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Background and purpose: The long-term impact of gadolinium retention in the dentate nuclei of patients undergoing administration of seriate gadolinium-based contrast agents is still widely unexplored. The aim of this study was to evaluate the impact of gadolinium retention on motor and cognitive disability in patients with MS during long-term follow-up. Materials and methods: In this retrospective study, clinical data were obtained from patients with MS followed in a single center from 2013 to 2022 at different time points. These included the Expanded Disability Status Scale score to evaluate motor impairment and the Brief International Cognitive Assessment for MS battery to investigate cognitive performances and their respective changes with time. The association with qualitative and quantitative MR imaging signs of gadolinium retention (namely, the presence of dentate nuclei T1-weighted hyperintensity and changes in longitudinal relaxation R1 maps, respectively) was probed using different General Linear Models and regression analyses. Results: No significant differences in motor or cognitive symptoms emerged between patients showing dentate nuclei hyperintensity and those without visible changes on T1WIs (P = .14 and 0.92, respectively). When we tested possible relationships between quantitative dentate nuclei R1 values and both motor and cognitive symptoms, separately, the regression models including demographic, clinical, and MR imaging features explained 40.5% and 16.5% of the variance, respectively, without any significant effect of dentate nuclei R1 values (P = .21 and 0.30, respectively). Conclusions: Our findings suggest that gadolinium retention in the brains of patients with MS is not associated with long-term motor or cognitive outcomes.

Diet is increasingly considered a major contributor to the chronic disease burden in Western societies. Plant-based diets are becoming more mainstream as a way to reduce disease risk and improve quality of life. Clinicians who understand the health benefits and risks associated with various plant-based diets can provide helpful advice to their patients. This article discusses six common beliefs about plant-based diets and reviews guidelines for plant-based eating.

BackgroundPolymyalgia rheumatica (PMR) is diagnosed and treated by both general practitioners (GP) and rheumatologists. How rheumatologists around the world manage the referral process of patients with PMR from GP’s has not been described. EULAR/ACR guidelines recommend initial prednisolone doses between 12.5 and 25 mg, but it is unknown if guidelines are followed in daily clinical practice1. In addition, the understanding of challenges for recruitment to clinical trials in PMR is currently limited.ObjectivesThis study aims to describe the management of referrals, treatment strategy, and recruitment to clinical trials in PMR among rheumatologists worldwide.MethodsAn English language questionnaire was drafted by a working group of rheumatologists and GP’s from 6 different countries. Questions concerned: 1: respondent, 2: referrals, 3: prednisolone, and 4: barriers to research. Questionnaires were distributed to rheumatologists via members of the International PMR/GCA study group. Answers were collected via an online survey tool (Redcap), from 2nd of November 2021 to 27th of January 2022. Countries were grouped by income and geographical region based on the World bank classifications. Data were weighted by number of inhabitants in a country, based on the United Nations age specific population count, divided by number of respondents in a country. Countries with more than 20 respondents were included.ResultsResults from 27 countries were analysed including 1000 responders in total (Figure 1). There was large variation in time from referral to first assessment, initial dose of prednisolone was high, duration of treatment was relatively short, and a large proportion of patients with newly diagnosed PMR received prednisolone prior to rheumatological evaluation (Table 1). Concerning the 15% of respondents who performed research in PMR, 52% had participated in clinical trials and 56% of the responders experienced difficulties with recruitment.Table 1.Characteristics of reponders, referrals, and treatment.Geographical regionIncomeThe worldEurope and Central AsiaNorth AmericaLatin AmericaEast Asia and PacificSouth AsiaMiddle East and AfricaHigh- income countriesLow- and middle- income countriesRespondersResponders (n), Completed questionnaire (total)875 (1000)294 (304)78 (81)136 (152)53 (53)53 (72)261 (338)446 (458)429 (542)Experience as rheumatologist (years)11 (6-20)12 (6-20)7 (4-20)11 (6-23)21 (10-30)7 (4-10)9 (5-18)11 (5-22)8 (5-12)ReferralsGP’s can discuss patients prior to referral, %647979575860677461Referred patients seen (%)100 (90-100)100 (90-100)100 (100-100)100 (100-100)100 (95-100)100 (100-100)100 (60-100)100 (100-100)100 (90-100)Evaluation > 2 weeks after referral, %26498060216185815PrednisoloneStarted prior to rheumatological evaluation (%)50 (20-50)60 (30-80)70 (50-80)50 (10-50)30 (20-50)50 (20-80)20 (0-50)50 (30-80)50 (10-70)Initial dose (mg)20 (15-40)20 (15-20)20 (15-20)20 (20-40)15 (15-15)20 (15-40)20 (15-40)15 (15-20)20 (15-40)Initial dose > 25 mg, %32964104143642Duration of treatment (months)12 (6-12)12 (12-18)12 (10-18)6 (3-12)18 (12-18)12 (6-12)6 (3-12)12 (12-18)9 (6-12)Data presented as weighted median (interquartile range) unless otherwise stated.GP: general practitionerConclusionThis is the first description of current practice in managing referrals and treatment of PMR by rheumatologists worldwide. In general, median treatment duration was according to EULAR/ACR guidelines, but initial dose of prednisolone was often higher than recommended in many parts of the world. PMR patients were often seen more than two weeks after referral, and treatment had started prior to first rheumatological evaluation.References[1]Dejaco C, Singh YP, Perel P, et al. 2015 Recommendations for the management of polymyalgia rheumatica: a European League Against Rheumatism/American College of Rheumatology collaborative initiative. Annals of the rheumatic diseases 2015; 74(10): 1799-807.AcknowledgementsThis study was endorsed by the international PMR/GCA study group.Disclosure of InterestsAgnete Overgaard Donskov: None declared, Sarah Mackie: None declared, Ellen-Margrethe Hauge Speakers bureau: AbbVie, Sanofi, Sobi, MSD, UCB, Consultant of: AbbVie, Sanofi, Sobi, MSD, UCB, Grant/research support from: Novo Nordic Foundation, Danish Rheumatism Association, Danish Regions Medicine Grants, Roche, Novartis, Celgene, MSD, Pfizer, Roche, Sobi, CARLOS TORO GUTIÉRREZ: None declared, Ib Hansen: None declared, Andrea Hemmig: None declared, Aatke van der Maas: None declared, Tamer A Gheita: None declared, Berit Dalsgaard NIelsen Paid instructor for: Roche, Karen Douglas: None declared, Richard Conway Speakers bureau: Janssen, Roche, Sanofi, Abbvie,, Elena Rezus: None declared, Bhaskar Dasgupta: None declared, Sara Monti: None declared, Eric Matteson Consultant of: Boehringer-Ingelheim,, Grant/research support from: Boehringer Ingelheim,, Sebastian E. Sattui Grant/research support from: AstraZeneca, Mark Matza: None declared, Vanessa Ocampo Speakers bureau: Abbvie, Andrea Bran: None declared, Simone Appenzeller Grant/research support from: GSK, Annelise Goecke Speakers bureau: Abbvie, Boehringer Ingelheim, Recalcine. Consultant Abbvie, Boehringer Ingelheim, NELLY COLMAN MC LEOD Speakers bureau: Laboratorios FAPASA (Farmacéutica Paraguay), Helen Keen Speakers bureau: Roche, Abbvie, Masataka Kuwana: None declared, Latika Gupta: None declared, Babur Salim: None declared, Ghita Harifi Speakers bureau: Abvie, Johnson and johnson, Lilly, Novartis, Mariama Erraoui: None declared, Nelly Ziade Speakers bureau: Abbvie, Eli Lilly, Janssen, Pfizer, Pierre Fabre, Roche, Novartis, Sanofi-Aventis, Paid instructor for: Abbvie, Eli Lilly, Sanofi-Aventis, Pfizer, Janssen, Novartis., Consultant of: Abbvie, Eli Lilly, Janssen, Pfizer, Roche, Novartis, Sandoz, Grant/research support from: Abbvie, Celgene - Algorithm, Bristol-Myers Squibb - NewBridge, Pfizer, Nizar Abdulateef Al-Ani: None declared, Adeola Ajibade: None declared, Johannes Knitza: None declared, Line Frølund: None declared, Max Yates: None declared, Victor Pimentel-Quiroz: None declared, Andre Lyrio: None declared, Maria Sandovici: None declared, Kornelis van der Geest Speakers bureau: Roche, Toby Helliwell Grant/research support from: Valneva, Elisabeth Brouwer Speakers bureau: Roche, Christian Dejaco Speakers bureau: Abbvie, Eli Lilly, Janssen, Novartis, Pfizer, Roche, Galapagos and Sanofi, Consultant of: Abbvie, Eli Lilly, Janssen, Roche, Galapagos and Sanofi, Kresten Keller: None declared

Airway compromise is the second leading cause of preventable death on the battlefield. Special operations medic comprise the majority of medics trained to perform endotracheal intubation (ETI), mostly by way of direct laryngoscopy (DL). The iView is a disposable, low-cost video laryngoscopy (VL) device, enabling its distribution to prehospital medical providers. We seek to compare time to intubation between DL and iView VL among special operations combat medics (SOCM).We conducted a prospective, randomized, crossover trial. We enrolled special operations medics assigned to Joint Base Lewis McChord, WA. We randomized subjects to first performing VL or DL. Subjects performed a total of 10 ETI, 5 by VL and 5 by DL, on adult airway manikins. The primary outcome was time (in seconds) for ETI completion.A total of 32 medics completed 160 with DL ETIs and 160 VL ETIs. A total of 10 of 32 (31.3%) medics reported no previous experience with VL devices. We found a significant difference in time to intubation between VL and DL (20.4 (95% CI 20.6 - 26.1) seconds versus 23.4 (95% CI 18.7 - 22.2) seconds; p = 0.03) in favor of VL. All VL attempts were successful while 96.9% of DL were successful (p = 0.10). With respect to end-user appraisal of devices, a significant number of medics preferred the iView VL over DL (23 versus 9; p is less than 0.00001). Additionally, medics considered iView VL easier to use (5 [5-6] versus 5 [4-5]; p=0.0004) and easier to learn, remember, and perform by combat medics (5 [5-5] versus 4 [4-5]; p=0.008).Special operations medics naïve to VL rapidly learned how to effectively utilize iView VL, as evidenced by a significant difference in time to intubation in favor of iView VL. Additionally, most medics favored iView VL and considered it easy to use, learn, and remember.

Naupactini is a tribe of Neotropical broad-nosed weevils highly diverse in South America. This group includes several parthenogenetic species, some of them harmful for agriculture and invasive around the world. Although some hypotheses based on polyploidy and hybridization have been proposed to explain the origin of parthenogenesis in weevils, the infection with the bacterium Wolbachia pipientis may be involved in the origin of parthenogenetic reproduction of some species. In this contribution, we studied the role of Wolbachia in the reproductive biology of Pantomorus postfasciatus Hustache (Coleoptera: Curculionidae) through a curing experiment using tetracycline. This weevil has a mixed mode of reproduction including sexual and parthenogenetic populations. Exposure to an antibiotic did not affect fecundity, but did reduce egg hatching in comparison with untreated individuals. Consequently, we inferred that Wolbachia most probably takes part in the reproduction of P. postfasciatus, either by exerting nutritive functions in oogenesis necessary for egg hatching, or by induction of thelytokous parthenogenesis. Although infection was not totally cured, Wolbachia load was significantly lower in treated than in control females. Thereby, we hypothesize that a minimum threshold density of Wolbachia is required for weevil reproduction. We conclude that all analyses support a role of Wolbachia in P. postfasciatus reproduction. Fil: Rodriguero, Marcela Silvina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina Fil: Scannapieco, Alejandra Carla. Instituto Nacional de Tecnología Agropecuaria. Centro de Investigación en Ciencias Veterinarias y Agronómicas. Instituto de Genética; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Monti, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina Fil: Chifflet, Lucila. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina Fil: Elías Costa, Agustín Jorge. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Museo Argentino de Ciencias Naturales "Bernardino Rivadavia"; Argentina Fil: Lanteri, Analia Alicia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata; Argentina Fil: Confalonieri, Viviana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina

International audience; Modelling and simulation (M&S) have gradually become irreplaceable tools in the field of Nuclear Science and Technology (NS&T), including nuclear energy systems. This is partly due to growing computational resources and advances in computational science and partly to the difficulties to finance, build and license new experimental facilities. However, the utilization of M&S for research and development (R&D) and education and training (E&T) applications is somewhat hampered by limited accessibility to controlled and sensitive nuclear M&S tools as well as by the desires of the developers of these tools to retain their intellectual property (IP). Open-source software and open-access data are growingly perceived as means to accelerate innovation by promoting synergistic collaborative developments while lowering the barriers associated to code distribution, modification, and sharing. Open-source software development is ideal for R&D and E&T purposes because it permits the enhancement of understanding, the use of advanced computational methods and it promotes the cooperation among researchers and scientists, without rigorous constraints on quality assurance or reliance on proprietary data for technology-specific validation. As a fundamental research tool, this helps to mitigate constraints related to dual use of such technology. It is in this context that an initiative is being launched under the aegis of the International Atomic Energy Agency (IAEA) to promote the development and application of open-source multi-physics simulation in support of R&D and E&T in NS&T. This paper presents scope and objectives of this initiative.

Objective: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. Methods: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients’ representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. Results: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. Conclusions: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

BackgroundPolymyalgia rheumatica (PMR) can be associated with giant cell arteritis (GCA), even in the absence of clinical suspicions of vasculitis. In addition, some studies have shown an association of PMR with the predominantly large vessel involvement.ObjectivesThe objective of our study was to assess the presence of subclinical GCA in patients with PMR and to compare its pattern of vascular involvement to patients with classical GCA.MethodsEight rheumatology European centers participated in the study. Cohort A represented consecutive newly diagnosed patients with PMR who fulfilled the 2012 EULAR/ACR Provisional Classification Criteria for Polymyalgia Rheumatica2 and had no symptoms or signs suggestive of GCA. Ultrasound (US) examination of four vessel territories (i.e. temporal, carotid, subclavian and axillary arteries) was performed bilaterally. Cohort B included all consecutive patients with the diagnosis of GCA evaluated on the fast-track clinic of one of the hospitals (HULP). The halo sign was considered as positive US finding for GCA3. In addition, intima-media thickness of arteries was measured, with a cut-off ≥0.34 mm for temporal arteries (TA) frontal and parietal, 0.42mm for common TA, and ≥1 mm for common carotid, axillary and subclavian arteries for positive result. The clinical characteristics of PMR patients were recorded and the frequency of subclinical GCA determined.ResultsCohort A included 41 PMR patients with subclinical GCA. Cohort B was formed by 97 GCA. The characteristics of the patients are shown in the Table 1. Figure 1 shows the different subtypes of vessel involvement in patients with PMR and subclinical GCA and in patients of the fast-track clinic with the diagnosis of GCA in a single hospital.Figure 1.Subtypes of vessel affectation in Subclinical GCA in PMR and in classical GCATable 1.Clinical characteristics of patients of Cohort A (Subclinical GCA in PMR n = 41/216) and B (GCA in the fast-track clinic n = 97)Cohort A (n = 41)Cohort B (n = 97)Sex female (%)17 (41.5%)53 (54.6%)Age (years) mean ± SD74±6.779 ± 12CRP mg/L49.6±49.146 ± 81.6Polymyalgia rheumatica41 (100%)47 (48.5%)Constitutional symptoms19 (35.18%)35 (36.1%)Subclinical PMR has a predilection for affectation of large vessels, followed by isolated cranial pattern (ie. Isolated temporal artery involvement) and by the mixed (cranial and extra-cranial) form. On the contrary, in classical GCA an isolated cranial involvement represents the more common pattern, followed by the mixed and finally isolated large vessel involvement.ConclusionSubclinical GCA in PMR shows a principal isolated extra-cranial involvement and with clearly different pattern than classical GCA.AcknowledgementsTo the GCA/PMR study groupDisclosure of InterestsNone declared

BackgroundJanus kinase inhibitors (JAKi) are efficacious drugs for the control of disease activity in rheumatoid arthritis (RA). The effect on patient-reported outcomes (PROs) has been shown in randomized clinical trials, but is still largely unknown in real-life scenarios.ObjectivesTo assess the time to onset and magnitude of improvement across a number of different PROs in patients with RA treated with JAKi.MethodsPatients were selected from centres involved in the LORHEN Registry. Patients with a diagnosis of RA initiating a JAKi (Baricitinib or Tofacitinib) between May 2019 and February 2020 were clinically assessed at baseline, 8 weeks and 16 weeks with DAS28 and SDAI. PROs were collected at baseline, 2 weeks, 4 weeks, 8 weeks and 16 weeks from JAKi initiation. The PROs assessed at each timepoint were: Patient Global Assessment (PGA), General Health (GH), 0-100 mm visual analogue scale (VAS)-pain, VAS-fatigue, Health Assessment Questionnaire (HAQ), The Clinical Arthritis Activity (PRO-CLARA) questionnaire.ResultsThirty-eight patients (female 76%, mean age 57±15) were enrolled for a total of 152 visits for PROs assessments. Patients had received a median of 2 (IQR 1;3) previous conventional synthetic DMARDs (csDMARD) and a median of 2 (0;3) biological DMARDs. Mean disease duration at time of JAKi initiation was 10±9.5 years. JAKi was prescribed as combination therapy with a csDMARD in 20 (53%), concomitant glucocorticoids (GC) in 28 (73%) patients, at a mean dose of 6±2 mg/day. Twenty-one (55) patients were on regular analgesics. DAS28-ESR reduced from 4.5±0.9 at baseline to 2.6±0.9 at 8 weeks (pBy two weeks, all PROs had a significant reduction compared to baseline (Figure 1). For PGA, VAS-pain, VAS-fatigue a further significant reduction was observed by week 4 to then stabilize between week 8 and 16. GH and HAQ had a significant reduction by week 2 and remained stable thereafter. All PROs were significantly lower during all time-points compared to baseline. The PRO-CLARA Road score to assess physical function significantly improved starting from week 2 from a score of 4±2 to 2±2 at the end of follow-up. The PRO-CLARA self-administered tender joint count was stable at week 2 (mean score 4±2) but recorded an improvement from week 4 onwards (pFigure 1.Improvement of patient-reported outcomes over the period of observationConclusionTreatment with JAKi ensures a very rapid and persistent improvement of several PROs, including pain, fatigue and physical function, as early as 2 weeks treatment even in patients with long-standing RA treated with several lines of previous DMARDs.Disclosure of InterestsNone declared

BackgroundNo large assessment of the general cancer occurrence in eosinophilic granulomatosis with polyangiitis (EGPA) has been reported.ObjectivesThe aim is to investigate the incidence of malignancies in EGPA patients and to examine the effect of immunosuppressive therapy on malignancy risk in these patients.MethodsThe occurrence of cancers was assessed in a cohort of 303 incident EGPA patients (54.8% female, 44% MPO-ANCA positive, 53 [41-61] years old at diagnosis), diagnosed between 1987 and 2019. Demographic, clinical and laboratory data, and the use of immunosuppressive drugs were assessed. Through linkage with Regional Italian Cancer Registries, information about any malignancy occurring before and after EGPA diagnosis was collected. For each patient, the person-years (PY) of follow-up was calculated till the first event: cancer occurrence, last follow-up or death. The PY was stratified by sex, age (in 5-year groups) and calendar-decades (2000-2009 and 2010-2019). Standardized incidence ratios (SIR) between observed and expected numbers (retrieved from the AIRTUM-AIOM database) of cancers were calculated with exact Poisson regression analysis and used as a measure of risk difference.ResultsThirty patients developed a total of 42 malignancies during a median follow-up of 4.4 [2.1-8.5] years. After excluding patients with a diagnosis of cancer before EGPA onset, 20 first malignancies were observed in 1276 PY observation period. The SIR (95% Poisson CI) malignancy risk was 1.99 (1.22-3.08; p=0.007) for all cancers at all sites, and 1.86 (0.98-2.75; p= 0.025) for all cancers excluding non-melanoma skin cancers. Incidence rates were significantly higher in ANCA positive patients (SIR 2.43 [1.30-4.16]; p=0.007) when compared to ANCA negative, and in those treated with cyclophosphamide (SIR 2.42 [1.11-4.60]; p=0.030) when compared to other immunosuppressive agents. Median latency from EGPA onset and first cancer diagnosis was 5 (2-11) years, with 63.3% of patients developing cancer within 1 and 5 years. Malignancy-free survival at 2, 5, and 10 years of follow-up was 96%, 91%, and 70%, respectively. Of these malignancies, 30% were skin cancers, 25% prostate cancers and 20% breast cancers. Comparing patients who developed malignancies with those who did not, any significant difference was noted regarding sex, ANCA status, age at diagnosis, clinical manifestations, BVAS, FFS, environmental exposure, smoking habit and cancer familiarity. Type of treatment and cumulative doses of cyclophosphamide were not associated with higher incidence of cancers.ConclusionEGPA patients have a two-fold risk of overall malignancy than the general population. This cancer excess might be driven by a combination of already known treatment-associated factors and other unknown disease-associated factors, which should be further investigatedReferencesNAFigure 1.Disclosure of InterestsNone declared

BackgroundThe 2008 and 2016 European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of ANCA-associated vasculitis (AAV)1,2 have supported clinicians with comprehensive recommendations for the treatment of patients with AAV in daily practice. During the past 5 years, the publication of several high-impact randomized-controlled studies have further improved the standard of care of AAV.ObjectivesThe aim of this systematic review was to collect evidence supporting the 2022 update the AAV management recommendations.MethodsThe recommendations were developed based on an evidence-based approach as outlined in the 2014 EULAR standardized operating procedures (SOP)3. Areas of interest were adopted from the 2016 recommendations and updated by identifying additional topics through a Delphi process. Key questions were framed in the PICO (Population, Intervention, Comparator, Outcome) format and a search strategy consisting of keywords identifying treatment-related topics of interest was created based on the PICO questions. Aspects of drug treatment and other therapeutic interventions in AAV were included in the search, with a focus on remission induction, maintenance treatment and steroid sparing protocols. Outcomes such as survival, remission/relapses, infectious complications and malignancies were also covered. PubMed (Medline), Embase and the Cochrane Library databases were searched for articles providing data on the search questions. Abstracts of the annual meetings of EULAR, ACR, ERA-EDTA, ASN and the Vasculitis and ANCA Workshops were also screened, but restricted to randomized controlled clinical trials (RCTs).After deduplication publications were sorted by title and abstract first. There was full text review for articles eligible after title/abstract screening. The data were extracted from included articles and grouped according to the PICO questions. Data extraction results were collected in evidence tables.The Cochrane revised tool for assessing risk of bias for RCTs (RoB2), ROBINS-1 for observational studies and AMSTAR II for meta-analyses were used for bias assessment. Evidence was categorized based on the GRADE system as per EULAR SOP3.ResultsBased on the results of the Delphi, 11 topics related to therapeutic interventions were identified that were transformed into PICO questions (Table 1). Other items that received lower scores were added in the format of subquestions. Based on these research questions, search strings for the SLR were created.Table 1.Key topics of interest for treatment strategies identified in the Delphi exercise grouped according to the PICO formatPatientsIntervention & ComparatorsOutcomeDiagnosisCyclophosphamideDisease-related outcomesGranulomatosis with PolyangiitisRituximabTreatment-related adverse eventsMicroscopic PolyangiitisMycophenolateEosinophilic Granulomatosis with PolyangiitisMethotrexateDisease severityAzathioprineNew-onset diseaseGlucocorticoidsRelapsing diseaseAvacopanOrgan- or life-threatening diseaseMepolizumabNot organ- or life-threatening diseasePlasma exchangeThe SLR was still ongoing at the time this abstract has been written and results of the SLR will be presented at the meeting.ConclusionThis SLR identified recent developments affecting key areas of AAV treatment, that provide systematic evidence to inform the 2022 update of the EULAR recommendations for the management of AAV, which will also be presented at this meeting.References[1]Mukhtyar C, et al. EULAR Recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2008;68:310-317.[2]Yates M et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94[3]van der Heijde D et al. 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis. 2015 Jan;74(1):8-13.AcknowledgementsThe project is funded by EULAR.Disclosure of InterestsJan Schirmer: None declared, Beatriz Sanchez-Alamo: None declared, Sara Monti: None declared, Bernhard Hellmich Speakers bureau: Abbvie, BMS, Chugai, GSK, MSD, Novartis, Pfizer, Roche, Vifor, Consultant of: Boehringer, BMS, Chugai, GSK, InflaRx, Novartis, Roche, Vifor, David Jayne Speakers bureau: Vifor, Consultant of: Astra-Zeneca, Boehringer, BMS, Chemocentryx, Chugai, GSK, Novartis, Roche

BackgroundThe 2008 and 2016 European Alliance of Associations for Rheumatology (EULAR) recommendations for the management of ANCA-associated vasculitis (AAV)1,2 have supported clinicians with recommendations for the accurate diagnosis, monitoring and for the management of the long-term complications of patients with ANCA-associated vasculitis (AAV). Since the publication of the last EULAR guidelines, several high-impact research articles have provided further evidence to improve diagnosis and monitoring of AAV-patients.ObjectivesThe aim of this systematic review was collecting evidence supporting the 2022 update of the AAV management recommendations.MethodsThe recommendations were developed based on the 2014 EULAR standardized operating procedures (SOP)3. Areas of interest were adopted from the 2016 recommendations and updated by identifying additional items through a Delphi exercise. Key questions were framed in the PICO (Population, Intervention, Comparator, Outcome) format. Keywords identifying topics of interest for the diagnosis and follow up were gathered based on the PICO questions and then incorporated into a search string. A systematic literature research (SLR) was performed according to the EULAR SOP. PubMed (Medline), Embase and the Cochrane Library databases were searched for articles providing data on the search questions. Abstracts of the annual meetings of EULAR, ACR, ERA-EDTA, ASN and the Vasculitis and ANCA Workshops were also screened, but restricted to randomized controlled clinical trials (RCTs).After deduplication, publications were first sorted by title and abstract and then full text review was done for eligible articles. The data were extracted from included articles and grouped according to the PICO questions. Data extraction results were collected in evidence tables.The Cochrane revised tool for assessing risk of bias for RCTs (RoB2), ROBINS-1 for observational studies, QUADAS II for diagnostic accuracy studies and AMSTAR II for meta-analyses were used for bias assessment. Evidence was categorized based on the GRADE system as per EULAR SOP3.ResultsBased on the results of the Delphi, 3 topics related to diagnosis and follow-up were identified that were transformed into PICO questions: the impact of tissue biopsies and positive ANCA testing to support the clinical diagnosis of AAV and the impact of clinical parameters and biomarkers on disease-related outcomes and treatment-related adverse events (Table 1). Other items that received lower scores in the Delphi exercise were added in the format of subquestions (e.g. diagnostic imaging). Based on these research questions, search strings for the SLR were created.The SLR was still ongoing at the time this abstract has been written and results of the SLR will be presented at the meeting.Table 1.Topics of interest for diagnostic and follow-up testing identified in the Delphi exercisePatientsDiagnostic / follow-up procedureOutcomeGranulomatosis with PolyangiitisTissue biopsyConfirmation of diagnosis of ANCA-associated vasculitisMicroscopic Polyangiitis Eosinophilic GranulomatosisANCA testing Clinical parametersDisease-related outcomes Treatment-related adversewith PolyangiitisImaging BiomarkerseventsConclusionThis SLR identified recent developments affecting key areas of AAV diagnosis and follow-up. The results of this SLR provide systematic evidence to inform the 2022 update of the EULAR recommendations for the management of AAV, which will also be presented at this meeting.References[1]Mukhtyar C, et al. EULAR Recommendations for the management of primary small and medium vessel vasculitis. Ann Rheum Dis. 2008;68:310-317.[2]Yates M et al. EULAR/ERA-EDTA recommendations for the management of ANCA-associated vasculitis. Ann Rheum Dis. 2016 Sep;75(9):1583-94[3]van der Heijde D et al. 2014 Update of the EULAR standardised operating procedures for EULAR-endorsed recommendations. Ann Rheum Dis. 2015 Jan;74(1):8-13.AcknowledgementsThe project is funded by EULAR.Disclosure of InterestsBeatriz Sanchez-Alamo: None declared, Jan Schirmer: None declared, Sara Monti: None declared, Bernhard Hellmich Speakers bureau: Abbvie, BMS, Chugai, GSK, MSD, Novartis, Pfizer, Roche, Vifor, Consultant of: Boehringer, BMS, Chugai, GSK, InflaRx, Novartis, Roche, Vifor, David Jayne Speakers bureau: Vifor, Consultant of: Astra-Zeneca, Boehringer, BMS, Chemocentryx, Chugai, GSK, Novartis, Roche, Takeda

BackgroundPolymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are closely related diseases. PMR occurs in approximately 50 % of patients with GCA1; however the prevalence of subclinical GCA in PMR has not yet been widely studied.ObjectivesThe aim of our multicenter, prospective study was to determine the prevalence of subclinical GCA in newly diagnosed PMR, using vascular ultrasound (US) as a diagnostic tool.MethodsEight European centers participated in the study. The studied cohort represented consecutive newly diagnosed patients with PMR who fulfilled 2012 EULAR/ACR Provisional Classification Criteria for Polymyalgia Rheumatica2 without symptoms or signs suggestive for GCA. All patients underwent ultrasound (US) of both hips and shoulders, as well as of four bilateral arterial territories (i.e. temporal, common carotid, subclavian and axillary arteries). Patients with positive halo signs were considered to have subclinical GCA 3. An intima-media thickness ≥0.34 mm for frontal and parietal TA, 0.42mm for common TA, and ≥1 mm for common carotid, axillary and subclavian arteries for positive result. Clinical demographic and laboratory characteristics of the PMR pure group were compared with the PMR/GCA patient group.ResultsA total of 258 patients were included, 137 (53.1%) females with a mean age of 73±8.4 years. Table 1 shows the main differences in PMR patients with and without subclinical GCA. The only statistical significant difference between the two groups was the higher prevalence of morning stiffness > 40 minutes in the pure PMR group (pThe different subtypes of vessel involvement were available in 216 cases. Data compatible with the diagnosis of GCA was found in 41 cases (19%): 10 (24.3%) had only temporal artery involvement (“cranial” GCA), 27 (65.8%) had an extra-cranial artery involvement and 4 (9.8%) a mixed form with both cranial and extra-cranial artery involvement (Figure 1).Table 1.Clinical and demographic characteristicsFigure 1.Subtypes of subclinical GCA in PMR in 216 patients with cranial and extra-cranial examinationConclusionOne fifth of PMR patients without symptoms or signs of GCA have ultrasound findings consistent with the diagnosis of GCA. Subclinical GCA in PMR shows a predilection for extra-cranial artery involvement.References[1]Buttgereit F et al. JAMA. 2016;315:2442-58.[2]Dasgupta B et al. Arthritis & Rheumatism. 2012; 64:943–954.[3]De Miguel E et al. Rheumatology 2018; 57:318-321.AcknowledgementsTo the GCA/PMR study groupDisclosure of InterestsNone declared

BackgroundThe advent of effective immunosuppressive treatments significantly improved the prognosis of ANCA-associated vasculitides (AAV), which have become chronic relapsing diseases. Patients with inflammatory rheumatic disorders are particularly prone to reduced bone mineral density (BMD) and fragility fractures (FF), due to chronic glucocorticoid therapy, immunosuppressant-induced hypogonadism, systemic inflammation, functional disability and comorbidities. At present, there is paucity of data concerning the risk of osteoporosis and FF in AAV.ObjectivesTo describe the occurrence of osteoporosis and major FF in a cross-sectional cohort of patients with AAV.MethodsPatients diagnosed with granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and eosinophilic granulomatosis with polyangiitis (EGPA), according to ACR criteria and/or Chapel Hill definitions and regularly followed-up in our vasculitis center were included. BMD was measured by dual-energy X-ray absorptiometry (DEXA) of the proximal femur and lumbar spine, between March 2016 and September 2021. Osteoporosis was defined by a T-score below –2.5 SD, whereas osteopenia was defined by a T-score between -1 and -2.5 SD, according to the World Health Organization criteria. Vertebral fractures were assessed by X-ray of the dorso-lumbar spine. Data on previous osteoporotic hip fractures were collected.ResultsSixty-two consecutive patients were included (59.7% female, mean age at time of DEXA 61.8±10.5 years, disease duration 97.0±76.1 months). Sixteen (25.8%), 8 (12.9%) and 38 patients (61.3%) were affected by GPA, MPA and EGPA, respectively. BMD findings indicating osteoporosis and osteopenia, at either the lumbar spine and/or the proximal femur, were observed in 15 (24.2%) and 39 patients (62.9%), respectively, whilst only 8 patients (12.9%) had normal BMD values at both sites. Fifteen patients (24.2%) reported 51 major FF (50 vertebral fractures, 1 hip fracture) during follow-up, with multiple major FF being recorded in 10 patients (16.1%). Osteoporosis, at least at one site, was frequent not only in post-menopausal women (19.4%), but also in 6 males (24%), 3 pre-menopausal women (50%) and 3 patients under 50 years of age (37.5%), respectively (Figure 1). Similarly, major FF occurred in 4 males (16.7%), 1 pre-menopausal female (16.7%) and 1 patient under 50 years of age (12.5%), respectively (Figure 1). Patients with osteoporosis presented a lower body mass index (BMI) (23.1±4.1 vs 25.9±4.4, P=0.03) and a higher prevalence of major FF (53.3% vs 14.9%, P=0.003) compared to patients without osteoporosis. Compared to patients without major FF, those affected by major FF were older (68.8±1.8 vs 59.4±9.3 years, P=0.003), had a higher disease duration (146.9±78.8 vs 81.8±68.9 months, P=0.003) and presented with lower proximal femur BMD values (0.657±0.122 vs 0.761±0.127 g/cm2, P=0.007) and proximal femur T-score (-2.0±0.9 vs -1.4±0.8 SD). Notably, 7 out 15 patients with FF (46.7%) did not exhibit BMD findings of osteoporosis. Other variables, including sex, disease subtype, ANCA status, chronic kidney disease or treatment with cyclophosphamide were not related to bone loss or FF.Figure 1.Proportion of patients with osteopenia, osteoporosis and major fragility fractures stratified according to sex, menopausal status and age.ConclusionPatients with AAV are particularly susceptible to BMD loss and fractures, with osteoporosis and major FF being reported in about a quarter of patients. Short-term and long-term monitoring for reduced BMD and FF is warranted in all patients with AAV, including male patients, premenopausal females and those under 50 years of age.Disclosure of InterestsNone declared

BackgroundThe ANCA-associated vasculitis patient-reported outcome (AAV-PRO) questionnaire is a 29-item disease-specific PRO measure for AAV[1]. The Italian version of the AAV-PRO questionnaire (AAV-PRO_ita) was translated in collaboration with Oxford and Bristol University (UK) and was preliminarily tested on a single-center Italian cohort[2].ObjectivesThe main objective of this multicentric study was to assess the internal consistency, feasibility, and reliability of the AAV-PRO_ita in a large cohort of Italian AAV patients. The secondary objective was to investigate the clinical characteristics of AAV patients associated with AAV-PRO_ita domains.MethodsThe AAV-PRO_ita is describes the following disease domains: (1) organ-specific and systemic symptoms and signs (SSS); (2) physical function (PF); (3) social and emotional impact (SEI). In this study, Italian-speaking AAV patients were recruited from Italian Centres (N=13) with a large experience in the diagnosis and treatment of systemic vasculitis, belonging to the Vasculitis Study Group of the Italian Society of Rheumatology. Inclusion criteria were: a confirmed diagnosis of GPA, MPA, or EGPA; ANCA positivity in at least once occasion or biopsy-proven AAV; and age ≥18 years old. Participants completed the AAV-PRO_ita at three different time-points: baseline, after 5-7 days, and at month 3.Results229 AAV-patients (56.3% women) with a median age of 61 (IQR 51-72) were recruited and completed the questionnaires. The subtype of AAV was mainly GPA (131, 57.2%), followed by EGPA (58, 25.3%), and MPA (40, 17.5%). Median BVASv3 at baseline was 0 (IQR 0-3), whereas the median BVASv3 at the onset of disease was 14 (IQR 9-20). Participants had a median duration of disease of 67 (IQR 24-126) months. Patients who experienced at least one relapse, one hospitalization, and one severe infection were 40.2%, 53.3%, and 24%, respectively. 83% of the patients were on immunosuppressant therapy and 71.6% were still receiving glucocorticoids (GC).AAV-PRO_ita questionnaire had good internal consistency (Cronbach’s Alpha range 0.81-0.93) and good test-retest reliability (ICCs range 0.93-0.96). Item response rates were high overall (maximum 0.87% missing data), supporting the feasibility of the questionnaire.Concerning the domains of the questionnaire, female AAV patients scored higher (i.e. worse) in all three domains, especially in the SEI domain (p-value0.3, p-valueConclusionThe AAV-PRO_ita questionnaire is a new 29-item, disease-specific PRO measure for use in AAV in the Italian language. It is a self-administered Italian questionnaire with good internal consistency, feasibility, and reliability. AAV-PRO_ita proved to be a useful tool to explore the AAV patient’s perception of quality of life, and it could become an important way of measuring the unmet needs of AAV patients.References[1]Robson, J.C. et al. Validation of the ANCA-Associated Vasculitis Patient-Reported Outcomes (AAV-PRO) Questionnaire. Ann. Rheum. Dis.2018, 77, 1157–1164, doi:10.1136/annrheumdis-2017-212713.[2]Treppo, E.; Palese, A.; Vita, S.D.; Quartuccio, L. AB0392 PRELIMINARY VALIDATION OF THE ITALIAN VERSION OF ANCA-ASSOCIATED VASCULITIS PATIENT-REPORTED OUTCOME (AAV-PRO_ita) QUESTIONNAIRE: FATIGUE AND CHRONIC PAIN AS UNMET NEEDS BY CURRENT TREATMENTS. Ann. Rheum. Dis.2021, 80, 1224–1224, doi:10.1136/annrheumdis-2021-eular.2123.AcknowledgementsWe thank the Italian Study Group on Systemic Vasculitis.Disclosure of InterestsNone declared

BackgroundRituximab (RTX) achieved high remission-induction and sustained maintenance rates for patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) [1], [2]. However, RTX is an expensive medication, which may potentially lead to serious side effects. Defining the best dose regimen for maintenance in AAV is still an unmet need.ObjectivesThe aim of the present study is to compare the effects of ultra-low dose RTX (500 mg or 1000 mg once per year) to standard low dose RTX (500 or 1000 mg twice per year) as remission-maintenance therapy in AAV patients.MethodsWe included consecutive AAV patients (classified as GPA and MPA [3]) referring to four different Rheumatology centers in Italy. We assessed all AAV patients who successfully achieved disease remission (BVASv3=0) with conventional RTX or cyclophosphamide regimens and have been subsequently treated with RTX for maintenance of remission. All included patients received at least three maintenance infusions with either 1000 mg or 500 mg, twice per year (standard low dose) or once per year (ultra-low dose). After a period of 18 months, we assessed the remission rate, damage (VDI), glucocorticoids intake, ANCA status, B-cells depletion and serum IgG levels.ResultsFrom January 2011 to December 2021, 83 AAV patients (mean age 51±16, 49.4% female, 95.2% ANCA positive, 65.8% anti PR3, 34.2% anti MPO), 61 classified as GPA and 22 MPA, achieved complete disease remission with conventional RTX induction regimen. After 7 [6-9] months, 29.9% patients started maintenance treatment with ultra-low dose RTX (once per year), while 70.1% patients with standard low dose (twice per year), for 18 months. No significant differences at baseline were noted between patients receiving ultra-low dose when compared to those treated with conventional low-dose.At the end of observation period, a disease flare was observed in 22.7% of the low-dose group, and 21.2% in those treated with the standard dose (p=0.881). Relapse-free survival was comparable between the two group (log-rank p=0.818, Figure 1).Figure 1.When comparing AAV patients treated with ultra-low dose regimen to those treated with low-dose, no differences were noted in negative ANCA rate (72.2% vs 67.1%, p=0.262), ANCA titer (0 [0-7.8] vs 0 [0-50] UI/mL, p=0.232), B-cells depletion rate (70.6% vs 75%, p=0.725), mean serum IgG (811 [146-922] vs 680 [429-861] mg/dL, p=0.367), mean daily glucocorticoid dosage (2.5 [0-5] vs 3.75 [0-5] mg/d, p=0.647), VDI (4 [1-5] vs 2 [1-4], p=0.098), hypogammaglobulinaemia rate (31.8% vs 36.5%, p=0.697) and deaths (4.5% vs 5.8%, p=0.831).Although not significant, patients treated with ultra-low dose had lower severe infection rate (10.5% vs 26.8%, p=0.154). Notably, in the all cohort 5 deaths were related to COVID19 pneumonia.ConclusionReduced exposure to RTX was not associated with an impaired efficacy of maintenance therapy in patients with AAV. Remission maintenance with ultra-low dose RTX is a safe and more cost-effective option.References[1]B. Terrier et al., “ANCA-associated vasculitides: Recommendations of the French Vasculitis Study Group on the use of immunosuppressants and biotherapies for remission induction and maintenance,” Press. Medicale, vol. 49, no. 3, 2020, doi: 10.1016/j.lpm.2020.104031.[2]S. V. Moiseev, N. M. Bulanov, A. S. Zykova, and P. I. Novikov, “Rituximab in ANCA-associated vasculitis: Fewer infusions or ultra low-dose maintenance therapy,” Ann. Rheum. Dis., vol. 78, no. 9, pp. 1–2, 2019, doi: 10.1136/annrheumdis-2018-213873.[3]J. C. Jennette et al., “2012 Revised International Chapel Hill consensus conference nomenclature of vasculitides,” Arthritis Rheum., vol. 65, no. 1, pp. 1–11, 2013, doi: 10.1002/art.37715.Disclosure of InterestsNone declared

BackgroundThe spread of COVID-19 pandemic raised the need to perform an additional vaccine dose to overcome the diffusion of the infection and possible life-threatening disease complications. Certain population subsets seem to be at increased risk of developing such complications, such as elderly and/or immunocompromised patients.ObjectivesTo assess the persistence of immunity following SARS-CoV-2 mRNA vaccine and the magnitude of the humoral response after the booster dose in a cohort of patients affected by giant cell arteritis (GCA).MethodsPatients with GCA regularly followed at the Rheumatology Department of the University of Pavia, Italy, who received a booster dose of SARS-CoV-2 mRNA vaccine (BNT162b2 Pfizer/BioNtech or mRNA-1273 Moderna) between October 1st and December 31st, 2021 were included. Humoral response was assessed by measuring SARS-CoV-2 Trimeric S (TSAbs) and Neutralizing (NAbs) antibodies, with a cut-off of 33.8 Binding Antibody Units (BAU)/mL and 1:10 dilution, respectively. Blood samples from each patient were drawn at least 4 months after the second and three weeks after the third vaccine dose.ResultsForty-two patients who received the booster dose of SARS-CoV-2 mRNA vaccine were enrolled. Thirty (71.4%) were females, mean age 73.2±4.7 years, disease duration 58±38 months, 19 (45.2%) had large-vessel vasculitis. Thirty-two (76.2%) were on glucocorticoids (GCs) at a mean dose of 4.9±7.8 mg/day prednisone equivalent, with 7 (16.7%) receiving ≥7.5 mg/day. Eighteen (42.9%) were on methotrexate (MTX) (mean dose 14.2±3.5 mg/week) and 8 (19.0%) were treated with subcutaneous tocilizumab (TCZ) 162 mg/week.SARS-CoV-2 serology was tested prior to the third vaccine dose at an average of 5.4±0.4 months from the former vaccination scheduled: 37 (88.1%) retained TSAbs and 30 (71.4%) NAbs. The median TSAb titre was 134 BAU/mL (IQR 97-292). Four out of 5 patients (80.0%) without TSAbs and 7 out of 12 (58.3%) without NAbs were on both GCs and MTX. Moreover, those on GCs plus MTX had lower pre-third dose TSAb titres as compared to other treatment subgroups (Figure 1A). GC doses ≥7.5 mg/day prednisone equivalents seemed to blunt NAb levels along time: 28.6% patients on GCs ≥7.5 mg/day prednisone equivalents had negative NAbs before the third dose vs. 80.0% of those taking Figure 1.(A) TSAb levels before and after the booster dose among patients on GC + MTX. (B) NAb titres before and after the booster dose according to treatment with prednisone ≥7.5 mg/day or (C) MTX in combination with GCs or (D) MTX alone.Data regarding antibody response after the booster dose were available for 35 patients (83.3%). Blood collection occurred at a median of 25 days (IQR 24-32) after the third vaccine dose. All patients developed TSAbs, even those who did not respond to the previous shots. The median TSAb titre rose to 2080 BAU/mL (IQR 2080-2080) (pThere were no serious adverse events from the vaccine. However, 3 patients (8.6%) experienced a disease relapse 24±5 days after the booster dose.ConclusionIn our cohort, most patients who seroconverted after the second dose of vaccine retained the humoral immunity, with excellent seroconversion rates following the booster dose. However, GCs, especially at doses ≥7.5 mg/day prednisone equivalents, may contribute to the waning of NAb titres. On the other hand, immunosuppressants like MTX, especially when combined with GCs, might impair the magnitude of the humoral response to the booster dose.Disclosure of InterestsNone declared

The use of different methodological approaches together with an exhaustive qualitative study has helped to recognize important morphological traits to distinguish species in a systematic and phylogenetic framework. Parabolinella triarthroides Harrington, 1938 was described based on two cranidia from the Quebrada de Coquena, Purmamarca, Jujuy province. The generic assignment of P. triarthroides has been questioned by a phylogenetic analysis, which resolves this species as the sister group of Bienvillia Clark, 1924. To explore the generic assignment of this species, a revision of the type material, plus a morphometric analysis including specimens of Parabolinella Brøgger, 1882 and Bienvillia were performed. In addition, the original matrix used in the published phylogeny was reviewed and enlarged, including more species of Bienvillia. Continuous characters were coded in different ways in order to compare how they could affect the ordering of specimens and their phylogenetic relationships. Finally, both methodologies were compared, especially in regard to the behavior of the quantitative characters included in the analyses. From the combined analyses, it is shown that similarities between the cranidium of P. triarthroides and all other Parabolinella species are true homologies instead of a by-product of evolutionary convergence. Therefore, P. triarthroides should be considered a member of this genus. Finally, this study demonstrates that the best strategy for solving systematic problems in groups where the morphological variation is the only source of information (i.e., fossil taxa without living representatives) is the implementation of an integrative approach, combining different methodological techniques and a good description of specimens. Fil: Monti, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina Fil: Confalonieri, Viviana Andrea. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina

Background:Ultrasound of the temporal ± axillary arteries showing a non-compressible halo sign is recommended for diagnosing patients with giant cell arteritis (GCA); however, its value for monitoring disease activity is still poorly understood.Objectives:To assess the sensitivity to change of ultrasound halo features and their association with disease activity and glucocorticoid (GC) treatment in patients with newly diagnosed GCA.Methods:Two centre prospective study of new patients with ultrasound confirmed-GCA who underwent serial ultrasound assessments of the temporal (TA) and axillary (AX) arteries at fixed time-points. The number of arterial segments with halo and the maximum halo intima-media thickness (IMT) per segment was recorded at each visit. Only time-points in which >80% of patients were assessed were considered for analysis. Sensitivity to change of the halo sign was calculated as standardised mean difference (SMD) for each time-point separately. Correlation between ultrasound findings and erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Birmingham Vasculitis Activity Score (BVAS), and GC treatment was performed using Spearman’s correlation coefficient. Logistic regression was used to determine the probability of being in remission for each unit increase (standardised) of the halo feature of interest. Remission was defined as the absence of relapse with a prednisolone dose Results:A total of 49 patients (73.5% females) with a mean age of 78.2 ± 7.4 years at baseline were assessed at 354 visits. TA involvement was reported in 47 (95.9%) patients and AX involvement in 11 (22.4%); 220 arterial segments with halo were recorded (201 TA, 19 AX). Halo sensitivity to change was calculated for weeks 1, 3, 6, 12 and 24, and showed a significant SMD between all time-points and baseline for the TA halo features, but only after week 6 for the AX halo features (Table and Figure). The number of TA segments with halo, sum of TA halo IMT and maximum TA halo IMT showed a significant correlation with ESR (0.41; 0.44; 0.48), CRP (0.34; 0.39; 0.41), BVAS (0.29; 0.36; 0.35) and GC cumulative dose (-0.34; -0.37; -0.32). The likelihood of achieving disease remission was lower in patients with a higher number of TA segments with halo (OR 0.39, pTable 1.SMD of halo features between baseline and different time-pointsWeek 1Week 3Week 6Week 12Week 24N of arterial segmentsSum of all segments with halo (n=49)-0.51-0.78-1.13-1.69-1.52Sum of TA segments with halo (n=47)-0.49-0.78-1.18-1.87-1.69Sum of AX segments with halo (n=11)-0.35--0.62-0.73-0.91Halo thickness (mm)Sum of all halo IMT (n=49)-0.98-1.44-1.37-1.60-1.48Sum of TA halo IMT (n=47)-1.01-1.55-1.54-1.81-1.69Sum of AX halo IMT (n=11)-0.15-0.45-0.81-0.84-0.98Max. TA halo IMT (n=47)-1.07-1.32-1.47-1.91-2.19Max. AX halo IMT (n=11)-0.04-0.29-0.94-1.13-1.01In bold pConclusion:Ultrasound is a reliable imaging tool to assess disease activity and response to treatment in patients with GCA. Future clinical trials in GCA should evaluate direct treatment effect on halo features as an outcome measure of interest.Acknowledgements:The first two authors contributed equally to this workDisclosure of Interests:None declared

Morphometrics can be an important tool in systematic studies, providing taxonomists with strong elements of quantification and formal hypothesis testing. Here, these tools are tested for the trilobite Leptoplastides marianus (Hoek) which was originally described on the basis of three deformed specimens from west Tarija, Bolivia. Following the conclusions of Harrington & Leanza, a wide range of morphological variation is accepted for this species, and the name was applied to a large number of specimens from north-western Argentina. Based on specimens collected from the quebrada Moya (Huacalera, Jujuy), as well as on material in the Harrington & Leanza collections in the University of Buenos Aires, traditional morphometric and geometric morphometric methods were used to evaluate the variation of the cranidial shape of L. marianus sensu Harrington & Leanza. The results allow discrimination between two clearly different morphotypes. The name L. marianus should be restricted to the type specimens, given the deformation of these materials. In addition, L. argentinensis and L. granulosus are both valid names for the two morphotypes recognized in the present paper. Fil: Monti, Daniela Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Ecología, Genética y Evolución de Buenos Aires. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Ecología, Genética y Evolución de Buenos Aires; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Ecología, Genética y Evolución; Argentina

The guidelines for setting environmental quality standards are increasingly based on probabilistic risk assessment due to a growing general awareness of the need for probabilistic procedures. One of the commonly used tools in probabilistic risk assessment is the species sensitivity distribution (SSD), which represents the proportion of species affected belonging to a biological assemblage as a function of exposure to a specific toxicant. Our focus is on the inverse use of the SSD curve with the aim of estimating the concentration, HCp, of a toxic compound that is hazardous to p% of the biological community under study. Toward this end, we propose the use of robust statistical methods in order to take into account the presence of outliers or apparent skew in the data, which may occur without any ecological basis. A robust approach exploits the full neighborhood of a parametric model, enabling the analyst to account for the typical real-world deviations from ideal models. We examine two classic HCp estimation approaches and consider robust versions of these estimators. In addition, we also use data transformations in conjunction with robust estimation methods in case of heteroscedasticity. Different scenarios using real data sets as well as simulated data are presented in order to illustrate and compare the proposed approaches. These scenarios illustrate that the use of robust estimation methods enhances HCp estimation.

To evaluate the basal/total ratio of daily insulin dose (b/T) in outpatients with diabetes type 1 (DM1) and type 2 (DM2) on basal-bolus regimen, by investigating whether there is a relationship with HbA1c and episodes of hypoglycemia.Multicentric, observational, cross-sectional study in Italy. Adult DM1 (Total daily insulin dose was significantly higher in DM2 patients (52.3 ± 22.5 vs. 46 ± 20.9 U/day), but this difference disappeared when insulin doses were normalized for body weight. The b/T ratio was lower than 0.50 in both groups: 0.46 ± 0.14 in DM1 and 0.43 ± 0.15 in DM2 patients (The b/T ratio was independent of glycemic control and incidence of hypoglycemia.

Within European Partitioning & Transmutation research programs, infrastructures specifically dedicated to the study of funda- mental reactor physics and engineering parameters of future fast-neutron-based reactors are very important, being some of these features not available in present zero-power prototypes. This presentation will illustrate the conceptual design of an ADS with high safety standards, but ample flexibility for measurements. The design assumes as base option the 70 MeV, 0.75 mA proton cyclotron facility planned to be constructed at the INFN National Laboratory in Legnaro, Italy and a Beryllium target, with Helium gas as core coolant. Safety is guaranteed by limiting the thermal power to 200 kW, with a neutron multiplication coefficient around 0.94, loading the core with fuel containing Uranium enriched at 20% and a solid-lead diffuser. The small decay heat can be passively removed by thermal radiation from the vessel. Such a system could be used to study, among others, some specific aspects of neutron diffusion in lead, beam-core coupling, target cooling and could serve as a training facility.