Search Results (34)

Osteoarthritis (OA) is the most common chronic arthropathy worldwide. OA synovitis is a common feature that predicts the development and progression of symptoms and joint damage. Although the OA synovium is a target for novel therapies, the development of ex vivo models remains an area requiring further research. We aim to develop a 3D tissue explant culture model of human OA synovium that preserves the architecture and cellular heterogeneity of the original tissue in vitro. We derived tissue explant models from seven patients with OA and followed the culture for up to 10 days, assessing their morphology and cellular composition by immunohistochemistry (IHC) and flow cytometry, respectively. IHC analysis of explant cultures showed that tissue integrity and viability were maintained in our in vitro system. Furthermore, cellular heterogeneity was essentially unchanged when considering CD4⁺ T cells, CD8⁺ T cells, and myeloid fractions in our model. No significant variation was observed in the CD90⁺ and CD90^-CD55⁺ fractions, which also maintained an activated state as indicated by high levels of FAP expression. An ex vivo OA synovial tissue explant model can maintain pathological tissue integrity for 10 days in culture. This simple and reliable culture system may be useful for analyzing the pathogenesis of OA disease and for the development and testing of therapeutic drugs. Full article

Introduction: Systemic lupus erythematosus (SLE) is associated with infection-related morbidity. The risk of adverse outcomes secondary to infections was exacerbated during the recent COVID-19 pandemic, prompting mass vaccination with the novel mRNA-based and viral-vectored vaccines. Limited data exist on the long-term impact of vaccination in patients with SLE. Methods: A post-vaccine group (PVG, n = 284) from a multicentric cohort of vaccinated patients with SLE from six tertiary referral centres in Northen Italy was compared with a control group (CG, n = 223) of similar demographics observed in the 2015–2019 period to investigate survival, hospitalisation, pregnancy, disease flare, disease progression, infection, and chronic complication accrual rates. Results: We did not observe excess SLE flares, SLE progression, hospitalisation, or pregnancy complications in the PVG. Cardiovascular complications due to comorbidities or to SLE were lower in the PVG than in the CG. Infections were more frequent in the PVG, related to COVID-19 in half of the cases, and were associated with SLE flares. Conclusions: Taken together, these data indicate that anti-COVID-19 vaccines are safe in the long-term when administered to patients with SLE. Stable, non-null rates of chronic comorbidity accrual and hospitalisation point out the existence of persistently unmet needs in patients with SLE. Full article

Background/Objectives: Psoriatic arthritis (PsA) is a chronic inflammatory condition that primarily affects the musculoskeletal system and skin. While biologic and targeted synthetic DMARDs have improved treatment, many patients still fail to achieve remission. Combining conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) with biologic (b) DMARDs or targeted synthetic (ts) DMARDs shows no added benefit over monotherapy with IL-17, IL-23 inhibitors, or JAK inhibitors, unlike TNFi, which benefit from csDMARD co-administration. Guselkumab (GUS) and risankizumab (RKZ) target IL-23 with high specificity. RCTs (DISCOVER 1 and 2, COSMOS) have confirmed GUS efficacy regardless of methotrexate (MTX) use, though liver toxicity was higher with MTX. Real-world data on GUS remain limited, with gaps in understanding its long-term effectiveness and drug survival. The aim of this study is to assess the following three points within a multicenter Italian real-life cohort of PsA patients treated with guselkumab (GUS) and followed for 12 months: (1) effectiveness and safety of GUS; (2) drug retention rate (DRR) and reasons for discontinuation; (3) impact of comorbidities on achieving minimal disease activity (MDA). Methods: This study utilized data from the GISEA registry, which includes centers in different parts of Italy (north, center, south, and islands), and included patients aged 18 and older diagnosed with PsA according to the CASPAR criteria. Results: Data on 170 PsA patients treated with GUS were collected. In the first 6 months, a prompt mean percentage improvement in all clinimetric indexes was observed compared to the baseline. At 6-month follow-up, ACR 20 was reached by 60% of patients, ACR 50 by 30%, ACR 70 by 15%, MDA by 28%, and DAPSA < 14 by 50% of patients in the overall group. Significant differences were found in the rate of ACR 50 in the bDMARD-naive group (50%) compared to one bDMARDs non-responder (NR) (8%) (p = 0.021). At 12-month follow-up, a notable gap was observed in the rate of patients reaching MDA between bDMARD-naive (60%) and one bDMARDs NR (22%) (p = 0.035) and between bDMARD-naive (60%) and ≥2 bDMARDs NRs (22%) (p = 0.024). By using multivariate binary logistic analysis, the predictors of reaching MDA at 12-month follow-up were naive bDMARDs (OR: 7.9, 95% CI: 1.3–44.8, p = 0.019) and a higher value of pGA at baseline (OR: 1.1, 95% CI: 1–1.5; p = 0.046). The presence of comorbidities, including fibromyalgia and obesity, did not seem to affect the reaching of MDA. At 12-month follow-up, the GUS retention rate was 76%, with a mean survival time of 10.5 months ± 0.2 (95% CI: 10–10.9). No significant differences in GUS survival time were found among bDMARD-naive, one bDMARDs NR, and ≥2 bDMARDs NR patients (in the latter, regardless of the previous mechanism of action: TNFi or other mechanism), as well as between patients treated with GUS in monotherapy and those treated in combination with csDMARDs. A low rate (17%) of discontinuation was found due to both primary NR and secondary NR. The high safety of GUS was recorded. In fact, discontinuation due to adverse events (all definable as minor) was observed in just 4% of patients. By using COX regression multivariate analysis, the factors associated with higher GUS discontinuation risk were a more severe baseline PASI (HR: 1.05, 95% CI: 1–1.1, p = 0.038) and higher baseline ESR (HR:1.06, 95% CI: 1–1.03, p = 0.05). Conclusions: Good performance of GUS was observed in both biologic-naive patients and those with failure of previous bDMARDs (regardless of the mechanism of action of the previous drug: TNFi or non-TNFi), presenting good persistence in therapy even when used as a third mechanism of action. Its high safety profile allows the use of GUS even in particularly complex patients. Full article

Background/Objectives: Pulmonary arterial hypertension (PAH) is a complication of systemic sclerosis (SSc), and several screening algorithms have been proposed for the early detection of PAH in SSc. This study aimed to evaluate the predicting values of the DETECT algorithm for SSc-PAH screening in patients with SSc undergoing right heart catheterization (RHC) based on 2015 ESC/ERS echocardiographic criteria in a real-life setting. Methods: Patients fulfilling the 2013 ACR/EULAR classification criteria for SSc and with available data for PAH screening with the DETECT algorithm and the 2015 ESC/ERS echocardiographic criteria were retrospectively enrolled from January to June 2017 and then followed for 5 years. Baseline and annual clinical, laboratory, and instrumental data were collected. Results: A total of 33 out of 131 (25%) patients were selected based upon the ESC/ERS echocardiographic criteria, but 30 (23%) underwent RHC, while 51 (39%) patients with SSc were positive based on the DETECT algorithm. PAH diagnosis was confirmed in 28/30 cases (93.3%). The DETECT algorithm showed lower specificity and positive predictive value (PPV) (p < 0.0001) but higher sensitivity and negative predictive value (NPV) (p < 0.0001) than ESC/ERS criteria. Notably, patients with SSc with a negative DETECT screening at baseline had a low probability of developing PAH during a 5-year follow-up (OR 0.15, 95% CI 0.10–0.60—p < 0.0001). Conclusions: The DETECT algorithm has proven to be an easy, fast, and inexpensive tool for screening PAH in patients with SSc. Overall, a low probability of PAH using DETECT is highly predictive of a good prognosis. Full article

The diagnosis of juvenile idiopathic arthritis (JIA) is often entrusted to the pediatric rheumatologist specialist. Timely referral to a specialized center is crucial. This study aims to assess the consultation and investigation patterns of patients with joint complaints before rheumatology referral. This longitudinal cohort study included patients with joint complaints who were referred to the Pediatric Rheumatology Unit. The cohort included 301 patients (58% female), 50 of them (17%) diagnosed with JIA. Compared to patients with orthopedic conditions or functional diseases, JIA patients had seen more specialists (p < 0.01) and received a quicker diagnosis (p < 0.01). Patients with early JIA diagnosis (within 3 months from symptoms onset) were younger (8.46 vs. 11.5 years old; p = 0.04), more frequently female (78% vs. 47%, p = 0.03), and with higher erythrocyte sedimentation rate (ESR) values (37 vs. 9 mm/h; p = 0.02) than those diagnosed later. Patients with a late diagnosis of JIA had a significantly longer median time between the first healthcare visit and the PR referral (25 vs. 101 days; p < 0.01). The main contributor to diagnostic delay in JIA was the time required for PR referral after the first healthcare consult. Younger age, female sex, and higher ESR values were associated with earlier diagnosis of JIA. Full article

Background: An unexplained condition that follows transcatheter aortic valve implantation (TAVI) is platelet count reduction (PR). According to published research, patients with balloon-expandable valves (BEVs) had a greater PR than those with self-expandable valves (SEVs). Objectives: The purpose of this study was to investigate the incidence and clinical effects of PR following TAVI. Methods: In total, 1.122 adult TAVI patients were enrolled. Propensity score matching was carried out in a 1:1 ratio between patients with BEVs and those with SEVs. The analysis included changes in platelet count, in-hospital mortality, and early postoperative adverse events. Results: Notably, 632 patients were matched (BEV:316; SEV:316). All patients’ post-procedural platelet counts changed according to a parabolic curve, using a mixed regression model for repeated analyses (estimate = −0.931; standard error = 0.421; p = 0.027). The platelet count varied comparably in patients with BEVs and SEVs (estimate = −4.276, standard error = 4.760, p = 0.369). The average time for obtaining the nadir platelet count value was three days after implantation (BEV: 146 (108–181) vs. SEV: 149 (120–186); p = 0.142). Overall, 14.6% of patients (92/632) had post-procedural platelet count <100,000/µL. There was no difference between the two prosthesis types (BEV:51/316; SEV:41/316; p = 0.266). Thrombocytopenia was found to be significantly linked to blood product transfusions, lengthier stays in the intensive care unit and hospital, and in-hospital mortality. Conclusions: TAVI, irrespective of the type of implanted valve, is linked to a significant but temporary PR. Thrombocytopenia increases the risk of serious complications and in-hospital death in TAVI patients. To explore and clarify the causes and associated effects, further prospective research is necessary. Full article

OTX homeobox genes have been extensively studied for their role in development, especially in neuroectoderm formation. Recently, their expression has also been reported in adult physiological and pathological tissues, including retina, mammary and pituitary glands, sinonasal mucosa, in several types of cancer, and in response to inflammatory, ischemic, and hypoxic stimuli. Reactivation of OTX genes in adult tissues supports the notion of the evolutionary amplification of functions of genes by varying their temporal expression, with the selection of homeobox genes from the “toolbox” to drive or contribute to different processes at different stages of life. OTX involvement in pathologies points toward these genes as potential diagnostic and/or prognostic markers as well as possible therapeutic targets. Full article

Background: Platelet count reduction (PR) is a common but unclear phenomenon that occurs after aortic bioprosthesis valve implantation (bio-AVR). This study aimed to investigate the occurrence and clinical impact of PR in patients receiving stented, rapid deployment (RDV), or stentless bioprostheses. Methods: 1233 adult bio-AVR patients were enrolled. Platelet count variation, early post-operative adverse events, and in-hospital mortality were analysed. Results: 944 patients received a stented valve, an RDV was implanted in 218 patients, and 71 patients had a stentless bioprosthesis. In all groups, the platelet count at discharge was lower than the baseline values (p < 0.001). The percentage of PR was 27% in the stented group, 56% in the RDV group, and 55% in the stentless group. A higher platelet reduction, reaching the minimum platelet value, was observed in the RDV (mean: −30.84, standard error (SE): 5.91, p < 0.001) and stentless (mean: 22.54, SE: 9.10, p = 0.03) groups compared to the stented group. A greater PR occurred as the size of the bioprosthesis increased in RDV (p = 0.01), while platelet count variation was not directly proportional to the stented bioprosthesis size (p < 0.001). PR was not affected by cardiopulmonary bypass (mean: −0.00, SE: 0.001, p = 0.635) or cross-clamp (mean: −0.00, SE: 0.002, p = 0.051) times in any of the groups. RDV subjects experienced more in-hospital adverse events. PR was found to be associated with ischemic strokes in the overall population. Conclusions: Bio-AVR is associated with significant but transient PR. RDV patients more likely experience significant PR and related adverse clinical events. PR is associated with ischemic strokes, regardless of the bioprosthesis type. Full article

Several rheumatologic diseases are primarily distinguished by their involvement of bone tissue, which not only serves as a mere target of the condition but often plays a pivotal role in its pathogenesis. This scenario is particularly prominent in chronic inflammatory arthritis such as rheumatoid arthritis (RA) and spondyloarthritis (SpA). Given the immunological and systemic nature of these diseases, in this review, we report an overview of the pathogenic mechanisms underlying specific bone involvement, focusing on the complex interactions that occur between bone tissue’s own cells and the molecular and cellular actors of the immune system, a recent and fascinating field of interest defined as osteoimmunology. Specifically, we comprehensively elaborate on the distinct pathogenic mechanisms of bone erosion seen in both rheumatoid arthritis and spondyloarthritis, as well as the characteristic process of aberrant bone formation observed in spondyloarthritis. Lastly, chronic inflammatory arthritis leads to systemic bone involvement, resulting in systemic bone loss and consequent osteoporosis, along with increased skeletal fragility. Full article

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-related disease (COVID-19) has spread pandemically with high rates of morbidity and mortality. COVID-19 has also posed unprecedented challenges in terms of rapid development of pharmacological countermeasures to prevent or contrast SARS-CoV-2 pathogenicity. Anti-SARS-CoV-2 antiviral agents and monoclonal antibodies have been specifically designed to attenuate COVID-19 morbidity and prevent mortality in vulnerable subjects, such as patients with immune-mediated diseases, but evidence for the safe and effective use of these drugs in this latter population group is scarce. Therefore, we designed a retrospective, multicentre, observational, case-control study to analyse the impact of these treatments in COVID-19 patients with systemic lupus erythematosus (SLE), a paradigmatic, multi-organ autoimmune disease. We identified 21 subjects treated with antivirals and/or monoclonal antibodies who were matched with 42 untreated patients by age, sex, SLE extension and duration. Treated patients had higher baseline SLE disease activity index 2000 scores [SLEDAI-2K median (interquartile range) = 4 (1–5) vs. 0 (0–2); p = 0.009], higher prednisone doses [5 (0–10) mg vs. 0 (0–3) mg; p = 0.002], and more severe COVID-19 symptoms by a five-point World Health Organisation-endorsed analogue scale [1 (0–1) vs. 0 (0–1); p < 0.010] compared to untreated patients. There was no difference between groups in terms of COVID-19 outcomes and sequelae, nor in terms of post-COVID-19 SLE exacerbations. Three subjects reported mild adverse events (two with monoclonal antibodies, one with nirmatrelvir/ritonavir). These data suggest that anti-SARS-CoV-2 antivirals and monoclonal antibodies might be safely and effectively used in patients with SLE, especially with active disease and more severe COVID-19 symptoms at presentation. Full article

To our knowledge, no studies so far have investigated the role of pizza and its ingredients in modulating disease activity in rheumatoid arthritis (RA). We assessed this question via a recent cross-sectional study including 365 participants from Italy, the birthplace of pizza. Multiple robust linear and logistic regression models were fitted with the tertile consumption categories of each available pizza-related food item/group (i.e., pizza, refined grains, mozzarella cheese, and olive oil) as independent variables, and each available RA activity measure (i.e., the Disease Activity Score on 28 joints with C-reactive protein (DAS28-CRP), and the Simplified Disease Activity Index (SDAI)) as the dependent variable. Stratified analyses were carried out according to the disease severity or duration. Participants eating half a pizza >1 time/week (vs. ≤2 times/month) reported beneficial effects on disease activity, with the significant reductions of ~70% (overall analysis), and 80% (the more severe stratum), and the significant beta coefficients of −0.70 for the DAS28-CRP, and −3.6 for the SDAI (overall analysis) and of −1.10 and −5.30 (in long-standing and more severe RA, respectively). Among the pizza-related food items/groups, mozzarella cheese and olive oil showed beneficial effects, especially in the more severe stratum. Future cohort studies are needed to confirm this beneficial effect of pizza and related food items/groups on RA disease activity. Full article

Rheumatoid Arthritis (RA) is a systemic disease with many different clinical phenotypes. RA could be classified according to disease duration, seropositivity for rheumatoid factor (RF) and/or anti-citrullinated protein antibodies (ACPA), joint subtype, clinical behaviourbehavior and many other subgroups. In this review, we summarize and discuss the multifaceted aspects of RA, focusing on the relationship between autoimmunity status and clinical outcome, achievement of remission and influence on treatment response, from the 2022 International GISEA/OEG Symposium. Full article

Background: Chronic nonbacterial osteomyelitis (CNO) is a rare autoinflammatory bone disorder that mainly involves children and adolescents. The association with other inflammatory disorders, such as inflammatory bowel disease (IBD), psoriasis, and arthritis, has been reported in the literature. In particular, the relationship between bone and intestinal inflammation is still poorly understood. For this purpose, our review aims to describe the cases reported in the literature concerning this association and to compare them with data from our single-center cohort of patients. Methods: We conducted a literature review of published cases of CNO associated with IBD. Eligible articles were identified through a Medline search in the PubMed database until December 2022. We retrospectively reviewed medical records of patients with CNO referred to G. Pini Hospital and compared them with the literature-review-based cohort. Results: Fifty-seven patients with a defined diagnosis of CNO and associated IBD were described in the literature (female 55%). The median age of onset of the disease (CNO or IBD) was 11 years. In 32/53 (60%), a diagnosis of Crohn’s disease (CD) was made, while 18 (34%) patients were classified as suffering from ulcerative colitis (UC) and 3 (6%) from undifferentiated IBD. The diagnosis of CNO preceded the diagnosis of IBD in 59% of cases; while in 24%, IBD anticipated CNO; and in 17%, the two conditions appeared simultaneously. The median time between the two events was 24 months. In our Italian cohort (n = 23 patients), no diagnosis of IBD was made. No significant differences were found when comparing clinical and demographical characteristics of the Italian vs. review-based cohort, except for a significant involvement of rachis in the Italian group. Conclusions: The correlation between autoinflammatory bone disease and intestinal inflammation should be further investigated. It is essential to promote awareness among pediatric rheumatologists and gastroenterologists about this possible association to facilitate the diagnosis and better optimize treatment. Full article

Juvenile idiopathic arthritis (JIA) associated uveitis (JIA-U) is the most common extra-articular manifestation of JIA, affecting 10–15% of patients, especially in oligoarticular JIA where its course may be faint. Therefore, JIA-U is one of the most challenging pediatric uveitis, associated with major ocular morbidity and possibly leading to irreversible structural ocular damage and to vision-threatening complications. Adequate management is crucial for avoiding visual impairment complications. Since the introduction of biologic disease modifying anti-rheumatic drugs (bDMARDS), the visual prognosis of JIA-U has dramatically improved over the decades. Tumor necrosis factor-α (TNF-α) blockers are the most used bDMARDs in treating JIA-U with large evidence of efficacy. However, inadequate response to these agents, either due to intolerance or inefficacy, may be observed, requiring a swap to other classes of immunosuppressive agents, including anti-IL-6, anti-CD20, and, more recently, JAK inhibitors. Tocilizumab is a humanized monoclonal antibody to the interelukin-6 receptor preventing IL-6 from binding to its soluble and membrane-bound receptors. A growing body of literature provides promising results about the efficacy of intravenous and subcutaneous tocilizumab in the treatment of JIA-U. A narrative review of the literature on this topic will improve our knowledge on the potential use of tocilizumab in JIA-U. Full article

Spondyloarthritis (SpA) contemplates the inflammatory involvement of the musculoskeletal system, gut, skin, and eyes, delineating heterogeneous diseases with a common pathogenetic background. In the framework of innate and adaptive immune disruption in SpA, neutrophils are arising, across different clinical domains, as pivotal cells crucial in orchestrating the pro-inflammatory response, both at systemic and tissue levels. It has been suggested they act as key players along multiple stages of disease trajectory fueling type 3 immunity, with a significant impact in the initiation and amplification of inflammation as well as in structural damage occurrence, typical of long-standing disease. The aim of our review is to focus on neutrophils’ role within the spectrum of SpA, dissecting their functions and abnormalities in each of the relevant disease domains to understand their rising appeal as potential biomarkers and therapeutic targets. Full article