POS1221 SARS-COV2 SEROLOGY SCREENING IN SPONDYLOARTHRITIS PATIENTS IN NORTH-EASTERN ITALY: A PILOT STUDY

Background:Serology could help defining the real extent of Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV2) diffusion in the population, especially in individuals considered at higher risk of SARS-CoV2 infection (COVID-19), such as Spondiloarthritis (SpA) patients undergoing immunosuppressive therapy or health care workers (HCW). In fact, COVID-19 detection is complicated by the fact that many patients can be asymptomatic. In these cases, it has also been suggested that a weaker immune response might be elicited.In this context, the role of anti-cytokine targeted therapy –commonly used as treatment in SpA- is uncertain, as it is not clear whether it is detrimental or protective towards severe disease forms.Objectives:The aim of the study was to explore the potential role of serology in detecting previous contact with SARS-CoV2 in SpA patients and HCW, and compare the frequency of positive findings with a control population.Methods:Consecutive patients affected by axial or peripheral SpA, classified according to Assessment of SpondyloArthritis international Society (ASAS) criteria and undergoing cytokine-targeted therapy, as well as HCW and controls from the pre-COVID-19 era (control group, 2015) were recruited. In SpA patients, disease activity was assessed by Ankylosing Spondylitis Disease Activity Score (ASDAS) and Disease Activity Score on 28-joint-count (DAS28).Sera from all patients were analysed through chemiluminescent analytical system (CLIA) for the presence of IgG and IgM anti-SARS-CoV2. Patients with a positive serological test (either IgM or IgG) additionally underwent real time Polymerase Chain Reaction (RT-PCR) in nasopharyngeal swabs in order to test for active infection. In SpA patients, serology was repeated after 3 months. Data across the 3 groups were compared by ANOVA or Chi-square, while comparison between 2 groups were conducted by Wilcoxon signed rank test or Chi-Square, for continuous and categorical data respectively. P ≤ 0.05 were considered as significant.Results:A total of 396 patients were recruited: 200 SpA, 95 HCW and 101 healthy controls. SpA patients were mostly (54%) males, with mean age 49.6 ±14.7 years, and all were treated with anti-TNFα (78%), anti-IL-17 (9%) and anti-IL-23 drugs (7%), or small molecules (6%). Their disease activity level was moderate-low as assessed by ASDAS (1.95 ±0.98) and DAS28 (2.33 ±2.02). Among HCW and controls, 35% and 62% were male, with mean age 46.7 ±12.9 and 50.6±10.6 respectively.Positive serology (IgM or IgG, or both) was found in 12.5% SpA patients, 8.4% HCW, 0% controls (p=0.001). Among these, IgM titres were higher in the SpA group than in HCW (2.76±2.94 versus 0.80±0.67 KU/L, p= 0.016), while IgG mean titres were lower in the SpA group than in HCW (0.88±3.18 KU/L versus 1.05±0.88, p= 0.035). SpA patients with positive serology more frequently reported COVID-19 like symptoms than those with negative serology (20% vs 4%, p=0.009) and 2 had COVID-19 as confirmed by RT-PCR, none with a severe disease course. None of the HCW reported symptoms or tested positive by RT-PCR. In the SpA patients, at 3 months, the mean IgM titre decreased from 2.76±2.93 to 2.38±2.95 (p=0.001), while the IgG titres decreased from 0.89±3.25 to 0.31±0.87 (p=ns). Interestingly, the IgM or IgG titer at a single-patient level did not seem to change much in terms of absolute value (Figure 1), except in one patient, with documented COVID-19 (positive RT-PCR), in whom IgG level even decreased at 3 months.Conclusion:Serology revealed that exposure to COVID-19 in SpA patients, as well as HCW, was higher than expected based on reported symptoms. Targeted anti-cytokine therapy could act as a protective factor for a severe disease course in SpA patients. However, in this population, IgG and IgM titres did not change in a clinically significant manner at 3 months, and patient did not seem to develop an immune profile consistent with durable response. This result could be due to a weaker immune response in mild infections, but further studies are warranted to clarify the pathophysiology beyond these observations.Figure 1.Disclosure of Interests:Augusta Ortolan: None declared, Chiara Cosma: None declared, Mariagrazia Lorenzin: None declared, Giacomo Cozzi: None declared, Andrea Doria Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Janssen, Glaxosmithkline, Mario Plebani: None declared, Roberta Ramonda Speakers bureau: Novartis, Abbvie, Pfizer, MSD, Jansse

SAT0245 RENAL INVOLVEMENT AT ONSET IN ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA)-ASSOCIATED VASCULITIS: A MAJOR INDEPENDENT RISK FACTOR FOR RENAL RELAPSE

Background:In ANCA-associated vasculitis (AAV), renal relapses are cause for concern as they are unpredictable and predictors of end-stage renal disease (ESRD).Objectives:We aimed to assess the frequency of major renal (MR) relapses in AAV in our cohort and identify independent predictors of the first MR relapse at diagnosis.Methods:We performed a retrospective monocentric observational study in our Vasculitis clinic from January 2000 to August 2019. Inclusion criteria were: 1) granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA) and limited kidney disease (LKD) diagnosis fulfilling EMA algorithm criteria; 2) achievement of a stable remission, defined as absence of vasculitis symptoms or signs and adherence to the prednisone taper during remission-induction treatment. We excluded patients who developed ESRD before remission and those with incomplete data during the follow-up. Major renal (MR) relapses were defined as occurrence of at least one major item of renal Birmingham Vasculitis Activity Score version 3 (BVASv3).All remitted patients were allocated in two subgroups: patients without MR relapse and patients with MR relapse. Univariate and multivariable analysis of first MR relapse predictors was performed with Fine and Gray (F&G) sub distribution hazards model to assess all competitive risks (progression to ESRD without MR relapse and death before MR relapse). Due to the relatively low frequency of events and the risk of overfitting, we performed several multivariable models with three variables, as recommended by Peduzzi e al1. The best multivariable model was selected accordingly to the Akaike information criterion (AIC).Results:96 (53% females) patients met the inclusion criteria: 74 GPA, 21 MPA and 1 LKD. Median age at diagnosis was 54 (44-64) years. ANCA testing was present in 94 patients, 85 were ANCA positive: 56 c-ANCA/PR3, 28 p-ANCA/MPO and 1 double positivity.During a median follow-up (FU) of 54.5 months (29.3-96.5), we observed 19 MR relapses in 17 patients while 2 patients progressed to ESRD, 3 died without events and 76 reported no MR relapse. Density-incidence of MR relapses since remission was 3.6/100 person-year (CI 95% 2.2-5.6). Median time to first MR relapse after remission was 33 months (14-67.5).At first MR relapse, 8 (53.3%) patients were on steroids while 10 (66.7%) were on immunosuppressant (5 azathioprine, 5 mycophenolate). In 2 cases, data about remission-maintenance treatment was not available.MR relapses were observed only in ANCA positive patients with a significantly higher frequency of skin, kidney and nerve involvement at diagnosis (41.2% vs 17.7%, p=0.034, 94.1% vs 57.0% p=0.004, and 52.9% vs 25.3% p=0.024, respectively); while Ear, Nose and Throat (ENT) involvement was significantly lower (35.3% vs 62.0% p=0.043). Mean BVASv3 at diagnosis scored significantly higher in MR relapse group (24.1±6.2 vs 18.1±8.1. p=0.007).At multivariable analysis with F&G model, renal involvement and induction treatment without cyclophosphamide and/or Rituximab at diagnosis were independent predictors of MR relapse (sHR 20.4 (2.6-158.2), p=0.004 and sHR 4.2 (1.5-12.0), p=0.007, respectively). Moreover, there was a trend of higher risk of MR relapse in PR3-ANCA (sHR 2.5 (0.9-7.1), p=0.091).Conclusion:Renal involvement at diagnosis and milder remission-induction treatment regimens resulted in a significantly higher risk of MR relapse during the FU in our cohort. PR3-ANCA specificity was not an independent predictor of MR relapse, even if we observed a trend of higher MR relapse risk with this covariate.References:[1]Peduzzi P et al. A simulation study of the number of events per variable in logistic regression analysis. J Clin Epidemiol. 1996;49(12):1373-9.Disclosure of Interests:Mara Felicetti: None declared, Augusta Ortolan: None declared, Anna Chiara Frigo: None declared, Roberto Padoan: None declared, Michela Gasparotto: None declared, Mariagrazia Lorenzin: None declared, Andrea Doria Consultant of: GSK, Pfizer, Abbvie, Novartis, Ely Lilly, Speakers bureau: UCB pharma, GSK, Pfizer, Janssen, Abbvie, Novartis, Ely Lilly, BMS, Roberta Ramonda Speakers bureau: Novartis, Celgene, Janssen, Pfizer, Abbvie, Lilly, Franco Schiavon: None declare

Subclinical atherosclerosis in patients with psoriatic arthritis: a case-control study. Preliminary data

Objective: The aim of this study was to evaluate the prevalence of subclinical atherosclerosis in patients with psoriatic arthritis (PsA), correlated with some traditional risk factors of atherosclerosis and with PsA-related disease factors. Methods: Forty-one patients and 41 healthy subjects were evaluated for intima-media thickness (IMT) and flow-mediated dilation (FMD), using carotid duplex scanning. IMT values were expressed like IMT mean (cumulative mean of all the IMT mean) and M-MAX (cumulative mean of all the higher IMT). Subclinical atherosclerosis markers were correlated with age, body mass index (BMI) and blood pressure in both groups, with duration of arthritis, duration of psoriasis, tender and swollen joints, BASDAI (Bath Ankylosing Spondylitis Disease Activity Index), BASFI (Bath Ankylosing Spondylitis Functional Index), erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in patients. Results: IMT mean and M-MAX were both higher in PsA patients compared with controls (0.7±0.15 vs 0.62±0.09 mm; p<0.01 and 0.86±0.21 vs. 0.74±0.13 mm; p<0.01 respectively). FMD was smaller in patients than in controls (5.9±2 vs 7.5±2.8%; p<0.01). Univariate analysis showed a correlation between IMT mean and SBP (r=0.217; p=0.05) and a correlation between M-MAX and age (r=0.392; p<0.001), BMI (r=0.252; p<0.05), SBP (r=0.446; p<0.001) in both groups. In PsA patients M-MAX resulted correlated with ESR (r=0.338; p<0.05) and BASDAI (r=0.322; p<0.05). Conclusions: PsA patients exhibited endothelial dysfunctions which is an early marker of subclinical atherosclerosis, as well as an higher IMT. An interesting correlation between M-MAX and PsA activity index (ESR and BASDAI) was found

Postoperative trends and prognostic values of inflammatory and nutritional biomarkers after liver transplantation for hepatocellular carcinoma

11noPreoperative inflammatory biomarkers such as the Platelet-to-Lymphocyte Ratio (PLR) and the Neutrophil-to-Lymphocyte Ratio (NLR) strongly predict the outcome in surgically treated patients with hepatocellular carcinoma (HCC), while nutritional biomarkers such as the Controlling Nutritional Status (CONUT) and the Prognostic Nutritional Index (PNI) show an analogue prognostic value in hepatic resection (HR) but not in liver transplant (LT) cases. Data on the impact of LT on the inflammatory and nutritional/metabolic function are heterogeneous. Therefore, we investigated the post-LT trend of these biomarkers up to postoperative month (POM) 12 in 324 HCC patients treated with LT. Inflammatory biomarkers peaked in the early post-LT period but at POM 3 leveled off at values similar (NLR) or higher (PLR) than pre-LT ones. CONUT and PNI worsened in the early post-LT period, but at POM 3 they stabilized at significantly better values than pre-LT. In LT recipients with an overall survival &gt;1 year and no evidence of early HCC recurrence, 1 year post-LT NLR and PNI independently predicted patient overall survival, while 1 year post-LT PLR independently predicted late tumor recurrence. In conclusion, at 1 year post-LT, the nutritional status of liver-transplanted HCC patients significantly improved while their inflammatory state tended to persist. Consequently, post-LT PLR and NLR maintained a prognostic value for LT outcome while post-LT CONUT and PNI acquired it.openopenopenPravisani R.; Mocchegiani F.; Isola M.; Lorenzin D.; Adani G.L.; Cherchi V.; De Martino M.; Risaliti A.; Lai Q.; Vivarelli M.; Baccarani U.Pravisani, R.; Mocchegiani, F.; Isola, M.; Lorenzin, D.; Adani, G. L.; Cherchi, V.; De Martino, M.; Risaliti, A.; Lai, Q.; Vivarelli, M.; Baccarani, U

Different promoter affinities account for specificity in MYC-dependent gene regulation

Enhanced expression of the MYC transcription factor is observed in the majority of tumors. Two seemingly conflicting models have been proposed for its function: one proposes that MYC enhances expression of all genes, while the other model suggests gene-specific regulation. Here, we have explored the hypothesis that specific gene expression profiles arise since promoters differ in affinity for MYC and high-affinity promoters are fully occupied by physiological levels of MYC. We determined cellular MYC levels and used RNA- and ChIP-sequencing to correlate promoter occupancy with gene expression at different concentrations of MYC. Mathematical modeling showed that binding affinities for interactions of MYC with DNA and with core promoter-bound factors, such as WDR5, are sufficient to explain promoter occupancies observed in vivo. Importantly, promoter affinity stratifies different biological processes that are regulated by MYC, explaining why tumor-specific MYC levels induce specific gene expression programs and alter defined biological properties of cells

Impact of Power Outages on Developing Countries: Evidence from Rural Households in Niger Delta, Nigeria

Nigeria is suffering from the worst energy crisis in its history, resulting in its rural communities being subjected to massive power outages, daily. Energy promotes economic well-being and makes social life worthwhile such that youths are less disposed to violent crimes. This study investigated the consequences of power outages on the social-economic life of rural households in the Niger Delta region of Nigeria. Primary data were collected through a semi-structured questionnaire circulated among unemployed youth, students, housewives, businessmen and professionals in the area. The study focused on the relationship between power outage and its impact on the everyday life of the people. This study adopted a descriptive research design using 1000 randomly selected members of 44 rural households in the areas mostly affected by incessant power outages. It was found that stunted economic growth, reduced leisure time as well as heightened criminality and insecurity are some of the major results of rampant power outages among rural households in the Niger Delta. It is concluded that power outages have severe negative impact on the social and economic lives of the people. The findings from this research would help improve the outlook of rural communities in Nigeria and other developing countries. Keywords: Nigeria, Power outage, Energy, Electricity, Rural households

Эксплуатационные показатели качества транспортной телекоммуникационной первичной сети Украины

Приведены статистические данные о количестве, причинах и характере повреждений подземных волоконно-оптических линий связи, которые являются основой транспортной телекоммуникационной первичной сети на примере Донецкой и Луганской областей за период с 2001 по 2010 годы. Сравнение значений этих характеристик со значениями аналогичных параметров за 2001—2005 гг. позволяет разработать рекомендации по повышению надежности телекоммуникационных сетей.В роботі наведено статистичні дані про кількість, причини та характер пошкоджень підземних волоконно-оптичних ліній зв’язку, які є основою транспортної телекомунікаційної первинної мережі, на прикладі Донецької та Луганської областей за період з 2001 по 2010 рр. Порівняння значень цих характеристик із значеннями аналогічних характеристик за 2001—2005 рр. дозволяє розробити рекомендації по підвищенню надійності телекомунікаціїйних мереж.The paper presents statistical data on the number, nature and causes of the damage to underground fiber-optic communication lines, on which the transport telecommunication primary network is based, using an example of Donetsk and Lugansk regions for the period between 2001 and 2010. Comparison of these characteristics with the values of similar parameters over 2001—2005 allows to develop recommendations for the improvement of the reliability of telecommunication networks

Association between the donor to recipient ICG-PDR variation rate and the functional recovery of the graft after orthotopic liver transplantation: A case series

Background: Despite current advances in liver transplant surgery, post-operative early allograft dysfunction still complicates the patient prognosis and graft survival. The transition from the donor has not been yet fully understood, and no study quantifies if and how the liver function changes through its transfer to the recipient. The indocyanine green dye plasma disappearance rate (ICG-PDR) is a simple validated tool of liver function assessment. The variation rate between the donor and recipient ICG-PDR still needs to be investigated. Materials and methods: Single-center retrospective study. ICG-PDR determinations were performed before graft retrieval (T1) and 24 hours after transplant (T2). The ICG-PDR relative variation rate between T1 and T2 was calculated to assess the graft function and suffering/recovering. Matched data were compared with the MEAF model of graft dysfunction. Objective: To investigate whether the variation rate between the donor ICG-PDR value and the recipient ICG-PDR measurement on first postoperative day (POD1) can be associated with the MEAF score. Results: 36 ICG-PDR measurements between 18 donors and 18 graft recipients were performed. The mean donor ICG-PDR was 22.64 (SD 6.35), and the mean receiver's ICG-PDR on 1st POD was 17.68 (SD 6.60), with a mean MEAF value of 4.51 (SD 1.23). Pearson's test stressed a good, linear inverse correlation between the ICG-PDR relative variation and the MEAF values, correlation coefficient -0.580 (p = 0.012). Conclusion: The direct correlation between the donor to recipient ICG-PDR variation rate and MEAF was found. Measurements at T1 and T2 showed an up- or downtrend of the graft performance that reflect the MEAF values

Nomenclature for renal replacement therapy and blood purification techniques in critically ill patients: practical applications

This article reports the conclusions of the second part of a consensus expert conference on the nomenclature of renal replacement therapy (RRT) techniques currently utilized to manage acute kidney injury and other organ dysfunction syndromes in critically ill patients. A multidisciplinary approach was taken to achieve harmonization of definitions, components, techniques, and operations of the extracorporeal therapies. The article describes the RRT techniques in detail with the relevant technology, procedures, and phases of treatment and key aspects of volume management/fluid balance in critically ill patients. In addition, the article describes recent developments in other extracorporeal therapies, including therapeutic plasma exchange, multiple organ support therapy, liver support, lung support, and blood purification in sepsis. This is a consensus report on nomenclature harmonization in extracorporeal blood purification therapies, such as hemofiltration, plasma exchange, multiple organ support therapies, and blood purification in sepsis