tbuckley/cabot-search huggingface dataset:
Transplantation of Livers From Viremic Hepatitis C Virus–Positive Donors Into Hepatitis C Virus–Negative Recipients
Authors: Paulo N. Martins
Journal: Hepatology (2018)

To the Editor: I have read with interest the paper by Dr. Bari et al. reporting on the use of livers from hepatitis C virus (HCV) antibody–positive, nucleic acid test–negative (nonviremic) donors into HCV negative recipients and would like to congratulate the authors for such important contribution.1 I would like to emphasize that, due to increasing mortality on the waitlist and excellent antiviral treatment, the transplant community should also use livers from HCV viremic donors for selected HCV negative recipients. In the United States, the rate of death from drug overdoses has increased exponentially.2 Using the United Network for Organ Sharing database from 2015 to 2016, Kling et al. showed that 4.35% of all donors were viremic for HCV, and this number is increasing with the opioid epidemic.3 The transplant community's interest in the use of HCV positive donors for HCV negative recipients has recently increased.2 However, it is controversial which HCV negative patients should receive those livers.2 Until more data on long‐term direct‐acting antiviral treatment is available, it makes sense to use them in patients with increased risk of mortality or patients with very poor quality of life and low chance of receiving a transplant. Recently, Chhatwal et al., using a Markov‐based simulation model, reported that accepting any liver regardless of HCV status versus accepting only HCV negative livers resulted in an increase in life expectancy only when Model for End‐Stage Liver Disease (MELD) was ≥20, and the benefit was highest at MELD 28, resulting in 0.172 additional life years.4 Another important issue with the allocation of viremic donors into uninfected patients is the high cost associated with treatment. However, this type of liver allocation will likely be cost‐effective because transplanting HCV negative patients with HCV positive donors will happen sooner, reducing costs associated with the treatment of complications of end‐stage liver disease. Very recently, a study showed that this type of allocation in kidney transplant patients was cost‐effective, with the costs breaking even only 4 years after transplant when compared with hemodialysis treatment.5 The use of livers from both aviremic and viremic donors could significantly decrease the waiting time and the mortality on the waitlist of HCV negative potential recipients. Potential conflict of interest Nothing to report.
AB0056 Measurement of the pro-coagulant activity of microparticles in patients with inflammatory rheumatic diseases: prospective study
Authors: C. Mekhail, X. Guillot, C. Prati, P. Saas, G. Mourey, D. Wendling
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Microparticles (MPs) are small membrane-bound vesicles that arise from activated and dying cells. Although the majority of MPs in the blood originate from platelets, all cells appear to be able to release MPs. Many studies have raised the implication of these MP in various processes: inflammation, thrombosis, angiogenesis. Previous studies reported inconsistent results in inflammatory rheumatic diseases. Studies have shown the correlation between the circulating MPs, platelet MPs and lymphocyte MPs in patients with spondyloarthritis (SpA) compared to control patients. For rheumatoid arthritis (RA), platelet MPs levels were correlated with DAS28. <h3>Objectives</h3> The aim of this study was to search a possible correlation between the disease activity and the pro-coagulant property of microparticles, potential indirect marker of inflammation. <h3>Methods</h3> The test used (STA Procoag PPL) is a standardised automated test. Results are expressed as coagulation times (in seconds). It is a functional test that provides information on the procoagulant potential of microparticles. The microparticles supply the phospholipids expressed on their membrane surface and the test provides calcium and factor Xa necessary to initiate coagulation: the shorter the coagulation time the greater the procoagulant activity of the phospholipids being studied, suggesting a higher number of MP. This is a prospective, single-centre study, including 39 patients with spondyloarthritis (ASAS criteria), 37 with rheumatoid arthritis (ACR criteria) and 26 control patients (healthy subjects, osteoarthritis). All patients underwent STA Procoag PPL test, and we collected medical data: disease activity (BASDAI, BASFI, DAS28vs and DAS28crp and HAQ), biological inflammation (VS, CRP), duration of disease, and current treatment. <h3>Results</h3> The <i>in vitro</i> clotting time of serum of patients with spondyloarthritis and rheumatoid arthritis compared with controls was not significantly different (p=0.23 and p=0.44, respectively). Regarding the activity scores of inflammatory rheumatic disease: BASDAI and BASFI, DAS28esr, DAS28crp and HAQ for patients with RA, no correlation between these data and coagulation time was found; the same goes for biological inflammation (ESR, CRP), duration and type of treatment (Nonsteroidal anti-inflammatory drugs, DMARDs, biologics). <h3>Conclusions</h3> In this study, there is neither difference in values of procoagulant activity of MPs between inflammatory rheumatic diseases and control subjects, nor correlation with their activity scores or biological inflammation. <h3>Disclosure of Interest</h3> None declared
PARE0012 The french patient’s association aflar: has generated the french national alliance against osteoporosis and the first general convention for osteoporosis, that is a campaign to create a national promoting tool to improve the management of osteoporosis.: 7 priorities to better treat patients i
Authors: L. Grange, B. Cortet, T. Thomas, F. Srour, P. Guggenbuhl, C. Roux, P. Monod, J. M. Feron, F. Alliot- launois, F. Tremollières, G. Chalés, J. Giraud, E. Senbel, G. Thibaud, P. Niemczynski, D.R. Bertholon, C. F. Roques, D. Buchon, C. Bonnet, H. Blain, C. Rolland, D. Lafarge, L. Carton
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoporosis is a major public health issue with 5 million of French affected. Overall, she seriously underestimated, and costs are barely covered in France. Considering this situation, AFLAR were urged to create the so-called National Osteoporosis Alliance made up of 15 various stakeholders and patients. <h3>Methods</h3> National consultations on osteoporosis rely methodologically on 2 pillars:First the bottom-up reporting on patient needs and expectations. Second the conduct of coordination meetings with various osteoporosis key stakeholders and patients as part of regional panel-discussions. The aim is to provide an overview of real obstacles contributing to the lack of government subsidies for osteoporosis and write consensual proposals compiled into a white paper. <h3>Results</h3> An online survey along with a citizen’s panel were key to provide feedbacks on difficulties, knowledges and believes but also patient needs. From November 2016 to June 2017, 10 days of dialogue and debate covering 5 various topics were convened in 10 different cities: Consultation and consolidation work regarding proposals made during various panel-discussions allowed synthesis around one call: the creation of a real public health plan against osteoporosis-related fractures relying on 7 key axis. <h3>Conclusions</h3> The human and medico-economic rational considering dramatic fallouts caused by osteoporosis has been illustrated many times over. The policy makers mobilization made by stakeholders through white paper release, a real manifesto for public health plan against osteoporosis-related fracture, remain a significant challenge to face. <h3>Disclosure of Interest</h3> L. Grange Grant/research support from: ucb Lilly Amgen expanscience Roche company, B. Cortet : None declared, T. Thomas : None declared, F. Srour : None declared, P. Guggenbuhl : None declared, C. Roux : None declared, P. Monod: None declared, J. M. Feron: None declared, F. Alliot- launois: None declared, F. Tremollières : None declared, G. Chalés : None declared, J. Giraud : None declared, E. Senbel: None declared, G. Thibaud: None declared, P. Niemczynski: None declared, D. R. Bertholon : None declared, C. F. Roques : None declared, D. Buchon: None declared, C. Bonnet : None declared, H. Blain : None declared, C. Rolland : None declared, D. Lafarge : None declared, L. Carton: None declared
SAT0005 Interleukin-33 ameliorates murine lupus via induction of regulatory t cells and m2 macrophage polarisation
Authors: M.Y. Mok, K. Law, W.Y. Kong, Y. Lo, E. Ng, C. Luo, F. Huang, G. Chan, K. Chan
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> The levels of IL-33, a Th2 promoting cytokine, and the soluble form of its receptor ST2 were reported to be elevated in serum of patients with active systemic lupus erythematosus (SLE), suggesting a role of the IL-33/ST2 axis in the pathogenesis of SLE. <h3>Objectives</h3> This study aims to examine the effect of IL-33 in disease severity of murine lupus. <h3>Methods</h3> IL-33 was injected intraperitoneally 3 times per week to pre-diseased MRL/lpr mice aged 12 weeks for 6 weeks. Control group was given 1% BSA injection. Urine protein was monitored weekly by albustix and protein assay. Immunophenotyping of splenocytes was examined by flow cytometry. Splenic CD11b+monocytic cells were isolated by microbeads for mRNA examination. <h3>Results</h3> IL-33-treated mice (n=9) developed significantly less proteinuria compared to BSA-treated group (n=9). Kidney histology of the IL-33-treated group showed remarkably less mesangial deposit, diffuse proliferative glomerular changes and crescents, and had significantly lower renal composite score compared to controls (median 2.0 vs 9.9, p&lt;0.001). Kidneys of these mice expressed lower mRNA levels of TNF-α (32.1±14.7 vs 77.0±27.8, p&lt;0.001), IL-6 (median 0.6 vs 4.7, p=0.003), IL-1β (31.1±10.1 vs 77.8±24.6, p&lt;0.001) and iNOS (p=0.006). Immunophenotyping of splenocytes showed significantly increased CD4 +CD25+regulatory T (Treg) cells (4.0%±1.2% vs 2.2±0.2%, p&lt;0.001) that expressed remarkably higher Foxp3 (76.0%±5.0% vs 59.3±12.6%, p=0.002). Splenic extracts showed predominant Gata3 (0.37±0.20 vs 0.12±0.09, p=0.01) and Foxp3 (0.42±0.16 vs 0.17±0.11, p=0.002) mRNA in IL-33-treated mice. These Treg cells expressed high cell surface ST2 (8.9%±2.7% vs 4.5±2.0%, p=0.008). There was significant expansion of splenic CD11b+population in IL-33-treated mice (17.8±10.5 vs 8.8±3.0, p=0.01) that expressed significantly higher CD206 (5.2%±0.9% vs 2.9±0.9%, p=0.002). Isolated splenic CD11b+cells expressed significantly higher mRNA of Arg1, FIZZI and Ym-1 and IL-10 (all p=0.01) with reduced expression of iNOS (p=0.02). Kidney extracts of IL-33 treated mice also had elevated mRNA levels of M2 markers including Arg1 (median 199.8 vs 36.1, p=0.004) and FIZZI (median 25.0 vs 2.7, p&lt;0.001) and reduced MCP-1 (12.7±6.5 vs 35.1±12.0, p&lt;0.001). There was also significantly higher levels of mRNA of Foxp3 (median 43.0 vs 20.8, p=0.006) and Gata 3 (1.7±0.5 vs 0.9±0.5, p=0.008) but lower Rorc (2.6±1.0 vs 3.8±0.8, p=0.008) and Tbx21 (12.6±6.0 vs 29.6±13.7, p=0.003) in the kidneys. <h3>Conclusions</h3> Exogenous IL-33 led to significantly less proteinuria and renal inflammation. These mice had significantly higher splenic Treg cells with prominent Foxp3 expression. Isolated CD11b+cells from spleen and kidney extracts demonstrated mRNA levels of M2 macrophage polarisation. <h3>Disclosure of Interest</h3> None declared
First-line FOLFOX plus panitumumab (Pan) followed by 5FU/LV plus Pan or single-agent Pan as maintenance therapy in patients with RAS wild-type metastatic colorectal cancer (mCRC): The VALENTINO study.
Authors: Filippo Pietrantonio, Federica Morano, Salvatore Corallo, Sara Lonardi, Chiara Cremolini, Lorenza Rimassa, Andrea Sartore-Bianchi, Marco Tampellini, Sara Bustreo, Matteo Clavarezza, Roberto Murialdo, Alberto Zaniboni, Vincenzo Adamo, Gianluca Tomasello, Monica Giordano, Fausto Petrelli, Raffaella Longarini, Vittorina Zagonel, Maria Di Bartolomeo, Filippo G. De Braud
Journal: Journal of Clinical Oncology (2018)

3505 Background: Since doublets plus anti-EGFRs were continued until progressive disease (PD) in mCRC first-line registration trials, there is scarce evidence if de-escalating treatment intensity after an anti-EGFR-based induction might be not inferior in terms of disease control, while reducing toxicity burden and improving quality of life. In MACRO-2, maintenance with cetuximab alone achieved a 9-month progression-free survival (PFS) rate non inferior than continued mFOLFOX + cetuximab in KRAS ex. 2 wt patients. Methods: RAS wt unresectable mCRC patients, stratified for prior adjuvant therapy and metastatic sites (1 vs ≥2), were randomized and received FOLFOX + Pan induction (8 cycles) followed by maintenance with Pan (arm B) or 5FU/LV + Pan (arm A) until PD/unacceptable toxicity/death. The primary endpoint was non-inferiority of PFS of arm B vs A. An overall sample size of 224 subjects (112 per arm) achieved 90% power to detect a 50% 10-month PFS rate in arm A and a maximum 15% difference in arm B, with a significance level of 0.1 and a 15% drop-out rate; non inferiority could be demonstrated if the upper boundary of the one-sided 90% CI of the hazard ratio (HR) was <1.515. Secondary endpoints were safety, quality of life, overall response rate (ORR), duration of response and overall survival. Results: From July 2015 to October 2017, 229 patients were randomized (117 arm A/112 arm B). Baseline characteristics were: males, 68%/66%; median age, 64/64; ECOG PS 0, 71%/72%; previous adjuvant therapy, 14%/18%; single metastatic site, 54%/58%; BRAF mutation, 3%/4%; right-sided primary, 15%/20%. The upper boundary of the one-sided 90% CI for the HR of Pan vs 5FU/LV + Pan was 1.946. At a median follow-up of 13.8 months, 10-m PFS was 52.8% for Pan vs 62.8% for 5FU/LV + Pan, with median time of 10.2 vs 13.0 months, respectively (stratified HR = 1.55, 95% CI: 1.09-2.20; p = 0.011). ORR was 66.6% and 67% in arm A and B, respectively. During maintenance phase, grade ≥3 adverse events (AEs) were mainly diarrhea 3.7%/1.4%; mucositis 6.2%/1.4%; hand-foot syndrome 2.5%/1.4%; neutropenia 2.5%/0%; skin rash 22.2%/13.7%. Overall, grade 1-2 AEs were 75.3%/64.4%. Conclusions: In RAS wild-type mCRC patients, maintenance with Pan alone following induction with FOLFOX + Pan achieves inferior PFS than 5FU/LV + Pan combination. Clinical trial information: NCT02476045.
OP0042 In acpa positive at-risk individuals, which mri and us findings best predict development of clinical synovitis?
Authors: L. Hunt, J. Nam, E.M. Hensor, K. Mankia, E. Rowbotham, A.J. Grainger, P. Emery
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> ACPA +individuals with non-specific MSK symptoms are at risk of inflammatory arthritis (IA) and may benefit from early intervention. Clinical, serological and US markers have previously been assessed to determine risk of progression.<sup>1</sup> <h3>Objectives</h3> Evaluate the value of MR and US imaging in characterising and quantifying risk in a large ACPA +cohort. <h3>Methods</h3> Eligible ACPA +individuals without clinical synovitis had gadolinium enhanced 3.0 T MRI of the dominant hand and wrist. Images were scored by 2 radiologists for synovitis, bone marrow oedema (BME), erosions and tenosynovitis (TSV) according to OMERACT RAMRIS. Joint counts for each abnormality at each joint were corrected for age using a healthy controls reference range.<sup>2</sup> US of the same regions were scored using OMERACT definitions. Maximum MRI and US abnormality scores observed per patient across all joints scored were dichotomised &lt;2,≥2. Potential associations between baseline US (greyscale (GS) and powerDoppler (PD)) and MRI findings and i) progression to IA and ii) development of clinical synovitis within a joint were identified using Cox and penalised regression. <h3>Results</h3> Imaging of 98 individuals (mean age 47, 69% female) was available. 30% (29/98) progressed to IA. Median time to progression was 31 weeks (IQR 24, 67). BME and erosions scores≥2 were reported in 10%, preferential location to the carpal bones/wrist joints. Synovitis score ≥2 was present in 9%, preferential location at MCP5 and radial carpal/intercarpal joints. TSV was the most frequent reported abnormality with 22% scoring ≥2, 40% scoring 1. US GS and PD scores≥2 were reported in 23% and 9% respectively. The unadjusted analysis HRs for all imaging abnormalities were high, indicating potential association with risk of progression. Controlling for variables, MRI TSV was associated with time to IA with an increased HR. US GS and PD were also independently associated with time to progression and confirmed on penalised regression, table 1. At the joint level MRI TSV, BME and US GS were associated with the risk of progression to clinical synovitis, HR=7.03 p&lt;0.001, HR 4.22 p=0.076 and HR 8.04 p&lt;0.001 respectively. <h3>Conclusions</h3> ACPA +at risk individuals have features on imaging which assists prediction of development to IA. MRI TSV provides additional predictive ability over and above the clinical and US variables. <h3>References</h3> [1] Rakieh C. 2014. [2] Mangnus L. 2016. <h3>Disclosure of Interest</h3> None declared
AB0788 Osteoarticular involvements in patients with systemic sclerosis
Authors: M. Tougorti, T. Ben Salem, I. Ben Ghorbel, M. Lamloum, M.H. Houman
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Osteoarticular involvements are common in systemic sclerosis (SS) and are considered as an important cause of disability. <h3>Objectives</h3> The aim of this study was to assess clinical, radiological and immunological characteristics of patients with systemic sclerosis and who present with osteoarticular involvements at any time of the disease course. Patients with arthralgia and/or arthritis and/or imaging abnormalities were included. <h3>Methods</h3> A retrospective descriptive and comparative study was performed in an internal medicine department. One hundred thirty one patients who fulfilled 2013 ACR/EULAR criteria for SS were studied. <h3>Results</h3> We identified 101 patients with osteoarticular involvements (77.1%); 92 women and 9 men. Mean age at SS diagnosis was 47.6±12.4 years. Disease was revealed by joint manifestations in 10.7% of cases. Arthralgia and arthritis were observed in 61.8% and 21.4% of cases respectively. Flexion deformities with disability were noted in 26 cases. X-Ray investigations revealed distal phalanges resorption (n=24), dystrophic calcifications (n=10) and joint space narrowing (n=9). Tendinitis was observed in one patient. Patients with osteoarticular manifestations developed more frequently digital ulcers (100% vs 78.3%; p&lt;0.001). Osteoarticular involvements was associated to diffuse cutaneous sclerosis (37.7% vs 12.5%; p=0.002) and to telangiectasis (91.3% vs 70%; p=0.027), gastrointestinal manifestations (90.1% vs 54.5%; p=0.001) and interstitial lung disease (92.7% vs 67.9%; p=0.001). SS was associated to sjögren syndrome (n=20), to systemic lupus erythematosus (n=15) and to rheumatoid arthritis (n=2). Patients received non<b>-</b>steroidal anti<b>-</b>inflammatory drug (n=26), corticosteroids (n=8) and methotrexate (n=8). <h3>Conclusions</h3> Osteoarticular involvement in systemic sclerosis has heterogeneous aspects. Its frequency ranges from 40% to more than 85% of cases in some studies. Early screening and treatment associated with physiotherapy session are essential to avoid complication and loss of function. <h3>Disclosure of Interest</h3> None declared
Angio-LncRs: LncRNAs that regulate angiogenesis and vascular disease
Authors: Bo Yu, Shusheng Wang
Journal: Theranostics (2018)

Long noncoding RNAs (lncRNAs) represent a large subgroup of RNAs that are longer than 200 nucleotides and have no apparent protein coding potential.They have diverse functions in different biological processes by regulating chromatin remodeling or protein translation.This review summarizes the recent progress of lncRNAs in angiogenesis and vascular diseases.A general overview of lncRNA functional mechanisms will be introduced.A list of lncRNAs, which are termed "Angio-LncRs", including MALAT1, MANTIS, PUNISHER, MEG3, MIAT, SENCR and GATA6-AS, will be discussed regarding their expression, regulation, function and mechanism of action in angiogenesis.Implications of lncRNAs in vascular diseases, such as atherosclerosis, hypertension, vascular retinopathies and tumor angiogenesis will also be discussed.
Spitzoid melanoma with histopathological features of <i> <scp>ALK</scp> </i> gene rearrangement exhibiting <i> <scp>ALK</scp> </i> copy number gain: a novel mechanism of <scp>ALK</scp> activation in spitzoid neoplasia
Authors: M. Farah, P. Nagarajan, J.L. Curry, Z. Tang, T.‐B. Kim, P.P. Aung, C.A. Torres‐Cabala, A.K. Eterovic, J.A. Wargo, V.G. Prieto, M.T. Tetzlaff
Journal: British Journal of Dermatology (2018)

Spitzoid neoplasms pose diagnostic difficulties because their morphology is not consistently predictive of their biological potential. Recent advances in the molecular characterization of these tumours provides a framework by which they can now begin to be categorized. In particular, spitzoid lesions with ALK rearrangement have been specifically associated with a characteristic plexiform growth pattern of intersecting fascicles of amelanotic spindled melanocytes. We report the case of an 87‐year‐old man with a 3‐cm nodule on his mid‐upper back comprised of an intradermal proliferation of fusiform amelanotic melanocytes arranged in intersecting fascicles with occasional peritumoral clefts. Immunohistochemical studies demonstrated diffuse, strong expression of SOX10 and S100 by the tumour cells and diffuse, weak‐to‐moderate cytoplasmic positivity for anaplastic lymphoma kinase (ALK), suggestive of ALK rearrangement. Fluorescence in situ hybridization revealed no ALK rearrangements but instead revealed at least three intact ALK signals in 36% of the tumour cells, confirming ALK copy number gain. To our knowledge, this is the first reported case of a plexiform spitzoid neoplasm exhibiting ALK copy number gain instead of ALK rearrangement. This case suggests that ALK copy number gain is a novel mechanism of ALK activation but with the same characteristic histopathological growth pattern seen among ALK‐rearranged spitzoid neoplasms.