Hospital de Santa Maria

Purpose To determine the normative values and reference equations of the 4-Meter Gait Speed Test (4MGS) at usual and maximal speed for Portuguese adults. We also assessed the participant experience during the performance of the 4MGS. Materials and methods A cross-sectional study was conducted with individuals without disabilities. Sociodemographic, anthropometric, smoking habits and physical activity (Brief Physical Activity Assessment Tool [BPAAT]) data were collected. Individuals performed 3 repetitions of 4MGS at usual and maximal speeds, and the best performances were recorded. Speed values were calculated by age and sex. Stepwise multiple regressions were used for the reference equations. Participants rated their comfort from 0 (‘not comfortable at all’) to 5 (‘very comfortable’) for each modality and indicated their preferences. Results A total of 287 individuals (62.4% female; 47.8 ± 19.5 years) were recruited. Speed was significantly reduced after the sixth decade of life compared with the other decades (p < 0.001). Reference equations were: Usual speed = 1.598 – (0.006 x age) + (0.060 x BPAAT classification), R2= 27% and Maximal speed = 2.272 – (0.010 x age) + (0.157 x sex) + (0.73 x BPAAT classification), R2= 38%. Most participants felt ‘very comfortable’ performing the 4MGS at usual speed (94.8%), maximal speed (75.6%) and no preference in 4MGS modalities (69%). Conclusions Speed is significantly affected by age. For the reference equations, age and physical activity explain the results of usual speed, and both associated with sex explain the results of maximal speed. Most participants were highly comfortable and expressed no preference in 4MGS modalities.

Burns are a global health problem and can be caused by several factors, including ultraviolet (UV) radiation. Exposure to UVB radiation can cause sunburn and a consequent inflammatory response characterised by pain, oedema, inflammatory cell infiltration, and erythema. Pharmacological treatments available to treat burns and the pain caused by them include nonsteroidal anti-inflammatory drugs (NSAIDs), opioids, antimicrobials and glucocorticoids, which are associated with adverse effects. Therefore, the search for new therapeutic alternatives is needed. Diosmetin, an aglycone of the flavonoid diosmin, has antinociceptive, antioxidant and anti-inflammatory properties. Thus, we evaluated the antinociceptive and anti-inflammatory effects of topical diosmetin (0.01, 0.1 and 1%) in a UVB radiation-induced sunburn model in mice. The right hind paw of the anaesthetised mice was exposed only once to UVB radiation (0.75 J/cm²) and immediately treated with diosmetin once a day for 5 days. The diosmetin antinociceptive effect was evaluated by mechanical allodynia and pain affective-motivational behaviour, while its anti-inflammatory activity was assessed by measuring paw oedema and polymorphonuclear cell infiltration. Mice exposed to UVB radiation presented mechanical allodynia, increased pain affective-motivational behaviour, paw oedema and polymorphonuclear cell infiltration into the paw tissue. Topical Pemulen® TR2 1% diosmetin reduced the mechanical allodynia, the pain affective-motivational behaviour, the paw oedema and the number of polymorphonuclear cells in the mice’s paw tissue similar to that presented by Pemulen® TR2 0.1% dexamethasone. These findings indicate that diosmetin has therapeutic potential and may be a promising strategy for treating patients experiencing inflammatory pain, especially those associated with sunburn.

BACKGROUND AND OBJECTIVES Although women seem to be more susceptible to pain, there are few studies comparing the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) diagnoses between women and men. Thus, this study aimed to verify the influence of gender on Temporomandibular Disorders (TMD) and their comorbidities in a Brazilian sample. METHODS Patients were assessed using the RDC/TMD. Diagnoses were obtained for Axis I (myofascial pain, disc displacement, and other joint conditions) and Axis II (depressive symptoms, chronic pain, somatization, and limitation of mandibular function). Logistic regression models were used to verify whether there is a difference in the prevalence and odds of developing TMD between women and men. RESULTS The sample included 310 patients. Women had more myofascial pain and were more likely to develop it (73.04%; OR: 1.91; IC 95%: 1.08 - 3.39), as well as more joint disorders (54.78%; OR: 2.07; IC 95%: 1.08 - 3.99), in comparison to men. Furthermore, women composed the majority of the sample, more often sought treatment, and had more severe levels of depressive symptoms, somatization of pain, limitation of mandibular function, and myofascial pain. CONCLUSION Women have more TMD and are more likely to develop it, and also show more severe levels of depressive symptoms, pain somatization, limited mandibular function, and myofascial pain. Keywords Facial pain; Gender characteristics; Temporomandibular joint disorders.

Background The aim of this study is to report the preliminary real-word clinical and hemodynamic performance from the MANTRA study in patients undergoing aortic valve replacement with Perceval PLUS sutureless valve. Methods MANTRA is an ongoing “umbrella” prospective, multi-center, international post-market study to collect real-life safety and performance data on Corcym devices (Corcym S.r.l, Saluggia, Italy). Clinical and echocardiographic outcomes were collected preoperatively, at discharge and at each follow up. KCCQ-12 and EQ-5D-5L quality of life questionnaires were collected preoperatively and at 30-days. Results A total of 328 patients underwent aortic valve replacement with Perceval PLUS in 29 International institutions. Patients were enrolled from July 2021 to October 2023 and enrollment is still ongoing. Mean age was 71.9 ± 6.4 years, mean EuroSCORE II was 2.9 ± 3.9. Minimally invasive approach was performed in 44.2% (145/328) of patients; concomitant procedures were done in 40.8% (134/328) of cases. Thirty-day mortality was 1.8% (6/328) and no re-interventions were reported. Pacemaker implant was required in 4.0% (13/328) of the patients. The assessment of the functional status demonstrated marked and stable improvement in NYHA class in most patients at 30-day follow-up, with significant increase of KCCQ-12 summary score (from 58.8 ± 23.0 to 71.8 ± 22.1, p < 0.0001) and EQ-5D-5L VAS score (from 64.5 ± 20.4 to 72.6 ± 17.5, p < 0.0001). Mean pressure gradient decreased from 46.2 ± 17.3 mmHg to 10.1 ± 4.7 mmHg at 30-day follow-up. Low or no incidence of moderate-to-severe paravalvular or central leak was reported. Conclusions Preliminary results demonstrate good clinical outcomes and significant improvement of Quality of Life at 30-days, excellent early hemodynamic performance within patient implanted with Perceval PLUS. Trial Registration The MANTRA study has been registered in ClinicalTrials.gov (NCT05002543, Initial release 26 July 2021).

This manuscript presents a new report on the in vitro antimicrobial photo-inactivation of foodborne microorganisms (Salmonella spp. and Listeria monocytogenes) using tetra-cationic porphyrins. Isomeric tetra-cationic porphyrins (3MeTPyP, 4MeTPyP, 3PtTPyP, and 4PtTPyP) were tested, and antimicrobial activity assays were performed at specific photosensitizer concentrations under dark and white-light LED irradiation conditions. Among the tested bacterial strains, 4MeTPyP exhibited the highest efficiency, inhibiting bacterial growth within just 60 min at low concentrations (17.5 μM). The minimal inhibitory concentration of 4MeTPyP increased when reactive oxygen species scavengers were present, indicating the significant involvement of singlet oxygen species in the photooxidation mechanism. Furthermore, the checkerboard assay testing the association of 4MeTPyP showed an indifferent effect. Atomic force microscopy analyses and dynamic simulations were conducted to enhance our understanding of the interaction between this porphyrin and the strain’s membrane.

This study aims to analyze the determinants of private investment in Brazil from 1971 to 2019 based on the peculiarities of emerging economies. These economies have characteristics that are different from those observed in developed countries and constitute the axioms that support the empirical studies usually carried out on the subject. The uncertainty of the political-economic environment, the low availability of credit, the scarcity of foreign exchange, exchange rate policies, and the precariousness of infrastructure are factors that influence investment decisions in emerging economies. Therefore, they should be part of empirical studies. The results of the econometric analysis—based on the Autoregressive Vectors (VAR) methodology and the Error Correction Model (VECM)—indicate that, both in the short and long term, public investment complemented private sector investment (crowding-in effect). This result indicates that public sector investments were channeled into infrastructure or into areas in which the private sector had no interest or capacity to act. This effect is confirmed by the positive result that investments in infrastructure have on the private sector in Brazil.

The need to replace nonrenewable sources is a global challenge, especially for emerging countries with financial constraints to invest in energy transition. In Brazil, electrical generation is predominantly renewable, since the hydraulic source is responsible for more than half of the domestic electricity supply. Other alternative sources, such as biomass, solar, and wind, complement the renewable portion of the Brazilian electrical matrix. However, periods of drought and climate disturbances threaten the stability of the electrical system and increase dependence on thermal generation. Based on the global movement to intensify the use of renewable sources, which are volatile and influenced by climate variations, the objective of this research is to predict electricity generation using the Heston model. This model, originally applied to predict option prices, assumes nonconstant volatility and has the ability to estimate the average value including the stochastic volatility process. The database is made up of monthly values of the volume of electrical energy generation from biomass, coal, fuel oil, hydraulic, industrial waste, natural gas, nuclear, solar, and wind sources. Compared to the Black-Scholes model, the chosen method proved to be superior in predicting the generation from coal, hydropower, and solar energy, according to the MAE, MAPE, and RMSE statistics. We conclude that a financial model can be effectively applied to the energy sector and the Heston model can be a useful instrument to assist in the planning and management of the national electrical system. One suggestion for the Brazilian case is to encourage the use of alternative energies and low-carbon sources, such as solar, wind, and natural gas, providing greater energy security and a more reliable electrical system.

Naphthenic acids (NA) are organic compounds commonly found in crude oil and produced water, known for their recalcitrance and toxicity. This study introduces a new adsorbent, a polymer derived from spent coffee grounds (SCGs), through a straightforward cross-linking method for removing cyclohexane carboxylic acid as representative NA. The adsorption kinetics followed a pseudo-second-order model for the data (0.007 g min−1 mg−1), while the equilibrium data fitted the Sips model (\({q}_{m}\) = 140.55 mg g−1). The process’s thermodynamics indicated that the target NA’s adsorption was spontaneous and exothermic. The localized sterical and energetic aspects were investigated through statistical physical modeling, which corroborated that the adsorption occurred indeed in monolayer, as suggested by the Sips model, but revealed the contribution of two energies per site (\({n}_{1}; {n}_{2}\)). The number of molecules adsorbed per site \((n\)) was highly influenced by the temperature as \({n}_{1}\) decreased with increasing temperature and \({n}_{2}\) increased. These results were experimentally demonstrated within the pH range between 4 and 6, where both C6H11COO−(aq.) and C6H11COOH(aq.) species coexisted and were adsorbed by different energy sites. The polymer produced was naturally porous and amorphous, with a low surface area of 20 to 30 m2 g−1 that presented more energetically accessible sites than other adsorbents with much higher surface areas. Thus, this study shows that the relation between surface area and high adsorption efficiency depends on the compatibility between the energetic states of the receptor sites, the speciation of the adsorbate molecules, and the temperature range studied.

Acacia mearnsii and Ilex paraguariensis are tree species of great social and economic importance in Brazil, demanding clonal cultivars. Their shoots possess a reservoir of totipotent cells with suitable potential for adventitious rooting, essential for mass production of high-quality seedlings. This study aimed to gain new insights into how anatomical barriers, i.e. sclerified tissues in the cortical region, may affect the adventitious rooting of cuttings from these species through histological examinations. For both species, histological analysis revealed significant diagnostic features. Tissue decay appears to be equivalent to an anatomical barrier in A. mearnsii. Starch abundance was notable in clones with higher rooting competence of I. paraguariensis, but they were not observed in the fundamental tissues of A. mearnsii, regardless of the rooting competence of the clone. The main differences in adventitious rooting were associated with the speed of response, initiated from cortical meristems, followed by differentiation of conductive tissue from newly formed tissue, connecting the periphery with the secondary vascular tissue. Thus, this newly formed tissue with parenchymatic structure provides the necessary structural basis for radial vascular connections. For both studied species, rhizogenesis presents distinct barriers to rooting, nevertheless these are not necessarily of anatomical nature.

This paper describes an extensive study in which a multiclass QuEChERS based approach was optimized for determination of 150 pesticides and 7 mycotoxins in table olives. Three versions of QuEChERS were evaluated and compared (unbuffered, citrate and acetate buffering). A combination of EMR-Lipid cartridges and liquid nitrogen or freezer freezing out were tested for clean-up of the oily olive extracts. Analysis of the extracts were performed by LC-MS/MS triple quadrupole. The best results were achieved using acetate QuEChERS with liquid nitrogen for clean-up. For validation, organic olives were ground and spiked at 4 concentrations with pesticides and mycotoxins (n = 5). The linearity of the calibration curves was assessed by analyzing calibration standards of 7 concentrations which were prepared separately in acetonitrile and in blank olive extract (n = 5). The validation study demonstrated that the calculated r2 was ≥0.99 for 144 pesticides and 6 mycotoxins, when the calibration curves were prepared in matrix extract, showing satisfactory linearity. Matrix effects were within the range of ±20% for only 46 pesticides and one mycotoxin. Then, to ensure reliable quantification, calibration standards had to be matrix-matched. In accuracy experiments 138 pesticides and 6 mycotoxins presented recoveries from 70 to 120% and RSD ≤ 20% for at least 2 of the 4 spike concentrations evaluated, being successfully validated. The integrated QuEChERS and LC-MS/MS method meet MRL for 11 of the 21 pesticides regulated for olives in Brazil and for 132 pesticides which are regulated in the EU law. Eleven commercial table olive samples were analyzed and 4 of them tested positive for pesticides. All the positive samples violate the Brazilian law and one sample violates also the European law.

Background Rheumatoid arthritis (RA) is a chronic, systemic, immune-mediated inflammatory disease that mainly targets the joints. The pathogenesis of RA involves dysregulations in immune pathways such as the JAK-STAT signaling pathway. JAK inhibitors (JAKi) are a class of disease modifying anti-rheumatic drugs that are approved for RA treatment. Objectives To compare the in-vitro cellular effect of two JAKi, tofacitinib and upadacitinib, in peripheral blood leukocytes from patients with untreated early rheumatoid arthritis (ERA), established refractory RA and healthy individuals. Methods Blood samples were collected and peripheral blood mononuclear cells (PBMCs) were isolated and cultured during 24 hours with either tofacitinib or upadacitinib. The frequency, phenotype, STAT phosphorylation levels (pSTAT) and apoptosis of B cells, T cells, monocytes and dendritic cells (DCs) were analysed by flow cytometry before and after cell culture with JAKi in all groups. Results We included 6 patients (50 % female, 55.0±22.1 years old, with a mean disease duration of 6.2 months). Changes in the frequency of B cells and DCs’ subpopulations, but not in T cells or monocytes, were observed after 24 hours of in vitro cell culture with both JAKi (Figure 1). Furthermore, phenotypic analysis has revealed a reduction in the expression of activation markers on B cells, T cells and monocytes after culture with upadacitinib and tofacitinib. In addition, changes in pSTAT levels measured by median fluorescence intensity (MFI) were also detected in all leukocyte populations after culture with both JAKi when compared to baseline and/or drug vehicle (Figure 2). Notably, JAKi did not significantly affect cell viability. Conclusion Overall, our data supports a similar immunomodulatory effect of tofacitinib and upadacitinib in peripheral blood leukocytes of early untreated RA. • Download figure • Open in new tab • Download powerpoint Figure 1. The frequency of total CD19+ B cells and B cell subsets (1.1), and the total dendritic cells (DC) and DC subsets (1.2) after 24 hours of in vitro cell culture with upadacitinib and tofacitinib. • Download figure • Open in new tab • Download powerpoint Figure 2. Changes in STAT phosphorylation levels in B cells (2.1), T cells (2.2), monocytes (2.3) and dendritic cells (2.4) after 24 hours of in vitro cell culture with upadacitinib and tofacitinib. REFERENCES NIL Acknowledgements NIL Disclosure of Interests None declared

Background Neurologic manifestations in antiphospholipid syndrome (APS) are common, and most often with an underlying thrombotic mechanism (ischemic stroke or transient ischemic attack [TIA]). The prevalence and range of neurological manifestations varies across studies, most of which lack a structured comprehensive neurological, cognitive and neuroimaging evaluation. Objectives To establish the prevalence and systematically characterize neurologic signs, symptoms, diagnosis and disability in our APS cohort. Methods We conducted a cross-sectional study to systematically evaluate adult (≥18 years) patients followed at the rheumatology clinic with a diagnosis of APS. We collected demographic, clinical, laboratory and imaging data. Patients were screened for neurological symptoms through a comprehensive neurological examination standardized with the Expanded Disability Status Scale (EDSS); headache characterization and headache impact assessment (HIT-6); and cognitive function screening using the Montreal Cognitive Assessment (MoCA) test. When appropriate, patients were submitted to a formal neuropsychological evaluation. Imaging studies were reviewed, and a brain MRI was obtained when clinically relevant. Recruitment for the study is still ongoing. Results We included 33 patients (91% female), with a median age of 50 years (IQR 45-61). Around two thirds (n=21, 64%) had APS secondary to connective tissue diseases (CTD). Full demographic and baseline characteristics are presented in Table 1. Before clinical evaluation, only 17 patients (52%) had a diagnosed neurological condition: stroke or TIA (n=7), headache (n=3), epilepsy (n=2), anxiety (n=9) and depression (n=7). On clinical evaluation, only 6 patients had a normal examination (EDSS=0), and the remaining majority (82%) had clinically evident neurological signs, mainly involving the pyramidal and cerebellar systems. Of note, 15% (n=5) had mild to moderate neurologic disability (EDSS>1.0). One patient had a multiple sclerosis-like white matter disorder on brain MRI deemed secondary to APS. 26 patients (79%) met diagnostic criteria for primary or secondary headache disorder, including 15 (46%) with migraine and 10 (30%) with tension-type headache. Of the patients that reported headaches, 21% had substantial or severe headache impact on their daily living (HIT-6≥56). Although none of the patients had a previous diagnosis of cognitive impairment or dementia, when asked 24/33 (73%) patients had subjective cognitive complaints, and 13 (40% of total) met criteria for mild cognitive impairment. Conclusion Clinically evident neurological signs, headache and cognition dysfunction were observed in most APS patients, with substantial disability, daily impact and burden. These data suggest that neurological dysfunction in APS is more common than previously reported and should be actively and systematically sought after in a close liaison between Rheumatologists and Neurologists.View this table: • View inline • View popup Table 1. Baseline characteristics REFERENCES NIL Acknowledgements NIL. This project was awarded a grant from Faculdade de Medicina da Universidade de Lisboa (18.ª Bolsa de Investigação Fundação AstraZeneca/FMUL, 2021). We would like to thank Sónia Figueiredo and the team from Centro de Investigação Clínica, Centro Académico de Medicina de Lisboa (CAML) for their help with logistics during patient recruitment and data storage. Disclosure of Interests None declared

Background Remission is nowadays an attainable target for most rheumatoid arthritis (RA) patients, but there is a lack of accurate remission markers for selecting patients for treatment taper. Although ultrasound (US) proved to detect minimal disease activity even in patients classified in clinical remission, other methods, such as contrast-enhanced ultrasound (CEUS), might be more sensitive and thus candidates to act as “true” remission markers in clinical practice. Objectives To test CEUS as a useful tool to detect minimal inflammation in RA patients in sustained clinical remission and correlate it with disease activity scores, greyscale US (GSUS), power Doppler US (PDUS), and Global OMERACT-EULAR synovitis score (GLOESS). Methods Thirty-two RA patients in persistent (> six months) remission (Disease Activity Score (DAS28) 4v ESR or Boolean remission), 10 RA patients with active disease (moderate or high DAS28 4v ESR), and 10 age and sex-matched healthy controls were recruited and clinically evaluated (joint counts, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) and patient-reported outcomes (PROs) and by US of 28 joints). GSUS, PDUS, and GLOESS total scores were calculated. The joints with higher synovitis score were selected to perform CEUS. CEUS videos were recorded in DICOM format and scored blindly using the semiquantitative International Arthritis Contrast Ultrasound Score (IACUS). CEUS quantification was performed using a dedicated software, allowing the calculation of time-intensity curves (TIC). From the TIC, the signal intensity maximum (SiMax) and minimum (SiMin) were collected, and the signal intensity ratio was calculated (SiR=SiMax/SiMin). Results At the time of the US evaluation, of the 32 screened patients in persistent clinical remission, 24 were still in remission, 5 in low, and 3 in moderate disease activity. Remission and low disease activity were merged into one group (RL, n=29), and the moderate disease activity group that came from the persistent remission cohort (n=3) was assessed together with the moderate and high disease activity group (MH, n=13). Healthy and RL groups had similar total scores of GSUS, PDUS, and GLOESS. MH groups had higher scores of GSUS, PDUS, and GLOESS compared to healthy and RL groups, with statistically significant differences in all scores when comparing with healthy but only in PDUS when comparing with RL (Table 1).Ninety-five joints were selected for CEUS examination, 20 from healthy controls. We detected more microvascularisation with the IACUS CEUS score than with PDUS: 25 vs 5% in the healthy controls, 54 vs 15% in the RL group and 90 vs 52% in the MH group (p-value <0.001) (Table 2). The Spearman’s correlation between CEUS quantification of single joints (using the SiR) and the other single joint US scores were 0.655 (moderate to strong), 0.509 (moderate), 0.289 (weak), and 0.286 (weak), respectively for IACUS CEUS, PDUS, GLOESS, and GSUS. Conclusion For most RA patients in persistent clinical remission, conventional US may also fail to detect microvascularisation potentially related to the subclinical disease. CEUS may be a useful tool to identify in clinical practice RA patients in “true” remission. REFERENCES NIL • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint Acknowledgements Neurology Department of Hospital de Santa Maria for allowing to use the equipment and space for the ultrasound procedures. Nurse staff of Rheumatology Department of Hospital de Santa Maria and Centro de Investigação Clínica of Hospital de Santa Maria. Disclosure of Interests Joaquim Polido-Pereira Abbvie, Lilly and Pfizer., Pharmakern, Abbvie and MSD., Manuel Silvério-António Menarini and Theramex., Nikita Khmelinskii: None declared, Marta Arese: None declared, Rui Lourenço Teixeira: None declared, Elsa Vieira-Sousa: None declared, Maria-Antonietta D’Agostino: None declared, Joao Eurico Fonseca: None declared

Background Interaction between T and B cells are critical for antibody production in germinal centres, but their role and immunophenotypic characterization is scarcely studied in primary antiphospholipid syndrome (pAPS). Whether antiphospholipid antibody (aPL) profile, including non-criteria aPL, dictates clinical, laboratory and immunological differences is unclear. Objectives To address whether pAPS patients differ clinically and immunologically based on current aPL status. Methods We prospectively recruited 92 adults with thrombotic PAPS (fulfilling Sidney criteria) and 75 age- and sex-matched healthy donors (HD). Clinical and laboratory data were collected at study entry. Regardless of lupus anticoagulant (LA) status, patients were categorized in two groups according to current aPL profile (IgM and/or IgG anti-cardiolipin [ACL], -ß2-glycoprotein [ß2GPI], -phosphatidylserine/prothrombin complex [PS/PT]; and IgG anti-Domain-1 of ß2GPI [D1- ß2GPI]): aPL+, positive for at least one aPL (n=43); and aPL-, negative for all abovementioned aPL (i.e., positive for LA in the past and/or currently) (n=49). We considered aPL <30 UQ as negative (ELISA immunoassays). Circulating Tfh (CD4⁺FoxP3⁻CD25⁻CD45RO⁺CXCR5⁺), activated Tfh (PD1⁺ICOS⁺ Tfh), Treg (CD4⁺CD25⁺FoxP3⁺), Tfr (CD4⁺CD25⁺FoxP3⁺CXCR5⁺), naïve B cells (CD19⁺CD27⁻IgD⁺), pre- (CD19⁺CD27⁺IgD⁺) and post-switch memory B cells (CD19⁺CD27⁺IgD⁻), transitional B cells (CD19⁺IgD⁺CD38⁺⁺) and plasmablasts (CD19⁺CD27⁺IgD⁻CD38⁺⁺) were analysed by flow cytometry. Results Most patients were women (n=53, 57.6%), with a median (IQR) age at disease onset of 44 (32-52.5) years and a median disease duration of 6 (3.5-14) years ( Table 1 ). Arterial thrombosis was the most common first thrombotic manifestation (51.3%). Prevalence of criteria-aPL positivity decreased from diagnosis to follow-up, respectively ( Table 1 ): LA (59.8%; 28.3%); ACL (47.8%; 28.3%); ß2GPI (40.2%; 30.4%). Non-criteria-aPL anti-PS/PT (IgM/IgG) and anti-D1-ß2GPI (IgG) were currently present in 28.3% and 19.6% of patients, respectively. Current age, disease duration, type of first thrombotic event, INR, d-dimers, erythrocyte sedimentation rate and c-reactive protein were comparable between aPL+ and aPL- pAPS patients ( Table 1 ). Only activated partial thromboplastin (p=0.046) time and gamma-globulin values (p=0.005) were increased in aPL+ patients ( Table 1 ). The frequencies of circulating Tfh and Treg cells were comparable between HD and pAPS patients ( Figure 1A and 1B ). Within the Tfh subset, activated Tfh cells were significantly increase in pAPS compared to HD (p=0.046), and in aPL+ compared to aPL- patients (p=0.037) ( Figure 1C ). Within the Treg subset, circulating Tfr and Tfr/Tfh ratio were significantly increased in aPL+ patients compared to aPL- patients (p<0.001; p=0.034) and HD (p<0.001) ( Figure 1D and 1E ). The frequencies of circulating naïve B cells, pre- and post-switch B cells, transitional B cells and plamablasts were similarly distributed between pAPS patients, HD, and specific aPL profile subgroups ( Figure 1F to 1J ). • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint Conclusion Despite clinical and laboratory similarities among thrombotic aPL+ and aPL- pAPS patients, an imbalance of circulating Tfh and Tfr subsets, but not B cells, was noted according to aPL profile. Increased activated Tfh and Tfr cells, and Tfr/Tfh ratio might indicate an active state of disease characterized by ongoing humoral response in aPL+ patients. aPL- patients displayed a similar immunological T and B cell profile compared to healthy individuals. REFERENCES NIL Acknowledgements This work is funded by National Funds through the Portuguese Funding agency FCT - Fundação para a Ciência e Tecnologia, I.P. Disclosure of Interests None declared

Background The adjusted Global Antiphospholipid Syndrome Score (aGAPSS) predicts thrombosis in antiphospholipid syndrome (APS). However, the influence of changes in aGAPSS over time on its ability to predict the risk of recurrent thrombosis has not been studied in primary APS (pAPS). Objectives To assess the accuracy of the aGAPSS at diagnosis and follow-up in predicting thrombotic recurrence in thrombotic pAPS. Methods Retrospective cohort study including 92 patients with thrombotic pAPS (Sidney criteria). We collected clinical and laboratory data at diagnosis and until the last available follow-up visit. We only considered recurrent events occurring during antithrombotic therapy. The aGAPSS were calculated at diagnosis and at the final visit by adding the weighted scores of hyperlipidaemia (3), hypertension (1); IgG/IgM anticardiolipin (ACL; 5), IgG/M anti-b2 glycoprotein I (ß2GPI; 4), and lupus anticoagulant (LA; 4). Using receiver operating characteristic (ROC) curves, we calculated the optimal cut-off of aGAPSS at diagnosis that predicted recurrence risk. Then, we applied the same cut-off value to aGAPSS at the last evaluation and explored the risk factors for recurrence using logistic regression. Areas under the curve (AUC) of the selected aGAPSS cut-off were determined. Results Most patients were women (57.6%), with a mean (SD) age at disease onset of 42.7 (13.9) years, and a mean disease duration of 8.9 (7.0) years. Arterial thrombosis was the most common presenting thrombotic manifestation (51.3%), followed by venous thrombosis (44.6%). Acute cerebrovascular events (48.9) and venous thromboembolic disease (40.2%) were the most common manifestations. Recurrent thrombosis affected 23 (25.0%) patients after a mean follow-up time of 4.7 (4.8) years (27 events per 1000 patient-years). Comparing disease onset to the last follow-up, the proportion of patients with positive LA (67.4% vs. 32.6%, p<0.001) and ACL (44.6% vs. 29.4%, p=0.033) decreased, unlike ß2GPI (39.1% vs. 30.4%, p=0.216) and triple positivity (17.4% vs. 18.5%, p=0.848), which remained stable. On the contrary, hypertension (28.3% vs. 42.4%, p=0.092) and hyperlipidaemia (25.0% vs. 45.7%, p=0.003) increased over time. In univariate analysis, disease duration (OR [95%CI], 1.08 [1.01-1.15], p=0.024), type of presenting thrombosis (arterial; OR 4.4 [1.5-13.2], p=0.008), ACL positivity at diagnosis (OR 3.10 [1.2-8.3], p=0.025), and persistent ACL (OR 3.0 [1.1-8.2], p=0.028), anti-ß2GPI (OR 3.6 [1.4-9.7], p=0.011), and triple positivity (OR 4.9 [1.6-14.9], p=0.005) at follow-up were associated with recurrent thrombosis. Persistent ACL (p=0.014), ß2GPI (p=0.013) and triple (p=0.009) aPL positivity remained significantly associated with recurrent thrombosis after adjusting for sex, age, disease duration and type of first event (arterial). The mean aGAPSS significantly decreased over time ( Figure 1A ) and was significantly higher in patients with recurrent thrombosis, both at diagnosis ( Figure 1B ) (OR 1.34 [1.2-1.6], p<0.001) and at follow-up ( Figure 1C ) (OR 1.1 [1.0-1.2], p=0.008). The AUC showed that aGAPSS at diagnosis had a better diagnostic accuracy compared to aGAPSS at follow-up ( Figure 2A ). The ROC curve analysis showed that maximal AUC was obtained for aGAPSS at diagnosis ≥7 ( Figure 2A ), which was strongly associated with recurrence (OR 9.2 [2.5-33.9], p=0.001), even adjusting for sex, age, disease duration and type of first thrombotic event (arterial) (OR 15.4 [3.0-79.3], p=0.001). The same cut-off for aGAPSS at follow-up underperformed, with lower AUC ( Figure 2B ) and lacking an independent association with thrombotic recurrence on multivariate analysis (OR 2.78 [0.91-8.45], p=0.072) adjusted to the same variables. Conclusion A value of aGAPSS ≥7 at diagnosis predicts recurrences in thrombotic pAPS with good accuracy. Given the expected rise in cardiovascular risk factors over time, the decrease of aGAPSS and its predictive power at follow-up is likely the result of seronegativization of individual aPL. aPL persistence may serve as a more reliable and easily accessible predictor of recurrent thrombosis, but need further investigation. • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint REFERENCES NIL Acknowledgements NIL Disclosure of Interests None declared

Background Inflammatory arthritides and other rheumatic diseases often present with clinical arthritis, leading to a significant personal and societal burden. Early arthritis clinics have been established worldwide to identify and treat patients within a window of opportunity, expecting to improve outcomes. Objectives To describe the organization of our early arthritis clinic, which manages patients with untreated inflammatory arthritis with less than 12 months of symptoms. Methods We included patients followed-up in our early arthritis clinic from 2015 to 2022. We collected demographic and clinical variables, including symptom duration, disease activity, treatment and final diagnosis. Patients were followed-up for up to 12 months, with visits at months 0, 1, 3, 6, 9 and 12. All patients were treated with short-term glucocorticoids and conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) with a treat-to-target approach. We herein report the proportion of patients achieving clinical remission, defined by Disease Activity Score 28-joints with 4 variables C-reactive protein (DAS-28-4V-CRP), at month 6 and 12 of follow-up. Results We assessed 292 patients in our clinic between 2015 and 2022. Mean (SD) symptom duration at baseline was 57.8 (16.0) months, with a mean DAS28-CRP of 3.5 (1.0) (Table 1). Seropositive (40.1%) and seronegative (17.3%) rheumatoid arthritis were the most common diagnoses, followed by psoriatic arthritis (12.4%). Most patients were treated with prednisolone (88.1%) and methotrexate (75.3%), while a short number of patients received leflunomide (4.5%), sulfasalazine (9.4%) and hydroxychloroquine (12.9%). Health Assessment Questionnaire (HAQ) improvement was 1.5 ± 0.4 points. As a whole, 83.7% of the patients achieved remission (DAS28-CRP<2.6) at 6 months and 92.1% of the patients at 12 months, with limited hand and feet structural progression (Table 2). Conclusion Our early arthritis clinic allowed for the prompt orientation, diagnosis, and treatment of patients with recent onset arthropathies. This has resulted in a high percentage of patients reaching disease remission, in accordance with a window of opportunity for timely treatment and improved outcomes. Our work highlights the relevance of early arthritis clinics in tertiary rheumatology centers. • Download figure • Open in new tab • Download powerpoint Table 1. Early arthritis cohort clinical and demographic characteristics • Download figure • Open in new tab • Download powerpoint REFERENCES NIL Acknowledgements NIL Disclosure of Interests None declared

Background Prognostic parameters for the risk stratification of patients with giant cell arteritis (GCA) at diagnosis or during the early phases of the disease are still lacking. The use of ultrasound (US) as a monitoring tool for the assessment of GCA during follow-up is being increasingly recognized. The provisional OMERACT GCA ultrasound score (OGUS) has been developed as a tool to monitor disease activity and has shown good sensitivity to change in a prospective study [1]. It remains unclear whether ultrasound findings play a prognostic role in predicting the risk of relapse, the need for immunosuppressive treatment, or the risk of ischemic complications. Objectives To test the prognostic role of the OGUS score at baseline, as well as its rapidity and degree of improvement during the initial weeks following the diagnosis of GCA. Methods Patients with a new onset of GCA and a positive US at diagnosis were prospectively recruited from three academic hospitals (Pavia, Italy; Lisbon, Portugal; Bonn, Germany). Patients were recruited if they had not received high-dose GCs (≥ 30 mg/day of prednisone equivalent) for more than 15 days. US was performed at baseline, 1 week, 3 weeks, 6 weeks, and 12 weeks during follow-up by the same expert sonographer in each centre (SM, CP, VS). OGUS was calculated as reported in (1). Clinical outcomes were assessed every 3-6 months during a 3-year follow-up and included the occurrence of relapses (defined as the recurrence of GCA-related symptoms or rise of inflammatory markers not otherwise explained and requiring glucocorticoid [GC] increase), need for adjunctive immunosuppressive drugs, and presence of ischemic events. Selection of treatment was at the physician´s discretion, following international recommendations. A multivariate Poisson model with robust variance was performed adjusting for the following confounders: age, sex, large-vessel (LV)-GCA, GC cumulative dose, baseline OGUS. A multiple imputation was used for handling missing data. Results We included 102 patients with GCA, of whom 35 (34%) experienced a total of 66 relapses, with a median time to relapse of 210 days (IQR 94.5-323.5). LV-GCA was recorded in 44 (43%) patients and visual loss in 30 (29.4%). 28 (26%) patients received an adjunctive immunosuppressive drug (IL-6 inhibitor or methotrexate) during follow-up. The median baseline OGUS score was 1.4 (IQR 1.1-1.7). The OGUS score at the time of diagnosis correlated with the risk of relapse during the following 12 months [incidence rate ratio (IRR) for 0.5 points-increase in OGUS: 3.779 (95%CI 1.170-12.208)]. The speed and extent of OGUS reduction within the first three weeks post-diagnosis were found to inversely correlate with the risk of future relapses during a 3-year follow-up. (Table 1). The OGUS score significantly increased in patients who experienced a relapse [median OGUS in patients at relapse vs non-relapsing patients: 1.07 (95%CI 0.81-2.04) vs 0.96 (0.79-1.78); p<0.05] (Figure 1). An OGUS normalization (reaching a score < 1) over the first 12 weeks from diagnosis was inversely associated with the need for adjunctive treatment with immunosuppressive drugs [IRR at 3 weeks: 0.571 (95%CI 0.345-0.945), IRR at 12 weeks: 0.558 (0.319-0.974)]. OGUS did not correlate with the risk for ischaemic events. Conclusion We demonstrated for the first time that the extent and severity of disease measured with ultrasound at diagnosis of GCA has a prognostic role. A higher OGUS score at diagnosis predicts early relapses during the following 12 months. An earlier reduction of OGUS during the first three weeks from diagnosis is associated with a lower long-term risk of relapse. The rapidity and degree of OGUS improvement correlated with the need for treatment intensification. REFERENCES [1] Dejaco C, Ponte C, Monti S, et al. The provisional OMERACT ultrasonography score for giant cell arteritis. Ann Rheum Dis 2023;82:556-64. • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint Acknowledgements NIL Disclosure of Interests None declared

Background Early inflammatory arthritis is a condition that may evolve to several known rheumatic diseases, such as rheumatoid arthritis (RA). Alterations in JAK-STAT signaling pathway have been documented in several immune-mediated disorders such as RA. We hypothesize that JAK- STAT pathway is key to chronic arthritis onset and its early inhibition might have a major effect on allowing lasting disease control. Objectives We aimed to characterize peripheral blood leukocyte populations of untreated early arthritis patients (with <1 year of symptom duration) and evaluate the effect of conventional treatment with methotrexate (MTX) on JAK-STAT signaling pathway. Moreover, a group of refractory established RA patients was recruited and the effect of upadacitinib (UPA), a JAK inhibitor approved for RA treatment, was assessed. Methods Blood samples from untreated early arthritis and established refractory RA patients were collected at baseline and after 6 months of treatment with MTX and UPA, respectively. Peripheral blood mononuclear cells (PBMC) were isolated by density-gradient centrifugation and the frequency, phenotype and STAT phosphorylation (pSTAT) levels were evaluated on peripheral blood leukocytes [B cells, T cells, monocytes and dendritic cells (DC)] by flow cytometry. A group of age and gender matched healthy controls was also included for comparison. Results We included 46 early arthritis patients (67% female, age 59.0±16.1 years, symptom duration 6.1±2.0 months). We found significant differences in both frequency and phenotype of immune cell populations in early arthritis patients, particularly in seropositive RA, when compared to controls (Figure 1). Treatment with MTX restored some of these alterations, increasing the frequency of total B cells, the percentages of pre-SM, post-SM and DN B cells and decreasing transitional and naïve B cell subsets. Cytotoxic T cells were also affected by treatment, with an increase in frequency when compared to baseline. No alterations were observed in monocytes and in the main DC populations. However, CD1c+ mDCs were significantly increased in percentage, whereas CD141+ mDCs became severely reduced after treatment. The measurement of pSTAT levels by median fluorescence intensity (MFI) showed decreased STAT activation in early disease in comparison with healthy controls (Figure 2), which was maintained after conventional treatment with MTX. In addition, 10 established refractory RA patients (80% female, age 54.0±9.5 years, disease duration 15.4±9.1 years) were included. After 6 months of treatment, UPA mainly affected the frequency of DC subpopulations and T cell phenotype, but did not significantly impact pSTAT levels in peripheral blood leukocytes. Conclusion Our data supports the immunomodulatory effects of both MTX and UPA in peripheral blood leukocytes from early and established arthritis patients and reinforce the role of JAK-STAT signaling pathway since early disease onset. • Download figure • Open in new tab • Download powerpoint Figure 1. Early arthritis patients present alterations in the frequency of circulating immune cell subpopulations when compared to controls • Download figure • Open in new tab • Download powerpoint Figure 2. STAT phosphorylation levels are altered in peripheral blood leukocyte populations from untreated early arthritis patients when compared to healthy controls. REFERENCES NIL Acknowledgements NIL Disclosure of Interests None declared

Background Biosimilar drugs are agents with highly similar characteristics to original biologic DMARDs. There is scarce data about their use in pregnancy, and for this reason they are not addressed in the latest EULAR, ACR or British Society guidelines on reproductive health for rheumatic patients. Objectives To describe maternal and perinatal outcomes in women using biosimilar TNFi during conception and gestation. Methods Single-centre observational retrospective study of pregnant rheumatic woman exposed to biosimilar TNFi. Results Five pregnancies in three caucasian women were included. Rheumatic diagnoses were rheumatoid arthritis (RA), axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA). Table 1 summarizes maternal and perinatal outcomes and relevant clinical data. At the time of conception, all patients were in remission under Bs therapy: one on Bs infliximab (IFXb) and two on Bs etanercept (ETAb).The first case refers to a nulliparous woman aged 35 diagnosed with axSpA. After conception, IFXb 5 mg/kg every 9 weeks was maintained up to the 18 week of gestation (WG). No adverse pregnancy outcomes (APO) or disease activity flares were noticed. Three years later, during a subsequent pregnancy, she remained on IFXb monotherapy at the same dosing scheme. At 18WG, she experienced a sacroiliitis flare, resolved after joint injection with methylprednisolone. IFXb was last administered at the 24WG, and the remaining pregnancy was uneventful. The second patient was a 30-year-old woman diagnosed with RA treated with ETAb 50mg weekly, sulfasalazine 1g/day and prednisolone (≤5mg/day). After conception, ETAb dosage was adjusted to 50mg every other week until 30WG due to sustained remission. No flares or APO were recorded. This woman had experienced a miscarriage at 8WG the year before, while on remission and under the above-mentioned treatment. The last case involves a 32-year-old woman with PsA under ETAb 50mg weekly in monotherapy. In this patient, ETAb was continued up to the 26WG, when it was stopped due to a mild urinary tract infection, successfully treated with a course of antibiotics. Although the arthritis remained under control, psoriasis relapsed after discontinuing the Bs, requiring the use of topical emollients. All women gave birth to healthy term babies. One neonatal infection (E.coli urosepsis) required intravenous antibiotics and resolved without sequelae. All women decided to breastfeed and resumed biosimilar therapy postpartum. Conclusion No safety or efficacy issues arose from the use of IFXb or ETAb during conception, pregnancy or breastfeeding. Our data are reassuring: patients under biosimilar TNFi should continue their usual therapy to reduce the risk of flares and of APO.REFERENCES: NIL. View this table: • View inline • View popup Table 1. Maternal and perinatal outcomes in women with rheumatic diseases treated with biosimilar TNF inhibitors during conception and pregnancy. Acknowledgements NIL Disclosure of Interests None declared

Background Rheumatic and musculoskeletal diseases (RMDs) frequently affect individuals of childbearing age. During pregnancy, disease control is vital, as disease activity leads to adverse outcomes for both the mother and the baby. Clinical guidance documents on the use of anti-rheumatics in pregnancy by the European Alliance of Associations in Rheumatology (EULAR), the British Society for Rheumatology (BSR), and the American College of Rheumatology (ACR), rely on systematic reviews of available data, but the recommendations are more liberal than the regulators reference safety information (RSI), creating inconsistent information. This misalignment challenges the shared decision-making process between healthcare providers (HCPs) and individuals with RMDs, potentially affecting their therapeutic choices during pregnancy. We hypothesize that such misalignment adversely affects the shared decision-making process and relationship between HCPs and individuals with RMDs. Objectives The PRAISE survey (Perception of health care providers Regarding Anti-rheumatics in pregnancy and breastfeeding: advice, Information and patient perSpEctives) was designed to explore the perspectives of HCPs on the shared decision-making process regarding the use of anti-rheumatics in pregnancy and breastfeeding, with particular focus on the scenario encompassing conflicting information. Methods We conducted a multinational, electronic survey among doctors, nurses and midwives in and outside of Europe from May and to December 2023. The survey was promoted by the EULAR Study Group on Reproductive Health & Family Planning (ReHFaP) and was distributed among networks of HCPs working with RMDs and pregnancy.The survey consisted of 24 questions that explored how HCPs feel about prescribing and advising on anti-rheumatic drugs in pregnancy and breastfeeding and their use of clinical guidance documents in clinical practice. It also explored how HCPs perceive different clinical scenarios involving conflicting information between guidance documents and RSI. Results Responses on all questions were collected from 414 participants from 24 countries (19 EU countries and 5 non-EU countries), 70% of respondents were women (median age of 44 years). The majority were doctors (82%), practicing for >10 years (63.5%), with experience in prescription of anti-rheumatics for pregnant or lactating individuals. The majority of prescribers (88%) felt comfortable when prescribing anti-rheumatics in pregnancy, and 65% responded that they frequently or very frequently collaborate with other medical specialties (Figure 1).The clinical guidance documents were used by 92% of respondents in daily practice, with 83% of respondents reporting them very or extremely useful. Twenty-five percent of the respondents were likely or very likely to discontinue an ongoing treatment if advice between the clinical guidance document and the RSI were conflicting, i.e. if the clinical guidance document supported the continuation of treatment and the RSI stated that the treatment was not compatible with use in pregnancy. On a Visual Analogue Scale from 0-100 (with 100 being “extremely likely”), 60 was the average score reported when questioned about the likelihood that their patient will stop taking a medication if the RSI states that the drug has “a small increased risk of major malformations and should not be used during pregnancy unless your doctor considers the benefits outweigh the risk”. Most importantly, 58% reported that conflicting information causes confusion and tension in the patient-doctor relationship (Figure 2). Conclusion The PRAISE survey highlights the crucial role of clinical guidance documents in instructing HCPs in managing anti-rheumatic drugs during pregnancy in patients with RMDs.However, the noteworthy finding that a quarter of respondents expressed readiness to cease medication use, when confronted with inconsistent advice, underscores the imperative of harmonizing recommendations between scientific societies and regulators. This would safeguard the well-being of mother and child, address patient apprehension and strengthen the patient-doctor relationship. REFERENCES: NIL. • Download figure • Open in new tab • Download powerpoint • Download figure • Open in new tab • Download powerpoint Acknowledgements Kirsten Frohlich (Danish Hospital for Rheumatic Diseases) is kindly acknowledged for her logistic support. Disclosure of Interests None declared