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Sustained smouldering, or low-grade activation, of myeloid cells is a common hallmark of several chronic neurological diseases, including multiple sclerosis 1 . Distinct metabolic and mitochondrial features guide the activation and the diverse functional states of myeloid cells 2 . However, how these metabolic features act to perpetuate inflammation of the central nervous system is unclear. Here, using a multiomics approach, we identify a molecular signature that sustains the activation of microglia through mitochondrial complex I activity driving reverse electron transport and the production of reactive oxygen species. Mechanistically, blocking complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in an animal disease model in vivo. Complex I activity in microglia is a potential therapeutic target to foster neuroprotection in chronic inflammatory disorders of the central nervous system 3 . Blocking mitochondrial complex I in pro-inflammatory microglia protects the central nervous system against neurotoxic damage and improves functional outcomes in vivo in an animal disease model.

Background 22% of the population in Europe currently has, or had experienced “long-term muscle, bone and joint problems”.1 Early referral to a rheumatologist for appropriate diagnosis and treatment prevent structural damage, disability and decrease mortality.2 ObjectivesTo launch a patient oriented campaign in Romania in order to increase awareness of rheumatic musculoskeletal diseases (RMDs) – early recognition of symptoms, ways of breaking down the barriers that delay early diagnosis. Also to educate the general public that rheumatic diseases may occur at any age and severe affect both children and young people.The long term goal of the campaign is to decrease the number of people with disabilities, work loss or early retirement as well as the health care costs.MethodsThe launch event of the campaign will be attended by patients, rheumatologists, GPs, HPs, media and also national and local authorities.A coordinated media plan will consist of pre-launch teasers, appropriate broadcasting of the event and post-event reminders as well as educational flyers/materials with the slogan “Don’t delay, Connect today”, handed out in shopping centres and other crowded areas.Online posts on the www.reumatism.ro website and the dedicated FB page will stimulate communication and mutual support among patients as well as spread information on RMDs to the general public.ResultsUp to 100 participants are expected to attend the launching event and get direct/live benefit from the information on early diagnosis and early treatment.Over 50% of the Romanian population will audience the campaign messages covered by 50 media articles (in Romanian) and over 10 000 people will receive e-messages (online and Facebook impressions/engagement). This coordinated media plan will stimulate communication and mutual support among people with RMDs.ConclusionsThe implementation of the EULAR campaign in Romania “Don’t delay, Connect today” aims an early referral to the rheumatologist for diagnosis and treatment and for a normal quality of life of patients with inflammatory rheumatic diseases.The campaign will have a communication peak around the launching event. Until the end of the year an on-going media and online communication strategy will be implemented.References[1] Health in the European Union Eurobarometer Special Report 272, September 2007.[2] Emery P, Breedveld FC, Dougados M, et al, Early referral recommendation for newly diagnosed rheumatoid arthritis: evidence based development of a clinical guide, ARD2002.Disclosure of InterestNone declared

Background Compression experiments are widely used to study the mechanical properties of materials at micro- and nanoscale. However, the conventional engineering stress measurement method used in these experiments neglects to account for the alterations in the material’s shape during loading. This can lead to inaccurate stress values and potentially misleading conclusions about the material’s mechanical behavior, especially in the case of localized deformation. Objective Our goal is to calculate true stress in cases of localized plastic deformation from standard experimental data (displacement-force curve, aspect ratio, shear band angle and elastic strain limit). Methods We use a simple mechanical-geometrical approach based on reasonable physical assumptions to get analytic formulas of true stress and eliminating the need for finite element computations. Furthermore, in numerical simulations of pillar compression, the formula-based true stress demonstrates strong alignment with the theoretical true stress. Results We propose analytic formulas for calculating true stress in cases of localized plastic deformation commonly encountered in experimental settings for a single band oriented in arbitrary directions with respect to the vertical axis of the pillar. Conclusions The true stress computed with the proposed formulas provides a more precise interpretation of experimental results and can serve as a valuable and simple tool in material design and characterization.

BackgroundSince the end of 2019, physicians became more and more familiar with SARS-CoV-2 infection and the variety of forms in which it may present and evolve. There have been a lot of studies trying to understand and predict why some patients develop a dysregulation of the immune response, with an exaggerated release of pro-inflammatory cytokines, called cytokine storm (1–4). There is scarce evidence in Romania regarding this aspect.ObjectivesThis study aims to verify the correlation between some laboratory parameters and the development of cytokine storm in SARS-CoV-2 infection in a cohort of over 200 patients admitted in a tertiary hospital from Romania, hoping that early identification of these risk factors of progression to a severe form of the disease can bring considerable benefit to patient care.MethodsThis is an analytical, observational, case-control study which includes 219 patients (all COVID-19 hospitalized patients on the Internal Medicine 3 department of Colentina Clinical Hospital, Bucharest, from 01 March 2020 to 1 April 2021). A series of data were collected, the laboratory parameters being the most important, including: albumin, lymphocyte (percentage), neutrophil (absolute value), aspartate aminotransferase, alanine aminotransferase, D-dimers, lactate dehydrogenase (LDH), anionic gap, chloremia, potassium and the BUN:creatinine ratio (BUN - blood urea nitrogen). The laboratory parameters used for the statistical analysis represent the average values of the first 7 days of hospitalization for those who did not develop cytokine storm, respectively until the day of its development, for the others. Patients were classified into these groups, those who developed cytokine storm, respectively those who did not have this complication taking into account the clinical and paraclinical criteria (impairment of respiratory function, elevations of certain markers 2-3 times above the upper limit of normal, those who died as a result of SARS-CoV-2 infection). Then Binary Univariate Logistic Regression was applied in order to verify the individual impact of every laboratory parameter on cytokine storm development. Furthermore, all laboratory parameters were subsequently included in the multivariate analysis, using the backward selection technique to achieve a model as predictive as possible.ResultsWe mention that the analysis of demographic data was previously performed, showing no statistically significant relationship between patient gender, age or comorbidities (history of neoplasm, lung diseases, cardiac pathology, obesity, type II diabetes and hypertension) and their evolution to cytokine storm. After performing binary univariate logistic regression we concluded that 8 of the 13 laboratory analyzes have had a significant change between groups (ferritin, PCR, albumin, Lymphocyte, Neutrophils, TGO, LDH, BUN:creatinine ratio). Only 150 patients were then included in the multivariate analysis. After the analysis, some of the variables lost their statistical significance, the final model including C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio. This model correctly predicts the development of cytokine storm in 88% of cases.ConclusionHigh C-reactive protein, neutrophilia, LDH, ferritin and the BUN:creatinine ratio are risk factors for cytokine storm development and should be monitored in all COVID-19 patients in order to predict their evolution.References[1]Pedersen SF et all. SARS-CoV-2: A storm is raging[2]Mehta P et al. COVID-19: consider cytokine storm syndromes and immunosuppression[3]Hu B et al. The cytokine storm and COVID-19.[4]Caricchio R et al. Preliminary predictive criteria for COVID-19 cytokine stormAcknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSjögren’s syndrome (SS) is accompanied by a number of autoantibodies as a result of B cell aberrant activation. The clinical manifestations, laboratory findings and evolution in seronegativity of a pSS patient changes compared to a seropositive pSS patient.ObjectivesThis study compared the clinical and serological characteristics of seronegative and seropositive primary Sjögren syndrome (pSS) patients and the differences in terms of treatment recommended during the follow-up period.MethodsWe performed a retrospective study in a single center, with 131 patients (128 women and 3 men) diagnosed with pSS. Clinical examinations, complete blood count, inflammatory and immunological parameters were determined at the initial visit. The patients were divided into two groups through the presence or absence of pathology-specific antibodies.ResultsNineteen of the 131 pSS patients (14.5%) were triple seronegative for ANA, anti-Ro, and anti-La autoantibodies. pSS patients with the specific antibodies absence performed accessory salivary gland biopsy and based on focus score they were diagnosed seronegative. No significant statistical differences were observed for age, sex distribution, disease activity scores and the administrated treatment, between the two groups. In terms of laboratory findings, only total proteins, RF and IgG were statistically lower in seronegative pSS patients (p < 0.05). While from glandular and extraglandular manifestations, singular xerostomia revealed a statistically significant between the two groups of pSS patients (p < 0.001). Cellular ratio, NLR was positively correlated with ESSDAI score and MLR, and negatively correlated with PLR, ESR, total proteins, IgG, C3 and C4, in seronegative pSS patients (p < 0.05).ConclusionThe extraglandular manifestations and the administrated treatment, were similar for the two groups of pSS patients, while only the glandular manifestation, xerostomia, has a statistically significant difference. The hematological parameter, NLR, was statistically correlated with disease activity score and immunological markers in triple seronegative pSS patients.References[1]C. Vitali, S. Bombardieri, R. Jonsson, H.M. Moutsopoulos, E.L. Alexander, S.E. Carsons, T.E. Daniels, P.C. Fox, R.I. Fox, S.S. Kassan, S.R. Pillemer, N. Talal, M.H. Weisman, Classification criteria for Sjögren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group, Ann. Rheum. Dis. 61 (2002) 554–558. https://doi.org/10.1136/ard.61.6.554.[2]Yazisiz V, Aslan B, Erbasan F, Uçar İ, Öğüt TS, Terzioğlu ME. Clinical and serological characteristics of seronegative primary Sjögren’s syndrome: a comparative study. Clin Rheumatol. 2021 Jan;40(1):221-229. doi: 10.1007/s10067-020-05154-9. Epub 2020 Jun 5. PMID: 32504193.[3]Chatzis LG, Pezoulas V, Voulgari PV, Baldini C, Exarchos TP, Fotiadis DI, Mavragani CP, Skopouli FN, Moutsopoulos HM, Tzioufas AG, Goules AV. Combined seronegativity in Sjögren’s syndrome. Clin Exp Rheumatol. 2021 Nov-Dec;39 Suppl 133(6):80-84. doi: 10.55563/clinexprheumatol/47a4kr. Epub 2021 Oct 4. PMID: 34665703.[4]Segal BM, Pogatchnik B, Henn L, Rudser K, Sivils KM. Pain severity and neuropathic pain symptoms in primary Sjögren’s syndrome: a comparison study of seropositive and seronegative Sjögren’s syndrome patients. Arthritis Care Res (Hoboken). 2013 Aug;65(8):1291-8. doi: 10.1002/acr.21956. PMID: 23335582; PMCID: PMC4137866.Acknowledgements:NIL.Disclosure of InterestsNone Declared.

BackgroundSjögren’s syndrome is a heterogeneous inflammatory disorder frequently involving peripheral nerves with a significant clinical and prognostic impact. The early detection of hematological and immunological parameters might improve disease control and even patients’ survival.ObjectivesThe objective of this study was to evaluate the predictive potential of hematological and immunological elements for the development of peripheral neuropathies (PN) in pSS patients.MethodsIn this single-centre, retrospective study, a total of 252 participants were included (131 pSS patients and 121 healthy controls). According to the neurologic examination and the result of the neuro electrophysiological examination, these patients were divided into two groups, with and without PN. Complete blood count, inflammatory and immunological parameters were determined at the initial visit. All patients underwent a periodical follow-up program when disease progression and response to therapy were monitored, including the emergence of PN.ResultsIn pSS patients, cellular count, Vitamin B12 and D values were significantly decreased compared to healthy subjects (p < 0.001), whereas cellular ratio- NLR, PLR, immunological and inflammatory parameters were significantly increased (p < 0.001). In the PN patients group (41 patients 31.29%), gammaglobulins negatively correlated with vitamin B12 and total proteins (p < 0.05), while ESSDAI scores positively correlated with NLR and PLR (p < 0.05). The multivariate analysis confirmed the independent predictive character for PN emergence in pSS for NLR (CI95% 0.034 to 0.254, p < 0.010), gammaglobulins (CI95% -0.409 to -0.114, p < 0.001), vitamin B12 (CI95% -0.001 to -0.001, p < 0.001) and vitamin D (CI95% -0.018 to -0.006, p < 0.001).ConclusionStandard hematological and immunological parameters, widely used in assessing pSS patients, such as NLR, gammaglobulins, vitamin B12 and D, could become valid elements that might be used for the early detection of patients at risk for the development of PN. The hematological parameters related to platelets appear to be modified in patients with SS and cutaneous manifestations. However, only the neutrophil-to-lymphocyte ratio is independently associated with cutaneous involvement in these patients.References[1]C. Vitali, S. Bombardieri, R. Jonsson, H.M. Moutsopoulos, E.L. Alexander, S.E. Carsons, T.E. Daniels, P.C. Fox, R.I. Fox, S.S. Kassan, S.R. Pillemer, N. Talal, M.H. Weisman, Classification criteria for Sjögren’s syndrome: A revised version of the European criteria proposed by the American-European Consensus Group, Ann. Rheum. Dis. 61 (2002) 554–558. https://doi.org/10.1136/ard.61.6.554.[2]R.I. Fox, Extraglandular Manifestations of Sjögren’s Syndrome (SS): Dermatologic, Arthritic, Endocrine, Pulmonary, Cardiovascular, Gastroenterology, Renal, Urology, and Gynecologic Manifestations, in: Sjögren’s Syndr., Springer New York, 2011: pp. 285–316. https://doi.org/10.1007/978-1-60327-957-4_17.[3]A. Alunno, F. Carubbi, E. Bartoloni, P. Cipriani, R. Giacomelli, R. Gerli, The kaleidoscope of neurological manifestations in primary Sjögren’s syndrome, Clin. Exp. Rheumatol. 37 (2019) S192–S198.[4]Mihai A, Caruntu A, Opris-Belinski D, Jurcut C, Dima A, Caruntu C, Ionescu R. The Predictive Role of Neutrophil-to-Lymphocyte Ratio (NLR), Platelet-to-Lymphocyte Ratio (PLR), Monocytes-to-Lymphocyte Ratio (MLR) and Gammaglobulins for the Development of Cutaneous Vasculitis Lesions in Primary Sjögren’s Syndrome. J Clin Med. 2022 Sep 21;11(19):5525.Disclosure of InterestsNone declared

BackgroundAccuracy of diagnosis and prompt therapeutic intervention are the mainstay in patients with ANCA-associated vasculitis(AAV) suffering from life-threatening complications [1].However, there is no definition of therapeutic window in vital AAV, nor its impact on patient outcome regarding length of hospital stay, intensive care unit(ICU) admission or survival.ObjectivesThe aim of the study is to analyze the process of care from the perspective of time management in vital organ involvement AAV patients and to identify potential risk factors for ICU admission.MethodsA retrospective multicenter study identified AAV patients with life-threatening organ involvement, defined as alveolar hemorrhage, rapidly progressive renal failure, myocarditis and cerebral granuloma. Demographic data was collected. Key time frames were recorded, namely the interval from acute symptom onset to hospital presentation, days until imaging(plain X-ray, cardiac ultrasound, CT-scan), time to therapeutic intervention with corticosteroids or biologic/non-biologic immunosuppression(cyclophosphamide or rituximab) and to renal replacement therapy(RRT) or plasmapheresis. Time to ICU admission, hospital length-of-stay, Birmingham Vasculitis Activity Score(BVAS) were also noted. Statistical analysis was performed using SPSS and Chi-square and Pearson correlation tests were applied.Results66 patients with AAV were enrolled, out of which 17 fulfilled inclusion criteria. Mean age in the study group was 58.6±11.1 years old,10 patients(58.8%) were females and 7 (41.2%) males.11(64.7%) patients were c-ANCA positive, while 6 (35.3%) had p-ANCA and all were diagnosed with AAV prior to life-threatening event. Two patients had COVID-19 triggered AAV.In the study group, the most frequent critical organ suffering was rapidly progressive renal failure(12), followed by alveolar hemorrhages(10), 2 cerebral granulomas and one acute myocarditis. Three patients(17.6%) had more than one vital manifestation. Ten patients(58.8%) had more than three additional non-organ-threatening manifestations. Mean interval from AAV diagnosis to emergency admission was 30.1± 61.1 days, median 3 and from severe episode onset to hospitalization 1.65±0.18 days, median 1. There was only one death in the study group. Three patients were admitted in the ICU in 0.59±1.5 days following hospital presentation and required either RRT or plasma exchange within 2.66 days. Imaging examination was performed unanimously the day upon hospital admission. All patients received corticosteroids in the first 5.95±14.3 days, while immunosuppression was given to 13(76.5%) patients within 11.5±15.5 days from hospitalization.12 patients(70.5%) suffered from associated infections. Mean BVAS(13.6±6.76) correlated to ICU admission(p 0.013, r 0.58).Patients in ICU revealed higher BVAS(22±9.53) versus non-ICU(11.8±4.76).Hospital length of stay was 14.7±10.7 days(median 14) and showed no relationship to the type of severe organ involvement. The need for ICU caring was dominant in males(p 0.05) and confirmed in patients with proteinuria(p 0.012) and at least two major organ damage.ConclusionThis study shows that severity risk factors for potential ICU admission for life-threatening AAV appear to be male gender, proteinuria and the number of affected organs.Moreover, BVAS should be considered a useful tool to predict patients’ risk for intensive care management since a higher score indicates a more aggressive disease.However, time to investigational or therapeutic intervention did not correlate to patient outcome in AAV.References[1]Geetha, D., Seo, P. (2011). Life-Threatening Presentations of ANCA-Associated Vasculitis. In: Khamashta, M., Ramos-Casals, M. (eds) Autoimmune Diseases. Springer, London. https://doi.org/10.1007/978-0-85729-358-9_8Acknowledgements:NIL.Disclosure of InterestsNone Declared.

Chronicling the 11th US–France Mechanics and physics of solids at macro- and nano-scales symposium, organized by ICACM (International Center for Applied Computational Mechanics) in Paris, June 2018, this book addresses the breadth of issues raised. It covers a comprehensive range of scientific and technological topics (from elementary plastic events in metals and materials in harsh environments to bio-engineered and bio-mimicking materials), offering a representative perspective on state-of-the-art research and materials. Expounding on the issues related to mesoscale modeling, the first part of the book addresses the representation of plastic deformation at both extremes of the scale – between nano- and macro- levels. The second half of the book examines the mechanics and physics of soft materials, polymers and materials made from fibers or molecular networks.

BackgroundThe diagnosis of Undifferentiated Connective Tissue Disease (UCTD) has raised controversy over the years regarding making the diagnosis, evolution and prognosis. Le Roy et al[1] in 1980 and most recently Mosca et al[2] in 2014 proposed classification criteria for UCTD, but confusion still exists regarding making the diagnosis of UCTD, evolution and prognosis of the syndrome and how the patient should be followed up over time.ObjectivesEvaluate disease evolution, treatment and follow up plan in patients with UCTD diagnosis. Assess whether there are any factors that may predict disease evolution and should require regular follow up.MethodsThis was a retrospective study of patients followed up in a specialist clinic in a tertiary referral centre (University College London Hospitals) with a diagnosis of UCTD, focusing on clinical and serological features, treatment, follow up and disease evolution over time.ResultsA total of 121 patients were included in the study: 93% were females; the mean age at disease onset was 39 years (range 20 to 80); and the patients were followed up for at least 1 year (mean 12 years, range 1 to 40). 78% of these patients had a stable diagnosis of UCTD, while in 22% diagnosis changed over time: 9% evolved into a specific connective tissue disease (CTD) - 4 Systemic Lupus Erythematosus, 3 Sjogren's Syndrome, 1 Rheumatoid Arthritis, 1 Systemic sclerosis and 1 Anti-synthetase Syndrome -, 7% had a change of diagnosis from a specific CTD to UCTD, 4% evolved into an overlap syndrome and 2% of the patients were no longer diagnosed as having any CTD at the end of the study. The most prevalent manifestations were joint pain (arthralgia/arthritis) in 89% of the patients, fatigue 80%, Raynaud's phenomenon 63%, skin rashes 49% and sicca symptoms 45%. Lung involvement was observed in 11% of the patients within which 8% had a nonspecific interstitial pneumonia (NSIP) and 3% had a usual interstitial pneumonia (UIP) pattern. 36% of the patients were noted to have associated gastro-oesophageal reflux disease. Serological features included positive ANA in 98%, anti-RNP 33%, anti-Ro 32%, Rheumatoid Factor 20% and hypocomplementemia was observed in 19% of the patients. 7% of the patients did not require any treatment for their UCTD, but the majority of patients were treated with Hydroxychloroquine only (75%), and the rest with other immunosupressants/immunomodulators.ConclusionsIn our study the majority of patients initially diagnosed with UCTD kept this diagnosis over time but 13% of patients evolved to a defined CTD or an overlap syndrome and in 2% of patients, symptoms and serological features eventually resolved. Although, UCTD is often mild, significant major organ involvement such as interstitial lung disease can occur[3], as well as evolution to a defined CTD or overlap syndrome. This should guide follow up of these patients in clinic.ReferencesLeRoy EC et al. Undifferentiated connective tissue syndromes. Arthritis Rheum.1980; 23 (3):341 - 343.M. Mosca et al The diagnosis and classification of undifferentiated connective tissue diseases Journal of Autoimmunity 48–49 (2014) 50e52.Fischer A, Interstitial lung disease in undifferentiated forms of connective tissue disease. Arthritis Care Res (Hoboken). 015;67(1):4–11.Disclosure of InterestR. Ionescu Grant/research support from: EULAR scientific training bursary, M. Leandro: None declared

BackgroundEnthesis involvement is considered as a key pathological lesion in psoriatic arthritis (PsA) patients. Recently, ultrasound (US) became an important tool to evaluate the enthesis involvement in PsA. Power Doppler (PD) is able to identify vascular abnormalities which are known to be associated with inflammation.ObjectivesTo perform a systematic literature review on how enthesis are evaluated by US in PsA.MethodsThe objective was reformulated according to the PICO approach. Several synonyms for the main components (i.e. ultrasound and enthesis) were used. No search limits were applied. The literature search was performed in Medline and Embase from databases inception to 1st October 2017. References identified were imported into a bibliographic manager. Firstly, duplicates were removed. Then, to identify eligible studies the remaining articles were assessed by title and abstract. Only articles in English and Latin languages were retained.From the selected studies, data about the examined structures, pathological findings and definition used to identify pathology were retired using a predefined data collection form.ResultsThe literature search resulted in 411 articles, of which 101 were captured in Medline and 310 in Embase. Figure 1 shows the study flow-chart for article selection. After removing duplicates and scanning titles and abstracts, 41 articles remained for the detailed review. After full-text review, 12 articles were excluded. The main reason for article exclusion after full-text review was the lack of explanation of US evaluation.29 articles were included in qualitative analysis. The mean (range; SD) number of patients evaluated was 66.3 (7–141; 41.9).The US was used for diagnostic in 26 (89.7%) articles and for monitoring in 7 (24.1%) articles. 4 (13.8%) evaluated also the US nail involvement. All articles used B mode evaluation and 26 (89.7%) used also Doppler mode, all of them using PD.Thickening was evaluated in 27 (93.1%) articles, hypoechogenicity in 21 (72.4%), the presence of enthesophytes in 21 (72.4%) articles, the presence of calcifications in 11 (37.9%) articles, the presence of erosions in 21 (72.4%) articles, irregularities in 8 (27.6%) articles and bursitis in 15 (51.7%) articles, peri-entheseal soft-tissue oedema in 2 articles.Triceps was evaluated in 8 (29.6%) articles, elbow extensors in 8 (29.6%) articles, quadriceps in 14 (51.9%) articles, proximal patellar in 12 (51.9%), distal patellar in 15 (55.6%), Achilles in 22 (81.5%), plantar fascia in 18 (66.7%) and finger extensor in 2 (7.4%), elbow flexors 3, medial collateral ligament in femur condyle 3, supraspinatus tendon in 1 articles, gluteus tendons in 1 article, first and seventh costo-sternal joints, anterior superior iliac spine, and iliac crest, the posterior superior iliac spine, and the fifth lumbar spinous process, rotator cuff in one article.OMERACT definitions were used in 6 (20.6%) articles. Qualitative evaluation was used in 12 (41.3%) articles, semi-quantitative evaluation in 4 (13.7%) articles. As global score, GUESS score was used in 5 (17.2%) articles and MASEI score was used in 4 (13.7%) articles.Abstract AB1311 – Figure 1ConclusionsAlthough the majority of the articles evaluated the same enthesis and the same US findings, we found a lack of consensus regarding the global score.Disclosure of InterestNone declared