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Nail melanoma (NM) is an important differential diagnosis in patients with longitudinal melanonychia. However, diagnosis is often challenging as it is difficult to differentiate from other pigmented nail disorders. The main challenge for diagnosis is obtaining adequate nail matrix biopsy specimens for histopathological assessment. Furthermore, the histopathological changes in the early stages of NM are subtle and contribute to a delay in diagnosis and care. Therefore, the integration of clinical and histopathological analyses is essential. Clinical and dermoscopic features, such as a broadened width of asymmetric bands in an irregular pattern, with multicolour pigmentation, periungual pigmentation, and continuous growth, are features that support the diagnosis of NM. The essential histological features that must be assessed are cellular morphology, architectural features, melanocyte density, and inflammatory changes. The reported mutations in NMs were BRAF (0-43%), NRAS (0-31%), KIT (0-50%), NF1 (0-50%), and GNAQ (0-25%). Surgery is the primary treatment for NM. The recommended treatment for in situ or minimally invasive NM is functional surgery, but cases with suspected bone invasion should be treated with amputation. Targeted therapy and immunotherapy are indicated for advanced stages of NM. This review summarizes the updated guidelines for the diagnosis and treatment of NM.

Over the past few decades, tetrafluoroethane (TFE, R134a Freon)-based gases have been widely used in the operation of phenolic resistive plate chambers (RPCs) in many high-energy experiments. However, TFE has a high global warming potential (GWP); therefore, a search for new eco-friendly gases to replace traditional TFE-based ones is now unavoidable. In this research, we present cosmic-ray test results of a prototype RPC for the SHiP (search for hidden particles) experiment using 1.6- and 1.4-mm-thick RPC electrodes containing mixtures of various gases, including 1,3,3,3-tetrafluoropropene (HFO1234ze), CO2, iC4H10 and SF6. We compare the performance data gathered with these new gas mixtures with those gathered with a traditional TFE-based gas used for RPCs in compact muon solenoid (CMS) and a toroidal LHC apparatus (ATLAS) experiments. The addition of CO2 to the HFO1234ze-based gas was found to be fairly effective in reducing the working-point high voltage (HVWP) for RPC operation. The results of our experiments lead us to the conclusion that adding 40% CO2 or less, when combined with HFO1234ze-based gas, is conducive to reliable detector performance for SHiP single-gap phenolic RPCs.

Background/Introduction Brugada syndrome (BrS) and arrhythmogenic right ventricular cardiomyopathy (ARVC) are inherited arrhythmias that may predispose to sudden cardiac arrest. Although its pathogenetic mechanisms differ, overlapping features between BrS and ARVC have been demonstrated previously. However, it remains to be determined whether genetic testing for ARVC-related gene is needed in patients with BrS. Purpose This study is aimed to analyze genetic profiles of BrS patients using next generation sequencing (NGS) based multigene panel including ARVC related genes. Methods Patients who were confirmed as BrS or clinically suspected as BrS with type 2 or 3 Brugada pattern electrocardiography were studied. Genetic testing using NGS panels (Illumina Inc., San Diego, CA, USA) included 30 genetic variants associated with inherited arrhythmia and genetic cardiomyopathy. Results Among the total 119 patients from BrS registry, 63 patients were confirmed as BrS and 56 patients were clinically suspected as BrS without fulfilling diagnostic criteria. One-hundred-fourteen patients (95.8%) were male, and mean age of onset was 43.6 year-old. Genetic variants were identified in 25 of 42 patients who received genetic testing. Six out of 25 patients (24.0%) showed ARVC-related genotypes (2 PKP2, 1 DSG2, 1 TMEM43, 1 JUP, and 1 DSP) (Figure 1 and Table 1). None of the patients showed structural or electrocardiographic features that fulfill diagnostic criteria of ARVC. It is notable that ARVC-related genotypes were mostly frequently accounted for BrS patients, following SCN5A and SCN10A. Conclusion In the clinic setting, ARVC-related genetic variants were identified in significant proportion of BrS patients, supporting that genetic testing of ARVC-overlapping is needed. This study suggests that follow-up including imaging study should be considered in BrS patients with ARVC-related genotypes to monitor disease progression as ARVC. Funding Acknowledgement Type of funding sources: None.

Background/Introduction Signal-averaged electrocardiography (SA-ECG) is a high-resolution electrocardiography that can detect late ventricular potential, which known to be a noninvasive tool for risk stratification of sudden cardiac death (SCD) by predicting reentrant ventricular tachyarrhythmia. There is a paucity of data with SA-ECG on SCD survivors without structural heart disease, whereas majority of previous studies had been focused on post myocardial infarction survivors. Purpose This study assessed the clinical utility of SA-ECG as a risk stratification modality for lethal arrhythmic event in patients at risk of SCD without definite structural heart disease. Methods Total 629 patients who experienced or had potential risk of SCD were studied with SA-ECG. Among them, 48 patients who were found to have significant structural heart disease were excluded, except arrhythmogenic right ventricular cardiomyopathy. Major arrhythmic event (MAE) was defined as composite of all-cause death, aborted SCD, and sustained VT during any time either before visit of clinic or during follow up period. Syncope and non-sustained VT was defined as non-major arrhythmic event. SA-ECG was defined positive when fulfilling three or more criterion: (1) unfiltered QRS duration ≥114ms, (2) filtered QRS duration ≥114ms, (3) duration of terminal QRS Results Among total 581 patients, 145 patients with positive SA-ECG showed higher incidence of MAE compared to patients with negative SA-ECG (21.4% vs. 6.7%, OR 3.816 [95% CI 2.208–6.597], p Conclusion This study showed that at least 3 out of 4 diagnostic criteria in SA-ECG can independently predict lethal arrhythmic events and the positive late potential was associated with lethal arrhythmic event that leads to SCD, suggesting risk prediction for SCD using SA-ECG in patients even without structural heart disease including inherited arrhythmias. Funding Acknowledgement Type of funding sources: None.

Background The predictive value of immune monitoring with circulating CD8+ T lymphocytes for treatment response to programmed cell death protein 1 (PD-1) inhibitors has not been explored in non-small-cell lung cancer (NSCLC), prompting us to investigate whether dynamic changes in PD-1+CD8+ T lymphocytes have predictive value for durable clinical benefit (DCB) and survival after PD-1 blockade. Methods Patients with recurrent and/or metastatic NSCLC treated with PD-1 inhibitors were enrolled (discovery cohort; n = 94). Peripheral blood was obtained immediately before and after one cycle of treatment with PD-1 blockade. Phenotyping of circulating CD8+ T lymphocytes was conducted using multi-colour flow cytometry. Predictive values of dynamic changes in circulating PD-1+CD8+ T lymphocytes during the first cycle were validated in an independent cohort (validation cohort; n = 54) of a prospective trial with a PD-1 inhibitor (NCT03486119). Results Circulating PD-1+CD8+ T lymphocytes were enriched with effector/memory populations with elevated expression of activation- and exhaustion-related markers. Reduction in the frequency of PD-1+ cells among CD8+ T lymphocytes after one cycle of treatment was associated with a higher probability of DCB and superior survival outcomes in the discovery cohort. Similar results were obtained in the analysis of tumour antigen NY-ESO-1-specific CD8+ T lymphocytes and the validation cohort. Mechanistically, PD-1 molecule expression on CD8+ T lymphocytes suppresses the effector functions of tumour antigen-specific CD8+ T lymphocytes. Conclusions Dynamic changes in circulating PD-1+CD8+ T lymphocytes predict clinical, and survival benefit from PD-1 blockade treatment in NSCLC, providing a useful tool to identify patient subgroups who will optimally benefit from PD-1 inhibitors.

Accurate prediction of intended gait speed is crucial for facilitating volitional muscle activity during robot-assisted gait training. Considering that most patients find it difficult to perform gait at relatively high speeds, it is also imperative that the prediction model performs well at slow gait speed. Furthermore, ample time for signal processing should be given prior to robot assistance such that the patient is not subjected to unwanted resistance or lag. Here, the authors propose to predict the intended speed of the contralateral limb via kinematics of the current swing limb. Three lower-limb positions were evaluated using an inertial measurement unit sensor during treadmill gait sessions. The results suggest that the authors’ model performs well even during slow gait speeds ( ≤ 2 km / h ) with R 2 values as high as 0.86.

Purpose: Immune-checkpoint inhibitors have shown therapeutic efficacy in various malignant diseases. However, anti-programmed death (PD)-1 therapy has not shown clinical efficacy in multiple myeloma. Experimental Design: Bone marrow (BM) mononuclear cells were obtained from 77 newly diagnosed multiple myeloma patients. We examined the expression of immune-checkpoint receptors in BM CD8+ T cells and their functional restoration by ex vivo treatment with anti–PD-1 and TGFβ inhibitors. Results: We confirmed the upregulation of PD-1 and PD-L1 expression in CD8+ T cells and myeloma cells, respectively, from the BM of multiple myeloma patients. PD-1–expressing CD8+ T cells from the BM of multiple myeloma patients coexpressed other checkpoint inhibitory receptors and exhibited a terminally differentiated phenotype. These results were also observed in BM CD8+ T cells specific to myeloma antigens NY-ESO-1 and HM1.24. BM CD8+ T cells from multiple myeloma patients exhibited reduced proliferation and cytokine production upon T-cell receptor stimulation. However, anti–PD-1 did not increase the proliferation of BM CD8+ T cells from multiple myeloma patients, indicating that T-cell exhaustion in multiple myeloma is hardly reversed by PD-1 blockade alone. Intriguingly, anti–PD-1 significantly increased the proliferation of BM CD8+ T cells from multiple myeloma patients in the presence of inhibitors of TGFβ, which was overexpressed by myeloma cells. Conclusions: Our findings indicate that combined blockade of PD-1 and TGFβ may be useful for the treatment of multiple myeloma.

The main goals of the Search for Hidden Particles (SHiP) experiment are to observe hidden particles and to run a high-statistics study of tau neutrino events. Two different types of resistive plate chambers (RPCs) will be used in the future SHiP experiment: one for triggers to select the decayed muons emitted via tau neutrino interactions and one for precision time measurements of charged particles, which are expected from the decays of hidden particles. In the present research, we constructed and tested a prototype RPC module to study the fundamental detector performance of the muon trigger RPCs in the tau neutrino detector of the SHiP experiment. The required detector characteristics, such as the intrinsic noise rate, the time response, and the spatial resolution, were proven through the test of the present prototype detector with cosmic muons.

BackgroundAlthough proliferative (class III or IV) lupus nephritis (LN) is the most common finding in the classification of LN, pure membranous (class V) or mesangial (class I or II) LN can occur as a form of LN. Even though non-proliferative LN (class I, II, or V) is a less severe form with good outcomes, data on long-term renal prognosis are limited.ObjectivesThis study investigated the long-term outcomes and prognostic factors in non-proliferative LN.MethodsWe retrospectively reviewed the medical records of patients with systemic lupus erythematosus who were diagnosed with LN class I, II, V or II+IV by kidney biopsy between 1997 and 2021 at a tertiary referral center. Clinical and laboratory data were compared between patients with and without poor renal outcomes. Poor renal outcome was defined as an estimated glomerular filtration rate (eGFR) of < 60 mL/min/1.73 m2 or death due to renal cause. Univariate and multivariate analyses were performed with the Cox proportional hazard model to identify the factors associated with poor renal outcomes.ResultsWe included 71 patients with non-proliferative LN (4: class I; 17: class II; 48: class V, 17; 2: class II+V). Median follow-up duration was 103 months (interquartile range 27–185) and the overall rate of poor renal outcomes at last follow-up was 29% (21/71), including end-stage renal disease (n=2) and renal death (n=1).Univariate analysis indicated that older age (HR 1.05; 95% CI: 1.00–1.09), low eGFR (HR 0.97; 95% CI: 0.95–0.99) and failure to reach complete remission at 6 months (HR 0.332; 95% CI: 0.12–0.92) were significantly associated with poor renal outcomes. Multivariate analysis revealed that low eGFR at 6 months (HR 0.97; 95% CI: 0.95–0.99) was significantly associated with poor renal outcomes.Figure 1.Renal outcomes at last follow upeGFR, estimated glomerular filtration rate (ml/min/1.73m2)Table 1.Univariate and multivariate Cox proportional hazard regression analyses of the factor associated with poor renal outcomesParameterUnivariate analysisMultivariate analysisHR95% CIp valueHR95% CIp valueClinical features Age1.0461.003-1.0910.0361.0020.960-1.0470.921 Sex1.6540.375-7.2980.506 SLEDAI1.0360.965-1.1120.327 Extra renal SLEDAI1.0380.971-1.110.272Renal profiles eGFR at LN diagnosis0.9930.976-1.0110.456 Proteinuria at LN diagnosis1.0001.000-1.0000.444 > 1g/24 hours0.6690.243-1.8410.437 > 3g/24 hours0.6240.229-1.6990.356 eGFR at 6M0.9670.948-0.9860.0010.9680.948-0.9880.002 eGFR at 12M0.9640.947-0.9810.000 Complete remission at 6M0.3320.119-0.9240.0350.5530.179-1.7070.303 Complete remission at 12M0.6670.232-1.9140.451 Transformation1.2460.423-0.7010.692Laboratory data Anti-dsDNA1.0010.999-1.0030.196 C31.0201.000-1.0410.051 C41.0270.969-1.0890.367 Albumin1.1800.661-2.1090.576ClassificationaClass I0.8020.102-6.3030.834Class II1.2980.412-4.0880.656Class V0.8870.308-2.5570.824Class II+V0.0480.000-16850.837Medicationsb ACEi/ARB1.6520.603-4.5280.329 Hydroxychloroquine1.3260.414-4.2420.635 Corticosteroid1.1860.154-9.1080.870 CNI2.4390.464-12.8240.292 MMF3.7880.959-14.9650.057 AZA0.5890.133-2.6110.486a LN classifications were based on the International Society of Pathology/Renal Pathology Society (ISN/RPS) classification.b Medications maintained at least one year since Lupus Nephritis diagnosis.HR, hazard ratio; 95% CI, 95% confidence interval; SLEDAI, systemic lupus erythematosus disease activity index; eGFR, estimated glomerular filtration rate; LN, lupus nephritis; anti-dsDNA, anti-double strand DNA; C3/C4; complement 3/4; ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CNI, carcineurin inhibitor; MMF, mycophenolate mofetil; AZA, azathioprine.ConclusionPoor renal outcomes occurred in approximately 30% of patients with non-proliferative LN (class I, II or V) after long-term follow-up.Our findings suggest that more active management may be needed for non-proliferative LN, particularly in patients with low eGFR at 6 months.Disclosure of InterestsNone declared

Between inner and outer shells of vacuum vessel, numerous in-wall shielding (IWS) blocks are installed to provide neutron shielding. Uniquely, the IWS ribs in sector 1 and 6 are manufactured by welding and its manufacturing design shall be secured for not only manufacturability but safety point of views. For the design of IWS ribs, complex loads for multiple directional electromagnetic force, coolant pressure, and earthquake shall be considered simultaneously. Moreover, in-service inspection (ISI) is impossible after commissioning ITER, and therefore, proper design assessment procedure should be applied with reasonable conservatism. In this paper, an approach for manufacturing design of welded IWS ribs is proposed. On the basis of that approach, four representative models are screened by geometric factors and load magnitude. Under the most conservative loads among multiple loading conditions, structural safety of each representative models is verified with RCC-MR. The deviation requests for this assessment were approved to IO and ANB. This approach and results could be used as a reference for the design of vacuum vessel components, which is impossible for ISI.

In this study, the electromagnetic characteristics of the insulated (INS), non-insulated (NI), and metal-clad (MC) racetrack coils are examined in a time-varying magnetic field. The delay in the generation of induced current and the amount of induced current when the coils are exposed to the time-varying magnetic field have been thoroughly examined. Additionally, the electromagnetic stability of each test coil was investigated under an overcurrent condition in the presence of an external magnetic ripple field. We also performed an AC loss test to investigate the effects of an MC layer on the magnitude of the AC loss. Based on the test results, the feasibility of using an MC winding technique for developing a highly stable high-temperature superconducting wind turbine generator with an enhanced electromagnetic response was thoroughly examined

Dark photons are hypothetical massive vector particles that could mix with ordinary photons. The simplest theoretical model is fully characterised by only two parameters: the mass of the dark photon m$$_{\gamma ^{\mathrm {D}}}$$ γ D and its mixing parameter with the photon, $$\varepsilon $$ ε . The sensitivity of the SHiP detector is reviewed for dark photons in the mass range between 0.002 and 10 GeV. Different production mechanisms are simulated, with the dark photons decaying to pairs of visible fermions, including both leptons and quarks. Exclusion contours are presented and compared with those of past experiments. The SHiP detector is expected to have a unique sensitivity for m$$_{\gamma ^{\mathrm {D}}}$$ γ D ranging between 0.8 and 3.3$$^{+0.2}_{-0.5}$$ - 0.5 + 0.2 GeV, and $$\varepsilon ^2$$ ε 2 ranging between $$10^{-11}$$ 10 - 11 and $$10^{-17}$$ 10 - 17 .

BackgroundThere is still controversy about the efficacy of COVID-19 vaccination and its extent in lowering immunogenicity of Rheumatoid Arthritis (RA) patients. The guideline in whether immunosuppressive agents need to be discontinued before the vaccination is continuously updated because it is considered to lower immunogenicity. Furthermore, there is great discussion on the effectiveness of the COVID-19 booster vaccine and interest in antibody generation in different types of vaccine, as in South Korea there are many patients who were prescribed the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine.ObjectivesThus, we investigated the differences of antibody production between patients who received only two doses of ChAdOx1-S nCoV-19 and those who received the mRNA booster vaccine. Also, antibody production under different types of immunosuppressive agents was analyzed.MethodsFrom October 14, 2021 to January 21, 2022 at a tertiary referral center, two patient groups diagnosed with RA were studied prospectively; one group that completed 1st and 2nd doses of ChAdOx1-S nCoV-19 vaccine, second group that completed mRNA booster vaccine as well as two doses of ChAdOx1-S nCoV-19 vaccine. SARS-CoV-2 antibody testing on the semiquantitative anti-SARS-CoV-2 S enzyme immunoassay was done, and differences in antibody titers were analyzed in patients who received different immunosuppressive agents such as csDMARD, TNF inhibitor, JAK inhibitor, Tocilizumab, Abatacept and Corticosteroid. Statistical analysis with a multivariate logistic regression model was performed.ResultsIn a total of 261 patients, 153 patients had completed two doses of ChAdOx1-S nCoV-19, 108 patients had completed third mRNA booster vaccine. Anti-SARS-CoV-2 RBD antibody positive rate (titer>0.8U/mL) was 97%(149/153) and 99%(107/108) respectively, and only 5 patients showed negative result. In the aspect of high antibody titer(>250U/mL), which is the upper limit of the RBD antibody immunoassay, the result showed rate of 31% (47/153) in the non-booster group and 94%(102/108) in the booster group respectively.Among the different immunosuppressive agents and other clinical aspects, multivariate analysis revealed that corticosteroid use (OR 0.91; 95% CI: 0.86-0.98), older age(OR 4.33; 95% CI: 1.34-13.91), and male gender(OR 0.35; 95% CI 0.16-0.75) were significantly associated with low rate of high antibody titer.Furthermore, out of 14 patients who underwent antibody test twice before and after the mRNA booster vaccine, other than four patients who already showed high titer of >250U/mL before the mRNA booster vaccine, 10 patients showed an increase in titer after the booster vaccine and 7 patients were acquired high titer of >250U/mL.Figure 1.Anti-SARS-CoV RBD antibody titer of two groupsTable 1.Analysis of immunosuppressive agents and other clinical aspects for high antibody titer(>250U/mL) after two doses of ChAdOx1-S nCoV-19Univariate analysisMultivariate analysisParameterOR95% CIp valueOR95% CIp valueClinical features Age0.9170.860-0.9780.0080.9170.857-0.9810.012 Sex3.6741.206-11.1910.0224.3301.348-13.9120.014 DAS 281.1440.670-1.9500.622 Duration0.9300.830-1.0430.214Medications csDMARD1.2730.639-2.5331.273 TNF inhibitor2.2110.795-6.1450.128 JAK inhibitor0.6650.275-1.6070.365 Abatacept0.3680.038-3.6020.391 Tocilizumab1.2640.438-3.6480.665 Corticosteroid0.4720.235-0.9490.0350.3490.163-0.7480.007Medication dose Methotrexate0.9930.919-1.0720.855 Corticosteroid0.8490.719-1.0030.054ConclusionAnti-SARS-CoV-2 RBD antibody positive rate was 97% or more regardless of the mRNA booster vaccination. However, patients who received the mRNA booster vaccine after two doses of ChAdOx1-S nCoV-19 vaccine showed high antibody titer (>250U/mL) three times more than those who did not receive the booster shot.Our findings also showed that corticosteroid use, old age, and male gender is significantly associated with low rate of acquiring high antibody titer.Disclosure of InterestsNone declared

BackgroundMacrophage activation syndrome (MAS) is a hyperinflammatory condition that is known to be secondary hemophagocytic lymphohistiocytosis (HLH) in patients with rheumatic disease.ObjectivesThe aim of study was to evaluate the clinical manifestations and outcomes in patients with MAS with rheumatic disease.MethodsWe performed a retrospective study of 20 adult patients who were diagnosed with MAS from 2012 to 2020. MAS was classified according to the HLH-2004 criteria. Patients’ information, including clinical features, laboratory findings, and treatment regimens, was collected, and the overall survival rate was estimated by the Kaplan–Meier method.ResultsTwenty patients (18 women, 35.6 ± 18.3 years) who met the HLH-2004 criteria also fulfilled the 2016 EULAR/ACR/PRINTO classification criteria for MAS, and HScore was higher than 169 (median, 238.5). Fourteen patients with systemic lupus erythematosus and 6 patients with adult-onset Still’s disease were included. All patients were treated initially with corticosteroids, and 16 patients required additional immunosuppressants. The overall survival at 3 and 6 months was 75.2% and 64.3%. In survivors, renal impairment was less common (23.1% versus 42.9%, p = 0.007), the levels of AST (202.0 versus 72.0 IU/L, p = 0.006) and LDH (1144.0 versus 343.0IU/L, p = 0.001), and platelet count (90.0 versus 46.0 × 109/L, p = 0.016) were higher in compared to non-survivors. Nine patients had opportunistic infections, five of whom died during admission.ConclusionThe mortality of patients with MAS remains high. Renal impairment, levels of AST and LDH, and platelet count might be associated with prognosis.Table 1.Treatments and management characteristics of patients with MASNo.Age/sexDiseaseDisease duration (months)1st Treatment (corticosteroids)2nd Treatment3rd TreatmentCombined infectionAlive/dead119/FSLE11 mg/kgIVIG + PPTCZ, RTXBacteremiaDead220/MSLE01 mg/kg---Alive320/FAOSD11 mg/kgVP16--Alive422/FSLE1100 mgIVIG + PP-PneumoniaDead522/FAOSD0500 mgIVIG--Alive623/FSLE1821 mg/kg---Alive723/FSLE411 mg/kg---Alive830/FSLE1461 mg/kgIVIGCsA-Alive932/FSLE1271 mg/kgIVIG + PPCsA, TCZPneumoniaAlive1035/FAOSD01 mg/kgCsA-Viral infectionAlive1137/FSLE651 mg/kgCsA, VP16-BacteremiaAlive1238/FSLE01 mg/kgIVIG + PPRTX-Dead1340/FAOSD00.5 mg/kgCsA--Alive1443/FSLE601 mg/kgIVIG + PPTCZ, RTX, CsA,PCP,DeadVP16, IFXViral infection1549/FSLE01 mg/kgCYC-BacteremiaAlive1651/FAOSD01 mg/kg---Alive1757/FSLE01 mg/kgIVIG + PPCsA, VP16Fungal infectionDead1861/FSLE21 mg/kgIVIG + PPTCZ-Dead1968/FSLE21 mg/kgIVIG + PPCsAFungal infectionAlive2070/MAOSD01 mg/kgIVIG + PPCsA, VP16Fungal infectionDeadSLE: Systemic lupus erythematosus, IVIG: Intravenous immunoglobulin, PP: Plasmapheresis, TCZ: Tocilizumab, RTX: Rituximab, AOSD: Adult-onset still’s disease, VP16: Etoposide, PCP: Pneumocystis pneumonia, CsA: Cyclosporin, IFX: Infliximab, MCTD: Mixed connective tissue disease.Disclosure of InterestsNone declared

BackgroundThe systemic lupus erythematosus (SLE) disease activity in patients with lupus nephritis (LN) generally declines after the initiation of renal replacement therapy (RRT); this is known as the “burn out” phenomenon that possibly occurs due to the suppression of cellular and humoral immunity in the end-stage renal disease (ESRD) state and elimination of disease pathogenic factor by dialysis [1-4]. However, several studies showed that SLE flares could occur even during RRT [5-8]. Nevertheless, the details of disease flares of SLE in patients under dialysis have not been studied yet.ObjectivesThis study aimed to investigate the clinical features, risk factors, and treatment details of SLE patients experiencing disease flare under RRT.MethodsThe medical records of SLE patients who received dialysis at two tertiary referral hospitals in Seoul and Ulsan, South Korea were reviewed. All patients in this study were either clinically or histologically diagnosed with LNResultsOf a total of 121 patients with SLE on dialysis, 96 (79.3%) were on hemodialysis (HD) and 25 (20.6%) were on peritoneal dialysis (PD). During a median follow-up of 45 months (IQR, 23–120) after the initiation of dialysis, 32 (26.4%) patients experienced SLE flare (HD, n = 25; PD, n = 7). The most common features of SLE flare were hematologic (40.6%) and constitutional manifestations (40.6%). Treatments for disease flares were based on corticosteroids, and 11 (34.3%) patients required additional immunosuppressants including cyclophosphamide and mycophenolate mofetil. There was no case of severe adverse events related to medication. non-renal SLE Disease Activity Index (SLEDAI) score before dialysis initiation (HR 1.235; 95% CI, 1.122–1.359; P = 0.001) was a significant risk factor for disease flare during dialysis.Table 1.Multivariable analysis of factors associated with SLE flare under dialysisHazard ratio95% CIP-valueNon-renal SLEDAI at the initiation of dialysis1.2351.122–1.3590.001Hematologic manifestation prior to dialysis1.2560.690–2.8260.150Cumulative amount of steroid during 1 year prior to the initiation of dialysis1.0400.995–1.0870.086Dialysis modality: hemodialysis0.7660.262–2.2430.630ConclusionMore than one-quarter of SLE patients experienced disease flare during dialysis, which most commonly had hematologic manifestations. Continued follow-up and appropriate treatments including immunosuppressants should be considered for patients with SLE under dialysis.References[1]Coplon NS, Diskin CJ, Petersen J, Swenson RS. The Long-Term Clinical Course of Systemic Lupus Erythematosus in End-Stage Renal Disease. New England Journal of Medicine 1983;308:186-90.[2]Lee P-T, Fang H-C, Chen C-L, Chiou Y-H, Chou K-J, Chung H-M. Poor prognosis of end-stage renal disease in systemic lupus erythematosus: a cohort of Chinese patients. Lupus 2003;12:827-32.[3]Pahl MV, Gollapudi S, Sepassi L, Gollapudi P, Elahimehr R, Vaziri ND. Effect of end-stage renal disease on B-lymphocyte subpopulations, IL-7, BAFF and BAFF receptor expression. Nephrology Dialysis Transplantation 2010;25:205-12.[4]Ribeiro FM, Fabris CL, Bendet I, Lugon JR. Survival of lupus patients on dialysis: a Brazilian cohort. Rheumatology 2013;52:494-500.[5]Okano K, Yumura W, Nitta K et al. Analysis of Lupus Activity in End-Stage Renal Disease Treated by Hemodialysis. Internal Medicine 2001;40:598-602.[6]Barrera-Vargas A, Quintanar-Martínez M, Merayo-Chalico J, Alcocer-Varela J, Gómez-Martín D. Risk factors for systemic lupus erythematosus flares in patients with end-stage renal disease: a case–control study. Rheumatology 2015:kev349.[7]Cucchiari D, Graziani G, Ponticelli C. The dialysis scenario in patients with systemic lupus erythematosus. Nephrology Dialysis Transplantation 2014;29:1507-13.[8]Kang S-H, Chung B-H, Choi S-R et al. Comparison of Clinical Outcomes by Different Renal Replacement Therapy in Patients with End-Stage Renal Disease Secondary to Lupus Nephritis. The Korean Journal of Internal Medicine 2011;26:60.Disclosure of InterestsNone declared

BackgroundProtein phosphatase Mg2+/Mn2+-dependent 1A (PPM1A) is a phosphatase which regulates various intracellular cell signaling pathways including inflammation. We previously suggested that the inflammatory signal decreased the PPM1A protein level in macrophage and this reduction had correlation with the chronic inflammatory bone disease, implying the possible role of PPM1A in inflammatory responses of macrophage.ObjectivesIn this study, we aim to elucidate the potential role of PPM1A in macrophage to regulate inflammatory response during the disease progression of systemic lupus erythematosus.MethodsWe generated macrophage-specific conditional gene-knockout (PPM1Afl/fl;LysM-Cre) mice and developed a lupus-like disease with immune complex glomerulonephritis in these PPM1Afl/fl;LysM-Cre mice by intraperitoneal pristane injection. Mouse serum was collected every 4 weeks after pristane injection. Serum anti-dsDNA IgG, anti-ssDNA IgG, interleukin-17 (IL-17) and tumor necrosis factor-α (TNF-α) was quantified by ELISA. After 41 weeks from pristane injection, histological changes in the kidney, spleen, and lung tissues were observed. To analyze M1/M2 polarization in vitro, LysM-Cre and PPM1Afl/fl;LysM-Cre mouse bone marrow-derived macrophages were cultured with lipopolysaccharide (LPS)/interferon-γ (IFN-γ) or interleukin-4 (IL-4) to check M1 or M2 related genes.ResultsWe found that macrophages of PPM1Afl/fl;LysM-Cre mice displayed different gene expression with LPS stimulation especially in M1/M2 related genes through the RNA-seq analysis and showed a decrease in both M1 and M2 polarization induced by LPS/IFN-γ or IL-4 stimulation. Notably, we found that PPM1Afl/fl;LysM-Cre mice with pristane injection showed a significant increase of anti-ssDNA IgG compared to LysM-Cre mice. PPM1Afl/fl;LysM-Cre mice showed severe lupus-like phenotypes such as global glomerular enlargement indicated by endocapillary proliferation and glomerular cellularity in kidney and lung inflammation accompanied by fibrosis, compared to LysM-Cre mouse by pristane injection. Together, serum IL-17 and TNF-α, which are proinflammatory cytokines, were increased in PPM1Afl/fl;LysM-Cre after pristane injection. These results indicate that PPM1A depletion in macrophage deteriorates inflammation and contributes to the tissue damage in a lupus-like disease.ConclusionOur findings suggest that the deficiency of PPM1A in macrophages impairs M1/M2 macrophage polarization leading to an immune imbalance in lupus-like disease model, providing a potential link between the loss of function of PPM1A in macrophages and its molecular target for treatment of systemic lupus erythematosus.References[1]Kwon, O. C., Choi, B., Lee, E. J., Park, J. E., Lee, E. J., Kim, E. Y., Kim, S. M., Shin, M. K., Kim, T. H., Hong, S., Lee, C. K., Yoo, B., Robinson, W. H., Kim, Y. G., & Chang, E. J. (2020). Negative Regulation of Osteoclast Commitment by Intracellular Protein Phosphatase Magnesium-Dependent 1A. Arthritis & rheumatology (Hoboken, N.J.), 72(5), 750–760. https://doi.org/10.1002/art.41180[2]Smith, S. R., Schaaf, K., Rajabalee, N., Wagner, F., Duverger, A., Kutsch, O., & Sun, J. (2018). The phosphatase PPM1A controls monocyte-to-macrophage differentiation. Scientific reports, 8(1), 902. https://doi.org/10.1038/s41598-017-18832-7Disclosure of InterestsNone declared.

BackgroundPatients with immune thrombocytopenia (ITP) have a risk of developing systemic lupus erythematosus (SLE). We sought to examine the clinical characteristics of patients with primary ITP who later developed SLE, and identified the risk factors for the development of SLE.ObjectivesWe retrospectively examined patients who were diagnosed with primary ITP at a tertiary hospital between August 2001 and November 2019. We compared the clinical characteristics according to the development of SLE. Logistic regression analysis was performed to identify the factors associated with the development of SLE.MethodsOf 130 patients with primary ITP, 10 (7.7%) were later diagnosed with SLE during follow-up (median, 30 months [IQR, 15.5–105]). The presence of skin bleeding, organ bleeding, lymphopenia, anemia, and positive antinuclear antibody (ANA) titer (> 1:160) were more common among patients who later developed SLE than did those who did not develop SLE. Multivariate analysis showed that young age (< 40 years; odds ratio [OR], 8.359 [95% confidence interval (CI), 1.230–56.793]; p = 0.033), organ bleeding (OR, 18.349 [95% CI, 2.771–121.517]; p = 0.003), and ANA positivity (>1:160; OR, 7.692 [95% CI, 1.482–39.910]; p = 0.015) were significantly associated with the development of SLE.ResultsYoung age (< 40 years), organ bleeding, and ANA positivity (> 1:160) were risk factors for the development of SLE in patients with primary ITP.ConclusionThese results suggest that continued follow-up for the detection of SLE development is needed for patients with ITP, particularly those with young age, ANA positivity, or organ bleeding.References[1]Zhu, Fang-Xiao, et al. “Risk of systemic lupus erythematosus in patients with idiopathic thrombocytopenic purpura: a population-based cohort study.” Annals of the rheumatic diseases 79.6 (2020): 793-799.Table 1.Factors associated with the development of SLE in patients with primary ITPUnivariateMultivariateOR95% CIP valueOR95% CIP valueYoung agea5.4441.332–22.2500.0188.3591.230–56.7930.033Female4.3330.530–35.4220.17BMI0.8730.717–1.0700.20Skin bleeding8.4191.034–68.5330.046Mucosa bleeding1.2500.247–6.3300.79Organ bleeding14.8643.633–60.815< 0.00118.3492.771–121.5170.003Platelet counts0.9110.828–1.0020.06ANA positivityb16.5003.984–68.341< 0.0017.6921.482–39.9100.015Neutropeniac2.1110.229–19.4990.51Lymphopeniad4.8461.189–19.7590.028Anemiae10.1182.044–50.0910.005SLE: systemic lupus erythematosus, ITP: immune thrombocytopenia, BMI: body mass index, ANA: antinuclear antibody, OR: odds ratio, CI: confidence interval.aYoung age = age < 40 yearsbANA positivity ≥ 1:160cNeutropenia = Absolute neutrophil count < 1500 μLdLymphopenia = Absolute lymphocyte count < 1500 μLeAnemia = Hemoglobin < 12 g/dLDisclosure of InterestsNone declared

There is need for a robust production mechanisms to meet the ever increasing demand for herbal medicine in the world today. In this study, we developed a standard protocol for the in vitro culture of Polygonum multiflorum to rapidly produce seedlings and promote the enlargement of its medicinal root tubers. Seeds were grown on Murashige and Skoog (MS) basal medium to obtain 1-week-old microseedlings. The ideal growth medium for these seedlings was determined by subculturing in different culture media. Maximal growth was observed on WPM, with a growth index of 160% after 5 weeks. Wood Plant Medium (WPM) supplemented with the kinetin and indole-3-acetic acid hormones yielded the highest average seedling shoot elongation, root initiation, and root elongation after 6 weeks. At 16 weeks after planting in the field, seedlings cultured in WPM + kinetin (1.0 mg/l) and IAA (1.0 mg/l) produced enlarged root tubers with an average dry weight of 31.10 g, as compared to 10.10 and 16.80 g for root tubers from plants propagated from P. multiflorum seed and stem cuttings, respectively. Fourier-transform infrared spectroscopy and hierarchical cluster analyses of the enlarged root tubers revealed that their chemical composition was the same as that of tubers sold on the market and from plants propagated through seeds and stem cuttings. Our findings provide a basis for large-scale in vitro propagation of P. multiflorum as a resource for traditional Chinese medicine.

This paper investigates the quench and recovery characteristics of second-generation high-temperature superconducting GdBCO coated conductors (CC) with variously patterned stabilizers in over-current conditions. A chemical etching method was used to produce various patterns of stabilizer on GdBCO CC without degrading current-carrying capacity. From the results of the over-current testing of GdBCO CC tapes with variously patterned stabilizers, the tape that had stabilizer with longitudinally disconnected patterns exhibited higher voltage increase and slower recovery time than those that had continuity of stabilizers along the longitudinal direction, because the excessive heat and current could not be transferred through the stabilizers in the former. Overall, uniform heat and current distributions along the stabilizer of GdBCO CC are among the critical factors determining thermal and electrical stabilities of a GdBCO magnet in over-current conditions, especially when quench occurs.

Candida albicans is a yeast pathogen known for its virulence and high morbidity rate, and it easily colonizes host tissues and implant devices and forms mature biofilms, which play an important role in pathogenesis and drug resistance. In this study, we investigated the abilities of thermoresponsive oligomers of N-vinylcaprolactam (OVCLs) to inhibit biofilm formation by C. albicans. One synthetic and four commercial OVCLs (≤MW 240 000) at a concentration of 5 μg ml-1 were found to decrease C. albicans biofilm formation by more than 90% at 37°C, but to be less effective at 25°C. Microscopic observations showed that OVCLs clearly inhibited hyphal formation and cell aggregation by C. albicans, and this appeared to be responsible for their antibiofilm effects. In addition, effective antibiofouling coatings of OVCL/poly(lactic-co-glycolic acid) polymer blends were prepared on glass surfaces. Significance and impact of the study The emergence of multidrug-resistant Candida strains has prompted searches for new antifungals. The antibiofilm and antihyphae properties of OVCLs and OVCL coating against a fluconazole-resistant Candida albicans strain are present in this study. These findings suggest that OVCL and OVCL-coated biomaterials are potentially useful for controlling fungal biofilm formation by and the virulence of antifungal-resistant C. albicans.

Hybrid molecules have been developed which are comprised of a tyrosine kinase-targeted, quinazoline-based scaffold and a flexibly linked dia(m)minechloridoPt(ii) moiety. The target compounds maintain high affinity and selectivity for ErbB family kinase proteins and one of the derivatives induces platinum adducts with a pharmacologically important cysteine residue.

In this paper, we briefly review our recent progress on development of core technologies for 2G HTS NMR/MRI magnets at Korea University. To outperform the current state-of-art NMR/MRI magnet systems, we have developed the following technologies: 1) a REBCO-REBCO superconducting joint for operation of persistent current mode; 2) partial and grease-insulation winding techniques for self-protection of the HTS magnets; 3) pre-shimming to reduce the screening-current-induced-field; and 4) optimization of multi-width winding to minimize conductor consumption and volume of the HTS magnets. The test results demonstrated the feasibility of employing the developed techniques to achieve ultra-high-field and LHe-free 2G NMR/MRI magnets possessing self-protecting feature.

Although immune checkpoint blockade therapies have demonstrated clinical efficacy in cancer treatment, harnessing this strategy is largely encumbered by resistance in multiple cancer settings. Here, we show that tumor-infiltrating T cells are severely exhausted in the microsatellite stable (MSS) colorectal cancer (CRC), a representative example of PD-1 blockade-resistant tumors. In MSS CRC, we found wound healing signature to be up-regulated and that T cell exhaustion is driven by vascular endothelial growth factor-A (VEGF-A). We report that VEGF-A induces the expression of transcription factor TOX in T cells to drive exhaustion-specific transcription program in T cells. Using a combination of in vitro, ex vivo, and in vivo mouse studies, we demonstrate that combined blockade of PD-1 and VEGF-A restores the antitumor functions of T cells, resulting in better control of MSS CRC tumors.

Supplemental material, LUP876695 Supplemental Table for Impact of stringent response in proteinuria on long-term renal outcomes in proliferative lupus nephritis by J Won, J S Lee, J S Oh, Y-G Kim, C-K Lee, B Yoo and S Hong in Lupus

Supplemental material, LUP890007 Supplemental Material for Recovery of renal function in patients with lupus nephritis and reduced renal function: the beneficial effect of hydroxychloroquine by JS Lee, JS Oh, Y-G Kim, C-K Lee, B Yoo and S Hong in Lupus

This study explored candidate causal single nucleotide polymorphisms (SNPs) to clarify the biological mechanism of prostate cancer (PCa). Identify candidate Causal SNPs and Pathways (ICSNPathway) analysis was applied using a PCa genome-wide association study (GWAS) dataset that included 473,736 SNPs in 1151 cases of PCa and 1156 controls of European ancestry. Five candidate causal SNPs, three candidate causal genes, and two candidate causal pathways were identified using integrating linkage disequilibrium analysis, functional SNP annotation, and pathway-based analysis. The ICSNPathway analysis suggested three hypothetical mechanisms of PCa. The first was rs13112390, rs13112358, rs2048074 to nei-like DNA glycosylase 3 (NEIL3) gene to damaged DNA binding. The second was rs3087386 to REV1, DNA directed polymerase (REV1) gene to damaged DNA binding. The third was rs1063134 to potassium channel, inwardly rectifying subfamily J, member 4 (KCNJ4) gene to inward rectifier potassium channel activity.

Background:An experience of particular treatment is one of the characteristics impacting on patients’ decisions to continue, discontinue, or alter their medical treatments.1Reports on patients’ treatment satisfaction would be weighty when selecting an optimal treatment reflecting the patient’s perspective.Objectives:We aimed to evaluate the treatment satisfaction of ankylosing spondylitis (AS) patients treated with tumor necrosis factor inhibitors (TNF-Is) and identify the factors associated with satisfaction in Korea.Methods:The study was conducted from July to November in 2018 at 4 hospitals representative in treating AS in Korea. Patients aged≥19, diagnosed as AS based on ‘Modified New York criteria 1984’, and treated with current TNF-Is and same type of device for≥3 months were included. We used ‘Treatment Satisfaction Questionnaire For Medication (TSQM)’ which is consisted of 4 domains; effectiveness, side effects, convenience, and global satisfaction. Scores (0 ~ 100) of satisfaction indicate the higher the better. Multivariable linear regressions with 95% of statistical significance level was performed to identify related factors.Results:Enrolled 497 patients (85.3% male, 40.3 years old) were prevalent with AS for mean 10 years and indicated average 3.1 in Bath AS Disease Activity Index (BASDAI). Adalimumab (39.6%) was the most commonly used, followed by etanercept (23.5%), infliximab (21.9%) and golimumab (14.9%). TNF-Is were prescribed at low, regular, and high dose for 24.9%, 70.5% and 4.7% of patients and as subcutaneous with pen type, syringe type, and intravenous injection for 50.9%, 26.8% and 22.3% of patients, respectively. Conventional disease-modifying antirheumatic drugs(cDMARDs) and steroids were concomitantly used for 5.4% and 8.3% of patients, respectively.Average score of TSQM was the lowest in convenience amongst 4 domains; 72.2 in effectiveness, 96.9 in side effects, 67.6 in convenience, and 71.4 in global satisfaction. Negative associations were shown between BASDAI and all domains of TSQM. Patients who prescribed TNF-Is at high dose were more satisfied to effectiveness while they were less satisfied to side-effect, as against patients prescribed it at low dose. TNF-Is, use of cDMARDs and steroids were not significantly associated with treatment satisfaction (Fig. 1).Conclusion:AS patients treated with TNF-Is in Korea were quite satisfied with their treatments. Since the worst satisfaction in the convenience domain was presented amongst 4 domains, more convenient treatment options may be required to enhance the entire satisfaction of patients. With the result of a negative association between disease activity and satisfaction, this study strengthened the previous studies reporting the positive relationship between health improvement and satisfaction.2References:[1]Feighner JP: Impact of anxiety therapy on patients’ quality of life. AJM 1987, 82: 14–19.[2]E. Batbaatar et al. Determinants of patient satisfaction, Perspectives in Public Health (2017) 137(2): 89-101Acknowledgments:Tae-Hwan Kim is the corresponding author.Disclosure of Interests:Sang-Hoon Lee Grant/research support from: This study was sponsored by Pfizer Pharmaceuticals Korea Limited., Seung Geun Lee Grant/research support from: This study was sponsored by Pfizer Pharmaceuticals Korea Limited., Yong-Gil Kim Grant/research support from: This study was sponsored by Pfizer Pharmaceuticals Korea Limited., Soo-Hyun Lee Employee of: I’m an employee of Pfizer pharmaceuticals Korea, Young-Joo Kim Employee of: I’m an employee of Pfizer pharmaceuticals Korea., Ja-Young Jeon Employee of: I’m an employee of Pfizer pharmaceuticals Korea., Hyung-Jeong Yoo Employee of: I’m an employee of Pfizer pharmaceuticals Korea, Juneyoung Lee Grant/research support from: This study was sponsored by Pfizer Pharmaceuticals Korea Limited., Tae-Hwan Kim: None declared

This study presents the investigation of superconducting joints fabricated using multifilament magnesium diboride (MgB

Surface science and surface characterization are not interchangeable terms. The former represents a comprehensive field of study; the latter identifies a collection of experimental methodologies that help establish the field. The surface science of heterogeneous electrocatalysis is the study of electrified solid–liquid interfaces. Early investigations placed emphasis on experimental aspects, largely on the (nondynamical) nature of the electrochemical double layer. Research interests and commercial demands then shifted to catalytic reactions that are more expediently studied via theoretical simulations of artificial systems rather than by methodical investigations under practical but precisely described conditions. Hence, computational work presently holds sway, even if factual representations of conceptually orchestrated interfacial structures and reaction sequences are nearly impossible to attain. A better balance and a stronger symbiosis between theory and experiment would benefit from advances in, and the proliferation of, empirical investigations. The present article catalogs different types (spectroscopy and microscopy) and classes (emersion, ex situ, in situ, and operando) of surface characterization alternatives in the atomic-level study of the CO 2 reduction to hydrocarbons and alcohols at well-defined copper electrodes.

In this study, we report lipid biomarker patterns and phylogenetic identities of key microbial communities mediating anaerobic oxidation of methane (AOM) in active mud volcanoes (MVs) on the continental slope of the Canadian Beaufort Sea. The carbon isotopic compositions (δ13C) of sn-2- and sn-3-hydroxyarchaeol showed the highly 13C-depleted values (−114 ‰ to −82 ‰) associated with a steep depletion in sulfate concentrations within 0.7 m of sediment depths. This suggested the presence of methanotrophic archaea involved in sulfate-dependent AOM, albeit in a small amount. The ratio of sn-2-hydroxyarchaeol to archaeol (> 1) and operational taxonomic units (OTUs) indicated that the anaerobic methanotrophic archaea (ANME) clades ANME-2c and ANME-3 were involved in AOM. Higher δ13C values of archaeol and biphytanes (BPs; -55.2±10.0 ‰ and -39.3±13.0 ‰, respectively) suggested that archaeal communities were also assimilating AOM-derived inorganic carbon. Furthermore, the distinct distribution patterns of methanotrophs in the three MVs appears to be associated with varying intensities of ascending gas fluids. Consequently, our results suggest that the niche diversification of active mud volcanoes has shaped distinct archaeal communities that play important roles in AOM in the Beaufort Sea.

This paper reports the optimization procedure for a no-insulation (NI) multi-width (MW) REBCO magnet, which enables the fabrication of a highly compact and competitively priced superconducting magnet. In order to identify the design considerations for the NI-MW magnet, the electromagnetic performances of 3 different magnets were investigated using the finite element method (FEM). Based on the comparison results, it was verified that the critical current distribution-factor (CCD-factor), which is the ratio of the highest pancake critical current (Ic) to the lowest pancake Ic within the magnet, should be close to 1.00 for the MW configuration to be most effective. In the optimized MW magnet, the center Bz (7.54 T) remarkably exhibited an ∼ 51% increase compared to the 4-mm single width magnet (5.00 T). Furthermore, the CCD-factor of the optimized MW magnet was 1.04, which is quite close to 1.00, sufficiently demonstrating the validity of the optimization process and result.

A capacitive-type MEMS acoustic sensor with a planarised TiN/plasma-enhanced chemical vapour deposition -Si3N4/TiN diaphragm based on a polyimide sacrificial layer is presented. The multi-layer diaphragm has the effective residual stress of +31.5 MPa. Furthermore, this sensor features a 21% lower parasitic capacitance and a 56% lower air-gap resistance in comparison with those of a sensor fabricated without planarisation. Five photomasks were used. In addition, to evaluate the frequency response, both an effective capacitance model and an equivalent circuit model equipped with a voltage-controlled voltage source are newly proposed and compared with conventional models. The open-circuit sensitivity is modelled to −45.4 dBV/Pa at 1 kHz with 9.6 V, indicating a difference of 0.9 dB in comparison with the open-circuit sensitivity of the conventional model.

This note presents a superconducting joint technique for the development of MgB

Background Renal involvement is a common and serious manifestation of SLE. Hyperuricemia may be associated with lupus nephritis as a result of renal damage. However, it is not yet well known whether hyperuricemia is independently associated with renal involvement even in patients without known predisposing factors for hyperuricemia such as decreased renal function, old age, male gender, menopause, and drugs. Objectives The aim of this study was to evaluate the association of baseline serum uric acid level and development of nephritis in patients diagnosed with SLE. Methods We retrospectively reviewed electronic medical records of 101 female SLE patients whose ages at the time of diagnosis (baseline) were 45 years old or below in a tertiary medical center from January 2000 to March 2015. SLE with renal involvement was diagnosed when patients met the renal disorder of the 1997 ACR criteria for SLE. We compared baseline serum uric acid levels of the SLE patients who had nephritis at the time of diagnosis or later (nephritis group) with the patients who had not developed nephritis (non-nephritis group) during follow-up period. Results Among 101 patients, 22 (22%) had hyperuricemia (serum uric acid ≥6 mg/dL) at baseline and 45 (45%) had developed nephritis during follow-up period (median 6.1 years). There were significant differences in baseline serum uric acid level, glomerular filtration rate (GFR), anti-dsDNA antibody and complement level between non-nephritis group and nephritis group (Table). Interestingly, among 59 patients with normal renal function (baseline GFR ≥90 mL/min/1.73m2), baseline serum uric acid level was also significantly higher in the nephritis group than non-nephritis group (Table). Moreover, the patients with hyperuricemia at baseline were more likely to develop nephritis than those without hyperuricemia during follow-up period (64% vs. 39%, p =0.042) (Figure). Conclusions These findings suggest that high serum uric acid level at the time of diagnosis in premenopausal women with SLE may be independently associated with nephritis. More careful evaluation would be required for development of nephritis in such patients. Disclosure of Interest None declared

Background Systemic lupus erythematosus (SLE) is a chronic systemic autoimmune disease of unknown etiology, and renal involvement is an important factor associated with a high morbidity and mortality. Immunoglobulin binding protein 1 (IGBP1) is a phosphoprotein associated with Ig-α of the B cell receptor complex. Intracellular IGBP1 interacts with the catalytic subunit of protein phosphatase (PP2A) and regulates differentiation, proliferation, and apoptosis of B cells. Functional studies reported that high PP2A levels alter the phenotype and function of T cells in SLE patients. Recently, we reported that urinary IGBP1 levels were associated with the pathologic activity in lupus nephritis (LN). However, the role of plasma IGBP1 (pIGBP1) in the clinical features including the development of nephritis has not been identified in SLE. Objectives To determine the role of pIGBP1 as a biomarker related with LN. Methods Blood samples of SLE patients were collected between Jan 2009 and Dec 2010 in a tertiary hospital. The levels of pIGBP1 were measured in SLE patients with (n=44) or without (n=39) nephritis, and healthy subjects (n=14). Clinical parameters including baseline characteristics, laboratory data, medications and SLE Disease Activity Index (SLEDAI) were collected from electronic medical record. Activity and chronicity index in renal pathology of LN were scored blindly by a renal pathologist. To identify factors related to the development of LN, Cox proportional hazard regression model and Kaplan-Meier curves were used. Results The concentrations of pIGBP1 in SLE patient were higher than those in healthy individual (9.6±8.4 ng/mL vs 4.5±2.4 ng/ml) and positively correlated with SLEDAI score. However, the concentrations were not different between LN and non-nephritis SLE and were not associated with activity index score in renal pathology. During follow-up more than 5 years, nephritis was developed in 8 patients (20.5%) among 39 SLE patients who did not have renal involvement at baseline. Interestingly, levels of pIGBP1 (p=0.002), CRP (p=0.009), or anti-dsDNA antibody (p=0.03) were significantly elevated in 8 patients who developed LN compared to who did not. Kaplan-Meier survival curve showed that initial pIGBP1 (>10.71 ng/mL) as well as anti-dsDNA (>30.7 IU/mL) were associated with high probability of LN development in the future. Conclusions Based on our results, high concentration of pIGBP1 could be a valuable marker to represent high SLE activity and a predictor for developing nephritis in SLE patients. References Lee EJ, Hong S, Lim DH, et al. Increased levels of immunoglobulin binding protein 1 are associated with disease activity including renal damage in patients with systemic lupus erythematosus. Presented in 2015 ACR/ARHP Annual meeting. Sunahori K, Nagpal K, Hedrich CM, et al. The catalytic subunit of protein phosphatase 2A (PP2Ac) promotes DNA hypomethylation by suppressing the phosphorylated mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) kinase (MEK)/phosphorylated ERK/DNMT1 protein pathway in T-cells from controls and systemic lupus erythematosus patients. J Biol Chem. 2013, 288(30):21936–44. Acknowledgements This work was supported by the National Research Foundation of Korea (NRF-2016R1A6A3A11930269). Disclosure of Interest None declared

Background Clinicians generally prescribe antiviral agents to patients with chronic hepatitis B (CHB) or to inactive carriers of the virus until 6–12 months after the cessation of biologic agents. However, the current antiviral prophylaxis regimen, in addition to biological therapy, is expensive and poses an economic burden to both patients and societies. We have had patients in our medical center quit or reduce antiviral prophylaxis due to economic reasons. Objectives To assess the outcome of tapering or discontinuation of antiviral agents in patients who were infected with hepatitis B virus (HBV) during biologic therapy. Methods We identified 45 patients who were infected with HBV and treated with biologic agents concomitantly from January 2005 to December 2016. They were diagnosed with rheumatoid arthritis (n=20), Crohn9s disease (n=13), ankylosing spondylitis (n=8), ulcerative colitis (n=3), and psoriatic arthritis (n=1). The criteria of HBV reactivation was a 10-fold rise in HBV DNA compared with previous HBV DNA titers, resulting in HBV DNA of greater than 20,000 IU/ml (HBeAg-positive patients) or 2,000 IU/ml (HBeAg-negative patients), and an increase in AST or ALT to more than twice the upper normal limit (40 IU/l). Results Sixteen CHB patients and 29 inactive carriers were treated with biologic agent for 4.1±2.7 years. No reactivation case was observed in 23 patients (10 of CHB and 13 of inactive carrier) who maintained antiviral prophylaxis for 4.0±2.3 years. Among them, 4 patients (3 treated with infliximab and 1 with adalimumab) taking antiviral prophylaxis regimen on alternate days did not experience HBV reactivation for 28–42 months of follow-up period. In the discontinuation group (n=9), no reactivation case was observed in all inactive carrier patients (2 treated with etanercept, 1 with infliximab, and 1 with rituximab) after discontinuation of antiviral prophylaxis for 6–33 months of follow-up period. In contrast, 3 patients (2 treated with etanercept and 1 with adalimumab) among the 5 patients with CHB experienced reactivation after discontinuation of antiviral prophylaxis for 3–29 months of follow-up period. Conclusions During biologic therapy, HBV reactivations were frequently found in CHB patients who ceased to take antiviral prophylaxis. However, no reactivation after the cessation of prophylaxis was found in inactive carrier patients who were previously treated with prophylaxis. Based on our experience, tapering or discontinuation of antiviral agent in inactive carriers with economic problem undergoing concomitant biologic agent therapy could be considered viable, albeit with caution. References Perez-Alvarez R, Diaz-Lagares C, Garcia-Hernandez F, Lopez-Roses L, Brito-Zeron P, Perez-de-Lis M, et al. Hepatitis B virus (HBV) reactivation in patients receiving tumor necrosis factor (TNF)-targeted therapy: analysis of 257 cases. Medicine (Baltimore). 2011;90(6):359–71.2. Mori S, Fujiyama S. Hepatitis B virus reactivation associated with antirheumatic therapy: Risk and prophylaxis recommendations. World J Gastroenterol. 2015;21(36):10274–89. Ryu HH, Lee EY, Shin K, Choi IA, Lee YJ, Yoo B, et al. Hepatitis B virus reactivation in rheumatoid arthritis and ankylosing spondylitis patients treated with anti-TNFalpha agents: a retrospective analysis of 49 cases. Clin Rheumatol. 2012;31(6):931–6. Disclosure of Interest None declared

Background In rare cases, Behcet9s disease (BD) can cause severe aortic regurgitation (AR) or aortic root destruction that might have lethal outcomes. Conventionally, simple aortic valve replacement (AVR) is performed for the management of severe AR in BD patients; however, the reoperation rate is as high as 78 to 100%, while mortality rate range from 20 to 47%. Recently, several series of case reports showed that compared to AVR, aortic root replacement (ARR) improved the surgical outcomes of AR in BD patients. Objectives To identify the factors associated with the long-term surgical outcomes of AR in BD patients. Methods We identified 23 patients who had been surgically treated for AR caused by aortic root involvement of BD from January 1996 through December 2013. We evaluated the occurrence of post-surgical adverse events, which were defined as follows: death, aortic valve/graft problem, infective endocarditis, cerebral infarction, and/or re-operation of aortic valve or root. Types of surgery were classified as simple aortic valve replacement (AVR), bioprosthesis aortic root replacement (bARR), and mechanical valved composite graft aortic root replacement (cARR). Clinical parameters including baseline characteristics, C-reactive protein (CRP), erythrocyte sedimentation rate, and medications were extracted from electronic medical records. Results Appropriate aortic valve or root surgery cases were 35 in total, with a mean follow up duration of 11±5 years in 23 patients. Out of the 11 cases that underwent AVR, post-surgical events were observed in 8 (73%) cases. Out of the 12 bARR cases (xenograft in 5 cases and homograft in 7 cases), 9 (75%) cases had post-surgical adverse events. Out of the 12 cARR cases, post-surgical adverse events occurred in 4 (33%) cases. Multivariable cox proportional hazards model indicated that levels of CRP at 1 month after discharge and age at operation were independent prognostic factors associated with event-free probability. Notably, performing cARR was the most significant factor that affected the surgical outcome (HR (95% CI) 0.147 (0.028 – 0.766), p=0.023). Conclusions In BD patients with severe AR, the occurrence rate of post-surgical adverse events was associated with the levels of CRP at 1 month after discharge, age at operation, and type of surgery. cARR may be a better surgical option in BD patients with aortic root involvement References Jeong DS, Kim KH, Kim JS, Ahn H. Long-term experience of surgical treatment for aortic regurgitation attributable to Behcet9s disease. Ann Thorac Surg. 2009;87(6):1775–82. Song JK, Kim MJ, Kim DH, Song JM, Kang DH, Lee I, et al. Factors determining outcomes of aortic valve surgery in patients with aortic regurgitation due to Behcet9s disease: impact of preoperative echocardiographic features. J Am Soc Echocardiogr. 2011;24(9):995–1003. Liu Q, Ye W, Liu C, Li Y, Zeng R, Ni L. Outcomes of vascular intervention and use of perioperative medications for nonpulmonary aneurysms in Behcet disease. Surgery. 2016;159(5):1422–9. Disclosure of Interest None declared