tbuckley/cabot-search huggingface dataset:
Imaging matrix metalloproteinase activity in multiple sclerosis as a specific marker of leukocyte penetration of the blood-brain barrier
Authors: Hanna Gerwien, Sven Hermann, Xueli Zhang, Eva Korpos, Jian Song, Klaus Kopka, Andreas Faust, Christian Wenning, Catharina C. Gross, Lisa Honold, Nico Melzer, Ghislain Opdenakker, Heinz Wiendl, Michael Schäfers, Lydia Sorokin
Journal: Science Translational Medicine (2016)

The enzymes gelatinase A/matrix metalloproteinase-2 (MMP-2) and gelatinase B/MMP-9 are essential for induction of neuroinflammatory symptoms in experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis (MS); in the absence of these enzymes, the disease does not develop. We therefore investigated the cellular sources and relative contributions of MMP-2 and MMP-9 to disease at early stages of EAE induction. We demonstrated that MMP-9 from an immune cell source is required in EAE for initial infiltration of leukocytes into the central nervous system and that MMP-9 activity is a reliable marker of leukocyte penetration of the blood-brain barrier. We then developed a molecular imaging method to visualize MMP activity in the brain using fluorescent- and radioactive-labeled MMP inhibitors (MMPis) in EAE animals and used the radioactive MMP ligand for positron emission tomography (PET) imaging of MMP activity in patients with MS. In contrast to traditional T1-gadolinium contrast-enhanced MRI, MMPi-PET enabled tracking of MMP activity as a unique feature of early lesions and ongoing leukocyte infiltration. MMPi-PET therefore allows monitoring of the early steps of MS development and provides a sensitive, noninvasive means of following lesion formation and resolution in murine EAE and human MS.
Epigenomic Profiling of Human CD4+ T Cells Supports a Linear Differentiation Model and Highlights Molecular Regulators of Memory Development
Authors: Pawel Durek, Karl Nordström, Gilles Gasparoni, Abdulrahman Salhab, Christopher Kressler, Melanie de Almeida, Kevin Bassler, Thomas Ulas, Florian Schmidt, Jieyi Xiong, Petar Glažar, Filippos Klironomos, Anupam Sinha, Sarah Kinkley, Xinyi Yang, Laura Arrigoni, Azim Dehghani Amirabad, Fatemeh Behjati Ardakani, Lars Feuerbach, Oliver Gorka, Peter Ebert, Fabian Müller, Na Li, Stefan Frischbutter, Stephan Schlickeiser, Carla Cendon, Sebastian Fröhler, Bärbel Felder, Nina Gasparoni, Charles D. Imbusch, Barbara Hutter, Gideon Zipprich, Yvonne Tauchmann, Simon Reinke, Georgi Wassilew, Ute Hoffmann, Andreas S. Richter, Lina Sieverling, Hyun-Dong Chang, Uta Syrbe, Ulrich Kalus, Jürgen Eils, Benedikt Brors, Thomas Manke, Jürgen Ruland, Thomas Lengauer, Nikolaus Rajewsky, Wei Chen, Jun Dong, Birgit Sawitzki, Ho-Ryun Chung, Philip Rosenstiel, Marcel H. Schulz, Joachim L. Schultze, Andreas Radbruch, Jörn Walter, Alf Hamann, Julia K. Polansky
Journal: Immunity (2016)
SAT0216 Chest Ultrasound Signs of Interstitial Lung Disease in Systemic Sclerosis Patients: A Comparison between High Resolution Chest Computed Tomography Findings
Authors: C. Rotondo, A. Chialà, M. Nivuori, L. Coladonato, M. Giannini, M.G. Anelli, G. Righetti, C. Scioscia, C. Fiorentini, G. Lopalco, G. Lapadula, F. Iannone
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Interstitial lung disease (ILD) is a typical clinical manifestation in Systemic Sclerosis (SSc). The high resolution chest computed tomography (HRCT) is the gold standard to evaluate and grade ILD. The presence of fibrotic tissue in the lung, or other structures beside the air, allows obtaining specific sonography images (such as ultrasound lung comet, higher pleural line thickness, irregular pleural margins and subpleural cysts) by chest ultrasound. In previous studies it was demonstrated that the ultrasound comets number increases in SSc patients. <h3>Objectives</h3> We aimed at correlating the specific lung sonography signs with ground glass and honeycombing pattern detected by chest HRCT. <h3>Methods</h3> A total of 60 SSc outpatients (54 female, mean age 56,2 ± 13,8 ys and disease duration of 9,57±8,7 ys), who fulfilled ACR/EULAR 2013 SSc classification criteria, were recruited. All patients underwent chest HRCT and US examination. The US examination was performed with 7,5 Mhz probe and conducted with patients in sitting position from paraspinal line to anterior axillary line, for each intercostals space. The presence of typical ultrasound signs as lung comets (pathological if &gt;35), higher pleural line thickness (pathological if &gt;2mm), irregular pleural margins, subpleural cysts and pleural effusion was detected. The sensitivity, specificity and accuracy of US patterns (compared to chest HRTC) were evaluated by ROC analysis. Statistic significance was set at p&lt;0.05. All results are expressed as mean ± 1 standard deviation. <h3>Results</h3> 23 patients had the CT honeycombing pattern, of which 92% had the US irregular pleural margins, 70% had US higher pleural line thickness and sub-pleural cysts, just 54% had US lung comets. 16 patients had the CT ground glass pattern, of these in 94% the US irregular pleural margins, in 87% US lung comets, in 60% US higher pleural line thickness were found. As regard the CT ground glass pattern the US sign with the highest specificity (91%), sensibility (85,7%) and accuracy (88%) was the lung comets; while regarding the CT honeycombing pattern the US sign with the highest specificity (92%), sensibility (69,6%) and accuracy (82%). <h3>Conclusions</h3> The lung US is a good diagnostic technique for its repeatability, low cost and risklessness. Although HRCT remains the best imaging technique to assess the ILD, in SSC the lung US could be a useful tool to detect the presence or the evolution of ILD and to improve the timing of HRTC without exposing the patients to high radiation doses over time. <h3>Disclosure of Interest</h3> None declared
Biologic Features and Clinical Outcomes According to Age Groups In Myelodysplastic Syndrome
Authors: Seungbum Lee, Je-Hwan Lee, Jung-Hee Lee, Dae-Young Kim, Sung-Doo Kim, Sung-Nam Lim, Yunsuk Choi, Young-Hoon Park, Miee Seol, Young-Shin Lee, Young-Ah Kang, Mijin Jeon, Kyoo-Hyung Lee
Journal: Blood (2010)
AB0683 Hip Involvement in Spondyloarthritis Patients: A Frequent and Serious Manifestation
Authors: F. Aguiar, T. Martins-Rocha, R. Fonseca, A. Bernardo, I. Brito
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The prevalence of hip involvement in spondyloarthritis (SpA) patients varies from 7–50%. It is a cause of significant functional impairment and a marker of poor prognosis. <h3>Objectives</h3> The aim of this study was to compare demographic, clinical, laboratory and treatment data among SpA patients with and without hip involvement. <h3>Methods</h3> Cross-sectional study including 187 SpA patients that fullfilled the modified New York criteria. The patients completed a questionnaire assessing age at diagnosis, disease subtype, clinical presentation, disease-activity (BASDAI, ASDAS) and functional-indices (BASFI) and BASMI was calculated. The patients9 records were consulted to asses the following parameters: presence of HLA-B27 antigen, inflammatory markers (ESR, CRP), radiographs of spine, hip and sacroiliac joints. Hip involvement was considered based on the BASRI-hip scoring system (hip involvement if ≥2). The statistical analysis was performed using SPSS 21.0 software, and <i>p</i>&lt;0.05 was taken to indicate statistical significance. To compare the differences between the groups, Mann-Whitney U, χ<sup>2</sup> and Fisher tests were used. <h3>Results</h3> 187 patients were included, with 55.6% males, median age 46.0 (range 21.0–79.0) years. In this study 75 (40.1%) patients had hip involvement, which was significantly more frequent in males (46.1% vs 32.5%, p=0.041). There were no statistically significant differences in age at diagnosis, age at evaluation, time of diagnosis, smoking habits, subtype of SpA, extra-articular manifestations or HLA-B27 positivity. Ankylosis of bilateral sacroiliac joints and syndesmophytosis were significantly more frequent in patients with hip involvement (56.2 vs 28.8% p&lt;0.001 and 57.3% vs 38.7% p=0.009). Median disease duration was significantly greater in SpA patients with hip involvement (19.0 vs 14.0 years, p=0.001). BASMI, BASFI and ASDAS-CRP were significantly higher in patients with hip involvement (median 5.0 vs 3.8, p&lt;0.001; median 5.1 vs 3.3, p=0.001 and 2.4 vs 2.0, p=0.038, respectively). Median BASDAI and ASDAS-ESR were also higher in these patients but this difference was not statistically significant (3.3 vs 2.8, p=0.361 and 2.3 vs 2.1 p=0.318, respectively). There were no differences in what concerns SpA treatment between the two groups. <h3>Conclusions</h3> This study shows that radiographic hip involvement is a frequent disease manifestation in SpA, and that it could be more common in male patients with long-standing disease. It also confirms that hip involvement reflects more severe disease, as it is associated with more axial damage and functional impairment. <h3>Disclosure of Interest</h3> None declared
PTH-078 Increasing Adherence to BSG Guidelines for Cancer Surveillance in IBD - Effective Strategies
Authors: RN Patel, O Mogwanja, Y El-Gazzar
Journal: Gut (2016)

<h3>Introduction</h3> Colorectal cancer (CRC) is the fourth commonest cancer worldwide. Inflammatory bowel disease (IBD) is one of the many risk factors. Ulcerative colitis (UC) and Crohn’s colitis both increase the risk of developing CRC by greater than 15 fold compared to the population without IBD. The National Institute for Health and Care Excellence (NICE) produced evidence-based recommendations in 2011 on the colonoscopic surveillance for prevention of CRC in people with UC, Crohn’s disease or adenomas. These are broadly consistent with those in the BSG 2010 guidelines. One of the key recommendations is that chromoscopy (pan-colonic dye spray) is the technique of choice. <h3>Methods</h3> We compared results from two audits (2012/13 and 2014/15) performed at Barking, Havering and Redbridge University Hospitals (BHRUH), each assessing adherence to the key features of the BSG guidelines. The interventions made between auditing included; adding a ‘surveillance’ option to the endoscopy request form, specifying ‘dye spray’ on the request and clerical staff dedicating 3 points (i.e more time) to perform the procedure. <h3>Results</h3> 100 patients undergoing surveillance colonoscopy from September 2014 to August 2015 at BHRUH (49% male, 65% UC) were analysed compared with 35 patients in the period September 2012 to August 2013 (66% male, 97% UC). The number of chromoscopies performed for CRC surveillance in IBD patients increased from 1 in the initial audit to 30 in the follow up audit, after implementation of changes (p = 0.003). 23% of colonoscopies were performed in patients with less than 10 years duration of disease in the first audit compared with 9% in the second (p = 0.03). Polyps and dysplasia were identified in 20% and 8.6% of patients in 2013, respectively. This is compared to 31% (p = 0.21) and 8% (p = 0.91)in 2015. <h3>Conclusion</h3> Adaptations to the way in which endoscopies are requested at BHRUH along with increased awareness amongst clerical staff booking the more time consuming surveillance colonoscopy has resulted in a significant increases in chromoscopy rates. However, there has not been a corresponding increase in the number of polyps or adenomas detected. This may be explained by the overall improvement in the quality of white light endoscopy and technical ability of endoscopists. Further work comparing chromoscopy, narrow band imaging and white light endoscopy in the detection of early cancers in IBD is required. <h3>References</h3> 1 Colonoscopic surveillance for prevention of colorectal cancer in people with ulcerative colitis, Crohn’s disease or adenomas. NICE Guidelines, 2011. 2 Guidelines for colorectal cancer for screening and surveillance in moderate and high risk groups (update from 2002). BSG Guidelines, 2010. <h3>Disclosure of Interest</h3> None Declared
Selective Clearance of Chronic Lymphocytic Leukemia Cells in Vivo Following Treatment with UC99961, an Anti-ROR1 Monoclonal Antibody
Authors: Eva Hellqvist, Christina C.N. Wu, George F. Widhopf, Alice Shih, Rommel Tawatao, Fitzgerald Lao, Bing Cui, Charles Prussak, Anil Sadarangani, Dennis A. Carson, Catriona Jamieson, Thomas J. Kipps
Journal: Blood (2012)
Changes In Incidence and Causes of Non-Relapse Mortality (NRM) After Allogeneic Hematopoietic Cell Transplantation (allo-HCT): Are Transplants Improving?
Authors: Saiko Kurosawa, Kimikazu Yakushijin, Takuhiro Yamaguchi, Yoshiko Atsuta, Tokiko Nagamura-Inoue, Hideki Akiyama, Shuichi Taniguchi, Koichi Miyamura, Satoshi Takahashi, Tetsuya Eto, Yasuo Morishima, Hisashi Sakamaki, Takahiro Fukuda
Journal: Blood (2010)
Pharmacological Chaperone Therapy for the Treatment of Gaucher Disease: Results of Phase 1 Clinical Trials and a Clinical Ex Vivo Response Study with a Survey of Blood Markers for 53 Gaucher Patients.
Authors: Neal J. Weinreb, G.A. Grabowski, G.M. Pastores, P.M. Fernhoff, P.B. Kaplan, D. Palling, C.W. Pine, B.E. Raines, F. Insinga, D.J. Lockhart, H.V. Do, B.A. Wustman
Journal: Blood (2007)
Unraveling the role of preexisting immunity in prostate cancer patients vaccinated with a HER-2/neu hybrid peptide
Authors: Ioannis F. Voutsas, Eleftheria A. Anastasopoulou, Panagiotis Tzonis, Michael Papamichail, Sonia A. Perez, Constantin N. Baxevanis
Journal: Journal for ImmunoTherapy of Cancer (2016)

Cancer vaccines aim at eliciting not only an immune response against specific tumor antigens, but also at enhancing a preexisting immunity against the tumor. In this context, we recently reported on the levels of preexisting immunity in prostate cancer patients vaccinated with the HER-2 hybrid peptide (AE37), during a phase I clinical trial. The purpose of the current study was to correlate between preexisting immunity to the native HER-2 peptide, AE36, and expression of HLA-A2 and -A24 molecules with the clinical outcome. Additionally, we investigated the ability of the AE37 vaccine to induce an antitumor immune response against other tumor associated antigens, not integrated in the vaccine formulation, with respect to the clinical response.We analyzed prostate cancer patients who were vaccinated with the AE37 vaccine [Ii-Key-HER-2/neu(776-790) hybrid peptide vaccine (AE37), which is a MHC class II long peptide vaccine encompassing MHC class I epitopes, during a phase I clinical trial. Preexisting immunity to the native HER-2/neu(776-790) (AE36) peptide was assessed by IFNγ response or dermal reaction at the inoculation site. Antigen specificity against other tumor antigens was defined using multimer analysis. Progression free survival (PFS) was considered as the patients' clinical outcome. Two-tailed Wilcoxon signed rank test at 95 % confidence interval was used for statistical evaluation at different time points and Kaplan-Meier curves with log-rank (Mantel-Cox) test were used for the evaluation of PFS.Preexisting immunity to AE36, irrespectively of HLA expression, was correlated with longer PFS. Specific CD8+ T cell immunity against E75 and PSA146-151 (HLA-A2 restricted), as well as, PSA153-161 (HLA-A24 restricted) was detected at relatively high frequencies which were further enhanced during vaccinations. Specific immunity against PSA153-161 correlated with longer PFS in HLA-A24+ patients. However, HLA-A2+ patients with high preexisting or vaccine-induced immunity to E75, showed a trend for shorter PFS.Our data cast doubt on whether preexisting immunity or epitope spreading specific for HLA-class I-restricted peptides can actually predict a favorable clinical outcome. They also impose that preexisting immunity to long vaccine peptides, encompassing both HLA class II and I epitopes should be considered as an important prerequisite for the improvement of future immunotherapeutic protocols. Protocol ID Code: Generex-06-07 National Organization for Medicines (EOF) ID Code: IS-107-01-06 NEC Study Code: EED107/1/06 EudraCT Number: 2006-003299-37 Date of registration: 07/06/2006 Date of enrolment of the first participant to the trial: Nov 1st, 2007.
AB0450 Systemic Lupus Erythematosus: A French Experience for 6 Years of Multidisciplinary Consultation in Brest
Authors: G. Carvajal Alegria, C. Capaldo, A.-M. Roguedas-Contios, C. Hanrotel, M. Pluchon, E. Pasquier, Y. Renaudineau, S. Jousse-Joulin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a complex disease and its diagnosis and treatment can require multiple capabilities easily available for the patients. <h3>Objectives</h3> Our objective was to set up a multidisciplinary consultation enabling patient support in occidental Brittany. <h3>Methods</h3> Given the complexity for the management of patients with systemic lupus erythematosus (SLE), a multidisciplinary consultation was set up to ensure optimal care for SLE patients at Brest University Medical School. This consultation was set on a quarterly base and gather rheumatologists, dermatologists, nephrologists, gynecologists and internal medicine physicians. A close collaboration with the immunology laboratory for biological diagnosis and follow-up was also set up. Clinical and biological data were collected. <h3>Results</h3> Of the 49 SLE patients followed since 2009, 45 were women (91.8%). The mean age was 47.1±17.7 years. Eighteen patients had malar rash (37.5%), 21 (43.8%) photosensitivity, 7 (14.6%) oral ulcers, 6 (12.5%) alopecia, 43 (89.6%) diffuse articular pain or arthralgia, 10 (20.8%) tenosynovitis, 15 (31.25%) lupus glomerulonephritis, 7 (14.3%) pericarditis, 2 (4%) cardiac vegetations, and 3 (6.1%) pleurisy. The mean SLEDAI score was 2.7±3.5, with values ranging from 0 to 17. Twenty patients were referred for diagnostic opinions (40.8%), 31 (63.3%) for therapeutic advice, 3 (6%) for pregnancy monitoring, and 16 (32.6%) for comorbidities management. The main comorbidities were cardiovascular risk factors and osteoporosis. <h3>Conclusions</h3> In conclusion, the multidisciplinary consultation helps to provide diagnostic and therapeutic aid due to the presence of experts from several disciplines. Patient enrollment for several services enables the creation of a valuable database whose analysis is ongoing. <h3>Disclosure of Interest</h3> None declared
OP0290 Ox40l Blockade Protects against Skin and Lung Inflammation-Driven Fibrosis
Authors: M. Elhai, J. Avouac, A.-M. Hoffmann-Vold, J. Sadoine, T. Guilbert, H. Akiba, V. Heissmeyer, A. Subramaniam, R. Resnick, G. Chiocchia, Y. Allanore
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Systemic sclerosis (SSc) is a severe fibrotic disease with no effective treatment. The OX40-OX40L axis is emerging as a new potential target in autoimmune diseases offering the advantage of a targeted approach on co-stimulatory signals with limited impact on the whole immune response and very preliminary data suggested its involvement in SSc. <h3>Objectives</h3> To investigate the contribution of OX40L in SSc <h3>Methods</h3> We assessed the expression of OX40L in fibrotic skin and in the serum of SSc-patients. The efficacy of a targeted therapy against OX40L <i>in vivo</i> was evaluated using complementary experimental mouse models. <h3>Results</h3> Expression of OX40L protein was higher in fibrotic skin of SSc-patients as compared to healthy controls (p=0.003), particularly in diffuse cutaneous forms. Soluble OX40 levels were significantly higher in SSc-patients (n=177) than in healthy controls (n=100). Longitudinal analyses of our cohort showed that high level of serum OX40L at baseline was highly predictive of worsening of dermal and lung fibrosis during the follow-up (HR: 8.28 [2.11–32.50] and 4.60 [1.52–12.18], P&lt;0.001). This was confirmed in a replication Norwegian cohort (n=241) dedicated to lung fibrosis analysis. In this cohort, in multivariate analyses, OX40L was a strong predictor of lung fibrosis including known risk factors for lung fibrosis. Invalidation of OX40L prevented dermal fibrosis in the bleomycin mouse model with a decrease in dermal thickness, hydroxyprolin content and myofibroblasts count. OX40L invalidation was associated with a decrease in T cell, B cell and macrophage infiltrates and in cytokine release (IL-6, TNF-α) in lesional skin of mice. A transcriptomic approach identified two main pathways regulated by OX40L blockade: NF kappa B and AP 1 signaling. Then pharmacologic approaches, using a monoclonal anti-OX40L antibody, demonstrated that the blockade of OX40L not only prevented dermal fibrosis, but also induced regression of established fibrosis. Thereafter, the use of this monoclonal antibody demonstrated in the fra-2 transgenic mouse model marked protection from fibrosing alveolitis (measured by CT-scan (Figure) and histology) and vessel remodeling leading to pulmonary arterial hypertension. <h3>Conclusions</h3> Altogether, our results show that OX40L is as an attractive target in inflammation-driven fibrosis. OX40L appears as a very promising biomarker in SSc and an appealing potential therapy to reduce both skin and lung fibrosis. <h3>Disclosure of Interest</h3> None declared
BALB/c- Specific L29V Polymorphism In SIRPA Determines The Efficient Engraftment Of Human Hematopoiesis In Xenogeneic Model
Authors: Chika Iwamoto, Katsuto Takenaka, Shingo Urata, Takahiro Shima, Takuji Yamauchi, Takuro Kuriyama, Shinya Daitoku, Yasuyuki Saito, Katsuhiko Itoh, Junji Kishimoto, Daisuke Kohda, Takashi Matozaki, Koichi Akashi
Journal: Blood (2013)
Ferrocenyl Nucleoside Analogs, a New Class of Cytostatic Drugs, Overcome Multiple Drug Resistance in Acute Lymphoplastic Leukemia Ex Vivo.
Authors: Aram Prokop, Moritz Eissmann, Patrick Jesse, Guenter Henze, Philippe James, Joerg Neudoerfl, Hans-Guenther Schmalz
Journal: Blood (2006)
Sixty seconds on . . . cryopreservation
Authors: Susan Mayor
Journal: BMJ (2016)

So did we. Many scientists say that marketing life after death by freezing bodies is downright exploitation and should be banned. But a landmark legal ruling last week propelled cryogenics into the limelight after a 14 year old girl became the first British child to have her body frozen after dying from cancer.1

After a doctor pronounces a person dead they are cooled rapidly with iced water. The Cryonics Institute near Detroit (www.cryonics.org), one of …
Patients taking dabigatran to prevent stroke should avoid simvastatin and lovastatin, study suggests
Authors: Barbara Kermode-Scott
Journal: BMJ (2016)

Patients taking the direct acting anticoagulant dabigatran for stroke prevention should not also take the statins simvastatin or lovastatin, researchers have warned.

A study published in the Canadian Medical Association Journal found that these two commonly used statins, when combined with dabigatran etexilate, increased the risk of major haemorrhage in two population based nested case control studies of over 45 000 patients.1

The Canadian Drug Safety and Effectiveness Research Network team identified 397 cases of ischaemic stroke and 1117 cases of major haemorrhage in 45 991 Ontarian patients over age 65 with non-valvular atrial …