of 10 patients with nonspecific chronic sialoadenitis (P < 0.01). This study provides the first evidence of increased circulating levels and salivary gland expression of IL-18 in SS, suggesting an important contribution of this cytokine to the modulation of immune inflammatory pathways in this condition

The Association Between Dyslipidemia and Lethality of Suicide Attempts: A Case-Control Study

Evidence supports the existence of an association between dyslipidemia, psychiatric disorders, and suicide risk due to the effects of altered lipid profiles on serotoninergic neuron membranes. The aim of this study was to investigate the differences in c-reactive protein (CRP), thyroid functioning, total cholesterol, high lipoprotein density cholesterol (HDL-c), low-lipoprotein density cholesterol (LDL-c), and triglycerides (TG) serum levels in low lethality (LLSA) vs. high lethality suicide attempters (HLSA) within 24 h from the suicide attempt and inpatients who never attempted suicide (NAS). After attempting suicide, subjects were admitted to the emergency ward of the IRCCS Ospedale Policlinico San Martino and later to the section of Psychiatry from 1st August 2013 to 31st July 2018. Socio-demographic and clinical characteristics, serum lipids profile, CRP, and thyroid functioning were collected. The sample consisted of 133 individuals with a HLSA, 299 subjects with LLSA, and 200 patients NAS. HLSA subjects were more likely to be males and diagnosed as having a bipolar disorder. Furthermore, HLSA subgroup showed significantly lower total cholesterol and LDL-c levels and higher CRP serum levels compared to LLSA and control group, respectively. LLSA subgroup showed higher HDL-c levels compared to HLSA subgroup (no differences between HLSA and control group were observed). Additionally, the control group reported higher triglycerides levels compared to patients admitted to psychiatric ward for a suicide attempt. Only male gender, having a diagnosis of bipolar disorder, lower total cholesterol, and higher CRP serum levels predicted HLSA. Investigating the relation between dyslipidemia and the severity of suicide attempts may contribute to reveal the complex determinants underlying at-risk behaviors such as suicide, thus playing a relevant role in the possible prevention of this disabling phenomenon

Relationship between retinal microvascular impairment and subclinical atherosclerosis in SLE

objectives: patients with SLE have higher cardiovascular (CV) risk compared with healthy controls (HC) and are characterised by accelerated atherosclerosis; intima media thickness (IMT), marker of subclinical atherosclerosis, is higher in patients with SLE than in HCs. Retinal microvascular impairment detected through optical coherence tomography angiography (OCTA) was investigated as a marker of systemic vascular involvement in SLE.the aim of the study was to evaluate the relationship between retinal vascular impairment and IMT in SLE. methods: cross-sectional study recruiting patients with SLE and HCs. Data of the study population were collected. CV risk was evaluated through the american college of cardiology/american heart association (ACC/AHA) guidelines, framingham and QRESEARCH risk estimator V.3 (QRISK3) scores. Both groups underwent OCTA and carotid ultrasound with IMT assessment.Statistical analysis was accomplished using Pearson/Spearman, t-test/Mann-Whitney or χ2 test. Variables statistically significant at univariate regression analysis were tested in an age-corrected and sex-corrected multivariate regression model. results: 43 patients with SLE and 34 HCs were recruited.patients with SLE showed higher triglycerides (p=0.019), triglycerides-glucose (TyG) Index (p=0.035), ACC/AHA guidelines (p=0.001), Framingham Risk Scores (p=0.008) and a reduced superficial (p&lt;0.001) and deep (p=0.005) whole retinal vessel density (VD) compared with HCs.In SLE univariate analysis, deep whole VD showed a negative correlation with IMT (p=0.027), age (p=0.001), systolic blood pressure (p=0.011), QRISK3 Score (p&lt;0.001), systemic lupus international collaborating clinics damage index (p=0.006) and apolipoprotein B (p=0.021), while a positive correlation was found with female sex (p=0.029). Age-adjusted and sex-adjusted multivariate analysis confirmed QRISK3 score (p=0.049) and IMT (p=0.039) to be independent risk factors for reduced retinal VD. conclusions: patients with SLE showed lower retinal VD and higher CV risk indicators compared with HCs. Among patients with SLE, QRISK3 Score and IMT were found to be independent risk factors for retinal vascular impairment, suggesting a role of OCTA in evaluating preclinical CV involvement in SLE. moreover, TyG index could represent a biomarker of CV risk in patients with SLE compared with HCs