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Background Uveitis is one of the most frequent ophthalmologic manifestations in rheumatology. Uveal inflammation can underlie a systemic inflammatory rheumatic disease (SIRD) in approximately 30% of cases with a significant burden on the quality of life since it represents a cause of blindness in up to 20% of cases in Western countries. Methods In this review, we provide a comprehensive overview of the pathophysiology of uveitis associated with SIRDs. According to our literature survey on the epidemiology of uveitis among SIRDs, spondyloarthritides, Behcet's disease and sarcoidosis get the major impact. Results In Behcet's uveitis, the key players are highly polarized Th1 and Th17 lymphocytes, natural killer T cells and gamma delta T cells. All contribute to a great destructive inflammatory environment with the most serious visual damage resulting from the involvement of the posterior segment of the eye. In contrast, spondyloarthritides-related uveitis derives from a complex interaction between genetic background and extra-ocular inflammatory mediators originating from enthesitis, arthritis, psoriatic lesions and microbiome pro-inflammatory alterations. In such conditions, the immune infiltration of CD4+ T cells, Th17 and natural killer cells along with pro-inflammatory cytokines, TNF-alpha among all, leads to intraocular inflammation. Lastly, granuloma formation represents the primary hallmark lesion in sarcoid uveitis. This suggests a profound link between the innate system that mainly recruits activated macrophages and adaptive system involving by Th1, Th17 and Th17.1 cells. Conclusions Awareness among rheumatologists of a potential severe ocular involvement generates new insights into targeted therapeutic approaches and personalized treatments for each patient.

Background Antiphospholipid syndrome (APS) is a systemic autoimmune disease characterized by specific vascular and obstetric manifestations and by antiphospholipid antibodies (aPL) positivity. Microvascular damage in the course of APS and “aPL carrier” patients without symptoms is poorly investigated. Objectives This study aims to compare nailfold videocapillaroscopy (NVC) microvascular parameters in APS patients and non-symptomatic "aPL carriers" and to investigate their possible correlations with different aPL subtypes. Methods NVC was performed during standard evaluations in 18 APS patients (mean age 50 ± 13.8 years), 24 "aPL carriers" without symptoms (mean age 46.4 ± 16.4 years), and 18 control patients (CTR) (mean age 74 ± 12.5 years) taking oral anticoagulants for non-immunological indications (i.e., cardiovascular accidents). All patients were investigated for the presence of dilated capillaries, giant capillaries, microhemorrhages, capillary loss, and further non-specific/specific abnormalities (i.e., branched “bushy” capillaries, sign of neoangiogenesis) by NVC. Every alteration was also classified according to a semi-quantitative score. Lupus anticoagulant, anticardiolipin antibodies, and antibeta2 glycoprotein I antibodies were tested in each patient. Results APS patients showed at NVC increased frequency of microhemorrhages (p = 0.039)—particularly a “comb-like” pattern (parallel hemorrhages) (p = 0.002)—than "aPL carriers". Of note, there were no significant differences concerning the isolated number of microhemorrhages between APS and the CTR group (p = 0.314), but “comb-like” hemorrhages were significantly more frequent in the APS group (p = 0.034). Not any significant correlation was found between the aPL subtypes and NVC parameters. Conclusions APS patients showed significantly a greater number of non-specific NVC abnormalities than "aPL carriers", particularly the “comb-like” NVC pattern. Oral anticoagulants may represent a confounding factor for isolated microhemorrhages. Not any correlation was found between aPL subtypes and NVC parameters. Further investigations are needed to better characterize the microvascular endothelium damage induced by aPL.

BackgroundDuring pregnancy profound physiologic changes are required to ensure fetal development and meet maternal needs. Microvascular remodelling is one major responsible for pregnancy haemodynamic adaptation, still it is not routinely evaluated in the obstetric field [1–2].ObjectivesTo investigate the role of nailfold capillaroscopy (NCV) as a gold-standard and safe technique in detecting microvascular changes during normal pregnancy and to explore its possible application in clinical obstetric setting.MethodsA population of 30 healthy pregnant women was longitudinally followed performing clinical assessment and NVC evaluation at each trimester and post-partum. Thirty non-pregnant age-matched healthy women having received at least two NVCs with a minimum 9 to 12-month interval were selected as controls. All NVC images were evaluated by a qualitative and semi-quantitative assessment using current standardised approach [3]. Statistical analyses were conducted to explore NVC parameters trend throughout gestation and its possible association with pregnancy course and clinical macrovascular parameters (i.e., systemic blood pressure, umbilical artery Doppler ultrasound).ResultsA progressive significant increase of capillary neoangiogenesis and a specular reduction in capillary dilations was observed during pregnancy (ppConclusionThis first comprehensive longitudinal NVC evaluation during normal pregnancy reports significant physiological microvascular variations throughout gestation, suggesting NVC as a safe and promising technique for further investigate and define patterns of microvascular changes in pregnant patients with rheumatic diseases.References[1]Thevissen et al. Expert Rev Med Devices. 2017;14(12):961–7.[2]Abdo et al. Physiol Res 2014;63:395–408.[3]Smith et al. Autoimmun Rev 2020; 19(3):102458.Disclosure of InterestsNone declared

Systemic sclerosis (SSc) is a connective tissue disease characterized by initial microvascular damage, immune system activation and progressive fibrosis with insufficiency of internal organs. Gastrointestinal (GI) involvement is characterized by atrophy of the smooth muscle and small bowel hypomotility, mainly resulting from an autonomic nerve dysfunction. These modifications significantly affect gut transit and nutrient absorption, thus leading to malnutrition deficit induced by malabsorption. Nutritional deficit induced by malabsorption might also lead to bone alterations. This study aims to evaluate the relationship between malnutrition and bone status. Thirty-six postmenopausal female patients fulfilling the ACR 2013 criteria for SSc underwent dual-energy X-ray absorptiometry scan (DXA) to detect quantitative lumbar spine bone mineral density (BMD) and trabecular bone score (TBS) analysis to detect bone quality. Data from DXA also allow to assess body composition and provide several quantitative parameters, including free fat mass index (FFMI) that identifies the patient with malnutrition (values &lt, 15 kg/m2 in women and 17 kg/m2 in men), according to the ESPEN criteria. Body mass index (BMI) was calculated for all SSc patients and every patient completed a diary reporting GI symptoms. Two groups of SSc patients with or without diagnosed malnutrition according to FFMI parameter were identified. Malnourished SSc patients showed significantly lower weight (p = 0.01) and BMI (p = 0.001), as well as lower serum levels of hemoglobin (p = 0.009), albumin (p = 0.002), PTH (p = 0.02) and 25OH-vitamin D (p = 0.008). DXA analysis showed significantly lower lumbar L1-L4 T-score (p = 0.009) and BMD values (p = 0.029) in malnourished SSc patients. Consistently, TBS values were significantly lower in malnourished patients (p = 0.008) and correlated with BMD (at any site) and serum albumin levels (p = 0.02). In addition, FFMI positively correlated with bone parameters as well as with symptoms of intestinal impairment in malnourished SSc patients. Finally, GI symptoms significantly correlated with BMD but not with TBS. This pilot study shows that in malnourished SSc patients (2015 ESPEN criteria: FFMI&lt, 15 kg/m2), an altered bone status significantly correlates with GI involvement, in terms of symptoms being mainly due to intestinal involvement together with the presence of selected serum biomarkers of malnutrition.

Background Systemic sclerosis (SSc) is a chronic autoimmune disease, characterized by microvascular damage and progressive fibrosis. Among clinical complications, abnormal body composition and sarcopenia have been reported in SSc patients(1,2). Nailfold videocapillaroscopy (NVC) is a safe diagnostic tool to assess microvascular progressive damage and may predict severe organ involvement in SSc(3). Objectives The aim of this study was to evaluate body composition in SSc patients and assess possible differences between patients with specific NVC patterns of microangiopathy. Methods 38 patients (6 men and 32 women) fulfilling ACR 2013 criteria for SSc underwent NVC to assess their NVC patterns (“Early”, “Active” and “Late” pattern)(4) and DXA to evaluate body composition(5). In particular we analyzed: total mass, total lean mass, total fat mass, bone mineral content(BMC), and bone mineral density(BMD) in seven body areas(head, upper limbs, lower limbs, trunk, spine, ribs, pelvis). Sarcopenia was diagnosed in patients with reduced skeletal muscle index (RSMI) below 5.45 Kg/m2 for females and 7.25 Kg/m2 for males(6). Statistical analysis was performed by non parametric tests. Results The mean age of patients was 64±11 years, mean disease duration 19.2 ±7.6 years, mean Rodnan skin score(mRSS) 11.5±9.3, and mean RSMI 6.3±1.05 g/cm2. All the patients showed a NVC “scleroderma pattern”: in particular 15 patients showed the “Late” pattern, 15 patients the “Active” pattern and 8 patients the “Early” NVC pattern. The “Late” NVC pattern group comparing to “Early/Active” group showed significantly lower total mass(58287±8217 vs 67238±11437 gr, p=0.01), lean mass(35249±3646 vs 41230±7954 gr, p= 0.05), RSMI(5.8±0.92 vs 6.6±1.02 g/cm2, p=0.02), BMC(1839±339 vs 2183±502 gr, p= 0.04), trunk BMD(0.70±0.12 vs 0.87±0.13 g/cm2, p=0.05) and spine BMD(0.91±0.17 vs 1.08±0.18 g/cm2, p=0.008). No statically significant difference between the two group was observed regarding total fat mass, total body BMD and BMD at upper limbs, lower limbs, head, ribs and pelvis. Interestingly, 24% of SSc patients were found affected by sarcopenia, and the most of sarcopenic patients showed the “Late” NVC pattern(67%). Comparing age, disease duration, mRSS between sarcopenic and non sarcopenic patients there was no difference between the groups, but sarcopenic patients presented a statistically significant lower BMI(p=0.02). Conclusion This study demonstrates in SSc patients a relationship between a more severe microvascular damage (”Late” SSc pattern) and the body composition, characterized by lower weight, total lean mass, bone mineral content and sarcopenia, without any significant variation in total fat mass. These clinical conditions seem not to be associated with severity of skin involvement and/or disease duration. Reference: [1] Caimmi C, et al. Clinical Rheumatology 2018;37:987-997.2.Thais FM, et al. Clin Rheumatol 2013;32:1037-44.3.Smith V, et al. J Rheumatol. 2013;40:2023-8.4.Cutolo M, et al. J Rheumatol 2000;27:155-60.5.Haarbo J, et al. Clin Physiol 1991;11:331-41.6.Baumgartner RN, et al. Am J Epidemiol 1998;147:755-63. Disclosure of Interests None declared

Background Hand arthralgia is often reported by breast cancer patients treated with adjuvant hormonal therapy. Aromatase inhibitors (AIs) improve survival in postmenopausal women with hormone-sensitive breast cancer, but can cause joint pain and stiffness (2). Low concentration of vitamin D in adults can cause musculoskeletal pain and joint discomfort (1). No data are available to date, on serum concentrations of (25-hydroxyvitamin D) [25 (OH) D3] vitamin D in AI-treated patients and possible relationship with arthralgia. Objectives To evaluate possible correlation between different 25 (OH) D3 serum concentrations and hand arthralgia in patients with breast cancer treated with AIs. Methods All patients that during the AIs therapy develop arthralgia referred to the rheumatologist; they reported the pain following the VAS (visual analogic scale) and contemporary performed a sample blood for dosage of vitamin D as well as biomarkers for inflammation and autoimmunity to exclude concomitant immune/inflammatory rheumatic musculoskeletal causes. Results In a group of 63 women taking AIs (mean age 62.3±9.8years; disease duration from first assumption of AIS 10.6±3.2 months) 81% reported hand arthralgia and stiffness within the first year of follow-up; the most prevalent site of pain localization was bilateral hands (85%). Symptom was associated with minimal increase of serum parameters of inflammation (the mean value of C-reactive protein was 7.1±3.0 mg(L (normal value 0-5) but negative autoimmune profile (negative rheumatoid factors and anticitrullinated protein antibodies). The mean 25(OH)D3 serum concentration was 18.4± 8.5 ng/ml. Only 9% of women had an adequate (≥ 30 ng/ml) [25 (OH) D3] vitamin D serum levels, 70% were insufficient (> 10 Conclusion Vitamin D serum concentrations in women treated with AIs are at lowest ranges in the majority of the patients analysed, but no apparent interference with musculoskeletal symptoms was found related to the different concentrations; the cause of arthralgia might be better related to estrogen deficiency induced by AIs their self. References [1] Kathryn R, et al. 2017 Ther Adv Musculoskelet Dis.9(6):131-135 [2] Hsieh KP, et al. 2014. PLoS One, 9, e87027. Disclosure of Interests None declared

Background:Vitamin D regulates the innate and adaptive immune system responses and low vitamin D levels have been associated with the increased risk of respiratory tract infections (1). Vitamin D deficiency has been recently reported to interfere with the prognosis of COVID-19 (2,3).Objectives:The aim of this study was to correlate the 25OH-vitamin D serum levels with lung involvement and disease severity, in a cohort of elderly patients hospitalized for SARS-CoV-2 infection.Methods:Sixty-five COVID-19 patients (mean age 76±13 years) and sixty-five sex- and age-matched control subjects (CNT) were included in the study. Respiratory parameters (PaO2, SO2, PaCO2, PaO2/FiO2), clinical and laboratory parameters (including 25OH-vitamin D, D-dimer, C-reactive protein) and type of radiological pulmonary involvement were collected at hospital admission. Statistical analysis was performed by non-parametric tests.Results:Vitamin D sufficiency (>30 ng/ml), insufficiency (between 20 and 30 ng/ml), deficiency (between 10 and 20 ng/ml) and severe deficiency (2 (p=0.05), PaO2 (p=0.03), PaO2/FiO2 (p=0.02). A statistically significant negative correlation was found between vitamin D serum levels and severity of radiologic pulmonary involvement: vitamin D was significantly lower in COVID-19 patients with either diffuse/severe interstitial lung involvement (p=0.05) or multiple lung consolidations (p=0.0001) than in those with mild radiological lung involvement. Significantly lower vitamin D serum levels were found in COVID-19 patients who died during hospitalization, compared to those who survived (median 3 vs 8 ng/ml, p=0.05). Finally, a statistically significant negative correlation was found between vitamin D serum levels and D-dimer (p=0.04), C-reactive protein (p=0.04) and disease duration (p=0.05).Conclusion:This study confirms that severe vitamin D deficiency is associated with more severe lung involvement, longer disease duration and risk of death in elderly COVID-19 patients.References:[1]Cutolo M, et al. RMD Open. 2020; 6(3):e001454.[2]Bilezikian JP, et al. Eur J Endocrinol. 2020; 183(5):R133-R147.[3]Weir EK, et al. Clin Med (Lond). 2020; 20:e107-e108.Disclosure of Interests:None declared

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease characterized by self-amplifying microvascular damage sustained by autoimmune response and progressive skin and visceral fibrosis. Besides, SSc patients show higher incidence of bone micro/macroarchitectural damages and bone fractures. Emerging data demonstrate that high serum levels of homocysteine (Hcy) could modulate osteoclastogenesis and are recognized as risk factors for osteoporosis (2). Furthermore, serum levels of Hcy were found to be higher in SSc patients than in healthy controls (3).Objectives:to evaluate the bone status according to HCy serum levels in a cohort of SSc patients.Methods:20 female patients fulfilling ACR 2013 criteria for SSc underwent a dual-energy X-ray absorptiometry scan (DXA) (Lunar Prodigy) to evaluate bone status. We analysed bone quantity and quality respectively by bone mineral density (BMD) and trabecular bone score (TBS). According to the WHO criteria, osteoporosis was defined as a bone density of 2.5 standard deviations below that of a young adult (T-Score). Fasting blood samples were obtained from all patients in order to test serum Hcy level and bone turnover markers after obtaining the informed consent. All subjects underwent morphometric spine X-Ray to evaluate vertebral fractures. Statistical analysis was performed using non-parametric tests.Results:The mean age of patients was 64.15 ± 10.8 years with a mean disease duration of 9.1 ± 2.3 years. The mean modified Rodnan Skin Score (mRSS) was 10.7 ± 8.5. All patients showed a “scleroderma pattern” at nailfold Videocapillaroscopy (NVC): in particular, 7 patients showed the “Late” pattern, 9 patients the “Active” pattern and 4 patients the “Early” NVC pattern. Hyperomocisteinemia (HHcy) was found in 25% of patients. Interestingly, SSc patients with the “Late” NVC pattern showed a significantly higher serum level of Hcy compared to the “Early/Active” group (11.15 ± 4.4 vs 17.17 ± 6.4, p=0.03). No significant differences were observed in relation to the autoantibody profiles. Of note, 60% of patients with HHcy were found osteoporotic and 40% had bone fractures.Considering the bone status, patients with Hcy showed a significantly lower TBS (p=0.03); the average values of BMD on the lumbar spine (p=0.79) and femoral neck (p=0.13) were found lower compared to, but without any statistical significance. Furthermore, no significant differences were observed in bone turnover markers according to Hcy levels.Conclusion:The study demonstrates a relationship between higher levels of Hcy and lower TBS values within SSc patients, particularly in those with most severe microvascular damage al NVC (“Late” SSc pattern). Therefore it is concluded that higher serum levels of Hcy associate to both bone microarchitectural and microvascular damage in SSc.References:[1]Cutolo M et al Expert Rev Clin Immunol 2019; 15: 753-64[2]Behera J et al. J Cell Physiol 2017;232(10):2704-2709[3]Yan-lie Zhang et al. Rheumatol 2018; 28(4):681-689Disclosure of Interests:None declared

Background:Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are tightly associated inflammatory conditions of the elderly [1]. Both disorders can exhibit an increased articular and vascular uptake of 18-fluorodeoxyglucose (18-FDG) at positron emission tomography (PET)/computed tomography (CT) scan [2].Objectives:This study evaluated if large-vessel vasculitis (LVV) detected by PET/CT in patients with PMR and/or cranial GCA had a negative prognostic value.Methods:108 patients (35 men and 73 women) with a median age of 74 years (range 50-92 years) were prospectively enrolled in our centre over 4 years. PMR was diagnosed by Bird et al. criteria and GCA by the ACR criteria. Six patients died shortly after the first visit (V0) and six were lost at follow-up. Of the remaining 96 patients, 77 were classified as PMR, 6 as GCA and 13 were affected by both diseases.At V0, patients underwent a clinical, laboratory and PET/CT evaluation, and were stratified according to the presence or not of LVV. Follow-up visits were performed every 6 months for a median of 40 months. Disease outcomes were: prednisone (PDN) use and its cumulative dosage, need of methotrexate (MTX), number of relapses, patients’ death, and PMR disease activity score (PMR-DAS). The independent variables were age, sex, disease duration, fever, C-reactive protein (CRP) concentration, platelet count (PLT), presence of cranial GCA, degree of joint and vascular uptake of FDG, and presence of LVV. The predictive role of LVV was tested by multiple regression.Results:LVV was seen in 47 patients (49 %), 31 with PMR, 6 with GCA and 10 with both diseases. Patients with or without LVV did not significantly differ in terms of demographic and laboratory parameters except for a non-significant higher number of PLT in patients with LVV. Clinical and laboratory parameters at V0, stratified per disease and considered together, did not significantly change between PET+ and PET- patients (table 1). Lastly, none of the independent variables, including LVV, could predict disease outcomes.Conclusion:The presence of a PET-detected LVV at diagnosis does not seem a negative prognostic factor in PMR and GCA. As a consequence, routine investigation by PET/CT of patients with PMR and GCA is not indicated to predict disease outcome.References:[1]Dejaco C, Duftner C, Buttgereit F, Matteson EL, Dasgupta B. The spectrum of giant cell arteritis and polymyalgia rheumatica: revisiting the concept of the disease. Rheumatology (Oxford). 2017 Apr 1;56(4):506-515. doi: 10.1093/rheumatology/kew273. PMID: 27481272.[2]Blockmans D, Coudyzer W, Vanderschueren S, Stroobants S, Loeckx D, Heye S et al. Relationship between fluorodeoxyglucose uptake in the large vessels and late aortic diameter in giant cell arteritis. Rheumatology (Oxford). 2008 Aug;47(8):1179-84. doi: 10.1093/rheumatology/ken119. Epub 2008 May 31. PMID: 18515868.Table 1.Clinical, laboratory and imaging features between PET+ and PET- patients at V0Features at V0PET+ patientsPET- patientspMorning stiffness (min)30 (0-480)60 (0-360)0.20Haemoglobin (g/dL)12.3±1.512.6±1.50.28Platelets (x 103/mm3)349 (108-643)297(159-571)0.08C-reactive protein (mg/dL)35.5 (3.4-149)36.2 (2-149)0.54Erythrocyte sedimentation rate (mm/h)62.5 (10-120)57.5 (10-120)0.29Total Vascular Score at PET20 (4-41)6 (0-12)0Total Joint Score at PET18 (5-30)18 (5-32)0.77Disclosure of Interests:None declared

Background:Fibroblast-to-myofibroblast transition is one of the fundamental steps involved in the fibrotic process that characterise systemic sclerosis (SSc) [1]. Myofibroblasts are α-smooth muscle actin (αSMA) positive cells that contribute to fibrosis through the excessive synthesis and deposition of extracellular matrix (ECM) proteins, primarily fibronectin (FN) and type I collagen (COL1) [2].Among the cells involved in the fibrotic process of SSc, circulating fibrocytes seem to have an emerging role as an important source of fibroblasts and myofibroblasts [3].Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis that interferes with the signalling pathways involved in the pathogenesis of fibrosis (4). Nintedanib was recently demonstrated to have a beneficial effect in patients with interstitial lung disease (ILD) associated with SSc (5).Objectives:To investigate nintedanib effect in inhibiting the in vitro transition of circulating SSc fibrocytes into myofibroblasts and their pro-fibrotic activity.Methods:Circulating fibrocytes were obtained from 14 SSc patients (mean age 64±14 years), who fulfilled the 2013 ACR/EULAR criteria for SSc and that underwent complete disease staging in a day-hospital setting at the Rheumatology Division of Genoa University. Five age-matched healthy subjects (HSs) were also analysed. All SSc patients and HSs signed the informed consent and the local EC approved the study. Peripheral blood mononuclear cells were isolated by density gradient centrifugation and plated on FN-coated dishes. After overnight culture, non-adherent cells were removed, and adherent cells were maintained in growth medium for 8 days (T8) to obtain fibrocytes [6]. T8-cultured SSc fibrocytes were maintained in growth medium (untreated cells) or treated with nintedanib 0.1μM and 1μM for 3 and 24 hours. Fibroblast specific protein-1 (S100A4) and αSMA, as markers of fibroblast/myofibroblast phenotype, together with COL1 and FN, were investigated by qRT-PCR and Western blotting. Non-parametric Mann-Whitney and Wilcoxon tests were used for the statistical analysis.Results:Significantly elevated gene and protein expressions of αSMA, S100A4, COL1 and FN were observed in SSc fibrocytes compared to HS fibrocytes (gene: αSMA p+ILD+) or Scl70 negative patients without ILD (Scl70-ILD-). Significant αSMA, S100A4, COL1 and FN gene expressions were found in fibrocytes from Scl70+ILD+ compared to HS fibrocytes (αSMA p+ILD+patients showed a more significant gene expression of fibroblasts/myofibroblasts markers compared to Scl70-ILD-patients (pNintedanib reduced the gene and protein expression of αSMA, COL1 and FN in SSc fibrocytes compared to untreated ones with different statistical significance.Noteworthy, nintedanib significantly downregulated αSMA, S100A4, COL1 and FN gene expression (all p+ILD+fibrocytes, whereas only that of S100A4 and FN was significantly downregulated (p-ILD- fibrocytes compared to untreated cells.Conclusion:Nintedanib seems to downregulate in vitro the transition of fibrocytes into myofibroblasts and their pro-fibrotic activity, particularly in cells isolated from Scl70+ILD+SSc patients.References:[1]Cutolo M et al. Exp Rev Clin Immunol. 2019;15:753-64.[2]Van Caam A et al. Front. Immunol. 2018;9:2452.doi:10.3389/fimmu.2018.02452.[3]Distler JH et al. Arthritis Rheumatol. 2017;69:257-67.[4]Distler O et al. New Eng J Med. 2019; 380:2518-28.[5]Maher TB et al. Arthritis Rheumatol.2020.doi:10.1002/art.41576.[6]Cutolo M et al. Arthritis Res Ther. 2018;20:157.doi:10.1186/s13075-018-1652-6.Acknowledgements:We thank Stefano-Lutz Willing for the scientific support through the study.Disclosure of Interests:Stefano Soldano: None declared, Paola Montagna: None declared, Emanuele Gotelli: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Alberto Sulli: None declared, Carlotta Schenone: None declared, Greta Pacini: None declared, Vanessa Smith: None declared, Maurizio Cutolo Grant/research support from: I received grant/research support from Bristol-Myers Squibb, Boehringer, Celgene

Background:Microvascular damage is a frequent feature in connective tissue diseases (CTDs) and can be easily detected trough nailfold videocapillaroscopy (NVC) (1,2). Mixed and Undifferentiated connective tissue diseases (MCTD and UCTD) do not show a specific and unique NVC pattern (3). However, a variety of microvascular abnormalities can occur in these two CTDs, both non-specific or specific for the scleroderma like-pattern (3-5).Objectives:To retrospectively assess and compare nailfold microangiopathy observed by NVC in MCTD and stable UCTD versus primary Raynaud’s phenomenon (PRP) (6). In addition, the aim was to correlate NVC findings with serum levels of autoantibodies (Abs) against extractable nuclear antigen (ENA) detected in UCTD.Methods:Files of fourty-six MCTD patients (Kasukawa’s criteria) (mean age 42.8±16 SD years), fourty-seven UCTD patients (mean age 47.7±16.1 SD years), fifty-one PRP (mean age 45.9±17.3 SD years) were retrospectively evaluated in the study. Among UCTD and MCTD patients 95% of both showed Raynaud’s phenomenon. Main NVC parameters (i.e. dilated capillaries, giant capillaries, microhemorrhages, abnormal shapes and number of capillaries) and related semiquantitative scale (score 0–3 for every parameter), were analyzed and compared between the two distinct CTD groups and PRP. Furthermore, ENA Abs (in particular, Ro/SSA, La/SSB, Scl70 and Jo1) were evaluated. The CTD patients were receiving different immunosuppressive treatments. Statistical analysis was performed by non-parametric tests.Results:Among UCTD group, 36% of patients showed a normal NVC pattern, 53% had non-specific NVC abnormalities and 11% had a scleroderma like-pattern. The latter was significantly more frequent in MCTD than in UCTD (pConclusion:NVC features in UCTD patients seem very close to the pattern observed in PRP (mostly non-specific capillary abnormalities), conversely in MCTD the scleroderma-like pattern was found significantly prevalent together with a significant capillary number reduction. The transition from the scleroderma-like to the scleroderma pattern (mean systemic sclerosis) is matter of actual investigation.References:[1]Cutolo M. et al. Best Pract Res Clin Rheumatol 2008; 22:1093-108.[2]Sulli A, Ann Rheum Dis. 2008;67:885-7.[3]Smith V. et al. Autoimmunity Reviews 2020; 19:102458.[4]De Holanda Mafaldo DA, et al. Lupus. 2007; 16:254–8.[5]Smith V, et al. Ann Rheum Dis 2010; 69: 1092-96.[6]Antunes M, et al. RMD Open. 2019, 26;4.Disclosure of Interests:None declared

Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune multisystemic disease, that can begin with a wide range of clinical manifestations, and requires immunosuppressive therapies (1). A treat-to-target strategy leads to a high rate of clinical remission among patients (2). Several “remission” definitions have been provided in the last years and Lupus Low Disease Activity State (LLDAS) seems one of the best tools to evaluate it in clinical practice (3).Objectives:To evaluate the prevalence of SLE signs and symptoms at onset and the drugs used to induce and maintain the clinical remission, evaluated by LLDAS, in a real-life cohort of SLE patients.Methods:Thirty female SLE patients (mean age 52±15 years; mean age at disease onset 34±16 years, mean disease duration 18±13 years) in clinical remission have been enrolled (EULAR/ACR 2019 criteria) (4). Remission was defined by LLDAS (SLEDAI-2K < 4 and no activity in major organ systems, no hemolytic anemia; no new features of activity compared with previous assessment, physician global assessment (PGA) ≤ 1, prednisone dose ≤7.5 mg/day, well tolerated and stable therapy with maintenance doses of immunosuppressive drugs). Clinical and serological manifestations, SLEDAI-2K and pharmacological treatments were recorded at baseline and during follow-up.Results:Mucocutaneous involvement (57%), arthritis (30%), serositis (30%), nephritis (27%), leukopenia (23%), thrombocytopenia (20%), hemolytic anemia (13%), antiphospholipid syndrome manifestations (16%), neuro-psychiatric lupus symptoms (6%) were present in various combinations at disease onset. Baseline mean SLEDAI-2K was 10.5±2.5. Patients were treated with different dosages of glucocorticoids (100%), hydroxychloroquine (HCQ, 73%), cyclofosfamide (20%), mycophenolate mofetile (MMF, 13%), azathioprine (AZA, 13%), methotrexate (MTX, 13%), cyclosporine A (CSA, 6%), rituximab (3%), abatacept (ABA, 3%). Glucocorticoids were prescribed together with a single DMARD in 50% of cases and with two DMARDs in the remaining 50% of patients. Patients reached LLDAS remission after a mean time of 14±12 years, with a mean remission duration of 4.2±3.2 years (mean SLEDAI-2K at last visit 1±1; Mean PGA 0.4±0.1). Maintenance therapies during remission were prednisone ≤ 5 mg/day and/or HCQ ≤ 400 mg/day and/or CSA ≤ 200 mg/day and/or MTX ≤ 10 mg/weekly and/or MMF ≤ 2 g/day and/or AZA ≤ 100 mg/day. In particular, only prednisone 7%, only HCQ 3%, prednisone + HCQ 53%, prednisone + single DMARD (different from HCQ) 7%, prednisone + HCQ + DMARDs 30%.Conclusion:After reaching the clinical remission by a treat to target strategy, the administration of low dose of prednisone and HCQ in the majority of SLE patients (63%) seems useful to prevent new SLE flares. The retrospective design and the absence of a control group of patients with active disease limit this study.References:[1]Lisnevskaia L et al. 2014.Lancet384(9957):1878-1888.[2]Van Vollenhoven RF et al. 2014.Ann Rheum Dis73(6): 958-967.[3]Franklyn K et al. 2016.Ann Rheum Dis. 75(9): 1615-21.[4]Aringer M et al. 2019.Arthritis Rheumatol.71(9): 1400-1412.Disclosure of Interests:Emanuele Gotelli: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Giorgia Ferrari: None declared, Greta Pacini: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Pietro Francesco Bica: None declared, Carmen Pizzorni: None declared, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha, Sabrina Paolino: None declared

Background:muscle actin (aSMA)+cells involved in the overproduction of extracellular matrix proteins, primarily fibronectin (FN) and type I collagen (COL1) at the level of damaged tissues (1). These cells may originate from different cell types including fibroblasts, endothelial and epithelial cells, and fibrocytes (1). Circulating fibrocytes are bone marrow progenitor cells expressing specific markers of hematopoietic (CD34, CD45, and MHC class II) and stromal cells (COL1 and COL3), chemokine receptors (CCR2, CCR7), and CXCR4 (2). CXCR4 regulates fibrocyte migration into injured tissues allowing their differentiation into fibroblasts/myofibroblasts (2).In vitro, fibrocytes differentiate from circulating CD14+monocytes showing an antigen-presenting capability through the expression of HLA-DR and costimulatory molecule CD86 (2). CTLA4-Ig fusion protein (abatacept) interacts with CD86 on cell surface of antigen presenting cells (APCs), such as macrophages and endothelial cells (3,4).Objectives:To investigate the possible effect of CTLA4-Ig treatment on cultured human fibrocytes and skin fibroblasts isolated from the same systemic sclerosis patients (SSc pts).Methods:Fibrocytes isolated from the peripheral blood mononuclear cells of SSc pts and healthy subjects (HSs) were cultured on fibronectin-coated plates in DMEM at 20% of FBS; for further 8 days (T8) to allow their complete differentiation. Differentiated fibrocytes were maintained in growth medium or treated with CTLA4-Ig at different concentrations (10, 50, 100, and 500μg/ml) for 3 hours. Fibroblasts were isolated from the skin biopsies of the same patients and HSs, cultured until the 3rdpassage in RPMI at 10% FBS and then treated with CTLA4-Ig for 24 and 48 hours. Fibrocytes were characterized as CD45+CXCR4+COL1+cells and the expression of CD86 and HLA-DR was also evaluated. The gene expression of aSMA, COL1, CXCR4, TGFb1 and CD86 was investigated by quantitative real-time polymerase chain reaction in cultured fibrocytes and skin fibroblasts. In cultured skin fibroblasts, COL1 and fibronectin synthesis was evaluated by Western blotting.Results:Treatment with CTLA4-Ig for 3 hours significantly downregulated aSMA and COL1 gene expression in cultured SSc fibrocytes at T8 (pConclusion:Due to their high expression of CD86, circulating fibrocytes seem to be more responsive to CTLA4-Ig treatment than the skin fibroblasts isolated from the same SSc patient.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15:753-64.[2]Bucala R. Mol Med.2015;2:S3-5.[3]Cutolo M et al. Clin Exp Rheumatol. 2015;33:250-4.[4]Brizzolara R et al. J Rheumatol. 2013;40:738-40.Disclosure of Interests:Stefano Soldano: None declared, Paola Montagna: None declared, Sabrina Paolino: None declared, Elisa Alessandri: None declared, Carmen Pizzorni: None declared, Greta Pacini: None declared, Federica Goegan: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Alternatively activated (M2) macrophages seem to play a role in the fibrotic process of systemic sclerosis (SSc) as potential inducers of tissue fibrosis through their secretion of specific cytokines and chemokines, such as interleukin-10 (IL-10), macrophage derived chemokine (CCL-22) and pro-fibrotic metalloproteases (i.e. MMP9) (1-3).Objectives:To investigate the presence of circulating cells belonging to the monocyte lineage showing an M2 phenotype in SSc patients (pts) and possible correlation with the clinical parameters of the disease. Moreover, to investigate if the treatment of cultured monocytes isolated from healthy subjects with serum derived from early SSc pts may induce theirin vitropolarization into M2 macrophages.Methods:Fifty female SSc pts (mean age 64±13 yrs), fulfilling the EULAR/ACR criteria, and 27 gender-matched healthy subjects (HSs, mean age 57±7 yrs) were considered at the Rheumatology Division of Genoa University after written informed consent. Nailfold videocapillaroscopy (NVC), serum SSc-related antibodies and skin involvement were investigated. Circulating cells belonging to the monocyte populations (CD45+and CD14+cells) were characterised by flow cytometry using specific surface markers of M2 phenotypes (CD204, CD206, CD163). Each SSc pt had been under stable treatment regimen for at least six months. Cultured monocytes, isolated by negative selection from peripheral blood mononuclear cells (PBMCs) of 8 HSs, stimulated for 48 hrs with 10% of serum of lcSSc pts with “Early” NVC pattern, as well as serum of dcSSc pts with “Active” and “Late” NVC patterns. Cultured monocyte human cell line (THP1) was differentiated into macrophages (5ng/ml of phorbol myristate acetate) and then stimulated with SSc sera. The expression of CD204, CD206 (M2 markers) and CD68 was investigated by immunocytochemistry, whereas MMP9 secretion was investigated by zymography. Statistical analysis was performed using Mann-Whitney and Kruskal-Wallis tests, and correlations were explored by bivariate Pearson’s analysis.Results:In SSc pts the percentage of circulating M2 cells (CD14+CD204+CD163+CD206+cells) was significantly increased compared to both HSs and SSc pts not under immunosuppressive treatment (pConclusion:The study confirmed that SSc pts are characterized by a significant increase of circulating M2 cells, suggesting their possible involvement in the pathogenesis of the disease. Interestingly, results insinuate that sera from SSc patients already in an “Early” NVC condition (sera known to contains specific profibrotic molecules such as cytokines, growth factors like TGFb1 or endothelin-1) seem able to inducein vitroa profibrotic M2 macrophage phenotype.References:[1]Cutolo M et al. ExpRevClin Immunol. 2019;15:753-64.[2]Stifano G et al. Curr Rheumatol Rep. 2016; 18:2. doi: 10.1007/s11926-015-0554-8.[3]Medeiros NI et al. Parasite Immunol. 2017;39: doi: 10.1111/pim.12446.Disclosure of Interests:Stefano Soldano: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Massimo Patanè: None declared, Emanuele Gotelli: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Greta Pacini: None declared, Federica Goegan: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Systemic sclerosis (SSc) is a complex autoimmune connective tissue disease, characterized by autoimmune inflammatory microvascular damage with progressive loss of capillaries, fibrosis and ischemia of skin and internal organs. (1) Nailfold videocapillaroscopy (NVC) is a safe toll for early diagnosis of SSc, it identify morphological changes of vessel that are predictive for clinical disease progression and organ involvement.(2) About clinical complication the loss of bone mass and body composition abnormalities, particularly muscle mass and strength loss (sarcopenia), are recognized in advanced disease.(3)Objectives:To evaluated in SSc patients, the body composition and the bone status according to the microvascular condition, assessed and scored by nailfold videocapillaroscopy (NVC, “Early”,”Active”,”Late” patterns).Methods:Body composition and bone mineral density (BMD) were assessed by DEXA in 35 female SSc patients classified according to the 2013 EULAR/ACR criteria and 32 sex-matched healthy subjects. Clinical, laboratory, body composition and bone parameters were analysed according to the different NVC patterns. Means were compared by the Student’s t test or one way analysis of variance; medians were compared by the Kruskall Wallis test; and frequencies by the chi square test.Results:Higher prevalence of vertebral (26.4%vs 9.3%) and femoral (32.3% vs 9.3%) osteoporosis (OP) was found in SSc. Particularly SSc patients with “Late” NVC pattern showed a significantly higher prevalence of vertebral (p=0.018) and femoral OP (p=0.016). Regional assessment of bone mass (BM) in 7 different body areas showed a significant lower BMD only at the total spine (P=0.008) and femoral neck (p=0.027) in advanced microvascular damage. Patients with “Late” NVC pattern showed lower whole body lean mass (LM) compared to “Early” and “Active” NVC patterns, particularly at upper limbs. To note, in all body sites, BMD correlate with LM and BMC according to NVC pattern severity.Conclusion:SSc patients with most severe microvascular damage show a significantly altered body composition and bone status suggesting a strong link between microvascular failure and associated muscle/bone sufference.References:[1]Cutolo M et al. Expert Rev Clin Immunol 2019; 15(7):753-64[2]Cutolo M et al. Clin Rheumatol 2019; 38(9):2293-7[3]Corallo C et al. Rheumatol Int 2019;39(10):1767-75.Disclosure of Interests:Sabrina Paolino: None declared, Emanuele Gotelli: None declared, Andrea Casabella: None declared, Francesco Cattelan: None declared, Carlotta Schenone: None declared, Massimo Patanè: None declared, Greta Pacini: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Nailfold videocapillaroscopy (NVC) abnormalities in subjects with isolated Raynaud’s phenomenon (RP) may be present before transition to secondary RP(SRP) and development of a NVC “scleroderma pattern” and are known to predict for evolution to a connective tissue disease (CTD) within few years [1]. In a previous study, we have demonstrated that the very early increase of capillary diameter over 30 μm is an independent predictor for development of Systemic Sclerosis (SSc) associated SRP [2].Objectives:Present pilot retrospective study aimed to investigate in a cohort of patients affected by CTD–related RP the presence of very early capillaroscopic morphological and quantitative abnormalities in the acquired pictures of NVC performed before the development of the NVC scleroderma-pattern. In particular, the study was addressed to identify a “very early”scleroderma pattern, in order to intercept patients with RP at high risk of evolution in a CTD, specifically SSc.Methods:We selected the NVCs of 273 SSc patients presenting one of the validated NVC “scleroderma patterns”. We enrolled 26 SSc patients having a NVC analysis performed before the development ofthe “very early”NVC pattern. As controls, we evaluated 26 patients affected by other CTDs with stable non-scleroderma pattern over time. The 16 images per patient obtained by NVC examination were analyzed for total number of capillaries, number and the limbs diameters of capillaries with a diameter >30 μm, and microhemorrhages. Statistical analysis was performed using non-parametric tests.Results:All 26 SSc patients showed dilated capillaries with a diameter >30 μm in their previous NVC. Patients later developing scleroderma pattern had statically higher number and percentage of capillaries with a diameter >30 μm (p=0.0004 and p=0.0005), as well as a larger apical dilatation >40 μm (p=0.002). A progressive and significant increase in all capillary diameters were only detected in patients later diagnosed for SSc (apical p=0.006, venous p=0.02, arterial p=0.03). A significant homogeneous and progressive dilation was observed from the apical region and then involving both venous and arterial branches, only in SSc patients (p=0.002).Conclusion:Present pilot study demonstrates, for the first time that, before to develop a validated NVC scleroderma-pattern, all potential SSc patients present significant very early morphological and quantitative NVC changes. In particular, the progressive and homogeneous capillary loop dilation over 40 μm in over 40% of total number capillaries significantly could contribute to identify RP patients who will develop a SSc pattern after 4-5 years.References:[1]Cutolo M, Sulli A, Pizzorni C, Accardo S. Nailfold videocapillaroscopy assessment of microvascular damage in systemic sclerosis. J Rheumatol. 2000;27:155-60.[2]Trombetta AC, et al. J Rheumatol 2016;43:599-606.Disclosure of Interests:Monica Pendolino: None declared, Carmen Pizzorni: None declared, Sabrina Paolino: None declared, Federica Goegan: None declared, Emanuele Gotelli: None declared, Carlotta Schenone: None declared, Francesco Cattelan: None declared, Massimo Patanè: None declared, Elisa Alessandri: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

Background:Systemic sclerosis (SSc) is a chronic connective disease characterized by microvascular alterations, dysregulated immune response and fibrosis [1,2]. Myofibroblasts are alpha-smooth muscle actin (alphaSMA)+cells and play a crucial role in fibrosis, through the excessive synthesis and deposition of extracellular matrix (ECM) proteins, in particular fibronectin (FN) and type I collagen (COL1) [3]. Despite myofibroblasts primarily derive from resident fibroblasts transition and differentiation, another important source is represented by circulating fibrocytes [4]. Nintedanib is a tyrosine kinase inhibitor approved for the treatment of idiopathic pulmonary fibrosis that interferes with the signalling pathways involved in the pathogenesis of fibrosis [5].Objectives:To investigate the possible effects of nintedanib in contrasting the ability of cultured mature fibrocytes from SSc patients to differentiate into profibrotic myofibroblasts.Methods:Circulating fibrocytes were obtained from peripheral blood mononuclear cells isolated from 5 limited cutaneous SSc patients (mean age 68 +/- 10 years) and then plated on FN-coated tissue culture dishes in growth medium (DMEM at 20% of fetal bovine serum, 1% of penicillin-streptomycin and 1% L-glutamine), to allow the adhesion of fibrocyte precursors. Adherent cells were maintained in growth medium for 8 days in order to allow their differentiation into fibrocytes. Differentiated fibrocytes were treated with nintedanib at the concentrations of 100nM and 1000nM for 3 and 24 hours (hrs) or maintained in growth medium without any treatment. The differentiation of fibrocytes into myofibroblasts was determined evaluating the gene expression of alphaSMA, fibroblast specific protein-1 (S100A4) COL1, FN and CXCR4 by quantitative real-time polymerase chain reaction, and the protein synthesis of alphaSMA, COL1 and FN by western blotting.Results:Nintedanib inhibited alphaSMA and S100A4 gene expression already at the concentration of 100nM in cultured fibrocytes and after 3 hrs of treatment, when compared with untreated cells. Furthermore, both concentrations of nintedanib (100nM and 1000nM) reduced the gene expression of COL1 and FN, whereas only 100nM downregulated the CXCR4 gene expression. At protein level, nintedanib 100nM and 1000nM reduced the synthesis of alphaSMA and COL1 after 24 hrs of treatment, whereas FN synthesis was reduced only by the nintedanib concentration of 1000nM.Conclusion:The preliminary results show that nintedanib may inhibit thein vitrotransition of SSc fibrocytes into myofibroblasts and their profibrotic activity, through the reduction of specific myofibroblast phenotype markers and ECM protein production. The results seem to suggest fibrocytes as further possible target of the antifibrotic action of nintedanib in SSc.References:[1]Cutolo M et al. Expert Rev Clin Immunol. 2019;15:753-64 2. Barsotti S et al. Clin Exp Rheumatol. 2016;34(Suppl.100):S3-S13 3. Wynn TA et al. Nat Med. 2012;18:1028-40. 4.Distler JHW et al. Arthritis Rheumatol. 2017;69:257-67 5.Hilberg F et al. Cancer Res. 2008;68:4774-82.Disclosure of Interests:Stefano Soldano: None declared, Giulia Martinelli: None declared, Samuele Tardito: None declared, Sabrina Paolino: None declared, Massimo Patanè: None declared, Emanuele Gotelli: None declared, Claudio Corallo: None declared, Carmen Pizzorni: None declared, Alberto Sulli Grant/research support from: Laboratori Baldacci, Carlotta Schenone: None declared, Vanessa Smith Grant/research support from: The affiliated company received grants from Research Foundation - Flanders (FWO), Belgian Fund for Scientific Research in Rheumatic diseases (FWRO), Boehringer Ingelheim Pharma GmbH & Co and Janssen-Cilag NV, Consultant of: Boehringer-Ingelheim Pharma GmbH & Co, Speakers bureau: Actelion Pharmaceuticals Ltd, Boehringer-Ingelheim Pharma GmbH & Co and UCB Biopharma Sprl, Maurizio Cutolo Grant/research support from: Bristol-Myers Squibb, Actelion, Celgene, Consultant of: Bristol-Myers Squibb, Speakers bureau: Sigma-Alpha

A design procedure for offset strip-fin (OSF) heat exchangers is proposed, on the basis of a minimum-entropy-production evaluation criterion. Proper dimensionless operational and geometric-parameters are introduced, and the thermodynamic impact of the OSF augmentation technique is Analyzed, for assigned heat exchanger working conditions, using available correlations for heat transfer and fluid friction coefficients. The proposed method allows the designer to determine the most suitable geometric configuration in order to achieve—under given operational constraints—the minimum dissipation effects of OSF heat exchangers.

The heat transfer characteristics of staggered, frontally shrouded fin arrays have been studied experimentally, in the case of forced convection of air. Nusselt number and Colburn number are given, for the range of Reynolds numbers from 2000 to 12000. The local Nusselt number distributions signal the existence of the periodically developed temperature field. Average Colburn number values are found to be in agreement, from an engineering standpoint, with correlations predicted for offset strip-fin heat exchangers.

The behaviour of two-phase high velocity flows in variable cross section ducts was investigated using a one-dimensional numerical model developed for the study of the annular flow configuration. Heat, mass, and momentum transfer between the phases during the flow were considered. The validation of the calculation procedure was made with some experimental data for the air-water couple, while the main application concerned the evaluation of momentum transfer from an expanding gas to an entrained liquid stream in droplet form. A liquid metal-gas flow was considered to simulate the process taking place in a plant where electrical power is generated by a liquid metal flowing in a magnetic field (MHD). The effectiveness of energy and momentum transfer between the liquid and the gas phase during the expansion was evaluated and the influence of nozzles with different convergence angles was investigated.

In the period from January 1986 to July 1988, Blastocystic hominis was found in moderate and numerous quantities in 103 (1.6%) of 6,262 stool specimens examined in our laboratory. There was no significant association of the detection of B. hominis with travel history or symptoms. Indeed, 20 patients (36%) with moderate to heavy infections had no gastrointestinal symptoms, and three symptomatic patients did not show clinical improvement after elimination of the parasite. Reexamination of stool samples revealed that eight untreated patients had spontaneous disappearance of B. hominis. We conclude that B. hominis probably is not responsible for clinical symptoms when detected, and additional investigations should be pursued for other etiologies of the patient's symptoms.

Four hundred fecal specimens which had been received for routine ova and parasite examination were concentrated by Formalin-ether sedimentation. Sediments were examined as saline and iodine-stained wet preparations and were stained with rhodamine-auramine O and a commercially available monoclonal fluorescent-antibody stain for oocysts of Cryptosporidium species. Examination with the fluorescent stains detected cryptosporidia in both positive specimens (0.5% prevalence), and routine direct wet-preparation examination detected cryptosporidia in one of them. Detection of only low numbers of positive specimens in our nonrisk population argues against routine use of specific and expensive stain reagents.

SYNOPSIS Degree-days are widely utilised to evaluate heating energy consumption in buildings. An auxiliary criterion, which can provide useful information about the diffusion of energy demand in a given territory, is the analysis of the population distribution performed on the basis of the local winter climate. This paper studies the possibility of correlating heating energy consumption in buildings and the territorial distribution of degree-days and population. The distribution of the Italian population was analysed in relation with heating degree-days and population-weighted degree-days were calculated. Correlated consumption indexes were then introduced and their nationwide distribution was analysed. These indexes enabled us to locate the distribution of energy demand and pick out the areas where consumption density is highest. The predictive method was successfully validated by comparison with real data on natural gas consumption in Italy for the winter heating of buildings.

The European Directive 2002/49/EU (END) has defined new indicators and instruments to evaluate environmental noise due to transport infrastructures. The Directive introduces the concept of “Strategic noise mapping” as “a map for the global assessment of noise exposure”, also defining roads, railways, airports and agglomerations that require to be analyzed trough this instrument. In order to foster an uniform approach in the member states, the European Commission Working Group on Assessment Exposure to Noise (WG-AEN) published a guideline named “Good Practice Guide for Strategic Noise Mapping and the Production of Associated Data on Noise Exposure”. The paper presents the procedures used in the noise maps of 8 important roads within the jurisdiction of the Provinces of Genoa and Savona, Ita-ly, a work that has been carried out as the first part of EU–funded LIFE+ NADIA project (Noise Abatement Demonstrative and Innovative Actions and information to the public). The procedures allow to create noise maps using of different levels of input data. The project also focused on the realization of noise action plans, sustainable noise abatement measures and innovative dissemination events. An important goal of NADIA project is in fact to determine different methodologies for the dissemination of noise information, considering various stakeholders (local authorities, engineers and consultants, high school students etc.), and to develop new multimedia tools, in order to encourage a better understanding of noise prob-lems and to increase the awareness of the citizens.

The still ongoing COVID-19 pandemic has dramatically impacted athletes, and, in particular, para-athletes and athletes with disabilities. However, there is no scholarly appraisal on this topic. Therefore, a critical scoping review of the literature was conducted. We were able to retrieve sixteen relevant studies. The sample size ranged from 4 to 183. Most studies were observational, cross-sectional, and questionnaire-based surveys, two studies were interventional, and two were longitudinal. One study was a technical feasibility study. Almost all studies were conducted as single-country studies, with the exception of one multi-country investigation. Five major topics/themes could be identified: namely, 1) impact of COVID-19-induced confinement on training and lifestyles in athletes with disabilities/para-athletes; 2) impact of COVID-19-induced confinement on mental health in athletes with disabilities/para-athletes; 3) impact of COVID-19-induced confinement on performance outcomes in athletes with disabilities/para-athletes; 4) risk of contracting COVID-19 among athletes with disabilities/para-athletes; and, finally, 5) impact of COVID-19 infection on athletes with disabilities/para-athletes. The scholarly literature assessed was highly heterogeneous, with contrasting findings, and various methodological limitations. Based on our considerations, we recommend that standardized, reliable tools should be utilized and new, specific questionnaires should be created, tested for reliability, and validated. High-quality, multi-center, cross-countries, longitudinal surveys should be conducted to overcome current shortcomings. Involving all relevant actors and stakeholders, including various national and international Paralympic Committees, as a few studies have done, is fundamental: community-led, participatory research can help identify gaps in the current knowledge about sports-related practices among the population of athletes with disabilities during an unprecedented period of measures undertaken that have significantly affected everyday life. Moreover, this could advance the field, by capturing the needs of para-athletes and athletes with disabilities and enabling the design of a truly "disability-inclusive response" to COVID-19 and similar future conditions/situations. Furthermore, follow-up studies on COVID-19-infected para-athletes and athletes with disabilities should be conducted. Evidence of long-term effects of COVID-19 is available only for able-bodied athletes, for whom cardiorespiratory residual alterations and mental health issues a long time after COVID-19 have been described., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Puce, Trabelsi, Ammar, Jabbour, Marinelli, Mori, Kong, Tsigalou, Cotellessa, Schenone, Samanipour, Biz, Ruggieri, Trompetto and Bragazzi.)