tbuckley/cabot-search huggingface dataset:
Number of individual ACPA reactivities in synovial fluid immune complexes, but not serum anti-CCP2 levels, associate with inflammation and joint destruction in rheumatoid arthritis
Authors: Azita Sohrabian, Linda Mathsson-Alm, Monika Hansson, Ann Knight, Jörgen Lysholm, Martin Cornillet, Karl Skriner, Guy Serre, Anders Larsson, Tomas Weitoft, Johan Rönnelid
Journal: Annals of the Rheumatic Diseases (2018)

Introduction Individual patients with rheumatoid arthritis (RA) show divergent specific anti-citrullinated protein/peptide antibodies (ACPA) patterns, but hitherto no individual ACPA specificity has consistently been linked to RA pathogenesis. ACPA are also implicated in immune complexes (IC)-associated joint pathology, but until now, there has been no method to investigate the role of individual ACPA in RA IC formation and IC-associated pathogenesis. Methods We have developed a new technique based on IC binding to C1q-coated magnetic beads to purify and solubilise circulating IC in sera and synovial fluids (SF) from 77 patients with RA. This was combined with measurement of 19 individual ACPA in serum, SF and in the IC fractions from serum and SF. We investigated whether occurrence of individual ACPA as well as number of ACPA in these compartments was related to clinical and laboratory measures of disease activity and inflammation. Results The majority of individual ACPA reactivities were enriched in SF as compared with in serum, and levels of ACPA in IC were regulated independently of levels in serum and SF. No individual ACPA reactivity in any compartment showed a dominating association to clinical and laboratory measures of disease activity and severity. Instead, the number of individual ACPA reactivities in the IC fraction from SF associated with a number of markers of joint destruction and inflammation. Conclusions Our data highlight the polyclonality of ACPA in joint IC and the possibility that a broad ACPA repertoire in synovial fluid IC might drive the local inflammatory and matrix-degrading processes in joints, in analogy with antibody-induced rodent arthritis models.
Nootropic nanocomplex with enhanced blood-brain barrier permeability for treatment of traumatic brain injury-associated neurodegeneration
Authors: Jeongmin Park, Eunshil Choi, Seulgi Shin, Sungsu Lim, Dohee Kim, Suji Baek, Kang Pa Lee, Jae Jun Lee, Byeong Han Lee, Bokyung Kim, Keunsoo Jeong, Ja-Hyun Baik, Yun Kyung Kim, Sehoon Kim
Journal: Journal of Controlled Release (2018)
Abstract IA18: Cancer evolution as a therapeutic target
Authors: Alberto Bardelli
Journal: Clinical Cancer Research (2018)

Abstract When metastatic cancers are challenged with targeted agents, almost invariably a subset of cells insensitive to the drug emerges. As a result, in most instances, targeted therapies are only transiently effective in patients. Strategies to prevent or overcome resistance are therefore essential to design the next generation of clinical trials. How can we overcome the near-certainty of disease recurrence following treatment with targeted agents? Addressing this question means considering as a target not only individual oncogenes but also the evolving nature of human tumors. We used colorectal cancer (CRC) as a model system to test the hypothesis that by understanding tumor's evolution, the emergence of drug resistance can be controlled. We find that clonal dynamics can be monitored in real time in the blood of patients, and liquid biopsies can be used to intercept the emergence of resistant clones before relapses are clinically manifest. We discovered that a multistep clonal evolution process driven by progressive increases in drug fitness underlies the development of resistance in cells and patient avatars. To have long-term efficacy, the use of targeted therapies must take into account the continuous evolution of cancer cells, that is to say, therapies must adapt to tumor evolution. One possibility is to anticipate the changes the tumors will make. For example, by knowing in advance how CRC cells overcome resistance to EGFR blockade, we devised further rounds of therapy. Another approach is to unleash the ability of the immune system to recognize drug-resistant cells. We tested this possibility in syngeneic mouse models of CRC sensitive to targeted therapies. Our findings indicate that manipulation of the mutational loads can trigger prolonged therapeutic responses that are not observed when cancer cells are challenged with targeted drugs alone. We postulate that rationally combined targeted and immunotherapies can restrain tumor evolution and can limit the emergence of drug resistance, thus leading to long-term responses. Citation Format: Alberto Bardelli. Cancer evolution as a therapeutic target [abstract]. In: Proceedings of the AACR International Conference held in cooperation with the Latin American Cooperative Oncology Group (LACOG) on Translational Cancer Medicine; May 4-6, 2017; São Paulo, Brazil. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(1_Suppl):Abstract nr IA18.
FRI0355 Predictive ability of available 10 years cardio-vascular risk algorithms in systemic lupus erythematosus: a retrospective study on 2 italian lupus cohort
Authors: D.P.E. Margiotta, S. Fasano, L. Navarini, L. Pierro, A. Riccardi, G. Dolcini, G. Valentini, A. Afeltra
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Patients with Systemic Lupus Erythematosus (SLE) present an increased incidence of Cardio-Vascular Events (CVE) compared to general population, and the difference with healthy subjects is particularly evident in young SLE women. <h3>Objectives</h3> The aim of this study is to assess the predictive ability of established 10 years CV risk models in SLE <h3>Methods</h3> A retrospective analysis of two Italian SLE prospective cohorts was performed. SLE patients without previous CVE, with age ≥25 years, a minimum continuative follow-up of 10 years and sufficient data to calculate the 10 years risk scores were enrolled. The 10 years CVE risk scores were calculated at the first observation and all CVE were prospectively recorded in the following 10 years. We calculated the following scores: the QRisk3, the Framingham CV disease 10 years score, the HeartScore (Europe Low Risk) and the SLE CV Risk Score proposed by Petri et al. Discriminatory ability for CV risk prediction was estimated by the area under the receiver operating characteristic curve. Hosmer-Lemeshov (HL) tests was used to evaluate calibration comparing the observed versus expected number of events <h3>Results</h3> Analysis was performed on 131 SLE patients (mean baseline age of 37±11 years). We observed 10 CVE during the 10 years follow-up from baseline (3 acute coronary syndrome, 4 stroke, 1 transitory ischaemic attack and 2 peripheral artery disease). The AUC values were 0.75 (95% CI 0.55–0.94) for QRisk3, 0.66 (0.45–0.88) for Framingham score, 0.62 (0.41–0.82) for the HeartScore and 0.7 (95% CI 0.55–0.85) for the SLE CV risk score. The p values of HL test were 0.8 for Qrisk3 and SLE CV score and 0.4 for Framingham score and HeartScore, suggesting a good model fit for all the CV risk scores. Considering scores with better discriminative ability and calibration, 20% of CVE were observed with Qrisk3 score lower then 3.6% and with SLE CV risk score between 6% and 8%. Discriminative ability and calibration were not improved by multiplying by 2 the Framingham score and the HeartScore. <h3>Conclusions</h3> The available CV risk scores demonstrate a moderate predictive ability of 10 years CVE in SLE. We observed a better model fit for QRisk3 and SLE CV risk score. Nevertheless, a considerable proportion of patients, with very low predicted CV risk, developed CVE during follow-up. <h3>References</h3> [1] Petri MLS. Systemic lupus erythematosus Cardiovascular Risk Equation. [Abstract]. Arthritis Rheum2012;64. [2] Urowitz MB, Ibañez D, Su J, et al. Modified Framingham Risk factor score for systemic lupus erythematosus. J Rheumatol2016;43:875–9. <h3>Disclosure of Interest</h3> None declared
Salvage procedure following lumen-apposing metal stent maldeployment during endoscopic ultrasound-guided biliary drainage
Authors: Dario Ligresti, Michele Amata, Antonino Granata, Fabio Cipolletta, Luca Barresi, Mario Traina, Ilaria Tarantino
Journal: Endoscopy (2018)

A jaundiced 82-year-old-woman was diagnosed with a cephalopancreatic, locally advanced adenocarcinoma. Endoscopic retrograde cholangiopancreatography was planned, but biliary cannulation was not achieved because of a large periampullary diverticulum ([Fig. 1]). We therefore decided to perform endoscopic ultrasound (EUS)-guided biliary drainage using an 8-mm electrocautery-tipped lumen-apposing metal stent (LAMS; AXIOS-EC, Boston Scientific, Marlborough, Massachusetts, USA).
Aggressive B-cell lymphomas in patients with myelofibrosis receiving JAK1/2 inhibitor therapy
Authors: Edit Porpaczy, Sabrina Tripolt, Andrea Hoelbl-Kovacic, Bettina Gisslinger, Zsuzsanna Bago-Horvath, Emilio Casanova-Hevia, Emmanuelle Clappier, Thomas Decker, Sabine Fajmann, Daniela A. Fux, Georg Greiner, Sinan Gueltekin, Gerwin Heller, Harald Herkner, Gregor Hoermann, Jean-Jacques Kiladjian, Thomas Kolbe, Christoph Kornauth, Maria-Theresa Krauth, Robert Kralovics, Leonhard Muellauer, Mathias Mueller, Michaela Prchal-Murphy, Eva Maria Putz, Emmanuel Raffoux, Ana-Iris Schiefer, Klaus Schmetterer, Christine Schneckenleithner, Ingrid Simonitsch-Klupp, Cathrin Skrabs, Wolfgang R. Sperr, Philipp Bernhard Staber, Birgit Strobl, Peter Valent, Ulrich Jaeger, Heinz Gisslinger, Veronika Sexl
Journal: Blood (2018)
Development and validation of response markers to predict survival and pleurodesis success in patients with malignant pleural effusion (PROMISE): a multicohort analysis
Authors: Ioannis Psallidas, Nikolaos I Kanellakis, Stephen Gerry, Marie Laëtitia Thézénas, Philip D Charles, Anastasia Samsonova, Herbert B Schiller, Roman Fischer, Rachelle Asciak, Robert J Hallifax, Rachel Mercer, Melissa Dobson, Tao Dong, Ian D Pavord, Gary S Collins, Benedikt M Kessler, Harvey I Pass, Nick Maskell, Georgios T Stathopoulos, Najib M Rahman
Journal: The Lancet Oncology (2018)
Song for a Soldier
Authors: Ted McMahon
Journal: JAMA (2018)

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Autologous CD19-Targeted CAR T Cells in Patients with Residual CLL following Initial Purine Analog-Based Therapy
Authors: Mark B. Geyer, Isabelle Rivière, Brigitte Sénéchal, Xiuyan Wang, Yongzeng Wang, Terence J. Purdon, Meier Hsu, Sean M. Devlin, Elizabeth Halton, Nicole Lamanna, Jurgen Rademaker, Michel Sadelain, Renier J. Brentjens, Jae H. Park
Journal: Molecular Therapy (2018)
Zinc phthalocyanine-soybean phospholipid complex based drug carrier for switchable photoacoustic/fluorescence image, multiphase photothermal/photodynamic treatment and synergetic therapy
Authors: Jinyuan Ma, Dengyue Chen, Yang Li, Yilin Chen, Qiuhong Liu, Xinyi Zhou, Kun Qian, Zongxi Li, Hang Ruan, Zhenqing Hou, Xuan Zhu
Journal: Journal of Controlled Release (2018)
Abstract 18454: Inhaled Nitric Oxide in ST-Elevation Myocardial Infarction: Two Year Follow-up of the NOMI Study
Authors: Maarten Vanhaverbeke, Jan Bogaert, Béla Merkely, Jaroslaw Zalewski, Pascal Vranckx, Peter Pokreisz, Peter Sinnaeve, Ann Belmans, Stefan Janssens
Journal: Circulation (2016)

Introduction:  Inhaled nitric oxide (iNO) during reperfusion confers cardioprotection in experimental myocardial ischemia-reperfusion injury. In the multicenter controlled NOMI trial (Nitric Oxide for inhalation in ST-elevation Myocardial Infarction), we randomized 250 patients with first-time STEMI to inhale oxygen with (iNO) or without (CON) 80 ppm NO for 4 hours following successful PCI. The primary efficacy endpoint, infarct size as a fraction of the LV mass assessed by MRI at 72 hours, was neutral, potentially attributable to an interaction between iNO and pharmacological nitrovasodilator use. The greater systolic LV function recovery at 4 months’ follow-up suggests that iNO-mediated effects may predominantly translate in long-term clinical benefit. We here report the 2 year clinical follow-up of NOMI.   Methods:  Patients enrolled in NOMI were followed-up for 2 years. The clinical endpoint was the composite of all-cause death, nonfatal recurrent MI, recurrent ischemia, stroke and rehospitalization. For all-cause mortality and the composite clinical endpoint, the log-rank test was used. For the other components of the composite endpoint the Pepe-Mori test was used to correct for competing risks.   Results:  In total, 245 patients completed follow-up. There was no difference in the composite clinical endpoint at 2 years (31.3% versus 33.0%,  p =0.54, figure 1). Although the event rates for reinfarction and recurrent ischemia were high, there was no difference between iNO and CON (5.3% vs 6.7%,  p =0.49 and 18.5% vs 16.7%,  p =0.71 respectively). At 2 years, all-cause mortality was 7.6% in iNO versus 8.0% in CON,  p =0.87.   Conclusion:  At 2 years follow-up, iNO during reperfusion in STEMI does not result in a better clinical outcome. Novel treatments expected to improve maladaptive LV remodeling or survival in STEMI patients mandate inclusion of patients with larger myocardial infarctions or with chronic ischemic cardiomyopathy.
Pomalidomide Alone or in Combination with Low Dose Dexamethasone As Maintenance Following Induction with Pomalidomide and Low Dose Dexamethasone in Relapsed and Refractory Myeloma (ALLG MM14)
Authors: Anna Kalff, Nola Kennedy, John Reynolds, Hang Quach, Phoebe Joy Ho, Noemi Horvath, Peter Mollee, James M. D'Rozario, Kerry Taylor, Jane Estell, Andrew Spencer
Journal: Blood (2018)
FRI0391 The relationship between oestrogen receptors and hyperuricemia in young female systemic lupus erythematosus patients
Authors: H.-J. Liu, L. Dai, X.-Y. Cai, J.-D. Ma, Y.-Q. Mo
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> We have found that the incidence of hyperuricemia of young female systemic lupus erythematosus (SLE) patients was higher than that of healthy young women<sup>[1]</sup>. Why the high level of oestrogen didn't show protection in uric acid (UA) level of fertile female SLE patients? There few few reports yet. <h3>Objectives</h3> To investigate the relationship between UA level and the levels of oestrogen, oestrogen receptors, antibodies to oestrogen receptors. <h3>Methods</h3> This was a cross-sectional study of 62 fertile female SLE patients that were divided into two groups including a high UA group (n=27) and a normal UA group (n=35). Serum UA levels, kidney index, SLE disease indicators and levels of oestrogen, oestrogen receptors, antibodies to oestrogen receptors were determined. Multiple linear regression analysis was applied to analyse the associations of UA levels with clinical features and levels of oestrogen, oestrogen receptors and antibodies to oestrogen receptors. <h3>Results</h3> 1. The mean ages of the two groups were (28.62±7.89) years and (28.82±8.28) years respectively, with on significantly different (t=0.096, p=0.924). There was no SLE patients manifested renal failure (CRE level higher than 120 μmol/l). All the SLE patients were at the onset of disease. 2. The mean UA levels of the high UA group and the normal UA group were (531.74±134.05) μmol/L and (238.86±61.32) μmol/L respectively, with significant difference (t=−11.48, p&lt;0.001). 3. In the high UA group, the levels of CRE, LDL, cystatin, urine protein and were dramatically higher than those were found in the normal UA group (t=−3.617,–3.319, -2.782,–2.979, and p=0.001, 0.002, 0.007, 0.004, respectively), and oestrogen receptor β level were significantly lower than that of the normal group (t=2.138, p=0.037). The positive rate of urine blood of the high UA group were significantly higher than that of the normal UA subgroup (χ2=6.213, p=0.012). 4. Multiple linear regression analysis revealed there were significant relationships between UA level and CRE, oestrogen receptor β, and urine protein, urine blood. <h3>Conclusions</h3> Hyperuricemia in young female SLE patients indicated the renal damage, and low level of oestrogen receptor β may contribute to hyperuricemia. <h3>Reference</h3> [1] Liu H.-J, Ma J.-D, Mo Y.-Q, et al. The study on the uric acid level of the fertile female systemic lupus erythematosus patients. Ann Rheum Dis, 2015;74(S2):1095–1096. <h3>Disclosure of Interest</h3> None declared
SAT0592 Hrct pulmonary manifestations in patients with synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO)syndrome
Authors: S. Liu, C. Li, W. Song, W. Xu, K. Xu, W. Zhang, X. Tian
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Synovitis, acne, palmoplantarpustulosis, hyperostosis and osteitis syndrome (SAPHO) is a rare syndrome that affects the skin, bones and joints.<sup>1</sup> SAPHO syndrome shares a variety of features with the seronegative spondyloarthropathies (SpAs), such as psoriatic arthritis (PsA).<sup>1</sup> While the extra-articular manifestations of PsA are well defined, the systemic involvements of SAPHO syndrome are only reported occasionally.<sup>2</sup> Previous cases of accompanied pleural effusion<sup>3, 4</sup> and organising pneumonia(<sup>5</sup>were reported. In clinical work, we observed that pulmonary lesions progressed when diseases aggravated. However, the relationship between pulmonary manifestations and diseases activity remains unclear. <h3>Objectives</h3> This study is to explore the pulmonary comorbidity with SAPHO syndrome. <h3>Methods</h3> Pulmonary HRCT images were reconstructed from whole-spine CT images in 67 SAPHO patientsHRCT images of 58 healthy controls were obtained and reviewed. Pneumonia and tuberculosis were excluded. We investigated the presence of different HRCT images findings with detailed examinations. <h3>Results</h3> In detailed HRCT evaluations, abnormalities were identified in 45 of all patients. We found stripe in 29 (43.3%) cases, patchy shadows in 22 (32.8%), ground-glass opacity in 11 (16.4%), pleural thickening in 9 (13.4%), solitary nodule in 6 (9%), bronchiectasis in 3 (4.5%), pulmonary bulla in 2 (3%), multiple nodules in 1 (1.5%), and interstitial change in 1 (1.5%). Compared with healthy controls, SAPHO patients have significantly higher rate of patchy shadows while significantly lower percentage of nodules (especially multiple nodules), although the overall rates of abnormal HRCT findings are similar. <h3>Conclusions</h3> Our study was the first to study HRCT pulmonary changes in SAPHO patients. SAPHO patients have significantly higher percentage of patchy shadows and significantly lower rate of pulmonary nodules than healthy controls. BASDAI and age are possible good predictors for abnormal HRCT pulmonary findings. <h3>References</h3> [1] Nguyen MT, Borchers A, Selmi C, et al. The SAPHO syndrome. Semin Arthritis Rheum2012;42(3):254–65. [2] Rozin AP, Hasin T, Toledano K, et al. Seronegative polyarthritis as severe systemic disease. Neth J Med2010;68(6):236–41. [3] Fernandez-Campillo J, Garcia-Pachon E. Pleural effusion associated with the SAPHO syndrome. Chest. 2001;120(5):1752. [4] Hasegawa S, Yabe H, Kaneko N, et al. Synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) Syndrome with Significant Bilateral Pleural Effusions. Intern Med2017;56(20):2779–83. [5] Hameed F, Steer H. A case of bronchiolitis obliterans organising pneumonia associated with SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome. BMJ Case Rep2017;2017. <h3>Disclosure of Interest</h3> None declared
Home Office scraps cap on doctors’ visas
Authors: Abi Rimmer
Journal: BMJ (2018)

The Home Office has announced that it will remove restrictions on the number of tier 2 visas available to doctors and nurses.

The move comes after The BMJ launched its Scrap the Cap campaign (bmj.com/scrap-the-cap) last month, which called for a review of immigration policies so that doctors from overseas who have been offered jobs in the NHS can take up their posts.

The current cap of 20 700 a year on tier 2 skilled worker visas has meant that thousands of visa applications for doctors who had been offered …
Microphysiological systems meet hiPSC technology – New tools for disease modeling of liver infections in basic research and drug development
Authors: Martin Raasch, Enrico Fritsche, Andreas Kurtz, Michael Bauer, Alexander S. Mosig
Journal: Advanced Drug Delivery Reviews (2018)

Complex cell culture models such as microphysiological models (MPS) mimicking human liver functionality in vitro are in the spotlight as alternative to conventional cell culture and animal models. Promising techniques like microfluidic cell culture or micropatterning by 3D bioprinting are gaining increasing importance for the development of MPS to address the needs for more predictivity and cost efficiency. In this context, human induced pluripotent stem cells (hiPSCs) offer new perspectives for the development of advanced liver-on-chip systems by recreating an in vivo like microenvironment that supports the reliable differentiation of hiPSCs to hepatocyte-like cells (HLC). In this review we will summarize current protocols of HLC generation and highlight recently established MPS suitable to resemble physiological hepatocyte function in vitro. In addition, we are discussing potential applications of liver MPS for disease modeling related to systemic or direct liver infections and the use of MPS in testing of new drug candidates.