tbuckley/cabot-search huggingface dataset:
SP0120 Recommendations for Prompt Pain Management in Inflammatory Arthritis and Osteoarthritis
Authors: R. Geenen
Journal: Annals of the Rheumatic Diseases (2016)

Pain is a predominant symptom for people with inflammatory arthritis (IA) and osteoarthritis (OA). Health professionals should have knowledge and skills to offer the first principles of assessment and management of pain to people with IA and OA. Aim of the EULAR project was to provide “recommendations” (advice with sufficient evidence) and “points to consider” (advice that cannot be substantiated by data) that enable HPs to provide prompt and knowledgeable pain management support for people with IA or OA. A task force of health professionals, patients and rheumatologists from Europe and the United States considered recommendations and points to consider with respect to 1) background knowledge 2) assessment of the patient and the pain, and 3) management options including core prompt and general pain management that virtually any HP should be able to give and referral to specialized pain management. The detailed recommendations and points to consider will be presented and discussed. <h3>Disclosure of Interest</h3> None declared
Establishment of a Novel Canine Mastocytoma Cell Line, NI-1: a Model for Studying Resistance Against KIT Tyrosine Kinase Inhibitors In Canine Neoplastic Mast Cells
Authors: Emir Hadzijusufovic, Barbara Peter, Harald Herrmann, Karina Schuch, Tuddow Thaiwong, Vilma Yuzbasiyan-Gurkan, Thomas Rülicke, Winfried Pickl, Michael Willmann, Peter Valent
Journal: Blood (2010)
Donor Lymphocyte Infusions (DLI) for the Treatment of Disease Relapse in Hematological Malignancies Following Allogeneic Transplantation: Similar Efficacy Following RIC or Myeloablative Regimen
Authors: Thierry Guillaume, Patrice Chevallier, Sameh Ayari, Jacques Delaunay, Laurence Lode, Francoise Mechinaud, Hervé Avet-Loiseau, Philippe Moreau, Jean Luc Harousseau, Mohamad Mohty
Journal: Blood (2008)
Nix (BNIP3L) Is Downregulated in High-Risk Myelodysplastic Syndromes and Acute Myeloid Leukemia and Its Silencing Enhances Decitabine-Mediated Apoptosis
Authors: Mariana Lazarini, João Agostinho Machado-Neto, Adriana Silva Santos Duarte, Fernando V Pericole, Karla Priscila Ferro, Paula de Melo Campos, Fabiola Traina, Sara T.O. Saad
Journal: Blood (2014)
Fludarabine-Based HLA-Identical Sibling HSCT for Patients with Severe Aplastic Anemia (SAA) Older Than 30 Years: A Study from the French (SFGM-TC) and Italian (GITMO) Registries.
Authors: S. Maury, B. Bruno, Z. Chir, F. Garban, D. Blaise, N. Contentin, H. Esperou, C. Cordonnier, A. Bacigalupo
Journal: Blood (2005)
HER2 Transmembrane Domain (TMD) Mutations (V659/G660) That Stabilize Homo- and Heterodimerization Are Rare Oncogenic Drivers in Lung Adenocarcinoma That Respond to Afatinib
Authors: Sai-Hong Ignatius Ou, Alexa B. Schrock, Eduard V. Bocharov, Samuel J. Klempner, Carolina Kawamura Haddad, Gary Steinecker, Melissa Johnson, Barbara J. Gitlitz, Jon Chung, Paulo V. Campregher, Jeffrey S. Ross, Philip J. Stephens, Vincent A. Miller, James H. Suh, Siraj M. Ali, Vamsidhar Velcheti
Journal: Journal of Thoracic Oncology (2016)

Erb-b2 receptor tyrosine kinase (HER2) transmembrane domain (TMD) mutations (HER2V659E, HER2G660D) have previously been identified in lung adenocarcinomas, but their frequency and clinical significance is unknown.We prospectively analyzed 8551 consecutive lung adenocarcinomas using hybrid capture-based comprehensive genomic profiling (CGP) at the request of the individual treating physicians for the purpose of making therapy decisions.We identified 15 cases (0.18%) of HER2 TMD mutations (HER2V659E/D, HER2G660D) through CGP of 8551 lung adenocarcinomas. HER2 TMD mutations were mutually exclusive from HER2 kinase domain mutations and other oncogenic drivers in lung adenocarcinoma. Only two cases with HER2 TMD mutations (13%) had concurrent Erb-b2 receptor tyrosine kinase 2 gene (HER2) amplification. Structural analysis of HER2 TMD association revealed that mutations at positions V659 and G660 to the highly polar residues glutamic acid, aspartic acid, or arginine should stabilize homodimerization and heterodimerization of HER2 in the active conformation. Treatment with afatinib, a pan-HER inhibitor, resulted in durable clinical response in three of four patients with lung adenocarcinoma, with two harboring HER2V659E and one with double HER2V659E/G660R mutations. HER2 TMD mutations (V659 and G660) are found in other non-NSCLC malignancies, and analogous TMD mutations are also found in EGFR, HER3, and HER4.HER2 TMD mutations represent rare but distinct targetable driver mutations in lung adenocarcinoma. CGP capable of detecting diverse HER2 alterations, including HER2 TMD mutations, should be broadly adopted to identify all patients who may benefit from HER2-targeted therapies.
The Acute Promyelocytic Leukemia-Associated Fusion Protein PML/RAR Blocks t-RA-Induced Differentiation in a Subset of Cells with Stem Cell Potential.
Authors: Xiaomin Zheng, Anita Seshire, Elena Puccetti, Hilal Gul, Tim Beissert, Dieter Hoelzer, Oliver G. Ottmann, Reinhard Henschler, Martin Ruthardt
Journal: Blood (2004)
Prognostic relevance of miRNA let-7e in localized intestinal GIST: A Spanish Group for Research on Sarcoma (GEIS) Study.
Authors: Javier Martin Broto, Antonio Fernandez-Serra, Jose Duran, Silvia Calabuig-Fariñas, Antonio Gutierrez, Irene Felipe-Abrio, Dolors Sanchez-Izquierdo, Javier Martinez-Trufero, Antonio Casado Herraez, Andres Poveda, Luis Rubio Martinez, Carmen Balana, Ferran Losa, Claudia María Valverde, Jordi Rubió, Josefina Cruz, Luis Miguel Gonzalez de Sande, Cristina Tous, Ricardo Cubedo, Jose Antonio Lopez-Guerrero
Journal: Journal of Clinical Oncology (2015)

10524 Background: Risk estimation of recurrence in localized GIST relies on factors as mitosis, size, site or capsule rupture. Recently, genotype has shown to add prognostic value at least in intermediate risk group. Nevertheless, there is a remarkable lack of molecular prognostic variables in localized GIST. We had previously performed miRNA arrays in a subset of localized intestinal GIST comparing relapsed vs no-relapsed patients. We identified let-7e (FC = – 1163.9; p < 0.0001) and miR-550 (FC = +204.2; p < 0.0001) as the most significantly downregulated and upregulated miRNAs respectively. Here we analyze the prognostic role of these miRNA in a validation set (VS) of intestinal GIST Methods: Selection criteria used for VS were intestinal GIST, R0 surgery, no tumor rupture, no adjuvant imatinib and size larger than 2 cm. RNA extraction was performed using the RecoverAll Total RNA Extraction kit (Ambion). The expression of miRNAs was determined by means qRT-PCR using specific Taq-Man probes. let-7e and miR-550 expression levels were categorized as above or below median values. Kaplan–Meier and log-rank test were the statistics used and relapse free survival (RFS) was the clinical endpoint Results: A subset of 112 patients was selected as VS, 23 of which were excluded (metastatic, tumor rupture, etc). Thus, 89 patients were selected, 58 of whom recurred after median follow of 117 months. Median of size and mitoses were 10 cm and 10 x50hpf. In univariate analyses, let-7e showed statistically significant difference in median of RFS: 26 (19.5-32.6) vs 50 (24.6-39.7) months for below and above median values respectively (p = 0.011). For miR-550 no significant differences were seen 35 vs 29 months (p = 0.99). Mitosis ≤ 5/ > 5 with 162 vs 26 months (p = 0.002) and size ≤ 10/ > 10 with 37 vs 29 months (p = 0.05) showed also prognostic relevance. In multivariate analysis, mitosis HR 2.7 (1.4-5.3; p = 0.004) and let-7e HR 2.1 (1.2-3.8, p = 0.009) were independent prognostic factors for RFS Conclusions: miRNA let 7-e has demonstrated to be a relevant prognostic factor for RFS in intestinal GIST patients and deserves to be explored for targeting purposes. A further analysis is planned in a larger series of GIST including also gastric cases
Addition of Fludarabine to Cyclophosphamide Lymphodepletion Improves In Vivo Expansion of CD19 Chimeric Antigen Receptor-Modified T Cells and Clinical Outcome in Adults with B Cell Acute Lymphoblastic Leukemia
Authors: Cameron J Turtle, Laila-Aicha Hanafi, Carolina Berger, Daniel Sommermeyer, Barbara Pender, Emily M Robinson, Katherine Melville, Tanya M Budiarto, Natalia N Steevens, Colette Chaney, Sindhu Cherian, Brent L Wood, Lorinda Soma, Xueyan Chen, Shelly Heimfeld, Michael C Jensen, Stanley R. Riddell, David G Maloney
Journal: Blood (2015)
SAT0453 Does Renin-Angiotensin-Aldosterone System Blockade Influence Pain, Function and Radiographic Progression in Knee Osteoarthritis? An Analysis of Osteoarthritis Initiative Data
Authors: I. Shirinsky, V. Shirinsky
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Renin-angiotensin-aldosterone system (RAAS) has been proposed as a potential target for the treatment of osteoarthritis (OA). In experimental studies, RAAS blockade led to the reduction of inflammation and modulated cartilage metabolism. Recently, a study showed chondroprotective effects of captopril in an animal model of OA [1]. The effects of RAAS blockade on knee OA have never been studied in humans. <h3>Objectives</h3> To investigate longitudinal effects of RAAS blockade on knee pain, function, and radiographic progression of knee OA. <h3>Methods</h3> For the current analysis we used data from the publically available Osteoarthritis Initiative (OAI) database. We assessed longitudinal data from OAI participants who did not use angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) on baseline (new user design) and who had radiographically suspected or confirmed knee OA. The evaluated clinical outcomes were WOMAC pain and WOMAC function subcategories. Radiographic progression was assessed using minimal joint space width (mJSW). The outcomes were measured annually from the baseline to year 4 of follow up. We used structural equation modeling to assess the correlations between the trajectories of ACEI/ARB use and WOMAC knee pain, WOMAC knee function, and mJSW. The models were adjusted for potential baseline confounders. <h3>Results</h3> A sample of 1796 OAI participants was analyzed. The proportion of ACEI/ARB users rose from 4.7% on year 1 to 15.14% on year 4 of follow up. No associations between ACEI/ARB use and knee pain, function, and knee OA radiographic progression trajectories were found in the analyses both adjusted or non-adjusted for baseline covariates. <h3>Conclusions</h3> RAAS system blockade has no influence on knee OA. <h3>References</h3> Tang Y, Hu X, Lu X. Captopril, an angiotensin-converting enzyme inhibitor, possesses chondroprotective efficacy in a rat model of osteoarthritis through suppression local renin-angiotensin system. Int J Clin Exp Med 2015; 8: 12584–12592. <h3>Disclosure of Interest</h3> None declared
Phase I Study of Recombinant Human Interleukin-18 (IL-18) in Combination with Ofatumumab after Autologous Peripheral Blood Stem Cell Transplantation (PBSCT) for Lymphoma
Authors: Michael J. Robertson, Lijun Ni, Jill Weisenbach, David Pelloso, Nagendra K. Prasad
Journal: Blood (2015)
AB0206 Treatment Patterns in Rheumatoid Arthritis after Methotrexate: Data from The Ontario Best Practice Research Initiatives Cohort
Authors: J. Pope, M. Movahedi, A. Cesta, X. Li, S. Couto, J. Sampalis, E. Rampakakis, C. Bombardier
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Guidelines support the use of combination conventional synthetic Disease-Modifying Antirheumatic Drugs (csDMARDs), switching csDMARDs and/or use of biologic DMARDs (bDMARDs) treatment in active rheumatoid arthritis (RA) after use of methotrexate (MTX). <h3>Objectives</h3> The purpose of this study was to determine treatment practices after use of MTX in patients with RA who were on either monotherapy or combination csDMARDs in a large observational cohort (OBRI) in order to determine contemporary practice where use of bDMARDs from government coverage is restricted to active RA (+RF and/or +ACPA) or erosions, SJC≥5 with MTX failure, combination failure (triple csDMARDs: MTX + hydroxychloroquine + sulfasalazine) or use of leflunomide. <h3>Methods</h3> Patients enrolled in OBRI with documented MTX failure defined as discontinuation due to side effect, primary/secondary failure, or patient/physician decision. Demographics and disease parameters at MTX failure were compared between monotherapy failures, double therapy (Rx) failures, and triple Rx failures. <h3>Results</h3> A total of 313 patients with MTX failure were included with a mean (SD) age of 58.8 (13.2) years and disease duration of 6.7 (8.2) years. Of these, 102 (32.6%) were on MTX monotherapy, 156 (49.8%) were double (MTX +1 csDMARD) Rx, and 55 (17.6%) were on triple or more (MTX + multiple csDMARDs)Rx, respectively, at the time of MTX failure. At the time of MTX failure disease duration was numerically higher in patients failing monotherapy and double Rx as compared to triple Rx (7.5 vs. 6.8 vs. 4.5 years, respectively; P=0.276) while patients failing triple Rx were more likely to have an erosion (43.1% vs. 37.2% vs. 61.8%; P=0.009) and had significantly higher patient global (3.5 vs. 3.9 vs. 4.8; P=0.046). When looking at patient transition to csDMARDs monotherapy, csDMARDs combination Rx or bDMARDs treatment, patients receiving monotherapy were more apt to have switches to other monotherapy (87% of patients), whereas those on combination Rx received more combination csDMARDs (78% and 74% of patients on MTX + 1 csDMARDs or MTX + multiple csDMARDs, respectively) and bDMARDs combination Rx (21% and 26%, respectively)(Figure 1). <h3>Conclusions</h3> There are inherent differences in the selection of subsequent treatment regimen between patients failing MTX monotherapy vs. MTX combination therapy. Overall, the results of the current analysis suggest the use of a sequential treatment intensification strategy in routine clinical practice in Ontario. <h3>Disclosure of Interest</h3> None declared
AB0858 Rare NOD2 Variants in Patients with Granulomatous Uveitis
Authors: C. Galeotti, G. Sarrabay, O. Fogel, I. Touitou, B. Bodaghi, C. Miceli-Richard, I. Koné-Paut
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Blau Syndrome is a rare autosomal dominant inflammatory disease characterized by early-onset granulomatous arthritis, dermatitis and recurrent uveitis (1). Mutations in the nucleotide-binding domain (NBD) of <i>CARD15/NOD2</i> gene (mainly R334W, R334Q and L469F) have been identified in Blau syndrome (2). Polymorphisms in the leucine-rich repeats (LRR) of <i>CARD15</i> are associated with Crohn9s Disease, and mutations in the NBD domain are observed in Blau syndrome (3). <h3>Objectives</h3> We describe two patients with granulomatous uveitis carrying rare genetic variants of NOD2. <h3>Methods</h3> The analysis of the coding exons of the <i>NOD2/CARD15</i> gene was performed in our two patients because they had a granulomatous uveitis. <h3>Results</h3> The first patient, a 14 years old boy, had an isolated bilateral granulomatous uveitis since he was 10 years old. He was treated by steroids and methotrexate. He carried the A725G variant of <i>NOD2</i> (rs5743278 MAF 0.018). The second patient, a 15 years old girl had an isolated bilateral granulomatous panuveitis since she was 5 years old. She was treated by azathioprine and steroids. She carried two other rare genetic variants of <i>NOD2:</i> H287Y and L682F (MAF=0.0002). <h3>Conclusions</h3> NOD2 is composed of three domains: a C-terminal LRR domain involved in ligand recognition, a central NBD and an N-terminal CARD domain. Our two patients carried a rare genetic variant located between the LRR and the NBD domains (A725G and L682F). The A725G variant has been previously described in patients with Crohn disease9s (CD) phenotype by Hugot et al (3) but our first patient had no clinical symptom related to CD. The second patient carried another rare variant located in the NBD domain (H287Y), compatible with the diagnosis of Blau syndrome. According to these observations, genetic variations located between the LRR and the NBD domains of NOD2 might be associated with the occurrence of granulomatous uveitis. It should be thus recommended to screen NOD2 mutations in patients with isolated granulomatous uveitis. <h3>References</h3> Blau EB. Familial granulomatous arthritis, iritis, and rash. The Journal of pediatrics. 1985 Nov;107(5):689–93. PubMed PMID: 4056967. Epub 1985/11/01. eng. Miceli-Richard C, Lesage S, Rybojad M, Prieur AM, Manouvrier-Hanu S, Hafner R, et al. CARD15 mutations in Blau syndrome. Nature genetics. 2001 Sep;29(1):19–20. PubMed PMID: 11528384. Epub 2001/08/31. eng. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cezard JP, Belaiche J, et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn9s disease. Nature. 2001 May 31;411(6837):599–603. PubMed PMID: 11385576. Epub 2001/06/01. eng. <h3>Disclosure of Interest</h3> None declared
A newly developed continuous zoom-focus endocytoscope
Authors: Youichi Kumagai, Kaiyo Takubo, Kenro Kawada, Morihiro Higashi, Toru Ishiguro, Jun Sobajima, Minoru Fukuchi, Kei-ichiro Ishibashi, Erito Mochiki, Junko Aida, Tatsuyuki Kawano, Hideyuki Ishida
Journal: Endoscopy (2016)

Background and study aims We report the features of a newly developed endocytoscopy system (ECS), the GIF-Y0074. Patients and methods The GIF-Y0074 offers high-definition resolution with a consecutive increase of magnification to × 500. Using ECS, we observed 32 cases of esophageal squamous cell carcinoma (ESCC), 11 cases of gastric cancer, and five cases of duodenal adenoma. Results The images of cells obtained using the GIF-Y0074 at maximum magnification were brighter and clearer than those obtained with previous ECS systems. For diagnosis of ESCC, clearer visualization of the nucleus made nuclear abnormality easier to recognize. Cancer cells were visualized in 10/11 cases of gastric cancer, but removal of mucus still remained a problem. Duodenal adenomas were found to have atypical cells with villi and tubules at the mucosal surface, thus assisting their histological diagnosis in vivo. Conclusion The GIF-Y0074 is an excellent ECS in terms of ease of use, satisfactory resolution, and magnification power, and therefore achieves a level of utility that makes its commercial release justifiable. This ECS heralds a new era of endoscopic and histological diagnosis.
Trough Level of First Dose of Busulfan (Cmin1) Is a Stronger Predictor of Graft Rejection Than Steady State Concentration (Css1) In Patients with Beta Thalassemia Major Undergoing Allogeneic Hematopoietic Stem Cell Transplantation
Authors: Poonkuzhali Balasubramanian, Salamun Desire, Pranavi Sugumaran, Kavitha ML, Aby Abraham, Auro Viswabandya, Biju George, Vikram Mathews, Mammen Chandy, Rajagopal Krishnamoorthy, Alok Srivastava
Journal: Blood (2010)
PWE-045 A Strong Correlation Exists between Morphologic and Genomic Heterogeneity in Hepatocellular Carcinoma (HCC)
Authors: W Fateen, H Wood, S Berri, H Thygesen, J Wyatt, M El- Meteini, C Millson, P Quirke
Journal: Gut (2016)

<h3>Introduction</h3> Morphological intra-tumour heterogeneity is well recognised in HCC. Genomic intra-tumour heterogeneity has recently been reported on a small number of cases. In this study we aim to correlate morphological and genomic heterogeneity in HCV related HCC to inform the need for multiple biopsies <h3>Methods</h3> We investigated DNA copy number profiles of 12 HCV induced nodules with morphological heterogeneity and 8 morphologically homogeneous nodules. Histologically homogenous nodules (n = 8) were sequenced at 29 areas. 5/8 nodules were divided into 4 equal quadrants and DNA was extracted from each of the quadrants. The remaining 3/8 nodules were embedded into several paraffin blocks (range 2–5) upon routine processing post operatively. One DNA sample was extracted from each paraffin block All grades of differentiation were included as well as dysplastic nodules. A total of 35 correlations were performed between DNA sequences from different areas in this group. Morphologically heterogeneous nodules (n = 12) were sampled from morphologically distinct areas showing variability in either differentiation, cytological or morphological patterns within the same tumour. A total of 16 correlations were performed from different areas in this group. Differences in copy number patterns were objectively analysed using Pearson’s correlation between normalised, non- smoothed, non-segmented ratios (n = 27,180 per each sample). <h3>Results</h3> Pearson’s correlation coefficients were consistently &gt;0.85 (mean = 0.92 after Fisher r to z to r transformation) indicating a strong positive linear correlation between the studied sequences in the morphologically homogenous group. Marked genomic heterogeneity existed in morphologically heterogenous samples. Mean correlation coefficient was 0.62 for tumours that were exclusively HCC (n = 7) and and 0.48 for tumours where an area of dysplasia was engulfed within the nodule (n = 5) respectively.The difference between correlations coefficients of morphological homogenous versus heterogenous groups was statistically significant (P = 0.01). <h3>Conclusion</h3> We therefore confirm the presence of intra-tumour heterogeneity in a number of HCV related HCC. However, we only identified intra-tumour heterogeneity in morphologically heterogeneous samples but not in those that harbour uniform morphology. Confirmation that morphologically homogenous samples are genetically homogenous is highly relevant clinically especially with rising doubts about the role of liver biopsy in HCC. <h3>Disclosure of Interest</h3> W. Fateen: None Declared, H. Wood: None Declared, S. Berri Employee of: Illumina, H. Thygesen: None Declared, J. Wyatt: None Declared, M. El- Meteini: None Declared, C. Millson: None Declared, P. Quirke: None Declared
An African Origin of the Eurylaimides (Passeriformes) and the Successful Diversification of the Ground-Foraging Pittas (Pittidae)
Authors: Alexandre Pedro Selvatti, Ana Galvão, Anieli Guirro Pereira, Luiz Pedreira Gonzaga, Claudia Augusta de Moraes Russo
Journal: Molecular Biology and Evolution (2016)

The Eurylaimides is one of the few passerine groups with a pantropical distribution. In this study, we generated a multi-calibrated tree with 83% of eurylaimid species diversity based on 30 molecular loci. Particular attention was given to the monotypic Sapayoidae to reconstruct the biogeography of this radiation. We conducted several topological tests including nonoverlapping subsampling of the concatenated alignment and coalescent species tree reconstruction. These tests firmly placed the South American Sapayoidae as the sister group to all other Eurylaimides families (split at ∼28 Ma), with increasing branch support as highly variable sites were removed. This topology is consistent with the breakup of the insular connection between Africa and South America (Atlantogea) that took place between the middle Eocene and the early Oligocene. We recovered Africa as the cradle of the core Eurylaimides, and this result is supported by all African lineages corresponding to the oldest splits within each family in this group. Our timescale suggests that desertification and the uplift of the Tibetan Plateau caused a parallel divergence between African and Asian lineages in all major clades in the core Eurylaimides at 22-9 Ma. We also propose that the ground-foraging behavior in the Pittidae ancestor allowed the pitta lineage to thrive and coexist with the older arboreal lineages of the core Eurylaimides. In contrast, the diversification of pittas in Australia was likely hindered by direct competition with the endemic ground-foraging oscines that had been well established in that continent since the Eocene.
Hematologic Responses In Myelodysplastic Syndromes (MDS) Patients Treated with Deferasirox: An EPIC Post-Hoc Analysis Using International Working Group (IWG) 2006 Criteria
Authors: Norbert Gattermann, Carlo Finelli, Matteo Della Porta, Pierre Fenaux, Michael Stadler, Agnès Guerci-Bresler, Mathias Schmid, Kerry Taylor, Dominique Vassilieff, Dany Habr, Andrea Marcellari, Bernard Roubert, Christian Rose
Journal: Blood (2010)