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Abstract Introduction Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection. Methods Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn’s disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded. Results Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8–10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2–73.8) and specificity of 84.4% (78.0–89.6) versus a sensitivity of 70.0% (34.8–93.3) and specificity of 74.3% (66.9–80.7). Both questionnaires performed less effectively than in other studies. Conclusion This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.

Abstract Introduction Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. Methods This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. Results After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. Conclusions UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.

Alen Zabotti,1 Nicola Cabas,1 Ivan Giovannini,1 Silvia Guella,1 Lorenzo Cereser,2 Chiara Zuiani,2 Giuseppe Stinco,3 Luca Quartuccio,1 Enzo Errichetti3 1Department of Medical and Biological Sciences, Rheumatology Institute, Azienda sanitaria universitaria Friuli Centrale, Udine, Italy; 2Department of Medicine, Institute of Radiology, Azienda sanitaria universitaria Friuli Centrale, Udine, Italy; 3Department of Medical and Biological Sciences, Dermatology Institute, Azienda Sanitaria Universitaria Friuli Centrale, Udine, ItalyCorrespondence: Enzo Errichetti, Institute of Dermatology, Department of Medical Area, University of Udine, Piazzale Santa Maria della Misericordia, 15, Udine, 33100, Italy, Tel +39 0432559822, Email enzoerri@yahoo.it

Abstract Introduction Biologic therapies are licensed for both psoriasis (PsO) and psoriatic arthritis (PsA) with some electronic medical record data suggest that IL (Interleukin)-23 blockers might be more protective in PsA prevention than TNF blockers; however, the findings have been inconsistent. Higher Psoriasis Area and Severity Index (PASI) scores have also been linked to an increased PsA risk. To clarify these unresolved issues we investigated biologic agents, methotrexate, phototherapy, and topical therapy for PsA prevention in patients with psoriasis. Methods This retrospective cohort study analyzed data from 58,671 patients with psoriasis from the Israeli Meuhedet Health Services Organization database was evaluated for incident PsA. Patients were categorized on the basis of treatment: group 1, topical therapy; group 2, phototherapy; group 3, conventional disease-modifying antirheumatic drugs (cDMARDs; methotrexate); group 4, biologic DMARDs which was also stratified according to biologic class. Results The PsA incidence rate was lower in the biologic agents’ group versus the methotrexate group (HR 0.46 [95% CI 0.35–0.62]). The incidence rates per 100 person-years varied across biologic treatment groups, with the anti‑IL‑12/23 or anti‑IL‑23p19 group at 4.57, the anti-IL-17 group at 4.35, and the TNF inhibitor group at 2.55. No differences were found between various biological agents in terms of preventing PsA. The phototherapy group exhibited a higher PsA development rate than the topical therapy group (HR 1.85 [95% CI 1.65–2.07]). Conclusion Biological agents are more effective than methotrexate in reducing incident PsA in patients with psoriasis. This lower rate of PsA on topical therapy compared to phototherapy supports the importance of psoriasis severity as a risk factor.

Abstract Background The Mothers’ Milk Tool, developed and launched by the Australian National University and Alive & Thrive in 2022, allows to estimate the volume and value of breastmilk using prevalence rates of breastfeeding by month of age from birth to 36 months. The objective of this study was to obtain these estimates for three cohort studies conducted in a region of Italy. Methods Breastfeeding data from three cohort studies carried out in 1999, 2007 and 2016, with follow-up to 12, 24 and 36 months of 842, 400 and 265 children, respectively, were entered into the downloadable version of the tool. Breastfeeding rates charts and tables with estimates of breastmilk production and value for breastfeeding of children aged 0–36 months were produced. Results The rates of initiation of breastfeeding were similar in the three cohorts, while the rates of any breastfeeding at subsequent ages increased over the years. The volumes and values of breastmilk per child increased accordingly, from around 130 L (13,000 USD) in 1999, to 200 L (20,000 USD) in 2007, to 226 L (22,600 USD) in 2016. The percentage of lost breastmilk decreased from 67.7% to 55.4% to 43.7%, respectively. Overall, the 1507 mothers of the three cohorts produced an estimated 250,000 L of breastmilk for their children aged 0–36 months. At 100 USD per litre, this would add up to around 25 million USD. Conclusions Our study shows that the Mothers’ Milk Tool can be used to estimate per child volumes and values of breastmilk produced and lost at local levels, and to provide simple indicators of the effects of breastfeeding interventions using the percentage of lost breastmilk, where datasets on rates of breastfeeding by month of age are available. The results of such studies can be used to advocate for better and adequately funded programmes for the protection, promotion and support of breastfeeding.

Objective Subjects with subclinical psoriatic arthritis (PsA), defined as the presence of arthralgia in psoriasis (PsO), are at higher risk of PsA but scant real-world data exist. Our aims were to (1) estimate the probability of PsA development in subclinical PsA, (2) characterise subclinical PsA symptoms and (3) determine the clinical patterns at PsA diagnosis.Methods Patients with PsO, mainly subclinical PsA, were evaluated longitudinally in two European cohorts. The key outcome was new-onset PsA. Musculoskeletal symptoms including inflammatory and non-inflammatory symptoms before PsA diagnosis were collected. Occurrence of PsA was analysed with survival analysis and cumulative incidence functions (CIFs).Results 384 patients with PsO were included with a mean follow-up of 33.0 (±20.9) months. 311 of 384 (80.9%) had subclinical PsA with a PsA incidence rate of 7.7 per 100 patient-years. Subclinical PsA displayed a higher risk of PsA development compared with PsO (HR=11.7 (95% CI 1.57 to 86.7), p=0.016). The probability of new-onset PsA estimated by the CIF was 9.4% (95% CI 4.7% to 10.6%) at month 12 and 22.7% (95% CI 17.2% to 28.6%) at month 36. 58.9% of cases reported inflammatory symptoms in the months immediately prior to PsA diagnosis but prior non-inflammatory symptoms were evident in 83.9% prior to PsA diagnosis. Peripheral joint swelling was the predominant PsA presentation pattern (82.1%).Conclusions The probability of PsA development among subclinical PsA was relatively high, emphasising the importance of emergent musculoskeletal symptoms when aiming for PsA prevention. Joint swelling was the dominant feature in new-onset PsA, likely reflecting clinical confidence in recognising joint swelling.

Abstract Background Upadacitinib (UPA) is a selective JAK inhibitor recently approved for the treatment of psoriatic arthritis (PsA). In this post-approval study, we aimed to evaluate the effectiveness and safety of UPA over 24 weeks and identify clinical predictors of response, in a multicentric cohort of patients affected by PsA. Methods One hundred and twenty-six patients with PsA treated with UPA were enrolled in 10 Italian centres. UPA effectiveness outcomes, such as the proportion of patients with MDA status, DAPSA remission, and low disease activity, ASDAS-CRP inactive and low disease activity, and change from baseline in DAPSA and ASDAS-CRP scores, were evaluated every 12 weeks until week 24. The proportion of DAPSA minor, moderate, and major improvement, and ASDAS clinically important improvement (CII) and major improvement (MI) were considered as well. All treatment-related adverse events were collected during the observation period. Clinical predictors of MDA response at week 24 were evaluated through multivariate analysis. Results At baseline, 124/126 (98%) and 54/126 (43%) patients showed peripheral and axial involvement, respectively; 110 (87%) patients were intolerant or resistant to biologic DMARDs. At 24 weeks, MDA status, DAPSA remission, and ASDAS-CRP inactive disease were achieved in 47%, 23%, and 48% of patients, respectively. Minor, moderate, and major DAPSA improvement was observed in 67%, 39%, and 23%, respectively; while 65% and 35% achieved ASDAS-CRP CII and MI, respectively. The mean change from baseline was 15.9 ± 13.5 (p

PURPOSETo evaluate the performance of radiology residents (RRs) when using a dedicated structured report (SR) template for chest HRCT in patients with suspected connective tissue disease-interstitial lung disease (CTD-ILD), compared to the traditional narrative report (NR).METHODSWe retrospectively evaluated 50 HRCT exams in patients with suspected CTD-ILD. A chest-devoted radiologist reported all the HRCT exams as the reference standard, pointing out pulmonary fibrosis findings (i.e., honeycombing, traction bronchiectasis, reticulation, and volume loss), presence and pattern of ILD, and possible other diagnoses. We divided four RRs into two groups according to their expertise level. In each group, RRs reported all HRCT examinations alternatively with NR or SR, noting each report's reporting time. The Cohen's Kappa, Wilcoxon, and McNemar tests were used for statistical analysis.RESULTSRegarding the pulmonary fibrosis findings, we found higher agreement between RRs and the reference standard reader when using SR than NR, regardless of their expertise level, except for volume loss.RRs' accuracy for "other diagnosis" was higher when using SR than NR, moving from 0.48 to 0.66 in the novel group (p = 0.035) and from 0.44 to 0.80 in the expertise group (p < 0.001). No differences in accuracy were found between ILD presence and ILD pattern. The reporting time was significantly lower (p = 0.001) when using SR than NR.CONCLUSIONSR is of value in increasing the reporting of critical chest HRCT findings in the complex CTD-ILD scenario and should be used early and systematically during the residency.

Michele Lorenzon,1 Erica Spina,1 Francesco Tulipano Di Franco,1 Ivan Giovannini,2 Salvatore De Vita,2 Alen Zabotti2 1Institute of Radiology, Department of Medicine, University of Udine, Udine, Italy; 2Rheumatology Clinic, Department of Medical and Biological Sciences, Azienda Sanitaria Universitaria Friuli Centrale c/o University of Udine, Udine, ItalyCorrespondence: Michele Lorenzon, Institute of Radiology, Department of Medicine, University of Udine, Udine, Italy, Tel +39 0432 559232, Email michele.lorenzon@gmail.comAbstract: Salivary gland ultrasound (SGUS) is the imaging modality of choice for the assessment of parotid and submandibular gland parenchyma. Being highly effective, non-invasive and easy to perform, SGUS has become increasingly popular among specialists in assessing salivary gland (SG) abnormalities, including those commonly found in primary Sjögren’s syndrome (pSS). SGUS may be useful in the assessment of pSS and its complications, the most serious being the development of non-Hodgkin’s lymphoma (NHL). SGUS may also be useful in the characterization and differential diagnosis of diffuse and focal abnormalities commonly associated with pSS, and may act as a guide for core-needle biopsy (CNB), an established, safe, and feasible technique, which provides enough viable tissue for the diagnosis and assessment of lymphoproliferative diseases of the SG. The combination of SGUS with other tools, such as sonoelastography and artificial intelligence (AI), could further improve the usefulness of SGUS in the management of pSS. In this perspective, we summarize current and future applications of SGUS in pSS.Keywords: primary Sjögren’s syndrome, major salivary glands, ultrasound, lymphoma, core needle biopsy

Background Identifying subjects at risk of imminent psoriatic arthritis (PsA) would allow these subjects to participate in therapeutic interventions to delay or prevent PsA development.Methods A systematic literature review (SLR) was conducted in 2021 in Medline, Embase, PubMed, Central databases and international congress abstracts (PROSPERO CRD42022255102). All articles reporting the characteristics of patients transitioning from psoriasis (PsO) to PsA and from undifferentiated arthritis (UA) to PsA were included. Clinical and imaging characteristics were collated before PsA onset and at time of PsA diagnosis.Results Eighteen of 23 576 references evaluated for PsO/PsA transition were analysed; 14 were cohort studies, 2 case-control studies. Two SLRs were used to enrich the project but were not analysed per se. Of 7873 references focusing on UA to PsA, 3 studies were included. Meta-analysis was not possible due to excessive data heterogeneity. Patients with PsO who developed PsA often reported joint pain, joint tenderness and functional limitations. Arthralgia (PsO, n=669; incident PsA, n=99) was associated with subsequent PsA development. On imaging, subclinical enthesopathy (PsO=325; Incident PsA=39) appeared linked to later PsA development. At the time of PsA onset (incident PsA, N=214), peripheral arthritis, mainly oligo-arthritis (ie, the mean number of swollen joints ranged from 1.5 to 3.2), was the most frequent pattern of clinical presentation.Conclusions Joint pain, arthralgia and entheseal involvement detected by imaging were frequent in individuals with PsO at risk for imminent PsA. Very early PsA was mainly oligoarticular. This review informed a EULAR taskforce on transition to PsA.

A contribuição da colaboração, em suas diversas possibilidades, tem sido apontada como fator determinante para a formação continuada de professores, pois supera o individualismo, possibilitando reflexões coletivas sobre situações problemáticas e promovendo o desenvolvimento profissional docente. O presente artigo propõe teorizar as compreensões emergentes do discurso de professores sobre formação continuada, mediante a proposição de um Grupo Colaborativo. A tipologia de pesquisa se caracterizou por ser pesquisa de campo, no qual utilizamos questionários para a constituição das informações da pesquisa. As informações foram analisadas segundo a Análise Textual Discursiva. A nova compreensão do fenômeno estudado, possibilitada pelo processo analítico, revelou a formação continuada como racionalidade técnica, no entanto, com o desenvolvimento do grupo, a maioria dos professores reconstruiu seus discursos. Tais reconstruções emergiram nas reflexões coletivas que se estabeleceram no grupo, com troca de experiências, vivências, entre outros aspectos. Entendemos que práticas colaborativas voltadas para estudos e discussões de temáticas específicas da Biologia na formação de professores, se constitui uma ferramenta essencial para o desenvolvimento profissional docente e, como consequência, para mudanças almejadas no ensino.

Paolo Gisondi,1 Francesco Bellinato,1 Martina Maurelli,1 Davide Geat,1 Alen Zabotti,2 Dennis McGonagle,3 Giampiero Girolomoni1 1Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy; 2Rheumatology Clinic, Department of Medical and Biological Sciences, University Hospital ‘Santa Maria della Misericordia’ c/o University of Udine, Udine, Italy; 3Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UKCorrespondence: Paolo Gisondi, Section of Dermatology and Venereology, Department of Medicine, University of Verona, Piazzale A. Stefani 1, Verona, 37126, Italy, Email paolo.gisondi@univr.itAbstract: Psoriatic arthritis (PsA) is a heterogeneous chronic inflammatory arthritis associated with psoriasis, which may manifest with different domains such as dactylitis, enthesitis, synovitis and spondylitis. The estimated prevalence of PsA in patients with psoriasis ranges widely between 6% and 42%. In most cases, PsA is preceded by skin involvement by an average time of 7– 8 years. In the complex patho-mechanisms involved in the transition from psoriasis to PsA, the gut and skin have been proposed as the sites of immune activation triggering or contributing to the development of PsA. In such a transition, a subclinical phase has been identified, characterized by enthesopathy where soluble biomarkers and imaging findings but no clinical symptoms are detectable. Recent studies have provided some evidence that timely treated psoriasis may reduce the risk of developing PsA.Keywords: psoriatic arthritis, psoriasis, therapy, prevention, early intervention, disease modification

Objectives Psoriatic arthritis (PsA) phenotypes are typically defined by their clinical components, which may not reflect patients’ overlapping symptoms. This post hoc analysis aimed to identify hypothesis-free PsA phenotype clusters using machine learning to analyse data from the phase III DISCOVER-1/DISCOVER-2 clinical trials.Methods Pooled data from bio-naïve patients with active PsA receiving guselkumab 100 mg every 8/4 weeks were retrospectively analysed. Non-negative matrix factorisation was applied as an unsupervised machine learning technique to identify PsA phenotype clusters; baseline patient characteristics and clinical observations were input features. Minimal disease activity (MDA), disease activity index for psoriatic arthritis (DAPSA) low disease activity (LDA) and DAPSA remission at weeks 24 and 52 were evaluated.Results Eight clusters (n=661) were identified: cluster 1 (feet dominant), cluster 2 (male, overweight, psoriasis dominant), cluster 3 (hand dominant), cluster 4 (dactylitis dominant), cluster 5 (enthesitis, large joints), cluster 6 (enthesitis, small joints), cluster 7 (axial dominant) and cluster 8 (female, obese, large joints). At week 24, MDA response was highest in cluster 2 and lowest in clusters 3, 5 and 6; at week 52, it was highest in cluster 2 and lowest in cluster 5. At weeks 24 and 52, DAPSA LDA and remission were highest in cluster 2 and lowest in clusters 4 and 6, respectively. All clusters improved with guselkumab treatment over 52 weeks.Conclusions Unsupervised machine learning identified eight PsA phenotype clusters with significant differences in demographics, clinical features and treatment responses. In the future, such data could help support individualised treatment decisions.

BackgroundIn psoriatic arthritis (PsA), low disease activity as defined by the Minimal Disease Activity (MDA) index is considered a good treatment target. However, as MDA is based only on clinical findings, it might not capture pauci-symptomatic inflammation. Sensitive imaging such as ultrasound (US) might disclose residual inflammatory signs in PsA patients in MDA.MethodsIn this cross-sectional multicentre study, adult PsA patients on biologic treatment in MDA for at least 6 months were consecutively enrolled for a thorough clinical and US examination. Data collection included demographics, personal history, main patient's reported outcomes, clinical and US findings of joints, tendon sheaths, tendons, bursae, and entheses involvement. All centers performed the US investigation in B-mode and Power Doppler (PD)-mode using a similar US machine equipped with a 18–6 and 13–5 MHz multifrequency linear probe. Statistical analysis included comparisons between groups and correlation tests.ResultsThe 72 PsA patients enrolled in the study had a median duration of MDA of 12 (6–65) months. Overall, US examination revealed a low number of acute lesions. However, 54% of patients had at least one PD signal in the examined tissues. A joint or enthesis positive PD signal was found in about 19 and 24% of patients, respectively. Synovial hypertrophy, at least one acute entheseal lesions, and bursitis were the most common changes, detected in 41.7, 41.7 and 26% of patients, respectively.ConclusionsPsA patients in a stable state of MDA may still have residual inflammation in peripheral articular structures detectable by US examination.

The aims of this systematic literature review (SLR) were to identify the effects of approved biological and targeted synthetic disease modifying antirheumatic drugs (b/tsDMARDs) on synovial membrane of psoriatic arthritis (PsA) patients, and to determine the existence of histological/molecular biomarkers of response to therapy. A search was conducted on MEDLINE, Embase, Scopus, and Cochrane Library (PROSPERO:CRD42022304986) to retrieve data on longitudinal change of biomarkers in paired synovial biopsies and in vitro studies. A meta-analysis was conducted by adopting the standardized mean difference (SMD) as a measure of the effect. Twenty-two studies were included (19 longitudinal, 3 in vitro). In longitudinal studies, TNF inhibitors were the most used drugs, while, for in vitro studies, JAK inhibitors or adalimumab/secukinumab were assessed. The main technique used was immunohistochemistry (longitudinal studies). The meta-analysis showed a significant reduction in both CD3+ lymphocytes (SMD −0.85 [95% CI −1.23; −0.47]) and CD68+ macrophages (sublining, sl) (SMD −0.74 [−1.16; −0.32]) in synovial biopsies from patients treated for 4–12 weeks with bDMARDs. Reduction in CD3+ mostly correlated with clinical response. Despite heterogeneity among the biomarkers evaluated, the reduction in CD3+/CD68+sl cells during the first 3 months of treatment with TNF inhibitors represents the most consistent variation reported in the literature.

Primary Sjögren’s syndrome (pSS) is a heterogeneous disease characterised by a wide spectrum of manifestations that vary according to the different stages of the disease and among different subsets of patients. The aim of this qualitative literature review is to summarise the recent advances that have been reported in pSS, ranging from the early phases to the established disease and its complications. We analysed the diagnostic, prognostic, and management aspects of pSS, with a look into future clinical and research developments. The early phases of pSS, usually antedating diagnosis, allow us to investigate the pathophysiology and risk factors of the overt disease, thus allowing better and timely patient stratification. Salivary gland ultrasound (SGUS) is emerging as a valid complementary, or even alternative, tool for histopathology in the diagnosis of pSS, due to a standardised scoring system with good agreement and performance. Other promising innovations include the application of artificial intelligence to SGUS, ultrasound-guided core needle biopsy, and a wide array of novel diagnostic and prognostic biomarkers. Stratifying pSS patients through the integration of clinical, laboratory, imaging, and histopathological data; differentiating between activity-related and damage-related manifestations; and identifying patients at higher risk of lymphoma development are essential steps for an optimal management and individualised treatment approach. As new treatment options are emerging for both glandular and systemic manifestations, there is a need for a more reliable treatment response evaluation. pSS is a complex and heterogeneous disease, and many distinct aspects should be considered in the different stages of the disease and subsets of patients. In recent years, efforts have been made to improve our understanding of the disease, and certainly in the coming years, some of these novelties will become part of our routine clinical practice, thus improving the management of pSS patients.

The present research is derived from State of Art and it aims to highlight what is being produced in academic researches, in the form of dissertations and theses, from 2006 to 2016, regarding the teaching of the themes Origin of Life and Biological Evolution. the analysis was performed using pre-printed descriptors based on Megid Neto (1999) and Teixeira (2008). 78 articles were found, being 65 dissertations and 16 theses. Half of the papers are dissertations on teaching Biological Evolution, and only one thesis investigates the teaching of the Origin of Life. We found three issues that were not well investigated in the researches: Curriculum and Programs, Non-Formal Education and School Organization. These results, as well as the researches focused on the analysis of academic production, can contribute to the deployment of more specific proposals of teaching formation and improvements in the teaching-learning of this theme.