Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs. © 2022 The Author(s

Investigational bispecific antibodies for the treatment of rheumatoid arthritis

Rheumatoid arthritis (RA) is an autoimmune disorder with a characteristic chronic inflammation of the synovium that may lead to the destruction of the joints in untreated patients. Interestingly, despite the availability of several effective treatments, many patients do not achieve remission or low disease activity or may experience disease relapse. Following the above unmet needs, bispecific antibodies (BsAbs) have emerged as a new approach to improve the disease’s treatment. BsAbs are designed to simultaneously target two different proteins involved in RA pathogenesis, leading to enhanced efficacy and reduced side effects compared to traditional monoclonal antibodies (mAbs). In this review, we discuss the development of BsAbs for RA treatment, including their mechanism of action, efficacy, and safety profile. We also deal with the challenges and future directions in this field. BsAbs show promise in preclinical and clinical evaluations for treating RA. Further research is needed to optimize design and dosage and identify ideal patient groups. BsAbs can benefit disease management and improve outcomes of RA patients.</p

Efficacy and safety of switching from infliximab to adalimumab: a comparative controlled study

OBJECTIVE: To describe the efficacy and safety of adalimumab in patients with rheumatoid arthritis (RA) who had previously discontinued infliximab treatment. METHODS: 24 patients with RA who discontinued treatment with infliximab (switchers) were treated with adalimumab (40 mg every 2 weeks, subcutaneously) for 12 months. The results were compared with those for 25 patients with RA receiving adalimumab who had not previously used an anti‐tumour necrosis factor α inhibitor (controls). Disease activity was measured with the 28 joint count Disease Activity Score (DAS28), and clinical response with the American College of Rheumatology (ACR) 20% response criteria. RESULTS: At baseline there were no differences in demographic, clinical, and laboratory features between the two groups. After 12 months' adalimumab treatment, clinical improvement was similar in both groups. More specifically, ACR 20% response criteria were achieved by 18/24 (75%) switchers and by 19/25 (76%) subjects in the control group. Four switchers discontinued the study—two because of adverse events and two because of lack of efficacy, while three control patients discontinued the study—one because of lack of efficacy and two owing to side effects. CONCLUSION: Adalimumab is a well tolerated and effective treatment for patients with RA, even when infliximab has been discontinued

Pelagic habitats in the Mediterranean Sea: A review of Good Environmental Status (GES) determination for plankton components and identification of gaps and priority needs to improve coherence for the MSFD implementation

At present there is no consistent approach for the definition of Good Environmental Status (GES) and targets in the Mediterranean Sea, especially for Biodiversity Descriptors, according to the Article 12 of the Marine Strategy Framework Directive (MSFD). The use of plankton indicators in the Mediterranean Sea refers mostly to pelagic habitats in coastal waters and to case studies connected with environmental pressures, e.g. in the Adriatic, Aegean etc. The aim of this review is to study the existing biodiversity indicators for different plankton groups in order to compare GES definitions for the Biodiversity Descriptor and identify the relevant gaps and priority needs to improve coherence for the MSFD implementation across the Mediterranean. For these purposes, we focus on plankton indicators for phytoplankton, zooplankton and prokaryotes. Regional conventions (OSPAR, HELCOM, Barcelona and Bucharest Conventions) have long considered phytoplankton as a key element for integrated assessment systems. Phytoplankton biomass, community composition, abundance, frequency and intensity of blooms are used for such assessment purposes. Chlorophyll a still remains the most widely used indicator mostly thanks to its time saving, cost-effective and reproducible analytical methods that provide easily comparable datasets. Despite some integrated indices proposed for phytoplankton in the literature at the Mediterranean level, a number of constrains still prevent their wide use. Regarding zooplankton communities, commonly used indicators have a taxonomic base while recently size structure and biomass can provide a valuable index of zooplankton population dynamics and ecosystem production. Jellyfish blooms’ occurrence and frequency are also considered important zooplankton indicators in specific areas, e.g. North Adriatic. Concerning the prokaryotes, so far MSFD takes into account only their pathogenic component. The revision of MSFD GES definitions shows that all Mediterranean MSs have defined GES at the Descriptor level (e.g. D1 Biodiversity), but our comparison of approaches shows a low level of coherence in GES related to pelagic habitats and plankton communities. Gaps mostly focus on the lack of thresholds and baselines for many biodiversity indicators, and on the scarcity of common and consistent methodological approaches for biodiversity assessment by the MSs. Suggestions to fill these gaps and inconsistencies among MSs include: integration of EU legislation and Regional Agreements and Conventions; targeting on priority species and habitats; testing of existing biodiversity indices with good performances in case studies; coordination and intercalibration actions for the establishment of threshold values and baselines; determination of common methodologies; undertaking of regular monitoring programs and impact assessment studies at regional and sub-regional levels

Primary Sj\uf6gren\u2019s Syndrome of Early and Late Onset: Distinct Clinical Phenotypes and Lymphoma Development

Objectives: To study the clinical, serological and histologic features of primary Sj\uf6gren\u2019s syndrome (pSS) patients with early (young 6435 years) or late (old 6565 years) onset and to explore the differential effect on lymphoma development. Methods: From a multicentre study population of 1997 consecutive pSS patients, those with early or late disease onset, were matched and compared with pSS control patients of middle age onset. Data driven analysis was applied to identify the independent variables associated with lymphoma in both age groups. Results: Young pSS patients (19%, n = 379) had higher frequency of salivary gland enlargement (SGE, lymphadenopathy, Raynaud\u2019s phenomenon, autoantibodies, C4 hypocomplementemia, hypergammaglobulinemia, leukopenia, and lymphoma (10.3% vs. 5.7%, p = 0.030, OR = 1.91, 95% CI: 1.11\u20133.27), while old pSS patients (15%, n = 293) had more frequently dry mouth, interstitial lung disease, and lymphoma (6.8% vs. 2.1%, p = 0.011, OR = 3.40, 95% CI: 1.34\u20138.17) compared to their middle-aged pSS controls, respectively. In young pSS patients, cryoglobulinemia, C4 hypocomplementemia, lymphadenopathy, and SGE were identified as independent lymphoma associated factors, as opposed to old pSS patients in whom SGE, C4 hypocomplementemia and male gender were the independent lymphoma associated factors. Early onset pSS patients displayed two incidence peaks of lymphoma within 3 years of onset and after 10 years, while in late onset pSS patients, lymphoma occurred within the first 6 years. Conclusion: Patients with early and late disease onset constitute a significant proportion of pSS population with distinct clinical phenotypes. They possess a higher prevalence of lymphoma, with different predisposing factors and lymphoma distribution across time

Prevalence of rheumatoid arthritis in Greece: results from the national health examination survey EMENO

Rheumatoid arthritis (RA) is considered the most common form of autoimmune arthritis. The disease’s prevalence is around 0.5–1% worldwide, but it seems to vary among different populations. The aim of this study was to estimate the prevalence of self-reported diagnosed RA in the general adult population in Greece. The data were derived from the Greek Health Examination Survey EMENO, a population-based survey performed between 2013 and 2016. Of the 6006 participants (response rate 72%), 5884 were eligible for this study. Prevalence estimates were calculated according to the study design. Prevalence of self-reported RA was estimated to be overall 0.5% (95% CI 0.4–0.7) being approximately three times higher in women than in men (0.7% vs 0.2%, p value = 0.004). A decrease in the prevalence of RA was observed in urban areas of the country. In contrast, higher disease rates were reported in individuals with lower socioeconomic status. Multivariable regression analysis showed that gender, age, and income were related to the occurrence of the disease. Osteoporosis and thyroid disease were the two comorbidities observed at statistically significant higher rates in individuals with self-reported RA. The prevalence of self-reported RA in Greece is similar to that reported in other European countries. Gender, age, and income are the main factors related to the disease’s prevalence in Greece. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature

Addressing the clinical unmet needs in primary Sjögren's Syndrome through the sharing, harmonization and federated analysis of 21 European cohorts

For many decades, the clinical unmet needs of primary Sjögren's Syndrome (pSS) have been left unresolved due to the rareness of the disease and the complexity of the underlying pathogenic mechanisms, including the pSS-associated lymphomagenesis process. Here, we present the HarmonicSS cloud-computing exemplar which offers beyond the state-of-the-art data analytics services to address the pSS clinical unmet needs, including the development of lymphoma classification models and the identification of biomarkers for lymphomagenesis. The users of the platform have been able to successfully interlink, curate, and harmonize 21 regional, national, and international European cohorts of 7,551 pSS patients with respect to the ethical and legal issues for data sharing. Federated AI algorithms were trained across the harmonized databases, with reduced execution time complexity, yielding robust lymphoma classification models with 85% accuracy, 81.25% sensitivity, 85.4% specificity along with 5 biomarkers for lymphoma development. To our knowledge, this is the first GDPR compliant platform that provides federated AI services to address the pSS clinical unmet needs