AB0623 RATE AND PREDICTIVE FACTORS ASSOCIATED WITH SUSTAINED REMISSION IN IDIOPATHIC INFLAMMATORY MYOSITIS

Background:Idiopathic inflammatory myositis (IIM) is a group of heterogeneous connective tissue diseases, characterised by chronic muscle inflammation, myositis-specific or myositis-associated autoantibodies and different extra-muscular features. Achieveing low disease activity or remission in patients with IIM has proven to be difficult due to the wide clinical spectrum of the different IIM types.Objectives:To retrospectively assess any predictive factors for sustained remission in IIM patientsMethods:We retrospectively analyzed data taken from medical charts, which included age at disease onset, gender, laboratory data as well as clinical features present at onset, organ involvement and treatment history. A total of 151 adult patients with IIM followed-up for > 1 year were retrospectively enrolled. Remission was defined as no clinical and laboratory evidence of disease activity persistent for more than 6 months during follow-up, while undergoing myositis therapy or under no medication. The remission of cutaneous involvement was defined as no current activity of skin rash, absence of Gottron's papules as well as heliotrope rash and erythema, whereas the remission of pulmonary involvement was considered as no requirement for intensification of immunosuppressive therapy during follow-up. Likewise, absence of muscle weakness or hyposthenia was taken into account for evaluating muscle involvement. Moreover, the clinical features were accompanied by normalization of myogenic enzymes such as creatine kinase (CK) and lactate dehydrogenase levels.Results:Among all 151 patients, 89 (58.9%) patients achieved sustained remission. By univariate analysis, overlap myositis (7.9% vs 27.4%; p=0.003; OR:0.22), cancer-associated myositis (CAM) (7.8% vs 19.35%; p=0.046; OR:0.3), as well as the presence of anti Ku (3.37% vs 12.9%; p=0.05; OR:0.23) and anti TIF-1 gamma (1.1% vs 8%; p=0.043; OR:0.13) antibodies and polyarthritis (11.2% vs 24.19%; p=0.045; OR: 0.397) at onset were significantly associated with active IIM, not achieving remission.Out of 89 patients in remission, 79 (88.8%) achieved long-term sustained remission, lasting at least 2 years, whereas 10 patients (11.2%) showed relapse. Most of relapsed patients showed a relapse/remitting disease, with no evident trigger for the relapse. We divided our cohort of 89 patients in remission in 2 subsets: 83 patients in remission undergoing therapy (93.3%) and 6 patients in drug-free remission (6.7%). No significant differences were found between two groups, except for younger age at onset (p=0.0002) found in patients achieving drug-free remission.Conclusion:Sustained remission occurs in about one half of patients with IIM. The presence of anti Ku and anti TIF-1 gamma antibodies as well as polyarthritis at onset lowers the chance of achieving sustained remission. Younger age at diagnosis has proved to predict drug-free long-lasting remission.Disclosure of Interests:None declare

Numerical and experimental investigations of a microwave interferometer for the negative ion source SPIDER

The electron density close to the extraction grids and the co-extracted electrons represent a crucial issue when operating negative ion sources for fusion reactors. An excessive electron density in the plasma expansion region can indeed inhibit the negative ion production and introduce potentially harmful electrons in the accelerator. Among the set of plasma and beam diagnostics proposed for SPIDER upgrade, a heterodyne microwave (mw) interferometer at 100 GHz is being explored as a possibility to measure electron density in the plasma extraction region. The major issue in applying this technique in SPIDER is the poor accessibility of the probing microwave beam through the source metal walls and the long distance of 4 m at which mw modules should be located outside the vacuum vessel. Numerical investigations in a full-scale geometry showed that the power transmitted through the plasma source apertures was sufficient for the microwave module sensitivity. An experimental proof-of-principle of the setup was then performed. The microwave system was tested on an experimental full-scale test-bench mimicking SPIDER viewports accessibility constraints, including the presence of a SPIDER-like plasma. The outcome of first tests revealed that, despite the geometrical constraints, in certain conditions, the electron density measurements are possible. The main issue arises from decoupling the one-pass signal from spurious multipaths generated by mw beam reflections, requiring signal cross correlation analysis. These preliminary tests demonstrate that despite the 4 m distance between the mw modules and the presence of metal walls, plasma density measurement is possible when the 80-mm diameter ports are available. In this contribution, we discuss the numerical simulations, the preliminary experimental tests and suggest design upgrades of the interferometric setup to enhance signal transmission

Anti-MIT3 antibodies in systemic sclerosis

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The role of clinically significant antiphospholipid antibodies in systemic lupus erythematosus

The objective is to investigate the role of clinically significant antiphospholipid antibodies (aPL) in a cohort of systemic lupus erythematosus (SLE) patients. All SLE patients followed for at least 5 years and with available aPL profile at the beginning of the follow-up in our center were studied. Clinically significant aPL were defined as: positive lupus anticoagulant test, anti-cardiolipin and/or anti- β2Glycoprotein I IgG/IgM >99th percentile on two or more occasions at least 12 weeks apart. Patients with and without clinically significant aPL were compared by univariate (Chi square or Fisher's exact test for categorical variables and Student's t or Mann-Whitney test for continuous variables) and multivariate analysis (logistic regression analysis). P values <0.05 were considered significant. Among 317 SLE patients studied, 117 (37%) had a clinically significant aPL profile at baseline. Such patients showed at univariate analysis an increased prevalence of deep venous thrombosis, pulmonary embolism, cardiac valvular disease, cognitive dysfunction and antiphospholipid syndrome (APS), but a reduced prevalence of acute cutaneous lupus and anti-extractable nuclear antigens (ENA) when compared with patients without clinically significant aPL. Multivariate analysis confirmed the association between clinically significant aPL and reduced risk of acute cutaneous lupus [p=0.003, odds ratio (OR) 0.43] and ENA positivity (p<0.001, OR 0.37), with increased risk of cardiac valvular disease (p=0.024, OR 3.1) and APS (p<0.0001, OR 51.12). Triple positivity was the most frequent profile and was significantly associated to APS (p<0.0001, OR 28.43). Our study showed that one third of SLE patients had clinically significant aPL, and that this is associated with an increased risk, especially for triple positive, of APS, and to a different clinical and serological pattern of disease even in the absence of APS

Frequency Evaluation of the Interleukin-6 −174G>C Polymorphism and Homeostatic Iron Regulator (HFE) Mutations as Disease Modifiers in Patients Affected by Systemic Lupus Erythematosus and Rheumatoid Arthritis

Autoimmune diseases are generally characterized by a multifactorial etiology and are often associated with a genetic predisposition. Both iron metabolism and the inflammatory cytokine system have been shown to play a pivotal role in the dysregulation of the immune response in many different autoimmune conditions, rheumatologic diseases included. The purpose of this work was to analyze the frequency of mutations altering the expression of IL-6 or influencing iron metabolism in patients affected by autoimmune diseases such as Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE). In this study, 144 patients were enrolled: 77 and 67 patients were affected by RA and SLE, respectively. In these cohorts, the frequency of the IL-6 polymorphism −174G>C located in the IL-6 gene promoter was tested. Moreover, the frequencies of the three HFE gene variations associated with iron overload were analyzed: p.His63Asp, p.Ser65Cys and p.Cys282Tyr. The two mutations p.His63Asp and p.Ser65Cys in the HFE gene did not reach statistical significance in any of the comparisons, regardless of the statistical model, cohorts of patients and control populations analyzed. The frequencies of the p.Cys282Tyr mutation and the IL-6 polymorphism −174G>C were found to be overall significantly decreased in RA and SLE patients when the Dominant model and Allele contrast were adopted with both the Odds Ratio and Chi-square. Although further investigation is needed, the examination of the frequencies of the −174G>C IL-6 promoter polymorphism and HFE mutations may add some valuable information on the interplay linking iron metabolism, inflammation and immunity in autoimmune diseases such as SLE and RA

ANALISIS INTERDEPENDENSI FOREIGN DIRECT INVESTMENT (FDI) DENGAN VARIABEL MAKRO EKONOMI

ABSTRAK Tujuan utama dari penelitian ini adalah untuk menganalisis interdependensi antara FDI dengan beberapa variabel yang lain, seperti PDB, Trade, Nilai Tukar, dan Tingkat bunga. Model VAR digunakan untuk menunjukkan pandangan yang komprehensif dari interdependensi ini. Hasil empiris menunjukkan bahwa melalui model VAR, interdependensi antara variabel FDI, PDB, Trade, Nilai Output Industri, Nilai Tukar dan Tingkat Suku Bunga telah diteliti dalam hubungan jangka panjang melalui kointegrasi vektor dan jangka pendek yang berdampak pada model VAR. Korelasi dinamis variabel telah diperoleh dengan analisis varian dan analisis respon impuls. Beberapa implikasi besar muncul dari hasil penelitian. Jika pemerintah Indonesia berkeinginan mendorong FDI dan pertumbuhan ekonomi, hal ini dapat dilakukan dengan output dan nilai tukar. Dalam jangka pendek maupun jangka panjang, keduanya sangat penting untuk stabilitas ekonomi. Kata Kunci : FDI, Pertumbuhan ekonomi, variabel makro dan model VARBanda Ace

ps1 3 analysis of c9orf72 expansions in patients with systemic lupus erythematosus and rheumatoid arthritis preliminary data

Background The most frequent genetic cause of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Dementia (FTLD) is a large hexanucleotide expansion (mostly hundred/thousand repeats) within a non-coding region of the C9orf72 gene. 1 The cut-off to distinguish normal and pathogenic expansions has not yet been defined, but most healthy individuals have 2–20 repeats. The pathogenic mechanism of the dominant mutation is most probably toxic gain of functions. Nonetheless, C9orf72 reduced expression has been observed in post-mortem brains of mutated patients. 2 Interestingly, while gene haploinsufficiency alone seems insufficient to cause neurodegeneration, decreased transcriptional activity with increasing numbers (>7) has been demonstrated in vitro 3 and knockout mice developped features of systemic lupus erythematosus (SLE). 4 We investigated C9orf72 gene in a cohort of patients with rheumatoid arthritis (RA) and SLE; as a control group we studied 49 ALS patients without pathogenic expansion. Methods 29 SLE and 50 RA pts were screened, by the use of a PCR-based protocol, validated in our laboratory. 5 A cut-off of ≥9 repeat units was considered in our analysis. Results No patients with large expansions were found. The average and median values of repeat units were 5.29 and 6 in SLE, 4.73 and 2 in RA and 4.8 and 5 in the control population. We individuated ≥9 repeat units in 5/30 (16.7%) SLE patients and 7/50 (14%) RA patients; a prevalence higher than ALS group (8.16%). We searched for clinical or serological differences among SLE pts with the normal and ≥9 repeat. Although those differences were not statistically significant, we reported a higher prevalence of kidney involvement in patients with a number of repeats ≥9 (5/6; 83.3% vs 7/23; 30.4%), p=0.056. Conclusion Our preliminary results indicate that ≥9 repeats within the C9orf72 gene are detectable in a non negligible number of patients with systemic autoimmune disease, confirming the possible role of C9orf72 in autoimmune system. The possible association with specific subset of disease must be confirmed in a larger cohort of patients. References . Neuron2011,72:245–56. . Lancet Neurol2015,14:291–301. . Mol Psychiatry2016,21:1112–24. . Atanasio A, et al. Sci Rep2016;6:23204. . Mol Cell Probes2017;32:60–64

Direct two-dimensional measurements of the eld-aligned current associated with plasma blobs

In simple magnetized toroidal plasmas, field-aligned blobs originate from ideal interchange waves and propagate radially outward under the effect of \grad B and curvature induced $E \times B$ drifts. We report on the first experimental two-dimensional measurements of the field-aligned current associated with blobs, whose ends terminate on a conducting limiter. A dipolar structure of the current density is measured, which originates from \grad B and curvature induced polarization of the blob and is consistent with sheath boundary conditions. The dipole is strongly asymmetric due to the nonlinear dependence of the current density at the sheath edge upon the floating potential. Furthermore, we directly demonstrate the existence of two regimes, in which parallel currents to the sheath do or do not significantly damp charge separation and thus blob radial velocity