tbuckley/cabot-search huggingface dataset:
AB0385 Tofacitinib in Rheumatoid Arthritis: Results of Post-Approval Investigator Initiated Trial: Table 1
Authors: D. Karateev, E. Luchikhina, D. Abdulganieva, S. Lapshina, A. Baranov, N. Lapkina, D. Petrov, O. Ivanova, T. Salnikova, V. Sorotskaya, O. Semagina, V. Mazurov, R. Samigullina, D. Chakieva, A. Babaeva, E. Kalinina, A. Sizikov, O. Chumasova, N. Demidova, A. Misiyuk, E. Nasonov
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Tofacitinib (TOFA) was approved in Russia for treatment of patients with rheumatoid arthritis (RA) in 2013, but published information about its post-approval use limited to some individual clinical observations. <h3>Objectives</h3> To study the efficacy and safety of TOFA in patients with severe active RA in clinical practice. <h3>Methods</h3> We present the preliminary results of ongoing investigator initiated study "Local open label multicenter observational study of efficacy and safety of Tofacitinib in patients with active rheumatoid arthritis with insufficient response to DMARDs", a part of a research program "Russian investigation of methotrexate and biologics in early active inflammatory arthritis" (REMARCA). We included 120 patients (pts) with severe active RA (97 females, 23 males), with median age 51,0 [41,25; 59,0] years and disease duration 60,0 [24,25; 120,0] months, 92 (76,7%) RF positive, 91 (75,8%) ACPA positive, who were non-responders to methotrexate (MTX) at least 15 mg/week and/or other synthetic DMARDs, and biological DMARDs (b-DMARDs). 9 of 30 b-DMARDs non-responders had 2–4 biologics in history. Tuberculin test and chest X-ray were performed in all pts before TOFA prescription. We use TOFA in all the pts in starting dose 5 mg BID per os with possibility to increase the dose to 10 mg BID if needed. The use of TOFA in combination or as monotherapy was a prerogative of the rheumatologist. By January 2016, 91 patients received TOFA for 3 months and 55 pts – for 6 months. <h3>Results</h3> TOFA used in combination with MTX in 84 (70%) pts, with Leflunomide in 12 (10%), as monotherapy – in 24 (20%) pts. Dose escalation to 10 mg BID was carried out in 25 (20,8%) pts. Results presented in the table. 20 episodes of adverse events (AEs) in 14 pts observed: liver test 2-fold elevation – 4 cases, Herpes simplex – 3, skin rash – 2, erysipelas – 1, Herpes zoster – 1, latent TB activation – 1, bronchitis – 1, nasopharyngitis – 1, cystitis – 1, hemorrhoids – 1, headache – 1, nausea – 1. No serious AEs were reported. TOFA has been withdrawn in 4 pts: three due to lack of efficacy, one due to allergic skin rash. <h3>Conclusions</h3> TOFA was effective in clinical practice for control of disease activity in patients with severe RA with multiple resistance to synthetic and biological DMARDs during short-term follow up. Safety was satisfactory; there were no cases of serious AEs. <h3>Acknowledgement</h3> Trial State registration number: 01201454666 (http://www.rosrid.ru/search). This scientific study was supported by Pfizer educational grant. <h3>Disclosure of Interest</h3> None declared
Comparison of Prognostic Models for Autologous Hematopoietic Stem Cell Transplantation (AHCT) for Relapsed Hodgkin Lymphoma.
Authors: Theresa Hahn, Philip L. McCarthy, Jeanette Carreras, Mei-Jie Zhang, Hillard M. Lazarus, Ginna G. Laport, Silvia Montoto, Parameswaran N Hari
Journal: Blood (2009)
Lower Dose of Imatinib Provides Outcomes Similar to the Standard Dose Imatinib in Japanese Patients with Early Chronic-Phase CML: The Interim Analyses of JALSG CML202 Study.
Authors: Kazunori Ohnishi, Miki Nishimura, Jin Takeuchi, Shin Fujisawa, Tadashi Nagai, Koichi Miyamura, Yukihiko Kimura, Fumiharu Yagasaki, Hideki Akiyama, Noriko Usui, Shigeki Ohtake
Journal: Blood (2007)
OC-049 Sessile Serrated Lesions: Easily Missed in a Heterogenous Cohort?: Abstract OC-049 Table 1
Authors: S Subramaniam, M Mitchison, M Rodriguez-justo, R Vega
Journal: Gut (2016)

<h3>Introduction</h3> Colorectal cancer is now thought to arise from more than one molecular pathway. Lately, the serrated pathway has been placed in the limelight as it may account for 20–30% of colorectal cancers. However, sessile serrated lesions are easily missed on colonoscopy and in histopathological analysis despite their neoplastic potential. We conducted an observational study to understand the presentation, characteristics and significance of sessile serrated lesions detected in colonoscopies done for a variety of indications. <h3>Methods</h3> A retrospective analysis of all sessile serrated lesions identified through the colorectal histopathological database from January 2012 – March 2015 was performed in our tertiary centre. Histology was reported by specialist gastrointestinal pathologists as per national standards. <h3>Results</h3> 138 colonoscopies were performed in 118 patients who were found to have sessile serrated lesions. The table below shows the breadth of indications for colonoscopy in these cases. A total of 351 serrated lesions were noted, with just over half in the right colon (180/351, 51.3%). 67/351 polyps were &gt;1 cm in size. 42/118 patients did have polyps noted on previous colonoscopies (19 had serrated lesions). The prevalence of co-existing adenomas in this cohort was 50% (59/118). A subgroup analysis identified 13 patients in the entire cohort who met the WHO criteria for serrated polyposis syndrome. 4 of these patients (4/13; 30.8%) had been diagnosed with colorectal cancer in the past compared with 16/105 (15.2%) in the non serrated polyposis syndrome group. Only 8/13 patients underwent genetic screening and of this, 2 had hyperplastic polyposis syndrome and 2 had MYH polyposis. <h3>Conclusion</h3> This large series of sessile serrated lesions has demonstrated the heterogeneity of circumstances in which they are detected during colonoscopy. Only 16% of patients were found to have serrated lesions on a previous colonoscopy. This may indicate that a large proportion of these polyps were missed or not recognised previously. A small proportion of these patients will have a serrated polyposis syndrome that increases their colorectal cancer risk even further and genetic screening is advocated in all these patients. <h3>Disclosure of Interest</h3> None Declared
Steroid-induced Deficiency of Mucosal-associated Invariant T Cells in the Chronic Obstructive Pulmonary Disease Lung. Implications for Nontypeable <i>Haemophilus influenzae</i> Infection
Authors: Timothy S. C. Hinks, Joshua C. Wallington, Anthony P. Williams, Ratko Djukanović, Karl J. Staples, Tom M. A. Wilkinson
Journal: American Journal of Respiratory and Critical Care Medicine (2016)

Mucosal-associated invariant T (MAIT) cells are a recently described abundant, proinflammatory T-cell subset with unknown roles in pulmonary immunity. Nontypeable Haemophilus influenzae (NTHi) is the leading bacterial pathogen during chronic obstructive pulmonary disease (COPD) exacerbations and is a plausible target for MAIT cells.To investigate whether MAIT cells respond to NTHi and the effects of inhaled corticosteroids (ICS) on their frequency and function in COPD.Eleven subjects with COPD receiving ICS, 8 steroid-naive subjects with COPD, and 21 healthy control subjects underwent phlebotomy, sputum induction, bronchoalveolar lavage, and endobronchial biopsy. Pulmonary and monocyte-derived macrophages were cultured in vitro with NTHi.Frequencies of Vα7.2+CD161+ MAIT cells, surface expression of the major histocompatibility complex-related protein 1 (MR1), and intracellular IFN-γ expression were measured by flow cytometry. MAIT-cell frequencies were reduced in peripheral blood of ICS-treated subjects with COPD (median 0.38%; interquartile range [IQR], 0.25-0.96) compared with healthy control subjects (1.8%; IQR, 1.4-2.5; P = 0.001) or steroid-naive patients with COPD (1.8%; IQR, 1.2-2.3; P = 0.04). MAIT cells were reduced in bronchial biopsies from subjects with COPD treated with steroids (0.73%; IQR, 0.46-1.3) compared with healthy control subjects (4.0%; IQR, 1.6-5.0; P = 0.02). Coculture of live NTHi increased macrophage surface expression of MR1 and induced IFN-γ from CD4 cells and CD8 cells, but most potently from MAIT cells (median IFN-γ-positive frequencies, 2.9, 8.6, and 27.6%, respectively). In vitro fluticasone and budesonide reduced MR1 surface expression twofold and decreased NTHi-induced IFN-γ secretion eightfold.MAIT cells are deficient in blood and bronchial tissue in steroid-treated, but not steroid-naive, COPD. NTHi constitutes a target for pulmonary MAIT-cell immune responses, which are significantly impaired by corticosteroids.
Adult Congenital Heart Disease
Authors: Thomas M. Bashore
Journal: Circulation (2007)

I t has variably been estimated that between 800 000 and 1 million patients with congenital heart disease are now adults and that by 2010 more patients older than 16 years will undergo surgery for congenital heart disease than those younger than 16 years. 1This review will focus on the clinical aspects of identifying and caring for the portion of the unique population that have right ventricular (RV) outflow tract lesions. Clinical Morphology of the RV Outflow TractThe left ventricle (LV) and RV both have inlet, apical, and outlet portions, although they differ considerably. 2The inlet of the RV includes the tricuspid valve, and it is separated from the pulmonary valve (PV) by the crista supraventricularis.This structure results in the PV being raised upward.The apical portion of the RV has coarse trabeculations.As shown in Figure 1, the septum is home to a large septomarginal (septal) trabeculation that divides into the anterior and posterior limbs in the outflow tract.A series of septoparietal trabeculations arise along the free wall.The crista supraventricularis inserts between these limbs and is made up of 3 components: the muscular outlet septum, the ventriculoinfundibular fold, and the inner curvature of the RV. 3 The small part that separates the RV and LV cavities is the outlet or conal septum.A loop including the septal trabeculation, the moderator band, septoparietal trabeculations, and the outlet septum can be conceptualized as circling the RV outflow tract.The PV is supported by the circular muscular infundibulum rising outside the RV proper.Abnormalities involving the RV outflow tract involve malpositioning of 1 or more of these structures.
CBIO-02KYNURENINE 3-MONOOXYGENASE INHIBITION SYNERGIZES WITH THE ALKYLATING CHEMOTHERAPY TEMOZOLOMIDE TO ATTENUATE PROLIFERATION IN HUMAN GLIOBLASTOMA CELLS
Authors: Seray Adams, Sonia Bustamante, illes Guillemin
Journal: Neuro-Oncology (2015)

BACKGROUND: Activation of the kynurenine pathway (KP) in cancer cells suppresses anti-tumor immunity, resulting partly from KP metabolite effects. The KP is the principal route of tryptophan metabolism leading to the production of metabolites, including kynurenine (KYN), anthralinic acid (AA) and nicotinamide adenine dinucleotide (NAD+). Kynurenine 3-monooxygenase (KMO) is a critical enzyme in the KP directly responsible for the production of the immunosuppressive metabolites, 3-hydroxyanthranilic acid (3-HAA) and 3-hydroxykynurenine (3-HK). Inhibition of one of the enzymes that degrades tryptophan in the KP, indoleamine 2,3-dioxygenase (IDO-1), suppresses cancer formation in animal models. However, no studies have evaluated the therapeutic potential of KMO inhibitors in brain cancer. METHODS: The effects of the KMO inhibitor, Ro 61-8048 (Ro), and the chemotherapeutic, temozolomide (TMZ), on glioblastoma (GBM) cell proliferation was evaluated using the MTS assay and GBM cell lines, U87, T98G and U138. KP metabolites were quantified using LC-MS/MS and KMO protein expression was evaluated using western blot. RESULTS: GBM cell lines expressed the KMO protein constitutively and following stimulation with the IDO-1 inducer, IFN-γ. GBM cell lines also produced the KP immunosuppressive metabolites, AA and 3-HK and increased KYN production concomitant with tryptophan catabolism following IFN-γ stimulation. KMO inhibition with Ro caused a dose-dependent decrease in GBM cell line proliferation. Ro also synergized with TMZ to decrease U87 cell proliferation more effectively than Ro treatment alone when cells were stimulated with IFN-γ. CONCLUSIONS: These findings suggest that KMO may play a significant role in GBM cell proliferation and highlight KMO inhibition as a potential new therapy for GBM. Clinically, KMO inhibition may shunt KP metabolism away from the immunosuppressive 3-HK and 3-HAA, restoring anti-tumor immunity while reducing the capacity for malignant cells to produce NAD + , which is necessary for cellular energy production, DNA repair and proliferation.
BCR/ABL-Mediated Myeloid Expansion Is Promoted by C/EBPβ, a Regulator of Emergency Granulopoiesis,
Authors: Yoshihiro Hayashi, Hideyo Hirai, Hisayuki Yao, Satoshi Yoshioka, Sakiko Satake, Naoka Kamio, Yasuo Miura, Eishi Ashihara, Yoshihide Fujiyama, Daniel G. Tenen, Taira Maekawa
Journal: Blood (2011)
PTH-077 Infliximab Antibody Levels May Highlight Ineffective Maintenance Treatment for IBD Patients in Remission
Authors: N Jamieson, H Younger, M Fraser, D Armour, A Watson, L Potts
Journal: Gut (2016)

<h3>Introduction</h3> Maintenance infliximab (IFX) is established as treatment for Crohn’s Disease (CD) and ulcerative colitis (UC). Efficacy is improved with regular dosing to reduce antibody (Ab) development, though antibodies may anyway develop. The optimal time to stop IFX in remission is unknown: there is no reliable guidance to indicate who will relapse. Patients may be reluctant to stop treatment which has served them well despite significant risks and costs in continuing ineffective treatment. The measurement of IFX drug and Ab levels may help decision-making. Undetectable trough drug levels and high antibody levels (IFX-Ab) may suggest ineffective treatment and support stopping IFX in those in remission. Our centre has measured IFX drug and Ab since Sept 2015. We present how this has influenced patient management. <h3>Methods</h3> We studied 80 IBD patients (55 CD/25 UC) receiving regular IFX to maintain remission. IFX trough drug levels and IFX-Ab levels were measured in all patients between Sept and Dec 2015. Samples were analysed at Exeter Clinical Laboratory International. Disease activity was assessed by the Harvey-Bradshaw Index (HBI) at time of last infusion and the most recent faecal calprotectin was recorded for each patient <h3>Results</h3> IFX was given at a median interval of 2 months (range 1–3 months) for a median of 29 months (range 5–130). 39 out of 80 had immunosuppression with azathioprine/6 MP or methotrexate when levels were measured. Eighteen (13 Crohn’s/5 UC) of 80 patients had no detectable IFX in the presence of IFX-Ab (median 328 AU/ml range 12 to &gt;500). This group had a similar duration of treatment (median 25 months range 8–89 months) but were less likely to be on immunosuppressant medication (4/18). Of these 18, 2 were clinically relapsing. The remaining 16 appeared in remission or minimally active (HBI median 1.5, range 0–6 a patient with bile-salt diarrhoea excluded), the median faecal calprotectin levels was 72 µg/g (range &lt;30 to 249) a median of 4 months from measured IFX levels. Results were discussed with patients and the decision made to stop IFX treatment. Immunosuppressant medication was started as appropriate. A further 18 patients had IFX-Ab in the presence of a measurable trough drug level <h3>Conclusion</h3> In 80 IBD patients on maintenance IFX, 16 (20%) had no detectable IFX trough levels but significant levels of IFX-Ab whilst in remission. Routine measurement of IFX levels and Ab as part of routine clinical practice may identify patients receiving no benefit from maintenance therapy, reducing costs, risks and treatment burden. Ongoing study is necessary to determine outcomes of patients stopping biologics and of patients in whom infliximab levels and infliximab antibodies co-exist <h3>Disclosure of Interest</h3> None Declared
Blood Stream Infection after Reduced- Intensity Unrelated Cord Blood Transplantation for Adults with Hematologic Diseases.
Authors: Hiroto Narimatsu, Masahiro Kami, Tomoko Matsumura, Tomohiro Myojo, Kazuhiro Masuoka, Chiho Inokuchi, Koichiro Yuji, Yuji Miura, Eiji Kusumi, Junichi Ueyama, Atsushi Wake, Shigesaburo Miyakoshi, Akiko Yoneyama, Michio Matsuzaki, Shinichi Morinaga, Yoshitomo Muto, Shuichi Taniguchi
Journal: Blood (2004)
Genetic Basis of Myeloid Proliferation Related to Down Syndrome
Authors: Kenichi Yoshida, Tsutomu Toki, Myoung-ja Park, Yusuke Okuno, Yuichi Shiraishi, Masashi Sanada, Ayana Kon, Yasunobu Nagata, Aiko Sato-Otsubo, Yusuke Sato, RuNan Wang, Kiminori Terui, Rika Kanezaki, Norio Shiba, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Daisuke Hasegawa, Kazuhiro Nakamura, Hirokazu Kanegane, Keiko Tsukamoto, Souichi Adachi, Satoru Miyano, Seiji Kojima, Shai Izraeli, Yasuhide Hayashi, Etsuro Ito, Seishi Ogawa
Journal: Blood (2012)
A Combination of Lenalidomide and Rituximab (ReRi) As Salvage Therapy in Elderly Patients Affected By Diffuse Large B Cells (DLBCL) Lymphoma Relapsed and Refractory
Authors: Guido Gini, Caterina Bocci, Michela Sampaolo, Silvia Trappolini, Sonia Cacciagiù, Jacopo Olivieri, Attilio Olivieri, Massimo Offidani, Serena Rupoli, Antonella Poloni, Anna Rita Scortechini, Debora Capelli, Mauro Montanari, Ilaria Scortechini, Pietro Leoni
Journal: Blood (2015)
AB0828 Changing Trends in Radiological Prevalence of Paget's Disease of The Bone in Lancashire, UK
Authors: S. Jmor, A. Chiphang, A. Ahmed, K. Binymin
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> It is widely recognised that the United Kingdom has a very high prevalence of Paget9s disease of the bone (PDB) alongside Western Europe, Australia and New Zealand. In 1980, Barker et al (1), concluded from a meta-analysis of surveys done throughout 31 towns in Britain, that Lancashire showed to be a remarkably localised area of high prevalence of PDB. In 2006, Cooper et al (2) updated the prevalence of PDB in certain British centres and found prevalence rates had fallen by 50%. <h3>Objectives</h3> As there have been no further studies around the Lancashire area since, we aim to build on the current literature and present the prevalence of PDB in some local towns within Lancashire, 20 years later. <h3>Methods</h3> We began with Southport and Ormskirk the NHS trust whose patients are geographically located within the county of Lancashire. A computer generated random sample was listed for all plain x-rays that include entire lumbar vertebrae, pelvis, sacrum and femoral heads in those aged over 55. We identified 1000 patients whose unique hospital numbers were entered into the PACS system to view each x-ray. <h3>Results</h3> Out of 1000 patient x-rays only four were found to have definite evidence of PDB, all confirmed with radiological report. This gives a prevalence rate of 0.4%. Of these, 50% were female and the age ranged from 72–88 years. <h3>Conclusions</h3> Southport and Ormskirk towns lie just on the verge of the Lancashire focus (Lancaster, Preston, Bolton, Wigan, Burnley and Blackburn) therefore using the methodology, it was assumed that prevalence rates would be as high (4–8%) as other Lancashire9s towns. (1). Consideration to the high socioeconomic status of many –albeit an older population- that live in the studied area and perhaps other environmental factors might explain the low prevalence (0.4%) of PDB. The influence of genetic factors seems less evident. Additionally, the overall downward trend of prevalence rates in the UK, as hypothesised by Cooper et al (2), could also explain our findings. This is an area that would be useful to investigate in further studies. An initial plan to re-study a high focus area such as Lancaster town, using the same methodology, might be extremely valuable. <h3>References</h3> Barker DJP, Chamberlain AT, Guyer PB, Gardener MJ. Paget9s disease of bone: The Lancashire focus. BMJ. 1980; 280(6222):1105–7 Cooper C, Harvey NC, Dennison EM, van Staa TP. Update on the epidemiology of Paget9s disease of bone. J Bone Miner Res. 2006; 21: 3–8 <h3>Disclosure of Interest</h3> None declared
OP0118 Development of The Eular Recommendations for The Use of Imaging in The Clinical Management of Osteoarthritis
Authors: G. Sakellariou, P.G. Conaghan, W. Zhang, J.W.J. Bijlsma, P. Boyesen, M.A. D'Agostino, M. Doherty, D. Fodor, M. Kloppenburg, J. Maeder, F. Miese, E. Naredo, M. Porcheret, A. Iagnocco
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> The increased availability of modern imaging in clinical practice has led to its more extensive use. In the field of osteoarthritis (OA), recommendations on the use of imaging in clinical trials have been developed, but there has been less focus on routine clinical management. <h3>Objectives</h3> To develop evidence-based recommendations for the use of imaging in the clinical management of OA. <h3>Methods</h3> A task force convened by the European League Against Rheumatism including rheumatologists, radiologists, generalists, methodologists and patients from 9 countries developed recommendations based on both evidence obtained through systematic literature review (SLR) and expert opinion. The task force initially identified the areas of application of imaging in OA and developed research questions to drive the SLR. Imaging modalities included were conventional radiography, ultrasound, magnetic resonance imaging, computed tomography, radioisotope scan. Anatomical areas of interest were knee, hip, hand and foot. Based on the priorities identified by the task force, the role of imaging in making a diagnosis of OA and identifying OA features (including soft tissue, bone and cartilage involvement), in detecting alternative diagnoses, the impact of imaging on disease management, in defining prognosis (natural history of the disease and response to treatment), in the follow up of the disease and to guide treatment were addressed. Research evidence was searched systematically for each question and separately for each anatomic area using PubMed and Embase. <h3>Results</h3> The systematic review retrieved 6858 references, after the assessment of 1317 full papers, 380 studies were included. The results of the systematic review were presented to the task force, and consensus recommendations derived. These cover areas such as (exact wording not included for brevity reasons): the lack of need for imaging in diagnosis of patients who present with usual OA symptoms; role of imaging in differential diagnosis; consideration of the challenges in using imaging for routine monitoring of OA where there is no change in clinical status; what should be the feasible first choice modality and what issues were relevant to how images were acquired; how anatomical site of OA may influence use and type of imaging; and the role of imaging and intra-articular injection. Significant gaps in the literature underpinned the recommendations for future research that were also developed. <h3>Conclusions</h3> Based on the results of a SLR and expert opinion, recommendations on the use of imaging in the clinical management of OA were developed. <h3>Disclosure of Interest</h3> None declared