tbuckley/cabot-search huggingface dataset:
FRI0479 Primary central nervous system vasculitis with tumor-like presentation
Authors: C. Salvarani, R.D. Brown, T.J. Christianson, C. Giannini, J. Huston, G.G. Hunder
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Primary central nervous system vasculitis (PCNSV) rarely presents as a tumor-like mass lesion (ML). <h3>Objectives</h3> The aim of this study was to determine the frequency of ML in a large cohort of patients with PCNSV and compare the presenting clinical, laboratory, and imaging features in those with ML to those without. <h3>Methods</h3> We retrospectively studied a cohort of 191 consecutive patients with PCNSV who were seen at the Mayo Clinic, Rochester, MN over a 35 year period. The diagnosis of PCNSV was based on brain/spinal cord biopsy or cerebral angiography. We compared PCNSV patients with tumor-like presentation to those without. <h3>Results</h3> 13/191 (6.8%) patients had tumor-like presentation. In all 13 patients PCNSV diagnosis was established by cerebral biopsy (stereotactic in 10, open-wedge in 3). 4 patients had cerebral angiography, and vasculitis was suggested in one patient. A granulomatous inflammatory histologic pattern was found in 11 biopsies, accompanied by vascular deposits of β-amyloid peptide in 7. In the other 2 biopsies a lymphocytic vasculitis was observed. The 13 patients with tumor-like presentation were compared with the 178 patients without. The patients with ML were more frequently males (77% vs 44%, p=0.04), were less likely to present with transient ischaemic attacks (TIA) (0 vs 27.5%, p=0.023) and more likely to present with seizures (46% vs 17%, p=0.022) at presentation. No significant differences in the CSF findings and ESR levels (normal in 100% and 82% of the patients, respectively) at diagnosis were observed in the two groups. Intracerebral gadolinium-enhancing lesions were more frequently observed in patients with ML (46% vs 21%, p=0.07), while meningeal gadolinium-enhancing lesions were equally observed (31% vs 20%, p=0.48). The frequencies of PCNSV recurrence (38% vs 29%), patients not requiring therapy at last follow-up (15% vs 25%), response to therapy (100% vs 74%), and poor outcomes (modified Rankin disability score ≥4) at last followup (8% vs 26%) were not significantly different in the two groups. No differences in survival were observed between the 2 groups (p=0.57). Considering all 191 patients, univariate Cox proportional hazards modelling showed an increased mortality rate in those with increasing age (hazard ratio, HR, 1.4), cerebral infarction on initial MRI (HR 2.95), and angiographic large vessel involvement (HR 3.2), while mortality rate was lower in those with gadolinium–enhancing lesions on MRI (HR=0.3). <h3>Conclusions</h3> Tumor-like presentation represents a subset of PCNSV characterised by vascular deposits of β-amyloid at biopsy, seizures at presentation, and gadolinium-enhancing cerebral lesions on MRI. As in PCNSV without ML, treatment response and prognosis was favourable in most patients. <h3>Disclosure of Interest</h3> None declared
OP0193 Tocilizumab and the risk for cardiovascular disease events among rheumatoid arthritis patients: a direct comparison in real world setting
Authors: F. Xie, H. Yun, E. Levitan, P. Muntner, J.R. Curtis
Journal: Annals of the Rheumatic Diseases (2018)

Conclusions:The beneficial properties on survival seen with HCQ use in other inflammatory diseases seem also applicable to RA patients.These results needs confirmation in a randomised setting but justifies the use of HCQ in combination with other conventional synthetic disease-modifying antirheumatic drugs even though the effect of HCQ, per se, on RA disease activity is limited.
Punching and Electroporation for Enhanced Transdermal Drug Delivery
Authors: Guang Yang, Yuqi Zhang, Zhen Gu
Journal: Theranostics (2018)

Transdermal delivery has made an indispensable impact to medical practice, but often been limited by low efficiency due to the barrier of the outer stratum corneum layer of skin.In Issue 9 of Theranostics, Huang et al. [1] proposed a new design of transdermal gene delivery strategy via the combination of a microneedle roller and a flexible interdigitated electroporation array.With the assistance of the microneedle roller, a deep and uniform electric field in the skin can be formed, accompanying an enhanced transport efficiency even at a low voltage.Furthermore, this combination strategy can promote the gene expression and siRNA transfection in mice skin in a safe and convenient process.
Non-conventional Inhibitory CD4+Foxp3–PD-1hi T Cells as a Biomarker of Immune Checkpoint Blockade Activity
Authors: Roberta Zappasodi, Sadna Budhu, Matthew D. Hellmann, Michael A. Postow, Yasin Senbabaoglu, Sasikanth Manne, Billel Gasmi, Cailian Liu, Hong Zhong, Yanyun Li, Alexander C. Huang, Daniel Hirschhorn-Cymerman, Katherine S. Panageas, E. John Wherry, Taha Merghoub, Jedd D. Wolchok
Journal: Cancer Cell (2018)
AB0420 Drug survival on certolizumab and predictors thereof in patients with rheumatoid arthritis, psoriatic arthritis, and axial-spondyloarthritis from the apulian biopure registry
Authors: A. Semeraro, G. Carlino, R. Bucci, F. D’Onofrio, P.C. Falappone, S. Lopriore, A. Marsico, N. Maruotti, D. Mazzotta, M. Muratore, L. Quarta, L. Santo, C. Zuccaro, F. Iannone
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> In BIO.PU.RE. Registry are collected data from patients being treated with Biologics from rheumatologic centres in Apulia (Southern Italy). <h3>Methods</h3> We analysed longitudinal data of consecutive patients, affected with RA, PsA or axial-SpA starting a treatment with certolizumab (CTZ) in the time frame from 1st January 2011 to 30th June 2017. Demographic and disease related characteristics were collected at baseline and at last observation visit. Primary endpoint was the persistence on CTZ, and secondary endpoint was the search of baseline predictors of drug survival and clinical outcomes. Drug survival was evaluated by Kaplan-Meier life table analysis. Estimates hazard ratios (HRs, 95% confidence intervals (CI)) of drug discontinuation or achievement of low-disease/remission in RA, and minimal disease activity (MDA) in PsA at last visit, adjusted for patient's demographics, disease characteristics and prior biologic treatments were computed by Cox-regression stepwise backward models. <h3>Results</h3> 345 patients were included in this analysis (table 1). Global median survival time (95% CI) was 30 [23–36] months. Drug survival rate was significantly higher in SpA (63.9%, p=0.009) than in RA (54.0%) or PsA (54.5%). Within each disease, naïve-CTZ patients showed higher survival rates than biologic-experienced patients in RA (63.4% vs 45.7%, p=0.0001), but not in PsA (59.1% vs 52.3%, p=0.60), or SpA (62.5% vs 64.4%, p=0.94). In the whole cohort, the only negative predictor of drug discontinuation was the CTZ-naïve status (HR 0.62, 95 CI 0.40–0.96, p=0.03). This association was even stronger for RA (HR 0.45, 95 CI 0.26–0.77, p=0.004). In SpA, patient's age at baseline was weakly correlated to CTZ stopping (HR 0.96, 95 CI 0.93–0.99, p=0.02), but no predictor of CTZ discontinuation was detected in PsA. No factor did correlate to the achievement of low disease/remission in RA, while co-medication with MTX was significantly associated to the achievement of MDA (HR 3.82, 95 CI 1.26–11.54, p=0.01) in PsA. Globally, the causes of discontinuation were: ineffectiveness (nr 94, 27.2%), adverse event (nr. 40, 11.6%), pregnancy (nr.1, 0.3%), remission (nr. 3, 0.9%), others (nr.13, 3.8%). <h3>Conclusions</h3> In our real-life experience CTZ seems to have better drug survival in PsA rather in RA and SpA; in all these polyarthritis was observed CTZ-naïve status as negative predictor of drug discontinuation. <h3>Disclosure of Interest</h3> None declared
Застосування еластографії у хворих із хронічними захворюваннями печінки
Authors: L.V. Zhuravlyova, O.V. Ogneva
Journal: GASTROENTEROLOGY (2018)

У статті розглянуті переваги й недоліки неінвазивного методу діагностики фіброзу печінки — еластографії. Описано види даного методу дослідження, області застосування. Вказані найбільш ефективні види еластографії для різних хронічних захворювань печінки (хронічні гепатити В і С, неалкогольна жирова хвороба печінки, аутоімунні захворювання гепатобіліарної системи та алкогольна хвороба печінки). Проаналізовані дані нових рандомізованих контрольованих досліджень.
SAT0668 Articular involvement in chronic hepatitis c infection – a preliminary ultrasound study
Authors: R.A. Ionescu, L.M. Pana, V.M. Pompilian, A. Voicu, S. Caraiola, D. Ramba, C.R. Baicus, A. Dan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Chronic hepatitis C is a public health issue. Extra-hepatic manifestations of this infection also include articular involvement, that sometimes mimics rheumatoid arthritis. <h3>Objectives</h3> Evaluation of potential articular involvement in patients diagnosed with chronic hepatitis C infection and possible correlations with biological abnormalities. <h3>Methods</h3> We evaluated 31 patients with chronic hepatitis C infection, using ultrasound (US) examination of both wrists and the second and fifth interphalangeal joints of the fingers. Then, we looked for possible correlations with various laboratory findings. <h3>Results</h3> 29% of patients were symptomatic (pain) at the time of the US examination. 10% of our patients had tenosynovitis of the extensor tendons, another 10% had active synovial hypertrophy (Doppler positive), 31.14% had inactive synovial hypertrophy, 20.9% had erosions and in 20% of them the US examination of the above mentioned joints was normal. 61.29% of patients having US abnormalities, where rheumatoid factor positive. All patients with erosions and inactive synovial hypertrophy, 83.3% of those with active synovial hypertrophy and 67% of those with tenosynovitis where cryoglobulins positive. We found low levels of C3 fraction of complement in 92.3 patients with erosions, 83.3 patients with active synovial hypertrophy, 84.2 patients wit inactive synovial hypertrophy and 50% of patients with tenosynovitis. In 85.7% of patients with active synovial hypertrophy, and 53.8% of pastients with erosions, the C-reactive protein (CRP) levels where elevated. No patient was diagnosed as also having rheumatoid arthritis <h3>Conclusions</h3> Even in asymptomatic patients with chronic hepatitis C infection, US examination of the wrists and of the second and fifth interphalangeal joins may reveal abnormalities. Certain types of these are probably correlated with the presence of cryoglobulins and possibly associated with CRP levels, C3 levels and rheumatoid factors positivity. Further studies are needed to verify our finding <h3>Disclosure of Interest</h3> None declared
AB0078 Systemic and local il-17a and mir-223 levels in rheumatoid arthritis patients
Authors: R. Shumnalieva, D. Kachakova, T. Velikova, R. Kaneva, Z. Kolarov, S. Monov
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> IL-17 is a proinflammatory cytokine, which overproduction promotes the autoimmune reaction in rheumatoid arthritis (RA). Recent studies have shown that IL-17 production in lymphocytes or its function could be regulated by miR-223 by targeting Roquin ubiquitin ligase or its receptors<sup>1–4</sup>. <h3>Objectives</h3> To examine a possible correlation between the expression levels of miR-223 and IL-17A in peripheral blood (PB) and synovial fluid (SF) of RA patients. <h3>Methods</h3> Expression levels of miR-223 were determined in matched PB and SF samples of RA patients by relative quantitation method 2<sup>-ΔΔCt</sup>. As reference control for normalisation RNU6B gene was used. Concentrations of IL-17A in matched serum and SF samples were determined by Human IL-17A ELISA kit (Gene probe, Diaclone). The results were compared to healthy control (HCs) as well as within the RA group. <h3>Results</h3> 58,73% of the RA patients showed overexpression of miR-223 in PB when compared to HCs (p=0.008) with AUC=0.673 (95 CI: 0.562/0.784), with 71.4% sensitivity and 46.9% specificity (p=0.006). miR-223 was overexpressed in 79.17% of RA SF (p=1.64 × 10–3) when compared to HCs SF with AUC=0.841 (95 CI: 0.724/0.958) with 87.5% sensitivity and 72.7% specificity (p=4.6 × 10–4). Within the RA group, SF miR-223 was underexpressed in 58.7% of the patients compared to its systemic levels. Levels of IL-17A were higher in RA SF compared to serum (8.645 pg/ml versus 0.315 pg/ml, p=0.012). <h3>Conclusions</h3> The difference between the systemic and local levels of miR-223 and IL17A in RA patients shows that the inflammatory disease process leads to their altered expression with a possible role of both molecules in the disease pathogenesis. The opposite changes in their systemic and local levels confirm the data about the possible role of miR-223 in regulating IL-17 function. <h3>References</h3> [1] Haneklaus M, Gerlic M, O'Neill LA, Masters SL. miR-223: infection, inflammation and cancer. J Intern Med. 2013;274(3):215–226. [2] Khan D, Ansar Ahmed SA. Regulation of IL-17 in autoimmune diseases by transcriptional factors and microRNAs. Front Genet. 2015;6:236. [3] Moriya N, Shibasaki S, Karasaki M, Iwasaki T. The Impact of MicroRNA-223–3p on IL-17 Receptor D Expression in Synovial Cells. PLoS One2017;12(1):e0169702. [4] Schaefer J, Nakra N, Montufar-Solis D, Vigneswaran N, Klein J. Role for miR-223 and Roquin in IL-10 mediated regulation of IL-17. J Immunol2013;190(1 Supplement):171.9. <h3>Acknowledgements</h3> The study was supported by Grant 14D/2012 and Grant 61/2015 funded by Medical University-Sofia, Bulgaria <h3>Disclosure of Interest</h3> None declared
AB1160 A syndrome of recurrent idiopathic hydrops fetalis, responding to anti-platelets/anti-coagulant prophylaxis. is it a new entity or a part of maternal hypercoagulation state; thrombophilia or anti-phospholipid syndrome (APS)?
Authors: S. Aamar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Anti-phospholipid (aPL) syndrome (APS) is defined in the presence of anticardiolipin (aCL), anti-β2 glycoprotein-I antibodies, or lupus anticoagulant (LAC) with hypercoagulability, including arterial/venous thrombosis episode(s), or pregnancy morbidity; early spontaneous abortions, stillbirth or prematurity with (pre)eclampsia. Beside these classification criteria the increased awareness for seronegative APS and non-criteria clinical manifestations, necessitate additional laboratory diagnostics for aPL's. Use of preventive treatment protocol; low-dose (100 mg/d) aspirin (ASA) and/or daily subcutaneous (SC) heparin, is highly effective and improves fetal vitality and pregnancy outcome. Beside APS, stillbirth and fetal loss may result from thrombophilia and Hydrops fetalis (HF). HF is described as fetal pathological fluid accumulation in serous cavities and soft tissues. It is accompanied with placental thickening and hydramnios. Most of the cases refer to non-immune (NIHF), not caused by red cell alloimmunization. Almost third of NIHF are idiopathic (iNIHF). The pathogenesis of tissue hypoxia with capillary leakage remains unclear. With advanced in-utero therapy mortality is still high (50%–95%). <h3>Objectives</h3> To describe the entity of recurrent idiopathic NIHF, resulting in habitual miscarriages. To document the use of APS prophylactic regimen for fetal loss, and its effect on iNIHF occurrence. <h3>Methods</h3> Data from medical files of women with previous iNIHF, who were treated in the rheumatology clinic, Hadassah Mount Scopus Hospital in Jerusalem, between years 2002–2017 were summarised (table 1). <h3>Results</h3> The present series illustrates the impact of the prophylactic regimen of APS in preventing obstetrical morbidities, including miscarriages and fetal death due to Hydrops fetalis (table 1). Thrombophilia and aPL profiles were normal. Five women who had multiple early abortions and 8 pregnancies with iNIHF, following treatment had a total of 12 successful pregnancies with uneventful delivery to healthy babies. ANA:anti nuclear antibodies, IUFD:intra uterine fetal death, IVF:<i>in vitro</i>fertilisation, CLX:Clexan=Enoxaparin (SC 40 mg/d), HCQ:Hydroxy-Chloroquine (200 mgx 2/d), PRD:Prednisone (10–20 mg/d) <h3>Conclusions</h3> Idiopathic NIHF, is a very serious condition with high fetal mortality and limited effective therapy, so prevention is very crucial. APS prophylaxis regimen, based on anti-platelets and anti-coagulant therapy during pregnancy, may have promising effects. <h3>Disclosure of Interest</h3> None declared
Phase I/II trial of cetuximab with 5-fluorouracil and mitomycin C concurrent with radiotherapy in patients with muscle invasive bladder cancer.
Authors: Syed A. Hussain, Laura Buckley, Baljit Kaur, Carey Hendron, Anjali Zarkar, Daniel Ford, Richard Viney, Isabel Syndikus, Zafar Malik, Chinnamani Eswar, Amisha Desai, Elizabeth Southgate, Stephen Mangar, Johannes Van Der Voet, Anna Lydon, Nicholas D. James
Journal: Journal of Clinical Oncology (2017)

4527 Background: This phase I/II trial assessed the safety, feasibility and efficacy of cetuximab (Cet) in combination with 5-fluorouracil (5FU) and mitomycin C (MMC) with concurrent radiotherapy (RT) for the treatment of muscle invasive bladder cancer (MIBC). BC2001 trial has previously reported significant improvement in locoregional control in patients (pts) with MIBC who were randomised to synchronous chemo-RT compared to RT alone (James, Hussain, Hall et al NEJM 2012). Results for phase I have been reported previously. This abstract reports the combined results of phases I/II. Methods: From September 2012 to October 2016, 33 pts were recruited (7 pts to phase I from 2 UK centres and 26 patients to phase II from 5 UK centres). Pts received loading dose of Cet 400 mg/m 2 followed by weekly Cet 250 mg/m 2 for 7 weeks, continuous infusion 5FU 500mg/m 2 /day during fractions 1-5 and 16-20 of RT and MMC 12mg/m 2 on day 1 in combination with radical RT 64 Gy in 32 fractions. Neoadjuvant chemotherapy was mandatory in phase I but optional in phase II. Primary outcomes in phase I were feasibility and toxicity. Primary outcome in phase II was 3 month pathological complete response (CR) rate, secondary outcomes included toxicity, progression free survival (PFS) and overall survival (OS). Results: Median age of pts was 70 (range 46.9-85.6). Treatment completion rates in phase I were RT 100%, 5FU 100 %, MMC 100%, Cet 96%. Of the 28 analysable pts, phase II primary outcome data was available for 25 pts at the time of analysis with a 3 month pathological CR rate of 88%. 5 local progressions and 4 deaths were reported. 12 pts suffered at least one SAE. Grade 4 toxicities observed were dyspnoea, atrial fibrillation, interstitial pneumonitis, sepsis, thromboembolism, neutropenia and palpitations. The commonest grade 3 toxicities were skin rash, diarrhoea, low platelet count, low white blood cell count, fever and haematuria. The most common grade 1 and 2 toxicities were diarrhoea and skin rash. Data on PFS and OS will be presented. Conclusions: It was feasible and safe to add cetuximab to full dose chemo-RT with 5FU/MMC. The CR rate is encouraging and further randomised studies with this combination are warranted. Clinical trial information: ISRCTN80733590.
Impact of Emergent Circulating Tumor DNA <i>RAS</i> Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer
Authors: Tae Won Kim, Marc Peeters, Anne Thomas, Peter Gibbs, Kristina Hool, Jianqi Zhang, Agnes Lee Ang, Bruce Allen Bach, Timothy Price
Journal: Clinical Cancer Research (2018)

Purpose: The accumulation of emergent RAS mutations during anti-EGFR therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status.Experimental Design: This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the PlasmaSelect-R 64-gene panel at 0.1% sensitivity.Results: Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval, 11.5-15.4) and 7.9 months (6.4-9.6), respectively (P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations.Conclusions: Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Clin Cancer Res; 24(22); 5602-9. ©2018 AACR.
Are we missing respiratory viral infections in infants and children? Comparison of a hospital-based quality management system with standard of care
Authors: M. Alchikh, T. Conrad, C. Hoppe, X. Ma, E. Broberg, P. Penttinen, J. Reiche, B. Biere, B. Schweiger, B. Rath
Journal: Clinical Microbiology and Infection (2018)
TCPOBOP‐Induced Hepatomegaly and Hepatocyte Proliferation are Attenuated by Combined Disruption of MET and EGFR Signaling
Authors: Bharat Bhushan, John W. Stoops, Wendy M. Mars, Anne Orr, William C. Bowen, Shirish Paranjpe, George K. Michalopoulos
Journal: Hepatology (2018)

TCPOBOP (1,4‐Bis [2‐(3,5‐Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP‐induced direct hyperplasia has been considered to be CAR‐dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and epidermal growth factor receptor (EGFR), are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP‐induced direct hyperplasia, not yet explored, is investigated in the current study. Disruption of the RTK‐mediated signaling was achieved using MET knockout (KO) mice along with Canertinib treatment for EGFR inhibition. Combined elimination of MET and EGFR signaling [MET KO + EGFR inhibitor (EGFRi)], but not individual disruption, dramatically reduced TCPOBOP‐induced hepatomegaly and hepatocyte proliferation. TCPOBOP‐driven CAR activation was not altered in [MET KO + EGFRi] mice, as measured by nuclear CAR translocation and analysis of typical CAR target genes. However, TCPOBOP‐induced cell cycle activation was impaired in [MET KO + EGFRi] mice due to defective induction of cyclins, which regulate cell cycle initiation and progression. TCPOBOP‐driven induction of FOXM1, a key transcriptional regulator of cell cycle progression during TCPOBOP‐mediated hepatocyte proliferation, was greatly attenuated in [MET KO + EGFRi] mice. Interestingly, TCPOBOP treatment caused transient decline in hepatocyte nuclear factor 4 alpha expression concomitant to proliferative response; this was not seen in [MET KO + EGFRi] mice. Transcriptomic profiling revealed the vast majority (~40%) of TCPOBOP‐dependent genes primarily related to proliferative response, but not to drug metabolism, were differentially expressed in [MET KO + EGFRi] mice. Conclusion: Taken together, combined disruption of EGFR and MET signaling lead to dramatic impairment of TCPOBOP‐induced proliferative response without altering CAR activation.