tbuckley/cabot-search huggingface dataset:
PB2335 COMPARISON BETWEEN FOUR AND FIVE DAYS OF G-CSF-INDUCED MOBILIZATION IN ALLOGENEIC STEM CELL DONORS
Authors: F. Martin Moro, C. Jiménez Prieto, I. García García, A. Sanz Rupérez, S. López González, B. Michael Fernández, A. J. Saez Marín, C. Núñez-Torrón Stock, A. Luna de Abia, M. Tenorio Núñez, A. Jiménez Martín, J. Marquet Palomanes, A. Chinea Rodríguez, P. Herrera Puente, V. García Gutiérrez, J. López Jiménez, G. Moreno Jiménez
Journal: HemaSphere (2019)

Background: Peripheral blood stem cells (PBSC) used for allogenic transplantation (SCT) are collected by apheresis after donors treatment with G-CSF. It was studied whether collection on the 4th day instead of the 5th day after initiation of G-CSF treatment might be feasible, which reduces exposure to the drug and potential adverse effects associated with its administration in healthy donors. Aims: To compare feasibility and effectiveness of Day 4 mobilization versus Day 5 in allogeneic stem cell donors. Methods: We performed a restrospective single-center study. Stem cell donors were stimulated with subcutaneous injections of 5 μg G-CSF (filgrastim)/kg body weight (BW) twice daily. The CD34+ target was 5 × 106/kg recipient BW for haploidentical SCT (haplo-SCT) and 4 × 106/kg for both HLA-matched related donors (MRD) and unrelated donors (UD) SCT. PBSC collection was performed with the Spectra Optia. Mobilization on Day 5 was performed during 2016-2017 and on Day 4 since 2018. CD34+ cells were counted in pre and postapheresis peripheral blood and product samples respectively by flow cytometry using a single-platform assay. We applied means of descriptive statistics, χ2 test and Student's t-test for comparisons, regression analysis and Pearson correlation coefficient (IBM SPSS Statistics 22). Results: We analyzed 87 PBSC allogeneic procedures: 45 (51.7%) performed on the 4th day of mobilization and 42 (48.3%) on the 5th day. Both apheresis groups were comparable with regard to donor and recipient characteristics (table 1). Distribution of SCT types was similar in both groups: MRD 23 (51.1%) vs 17 (40.5%), UD 8 (17.8%) vs 10 (23.8%) and haplo 14 (31.1%) vs 15 (35.7%) respectively for Day 4 and Day 5 (p = 0.59). We found no differences in G-CSF-related adverse effects nor in apheresis collection procedures between both groups. G-CSF global treatment price difference between 4 days and 5 days was 1,355€ (11,360€ vs 12,715€; p < 0.001). Correlation between PBSC pre-apheresis and post-apheresis sample CD34+ cell count (/μl) of each group is presented in Figure 1. The CD34+ cells count in post-apheresis products did not differ between Day 4 and Day 5 groups (table 1). Donors who failed the CD34+ target quantity on first apheresis (7/45 of Day 4 and 6/42 of Day 5) reached it on a second procedure; no donor received plerixafor. Main charasteristics are summarized in table 1.Summary/Conclusion: Our results suggest that apheresis on the 4th day of low-dose G-CSF-induced mobilization in allogeneic stem cell donors is as feasible and effective as collection on Day 5, reducing G-CSF exposure to healthy donors and global costs.
PB2383 FACTORS ASSOCIATED WITH EFFECTIVE HARVESTING AND ENGRAFTMENT OF AUTOTRANSPLANT IN PATIENTS WITH MULTIPLE MYELOMA
Authors: I. Kostroma, A. Zhernyakova, Z. Chebukina, N. Semenova, I. Zapreeva, S. Tiranova, S. Bessmel’tsev, A. Chechetkin, S. Gritsaev
Journal: HemaSphere (2019)

Background: The effectiveness of autologous stem cell transplantation (AutoSCT) depends on the speed of autotransplant engraftment which in return is adjoined by quantity of harvested and infused CD34+ cells. Aims: The aim of the study was to determine predictors of AutoSCT effectiveness in patients with multiple myeloma (MM) as new medicines were introduced in induction therapy and mobilization schemes. Methods: Retrospective analyses of autotransplant harvesting in 75 patients and autotransplant engraftment during 112 AutoCST was performed. Cyclophosphamide and vinorelbine in combination with granulocy colony‐stimulating factor (G‐CSF) were used for mobilization. Conditioning regimens were Mel200, Mel140 and Thio/Mel140. All patients received G‐CSF during posttransplant period. Standard criteria of engraftment were used. Results: One induction scheme (p = 0.0315) and cyclophosphamide in mobilization regimen (p = 0.0001) were the positive predictors of increased number of CD34+ cells in autotransplant. The rate of engraftment was dependent on the serial number of AutoSCT and number of CD34+ cells infused. The role of the serial number of AutoSCT is attributed to the less intensity of the second conditioning regimen: Mel140 versus Mel200 and Thio/Mel140 during the first AutoSCT. Summary/Conclusion: Autotransplant quality and the rate the engraftment in patients with MM are dependent on the fectiveness of induction therapy and intensity of mobilization regimen. So, we conclude that the choice of induction therapy variant and mobilization regimen intensity has to be adapted to the individual patient, prognostic variant of MM, possibility to respond to standad induction therapy and number of planned AutoSCT.
Glioma Stem Cell–Specific Superenhancer Promotes Polyunsaturated Fatty-Acid Synthesis to Support EGFR Signaling
Authors: Ryan C. Gimple, Reilly L. Kidwell, Leo J.Y. Kim, Tengqian Sun, Anthony D. Gromovsky, Qiulian Wu, Megan Wolf, Deguan Lv, Shruti Bhargava, Li Jiang, Briana C. Prager, Xiuxing Wang, Qing Ye, Zhe Zhu, Guoxin Zhang, Zhen Dong, Linjie Zhao, Derrick Lee, Junfeng Bi, Andrew E. Sloan, Paul S. Mischel, J. Mark Brown, Hu Cang, Tao Huan, Stephen C. Mack, Qi Xie, Jeremy N. Rich
Journal: Cancer Discovery (2019)

Glioblastoma ranks among the most aggressive and lethal of all human cancers. Functionally defined glioma stem cells (GSC) contribute to this poor prognosis by driving therapeutic resistance and maintaining cellular heterogeneity. To understand the molecular processes essential for GSC maintenance and tumorigenicity, we interrogated the superenhancer landscapes of primary glioblastoma specimens and in vitro GSCs. GSCs epigenetically upregulated ELOVL2, a key polyunsaturated fatty-acid synthesis enzyme. Targeting ELOVL2 inhibited glioblastoma cell growth and tumor initiation. ELOVL2 depletion altered cellular membrane phospholipid composition, disrupted membrane structural properties, and diminished EGFR signaling through control of fatty-acid elongation. In support of the translational potential of these findings, dual targeting of polyunsaturated fatty-acid synthesis and EGFR signaling had a combinatorial cytotoxic effect on GSCs. SIGNIFICANCE: Glioblastoma remains a devastating disease despite extensive characterization. We profiled epigenomic landscapes of glioblastoma to pinpoint cell state-specific dependencies and therapeutic vulnerabilities. GSCs utilize polyunsaturated fatty-acid synthesis to support membrane architecture, inhibition of which impairs EGFR signaling and GSC proliferation. Combinatorial targeting of these networks represents a promising therapeutic strategy.See related commentary by Affronti and Wellen, p. 1161.This article is highlighted in the In This Issue feature, p. 1143.
THU0484 ESTIMATION OF PATIENT ACCEPTABLE SYMPTOM STATE FOR PATIENT-REPORTED OUTCOMES BETWEEN 2 POPULATIONS OF PATIENTS WITH NON-SPECIFIC CHRONIC LOW BACK PAIN
Authors: Camille Daste, Frantz Foissac, Hendy Abdoul, Marie-Martine Lefevre Colau, François Rannou, Serge Poiraudeau, Christelle Nguyen
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Clinical relevance of commonly used patient-reported outcomes (PROs) is unclear in people with non-specific chronic low back pain (cLBP) (1). <h3>Objectives</h3> To estimate and compare patient acceptable symptom state (PASS) at 1 month post-intervention for 4 PROs between 2 populations of patients with non-specific cLBP and to determine which baseline variables contribute to having an acceptable symptom state at 1 month. <h3>Methods</h3> Overall, we included 256 patients: 135 patients with cLBP and active discopathy participated in a randomized controlled trial assessing the efficacy on pain at 1 month of a single glucocorticoid intradiscal injection compared to contrast alone (2), and 121 patients with cLBP and without active discopathy participated in a randomized controlled trial assessing the efficacy on pain at 4 months of 12 sessions of immersive virtual reality (VR) compared to usual care (3). Using an anchor-based method, PASS estimates for PROs were obtained using the 75<sup>th</sup> percentile method (4). Logistic regression was used to determine baseline variables contributing to achieving PASS at 1 month. <h3>Results</h3> At 1 month, 137/256 (53.52%) participants self-rated their health as acceptable. In the whole population, PASS (95% IC) were 47.50 (40.00 to 50.00) for the lumbar-pain VAS, 30.50 (30.00 to 40.00) for the radicular-pain VAS, 39.27 (33.60 to 45.26) for the QUEBEC score, 9.95 (9.16 to 10.00) for the HAD anxiety subscale and 6.70 (6.00 to 8.00) for the HAD depression subscale. The PASS estimates did not differ between the 2 populations of cLBP patients for any of the PRO. The only baseline variable contributing to having an acceptable symptom state at 1 month was symptom intensity. <h3>Conclusion</h3> PASS estimates at 1 month did not vary across 2 independent samples of people with cLBP and 2 distinct nociceptive sources of cLBP. The main contributor of the PASS was symptom intensity at baseline. Our findings can be useful in interpreting the clinical relevance of PROs values. <h3>References</h3> [1] Tubach F, Ravaud P, Baron G, Falissard B, Logeart I, Bellamy N, et al. Evaluation of clinically relevant states in patient reported outcomes in knee and hip osteoarthritis: the patient acceptable symptom state. Ann Rheum Dis. 2005;64(1):34-7. [2] Nguyen C, Boutron I, Baron G, Sanchez K, Palazzo C, Benchimol R, et al. Intradiscal Glucocorticoid Injection for Patients With Chronic Low Back Pain Associated With Active Discopathy: A Randomized Trial. Ann Intern Med. 2017;166(8):547-56. [3] Nguyen C, Boutron I, Perrodeau É, Sanchez K, Borderie D, Palazzo C et al. 3D immersive virtual reality in patients with chronic low back pain: a randomized controlled trial. PlosOne (under review). 2017. <h3>Disclosure of Interests</h3> None declared
THU0004 MICRORNA-223 NEGATIVELY REGULATE GOUTY INFLAMMATION BY TARGETING THE NLRP3 INFLAMMASOME WITHOUT INFLUENCING IL-37 AND TGF-î’1
Authors: Yu-Feng Qing, Dan Zhu, Ting Yi, Jian-Xiong Zheng, Qin Xiong, Quan-Bo Zhang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> MicroRNA-223 (miR-223) serves as an important regulator of inflammatory and immune responses and is implicated in several auto-inflammatory disorders[1]. To date, no relevant studies have reported the expression levels of miR-223 in gout patients or assessed whether miR-223 participates in negatively regulating gouty inflammation via regulating cytokines (such as IL-1β, tumor necrosis factor (TNF)-α, IL-37 and TGF-β1) by targeting the NLRP3 inflammasome. <h3>Objectives</h3> To determine the function of miR-223 in monosodium urate (MSU)-induced gouty inflammation. Methods: miR-223 was detected among 107 acute gout patients (AG), 58 intercritical gout patients (IG), and 75 healthy subjects (HC). RAW264.7 macrophages were cultured and treated with MSU. Over-expression or under-expression of miR-223 was inducted in RAW264.7 macrophages to investigate the function of miR-223. Real-time quantitative PCR, ELISA and western blotting were used to determine the expression levels of miR-223, cytokines and the NLRP3 inflammasome. <h3>Results</h3> 1. <i>Expression of miR-223 in PBMCs among the AG, IG and HC groups(Figure1)</i> 2. 2.<i>Altered expression of miR-223, the NLRP3 inflammasome and cytokines in MSU-induced RAW264.7 murine macrophage inflammation(Figure2)</i> 3. Effect of miR-223 on cytokine secretion from RAW264.7 macrophages treated with MSU(Figure3) 4. No effect on RAW264.7 macrophage apoptosis(Figure4) 5. Effect of miR-223 on NLRP3 inflammasome expression in RAW264.7 macrophages treated with MSU(Figure5) <h3>Conclusion</h3> Our findings suggest that miR-223 provides negative feedback regulation of gouty inflammation development by suppressing production of IL-1β and TNF-α, but not by regulating IL-37 and TGF-β1, and that miR-223 regulates cytokine production by targeting the NLRP3 inflammasome. These findings provide novel insight into the regulatory role of miR-223 in the spontaneous resolution of acute gouty inflammation. Finally, these results suggest that targeting miR-223 in macrophages might be an effective therapeutic strategy for the treatment of gout flare. <h3>References</h3> [1] Henshall DC, Hamer HM, Pasterkamp RJ, Goldstein DB, Kjems J, Prehn JHM, Schorge S, Lamottke K, Rosenow F: MicroRNAs in epilepsy: pathophysiology and clinical utility. Lancet Neurol 2016; 15:1368-1376. <h3>Disclosure of Interests</h3> Yu-Feng Qing Grant/research support from: Sichuan Youth Science and Technology (2016JQ0053), and the Department of Science and Technology of Sichuan Province (2018JY0257), Dan Zhu: None declared, Ting Yi: None declared, Jian-Xiong Zheng: None declared, Qin Xiong: None declared, Quan-Bo Zhang: None declared
Monitoring antimicrobial resistance trends in commensal Escherichia coli from livestock, the Netherlands, 1998 to 2016
Authors: Ayla Hesp, Kees Veldman, Jeanet van der Goot, Dik Mevius, Gerdien van Schaik
Journal: Eurosurveillance (2019)

Background Monitoring of antimicrobial resistance (AMR) in animals is essential for public health surveillance. To enhance interpretation of monitoring data, evaluation and optimisation of AMR trend analysis is needed. Aims To quantify and evaluate trends in AMR in commensal Escherichia coli , using data from the Dutch national AMR monitoring programme in livestock (1998–2016). Methods Faecal samples were collected at slaughter from broilers, pigs and veal calves. Minimum inhibitory concentration values were obtained by broth microdilution for E. coli for 15 antimicrobials of eight antimicrobial classes. A Poisson regression model was applied to resistant isolate counts, with explanatory variables representing time before and after 2009 (reference year); for veal calves, sampling changed from 2012 represented by an extra explanatory variable. Results Resistant counts increased significantly from 1998-2009 in broilers and pigs, except for tetracyclines and sulfamethoxazole in broilers and chloramphenicol and aminoglycosides in pigs. Since 2009, resistant counts decreased for all antimicrobials in broilers and for all but the phenicols in pigs. In veal calves, for most antimicrobials no significant decrease in resistant counts could be determined for 2009–16, except for sulfamethoxazole and nalidixic acid. Within animal species, antimicrobial-specific trends were similar. Conclusions Using Dutch monitoring data from 1998-2016, this study quantified AMR trends in broilers and slaughter pigs and showed significant trend changes in the reference year 2009. We showed that monitoring in commensal E. coli is useful to quantify trends and detect trend changes in AMR. This model is applicable to similar data from other European countries.
Molecular MRD status and outcome after transplantation in NPM1-mutated AML
Authors: Richard Dillon, Robert Hills, Sylvie Freeman, Nicola Potter, Jelena Jovanovic, Adam Ivey, Anju Shankar Kanda, Manohursingh Runglall, Nicola Foot, Mikel Valganon, Asim Khwaja, Jamie Cavenagh, Matthew Smith, Hans Beier Ommen, Ulrik Malthe Overgaard, Mike Dennis, Steven Knapper, Harpreet Kaur, David Taussig, Priyanka Mehta, Kavita Raj, Igor Novitzky-Basso, Emmanouil Nikolousis, Robert Danby, Pramila Krishnamurthy, Kate Hill, Damian Finnegan, Samah Alimam, Erin Hurst, Peter Johnson, Anjum Khan, Rahuman Salim, Charles Craddock, Ruth Spearing, Amanda Gilkes, Rosemary Gale, Alan Burnett, Nigel H. Russell, David Grimwade
Journal: Blood (2020)
Abstract 11606: Significance of Non-PV Triggers in Patients With Persistent Atrial Fibrillation: Results From 5 Years of Follow-up
Authors: Chintan Trivedi, Sanghamitra Mohanty, Carola Gianni, J. David Burkhardt, Javier Sanchez, Rodney Horton, G. Joseph Gallinghouse, Richard Hongo, Salwa Beheiry, Amin Al-Ahmad, Luigi Di Biase, Andrea Natale
Journal: Circulation (2017)

Introduction: Pulmonary vein antrum isolation (PVAI) alone is reported to have limited success rate in patients with persistent AF (PerAF). Hypothesis: This study evaluated the prevalence of trigge...
FRI0242 SUBPOPULATION COMPOSITION OF INFLAMMATORY INFILTRATES OF THE MINOR SALIVARY GLAND AS AN ADDITIONAL DIAGNOSTIC CRITERION FOR PRIMARY SJOGREN’S SYNDROME
Authors: Evgenii Kuvardin, Irina Grigor’eva, Irina Bekhtereva, Valentina Myachikova
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Primary Sjogren's syndrome (pSS) is frequent nosological forms among the diffuse connective tissue diseases. Histological examination of the minor salivary gland (MSG) is important diagnostic method. The currently established histological criteria for pSS indicates 61.2-93.7% sensitivity and 61.2-100% specificity respectively, which makes the search for additional hallmark highly relevant. Immunohistochemical study of MSG is the most appropriate for this purpose. <h3>Objectives:</h3> To study of the qualitative and quantitative compositions of cellular subpopulations minor salivary gland mononuclear foci as additional histological criteria of pSS. <h3>Methods:</h3> The study included 56 patients with a definite diagnosis of pSS according to the criteria of ACR\EULAR 2016. The control group consisted of 19 healthy volunteers. The biopsy of the minor salivary gland was performed for all the subjects, followed by an immunohistochemical study to evaluate the expression of CD3, CD4, CD8, CD20, CD21, CD68, CD138. A statistical analysis of the data obtained during the study was carried out using the SPSS 23 statistical software for Windows (IBM, United States of America). Diagnostic threshold for each biomarker was determined by ROC analysis. Operating characteristic curve, area under the curve (AUC), specificity, sensitivity, diagnostic accuracy (DT), diagnostic thresholds (DP), positive likelihood ratio (LR+) and negative likelihood ratio (LR-) were also calculated. The construction of classification models, including several markers, was performed using linear discriminant analysis. <h3>Results:</h3> The largest AUC were observed in CD3 - 0.795 [95% confidence interval (CI) 0.697 - 0.893] and CD20 - 0.796 (95% CI 0.698 - 0.894), which at the specified DP corresponded to the sensitivity of 67.9% (95% CI 54.04 - 79.71) and 71.4% (95% CI 57.79 - 82.7), specificity of 95% (95% CI 73.97 - 99.87) and 95% (95% CI 73.97 - 99.87). The CD21 marker was detected only in the PSS group. AUC for this biomarker was 0.652 (95% CI 0.525 - 0.778), sensitivity - 30.4% (95% CI 18,78 - 44.1), specificity - 100% (95% CI 82,35 - 100). Using the method of discriminative analysis, we designed classification models that included various combinations of the markers under study. The combination of the decimal logarithms CD3 and CD68 had AUC 0.873 (95% CI 0.794 - 0.953), sensitivity - 76.8% (95% CI 63.58 - 87.02), specificity - 95% (95% CI 73.97 – 99.87). <h3>Conclusion:</h3> CD3 and CD20 can be considered as additional histological criteria for pSS. CD21 was observed only in patients with pSS. The combined quantitative assessment of CD3 and CD68 had a greater diagnostic value compared to CD3 and CD68 separately. <h3> Disclosure of Interests:</h3> None declared
FRI0504 TOCILIZUMAB CONTROLS BONE TURNOVER IN EARLY POLYMYALGIA RHEUMATICA
Authors: ALEGRIA Guillermo CARVAJAL, Eleonore Bettacchioli, Alain Saraux, Divi Cornec, Valerie Devauchelle-Pensec, Yves Renaudineau
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Tocilizumab has been proved to be an alternative to corticosteroids in treating polymyalgia rheumatica. Considering the action on interleukin-6 on bone turnover an effect of tocilizumab is supposed. Few data are available about bone turnover in rheumatoid arthritis patients treated with tocilizumab but no data are available in polymyalgia rheumatica patients. <h3>Objectives</h3> This study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR). <h3>Methods</h3> Twenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W)12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients. <h3>Results</h3> Polymyalgia rheumatica patients were characterized by higher levels of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (<i>p</i>=0.0008<i>, versus</i> W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (<i>p</i>=0.001<i>, versus</i> W0) (figure 1). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r=0.255 at W0 <i>versus</i> r=0.641 in healthy controls) and its correction after treatment (r=0.760 at W12 and r=0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy. <h3>Conclusion</h3> Control of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of polymyalgia rheumatica. <h3>Disclosure of Interests:</h3> Guillermo CARVAJAL ALEGRIA: None declared, Eleonore Bettacchioli: None declared, Alain Saraux Consultant for: Roche SAS, Speakers bureau: Chugai Pharma France, Divi Cornec: None declared, Valerie Devauchelle-Pensec Grant/research support from: Roche-Chugai, Speakers bureau: MSD, BMS, UCB, Roche, Yves Renaudineau: None declared
A Subset of Skin Macrophages Contributes to the Surveillance and Regeneration of Local Nerves
Authors: Julia Kolter, Reinhild Feuerstein, Patrice Zeis, Nora Hagemeyer, Neil Paterson, Paolo d’Errico, Sebastian Baasch, Lukas Amann, Takahiro Masuda, Anne Lösslein, Kourosh Gharun, Melanie Meyer-Luehmann, Claudia Waskow, Claus-Werner Franzke, Dominic Grün, Tim Lämmermann, Marco Prinz, Philipp Henneke
Journal: Immunity (2019)