tbuckley/cabot-search huggingface dataset:
Phase II Multicenter Study of Busulfan-Fludarabine Conditioning Regimen for cord Blood transplantation in Pediatric Acute Myeloid Leukemia
Authors: Hee Young Ju, Hyoung Jin Kang, Ji Won Lee, Hyery Kim, Kyung Duk Park, Hee Young Shin, Soo Hyun Lee, Keon Hee Yoo, Ki Woong Sung, Hong Hoe Koo, Jae Wook Lee, Nak Gyun Chung, Bin Cho, Hack Ki Kim, Young Ho Lee, Eun Sil Park, Jae young Lim, Eun Sun Yoo, Kyung Ha Ryu, Kyung Nam Koh, Ho Joon Im, Jong Jin Seo, Sang Kyu Park, Hyun Joo Jung, Jun Eun Park, Yeon Jung Lim, Hyo Seop Ahn
Journal: Blood (2012)
Preliminary Results from a Phase 2 Trial of AG-858, an Autologous Heat Shock Protein-Peptide Vaccine, in Combination with Imatinib in Patients with Chronic Phase Chronic Myeloid Leukemia (CML) Resistant to Prior Imatinib Monotherapy.
Authors: David Marin, Michael Mauro, John Goldman, Brian Druker, Steven Devine, Richard E. Clark, Ronald Paquette, Asad Bashey, Martin S. Tallman, April Dovholuk, Axel Hoos, Pramod Srivastava
Journal: Blood (2005)
SP110b Controls Host Immunity and Susceptibility to Tuberculosis
Authors: Jia-Shiun Leu, Mei-Ling Chen, So-Yi Chang, Sung-Liang Yu, Chia-Wei Lin, Hsuan Wang, Wan-Chen Chen, Chin-Hao Chang, Jann-Yuan Wang, Li-Na Lee, Chong-Jen Yu, Igor Kramnik, Bo-Shiun Yan
Journal: American Journal of Respiratory and Critical Care Medicine (2017)

Rationale: How host genetic factors affect Mycobacterium tuberculosis (Mtb) infection outcomes remains largely unknown. SP110b, an IFN-induced nuclear protein, is the nearest human homologue to the mouse Ipr1 protein that has been shown to control host innate immunity to Mtb infection. However, the function(s) of SP110b remains unclear.Objectives: To elucidate the role of SP110b in controlling host immunity and susceptibility to tuberculosis (TB), as well as to identify the fundamental immunological and molecular mechanisms affected by SP110b.Methods: Using cell-based approaches and mouse models of Mtb infection, we characterized the function(s) of SP110b/Ipr1. We also performed genetic characterization of patients with TB to investigate the role of SP110 in controlling host susceptibility to TB.Measurements and Main Results: SP110b modulates nuclear factor-κB (NF-κB) activity, resulting in downregulation of tumor necrosis factor-α (TNF-α) production and concomitant upregulation of NF-κB–induced antiapoptotic gene expression, thereby suppressing IFN-γ–mediated monocyte and/or macrophage cell death. After Mtb infection, TNF-α is also downregulated in Ipr1-expressing mice that have alleviated cell death, less severe necrotic lung lesions, more efficient Mtb growth control in the lungs, and longer survival. Moreover, genetic studies in patients suggest that SP110 plays a key role in modulating TB susceptibility in concert with NFκB1 and TNFα genes.Conclusions: These results indicate that SP110b plays a crucial role in shaping the inflammatory milieu that supports host protection during infection by fine-tuning NF-κB activity, suggesting that SP110b may serve as a potential target for host-directed therapy aimed at manipulating host immunity against TB.
PP2A Activating Drugs (PAD): Anti-Leukemic and Non-Toxic Activity of Two Novel and Non-Immunosuppressive FTY720 Derivatives
Authors: Christopher Walker, Joshua J Oaks, Paolo Neviani, Jason G Harb, Ramasamy Santhanam, Y. Ma, Guido Marcucci, James Van Brocklyn, Ching-Shih Chen, Robert Bittman, Danilo Perrotti
Journal: Blood (2010)
Inhibition of Graft-Versus-Host Disease (GVHD) by Histone Deacetylase Inhibitor (HDAC) SAHA Leads to Downregulation of STAT1 Activation.
Authors: Corinna Leng, Cuiling Li, Judy Ziegler, Anna Lokshin, Suzanne Lentzsch, Markus Y. Mapara
Journal: Blood (2005)
THU0573 Semen Analysis in Adolescent with Familial Mediterranian Fever
Authors: G.K. Aksoy, M.F. Usta, M. Koyun, E. Comak, A. Gemici, S. Akman
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Familial Mediterranean Fever (FMF) is a genetic disease that has characteristics like fever, sterile peritonitis, pleurisy, joint pain and rashes that are similar to erysipelas. In male patients, scrotal involvement is seen especially in children and adolescents with the frequency being below 5%.<sup>1</sup> Colchicine is an agent which regulates microtubules in cell9s structure, pauses metaphase stage in cell division and stops microtubule dependent cell movement<sup>2</sup>. Colchicine is principal for treatment of FMF. Colchicine has a negative effect on sperm count and motility as it effects microtubules. <h3>Objectives</h3> We aimed to observe the relationship between sperm count and function with disease activity and colchicine usage in adolescent male patients with FMF. <h3>Methods</h3> Male patients between the age of 14–19 years old with FMF investigated retrospectively. Tel Hashomer and Turkish FMF Pediatric Criteria were used for diagnosis of FMF. Genetic screening was performed in all patients at the time of diagnosis. Sperm analysis was performed in 19 patients on treatment with colchicine. Demographic and clinical parameters of patients were analyzed. <h3>Results</h3> Mean age at the diagnosis was 11.13±3.82 years old, mean age at the study was 14.50±0.70 and mean follow-up period was 4.68±3.94 years. Homozygote, compound heterozygote and heterozygote mutations were found in eight, seven and one patients, respectively; no mutations in 3 patients. Mean colchicine dose was 1.16 mg/day at the start of treatment and 1.47 mg/day when sperm samples were collected. Mean sperm concentration was found as 66.26±41.02 million/ml (N&gt;15), sperm count 113.42±132.39 million (N&gt;35) and motility %51.78±23.70 (N&gt;50%). Only 8 patients out of 19 had normal sperm parameters. Sperm concentration was reduced in two cases; sperm count was reduced in four patients whereas motility was reduced in nine cases. No relation was determined between sperm volume, count, concentration and motility results with age at diagnosis, follow-up period, symptoms on admission and inflammatory markers (CRP and erythrocyte sedimentation rate). Patients that had sedimentation values above 30 mm/hour during follow-up had sperm count below &lt;35 million, with a specificity of 100% and sensitivity of 73.3% (AUC=0.858, p=0.032). It was found that patients who had FMF attacks during treatment had low sperm count and motility than patients without attacks (p: 0.034 and p: 0.02, respectively). There was an inverse relationship between the dose of colchicine with sperm motility (p: 0.025). <h3>Conclusions</h3> A high number of adolescents with FMF had abnormal sperm parameters, mostly sperm motility. It seems that both colchicine and uncontrollable attacks of FMF may be the reason of abnormal sperm parameters. We suggest that all adolescents with FMF should be screened for semen analysis. <h3>Disclosure of Interest</h3> None declared
Oral cancer rates rise by two thirds
Authors: Anne Gulland
Journal: BMJ (2016)

GPs are being urged to be aware of the signs of oral cancer, as new figures from Cancer Research UK show that rates of the disease have increased by 68% in the past 20 years.1

The figures show that the rate of oral cancer in 1992-95 was eight cases per 100 000 people, but that figure has increased to 13 per 100 000 people in 2012-14.

Men aged over …
AB0381 Expression of Toll-like Receptors and Distribution of Immune-Cells in Rheumatoid Synovial Tissues of The Patients Treated by Abatacept
Authors: Y. Takakubo, Y. Naganuma, H. Oki, S. Yang, K. Sasaki, M. Takagi
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> Rheumatoid arthritis (RA) is a progressive chronic autoimmune and autoinflammatory disease affecting multiple joints simultaneously<sup>1</sup>. Abatacept (ABT) which is cytotoxic T-lymphocyte-associated protein (CTLA) 4-Ig agent is one of biologics<sup>2</sup>. <h3>Objectives</h3> The aim of this study is to examine the effect of ABT for evaluating immune-reactive cells with toll-like receptors in the synovial tissue samples of RA patients with ABT therapy (ABT groups) compared to them with non-biological therapy (Non-BIO groups). <h3>Methods</h3> Synovial tissue samples of 20 RA (10 ABT and 10 Non-BIO samples) were immunohistochemically stained with TLR+ and immune-reactive cells including T cells (CD2), B cells (CD20), macrophage (CD68), conventional dendritic cells (cDC; S100, DC-LAMP), regulatory T cells (FoxP3) and indoleamine 2,3-dioxygenase+ cells (IDO). Positive cells were counted per 10 fields (x 200) by microscopy. TLR positive cells were analyzed by double Immunofluorescent methods with T cell, B cell, macrophage, cDC and plasmacytoid DC (pDC; CD123)-markers and IDO. Synovial inflammation was estimated by Krenn grading score. <h3>Results</h3> ABT and non-BIO group was shown the similar grading scores (2.3 vs 2.0), DAS28CRP4 (5.1 vs 4.3) and CRP (1.3 vs 0.9). IDO+ and FoxP3+ cells, not CD3+, CD20+ and CD68+ cells were correlated significant with DAS28CRP (4) in lymphoid aggregation in ABT groups (p&lt;0.01). TLR immunoreactivity was also confirmed in pDCs and IDO+ cells by immunofluorescent staining (Fig. 1). <h3>Conclusions</h3> ABT was reported the similar remarkable effect with other biologics. We have already shown the residual inflammation of synovitis with TLR expressions in the RA patients who were received TNF-blockers<sup>3</sup>. TLR+ cells were observed with T cells and B cells related local inflammatory grading in ABT groups, however regulatory immune-cells might be increased and regulate inflammatory simultaneously. CTLA-4 and IDO was recently revealed the generation of osteoclast <sup>4,5</sup>. IDO+ cells increased in synovial tissues of ABT group compared to no-BIO group. ABT may not only regulate the immunosuppression but also suppress the activation of osteoclast in RA. <h3>References</h3> Klareskog L, et al: Lancet 2004; 363: 675–681, Sokolove J, ARD, 2015, [Epub ahead of print] Takakubo Y, et al: Clin Rheumatol, 2013; 32: 853–61, Bozec A, et al: SciTranMed, 2014; 7; 235:235ra60 Schiff M, et al: ARD, 2014;73: 2174–7. <h3>Acknowledgement</h3> We sincerely thank a lot to Ms. Eiko Saito for her skillful technical support in immunohistochemistry. <h3>Disclosure of Interest</h3> None declared
PWE-107 Short-Term Clinical Outcomes of Endoscopic Resection of Giant (&gt;3CMS) Colorectal Polyps: Could it Be A Safe Colon Sparing Therapeutic Option?
Authors: K Marimuthu, T Amuthalingam, R Mahmood, P Stonelake, A Kawesha, S Ishaq
Journal: Gut (2016)

<h3>Introduction</h3> Modern endoscopic practice offers definitive management of colorectal polyps. However the role of this colon sparing minimally invasive modality is not clearly established in technically challenging “giant” polyps. Aim of this study was to evaluate the safety &amp; short-term clinical outcomes of endoscopic resection of large colorectal polyps measuring 3 cm or more. <h3>Methods</h3> All patients with colorectal polyps measuring ≥3 cm who underwent endoscopic or surgical treatment in our hospital from 2009 to 2016 were included in the study. Patient demographics &amp; clinical data were collected from endoscopic and hospital database. <h3>Results</h3> Over seven year period, 100 patients (median age: 72 years) were identified but complete data was available for 98 patients (25 right colon &amp; 73 left colon). Median colorectal polyp size was 4.5 cm (range: 3–16 cm, &amp; majority of polyps were in the rectum &amp; sigmoid colon (69/98,69%) &amp; predominantly sessile Paris type 1 s polyps. Four patients (4/98,4.1%) decided not to have treatment. Sixty-eight polyps (68/94,72.3%) were removed by endoscopic mucosal resection (EMR) or piece meal technique, of these fourteen patients (14/68,20.6%) needed more than one EMR session for the complete removal of the polyp. During follow-up, six patients (6/68,8.8%) who underwent previous EMR required additional surgical procedure in order to obtain complete polyp clearance. Following initial endoscopic assessment, surgical resection was deemed appropriate in twenty-six patients (26/94,26.5%) due to difficult location of the polyp &amp; suspected/confirmed malignancy. Majority of the removed polyps were tubulovillous adenoma on histological confirmation. In the endoscopy group, twelve patients in endoscopy group (12/68,17.6%) had high-grade dysplasias (HGD) &amp; four patients had invasive cancers (4/68,5.9%), of which two were considered cured &amp; other two patients underwent further surgery. Among the surgical group seven (7/26,27%) &amp; five (5/26,19%) patients had invasive cancer &amp; HGD respectively. There were twelve procedure-related adverse events (12/68,17.6%) occurred in the endoscopy group, mainly occurred between 2008 &amp; 2013 (eight minor bleeding requiring clips or additional cauterization). We have encountered only four complications between 2014 &amp; 2016 (two minor &amp; one major bleeding &amp; one incidence of hypotension) despite performing more polypectomies. Outcome data for the surgical group was not available at present. <h3>Conclusion</h3> Colorectal EMR for polyps of ≥3 cm can be performed at experienced endoscopy centres with a low rate of major complications. This modality offers a safe non-surgical option in management of large colorectal lesions especially in the elderly patients. <h3>Disclosure of Interest</h3> None Declared
HLA Specificities and Predisposition to the Development of Multiple Myeloma (MM).
Authors: Meral Beksac, Martin Maiers, Loren Gragert, Stephen Spellman, Smriti Shrestha, Mei-Jie Zhang, Angela Dispenzieri, Donna E. Reece, David H. Vesole, Parameswaran Hari
Journal: Blood (2008)
AB0215 The Combination of Methotrexate with Hydroxychloroquine Is More Effective than Monotherapy in Early Rheumatoid Arthritis: A Quasi-Experiment
Authors: L.A.H.A. Gevers, W.M.T. van den Hombergh, L.G. Schipper, I.L. Meek, J. Fransen
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Background</h3> A tight-control strategy starting with a combination of methotrexate (MTX) and hydroxy-chloroquine (HCQ) was implemented between 2010–2015 in our clinic; without evidence from RCTs for the combination of MTX with HCQ in early RA (1). Some physicians chose not to adhere to this combination, which post-hoc gave the opportunity for a quasi-experiment. <h3>Objectives</h3> To investigate the effect of starting with MTX + HCQ combination therapy, versus MTX or HCQ mono therapy, on the DAS28 at 6 and 12 months in patients with early RA, while treating to the target of remission (DAS28 &lt;2.6). <h3>Methods</h3> All patients with early RA (ACR-EULAR criteria) between April 2010 and October 2015 were eligible. Two sub cohorts were formed according to whether the treatment was started with MTX+HCQ as intended, or with MTX or HCQ. There were n=50 patients in the adherent-group and n=38 patients in the non-adherent group who were initially treated with MTX or HCQ mono therapy (sometimes with addition of the other drug after more than four weeks). The primary outcome was the ΔDAS28 at 6 months. <h3>Results</h3> In the study period 176 RA patients were treated and 88 could not be included due to lack of follow-up data. At baseline, there were no large or significant (p&lt;0.05) differences between MTX+HCQ and mono therapy groups regarding age (mean 57 years), gender (73% female), disease duration (median 21 weeks). Also, rheumatoid factor positivity (48% and 34%), mean baseline DAS28 (4.3 (1.3) and 4.2 (1.1)) were not different (p&gt;0.05) between MTX+HCQ and mono therapy groups. In the mono therapy group, 30 patients started with MTX and 8 started with HCQ. After 6 months, the DAS28 decreased – 1.4 in the MTX+HCQ group and – 0.8 in the non-adherent group (p=0.044). After 12 months, the DAS28 decreased – 1.7 in the MTX+HCQ group and – 0.8 in the non-adherent group (p=0.007). After 12 months, 48% of adherent patients were in DAS28 remission compared to 26% of non-adherent patients (p=0.039). There were no baseline confounders operational. <h3>Conclusions</h3> In early RA starting with MTX and HCQ combination therapy leads to a larger decrease in DAS28 after 6 and 12 months and higher percentages of remission after 12 months in comparison with mono therapy with MTX or HCQ. <h3>References</h3> Ma MH, Kingsley GH, Scott DL. A systematic comparison of combination DMARD therapy and tumour necrosis inhibitor therapy with methotrexate in patients with early rheumatoid arthritis. Rheumatology (Oxford, England). 2010;49(1):91–8. <h3>Disclosure of Interest</h3> None declared
Clinicopathologic Analysis of Follicular Lymphoma (FL) Patients with Coexisting Diffuse Large B-Cell Lymphoma (DLBCL) Undergoing Rituximab-Containing Chemotherapy
Authors: Suguru Fukuhara, Dai Maruyama, Ken-ichi Miyamoto, Sung-Won Kim, Takashi Watanabe, Yukio Kobayashi, Hirokazu Taniguchi, Akiko Miyagi Maeshima, Kensei Tobinai
Journal: Blood (2012)
Serious Pulmonary Toxicity with SGN-30 and Gemcitabine, Vinorelbine, and Liposomal Doxorubicin in Patients with Relapsed/Refractory Hodgkin Lymphoma (HL): Cancer and Leukemia Group B (CALGB) 50502
Authors: Kristie A. Blum, Jeffrey L Johnson, Sin-Ho Jung, Bruce D. Cheson, Nancy L. Bartlett
Journal: Blood (2008)
Proteomic Analysis for the Identification of Disease Biomarkers and Therapeutic Targets in Natural Killer Cell Lymphoma.
Authors: Hojung Lee, Evan Shereck, Mitchell S. Cairo, Seiler E Seiler, Venkatesha Basrur, Damian Fermin, Kojo SJ Elenitoba-Johnson, Megan S Lim
Journal: Blood (2008)
SAT0536 Utility of 18F-Fluoro-Dexoxyglucose Positron Emission Tomography for The Diagnosis of Polymyalgia Rheumatica: A Controlled Study:
Authors: M. Sondag, X. Guillot, F. Verhoeven, O. Blagosklonov, C. Prati, H. Boulahdour, D. Wendling
Journal: Annals of the Rheumatic Diseases (2016)

<h3>Objectives</h3> To compare<sup>18</sup>f-Fluoro-Dexoxyglucose Positron Emission Tomography (FDG-PET/CT) findings in patients with polymyalgia rheumatica (PMR) and controls without rheumatologic disease. <h3>Methods</h3> We have retrospectively included 50 patients with a diagnosis of PMR (EULAR/ACR criteria), who have had a FDG-PET/CT. For comparison, 53 patients who have had a FDG-PET/CT for initial staging or follow-up of neoplasm have been included as controls. 17 sites have been analyzed (2 shoulders, 2 acromio-clavicular and 2 sterno-clavicular joints, 2 greater trochanters, 2 hips, 2 ischial tuberosities, 2 iliopectinal bursitis, 2 pubic symphysis enthesis and only the interspinous space with the most FDG uptake). An FDG uptake score has been used (semi-quantitative scoring system, by Goerres and al. to evaluate visually FDG uptake (0 to 3 compared to liver uptake) into these sites. We calculated the FDG uptake score corresponding to the mean of intensity over all sites, and the number of sites with significant uptake (FDG uptake 2 or 3) for each patient. The cut offs for number of sites with high activity and for FDG uptake score were assessed using ROC curves and Odds Ratios. <h3>Results</h3> The two groups were comparable for the median patient age (69.3 years for PMR vs. 68.1 for controls). Significant differences between the two groups were found for FDG uptake score (1.12 vs 0.34, p&lt;0.00001) and for number of sites with significant uptake: 6.36 sites vs 1.49 sites, p&lt;0.00001. The presence of 3 or more sites with significant uptake was correlated with the diagnosis of PMR with 74% sensitivity, 79% specificity [OR =10.8]. For the FDG uptake score the cut off is 0.53 [Se 80%, Sp 77%; OR 13.6]. We found significant differences in all sites for FDG uptake score, and number of sites with significant uptake, particularly marked for shoulders, ischial tuberosities and interspinous bursitis (p&lt;0.00001 for FDG uptake score). <h3>Conclusions</h3> We found significant uptake in all sites studied in PMR compared to controls. We propose the number of 3 sites with significant uptake and a FDG uptake score superior at 0.53 for the diagnosis of PMR. <h3>Disclosure of Interest</h3> None declared
Fludarabine (Flu) Based Cytoreductive Regimen and T-Cell Depleted Grafts from Unrelated or Mismatched Related Donors for the Treatment of High Risk Patients with Fanconi Anemia (FA).
Authors: Farid Boulad, Arleen D. Auerbach, Nancy A. Kernan, Trudy N. Small, Susan E. Prockop, Sonali Chaudhury, Joanne Castanza, Anne Casson, Catherine Copeland, Heidi Abendroth, Nancy Collins, Richard J. O’Reilly
Journal: Blood (2004)
SP0087 Natural Occurring Lubricants To Maintain Joint Homeostasis
Authors: J. Klein
Journal: Annals of the Rheumatic Diseases (2016)

Cartilage surfaces sliding past each other in the major joints (such as hips and knees) exhibit extremely low levels of friction under physiologically-high pressures, a lubricity which is essential for their healthy perfomance. A detailed molecular-level understanding of this could benefit treatments of osteoarthritis (OA), as well as improved prosthetic joint implants. Any insight must, first and foremost, be able to account for the low friction (coefficient of friction (CoF) down to ca. 0.001) at the high pressures (which can reach 100 atm or higher) of the joints. However, the main molecular "suspects" thought to constitute the lubricating boundary layer on cartilage, namely hyaluronic acid, lubricin or phospholipids, do not, individually, provide especially good lubrication. Recently<sup>1</sup> we discovered that hyaluronan (HA) which is attached to a surface – to resemble its configuration at the outer cartilage surface – may complex with phosphatidylcholines (PCs), lipids that are ubiquitous in synovial joints, to form robust boundary layers. These layers act synergistically to provide the very low friction (CoF $≈ $ 0.001) characteristic of cartilage, at the highest physiological pressures, and contrast with surface-attached HA on its own, which leads to considerably higher friction. The very low friction is ultimately due to the phosphocholine groups exposed by the HA/PC surface complexes; these groups are known to be strongly and highly-hydrated, and they lubricate via the recently elucidated hydration-lubrication mechanism<sup>2</sup>. Our results thus point to a scenario<sup>3</sup> where HA, PCs and lubricin, each with a very different role, act together synergistically to reduce friction of cartilage in articulating joints. Hyaluronan, anchored at the outer surface of articular cartilage by lubricin molecules (which are known to be present in the outer superficial zone), complexes with joint phosphatidylcholines to provide the extreme boundary lubrication of synovial joints via the hydration-lubrication mechanism. 1. Seror, J., Zhu, L., Goldberg, R., Day, A.J. and Klein J. Supramolecular synergy in the boundary lubrication of synovial joints. <b>Nature Communications</b>, | 6:6497 | DOI: 10.1038/ncomms7497 (2015) 2. Ma, L., Gaisinskaya, A., Kampf, N. and Klein, J. Origins of hydration lubrication. <b>Nature Communications</b>, | 6:6060 | DOI: 10.1038/ncomms7060 (2015) 3. Jahn S, Seror J, Klein J., Lubrication of articular cartilage. <b>Annu. Rev. Biomed. Eng</b>. 18:in press. DOI: 10.1146/annurev-bioeng-081514–123305 (2016) <h3>Disclosure of Interest</h3> None declared
A Phase II Trial of Pegylated Interferon α-2b in Polycythemia Vera and Essential Thrombocythemia. Clinical Responses, Effects on PRV-1 Expression and Impact on Quality of Life.
Authors: Jan Samuelsson, Hans Hasselbalch, Oystein Bruserud, Heike Pahl, Mats Merup, Olle Linder, Yvonne Brandberg, Poul Gram-Hansen, Magnus Bjorkholm, Waleed Ghanima, Claes Malm, Berit Markevarn, Torben Mourits-Andersen, Peter Johansson, Lars Nilsson, Gunnar Birgegard
Journal: Blood (2004)