tbuckley/cabot-search huggingface dataset:
SAT0211 LYMPHOPENIA WITH SYSTEMIC LUPUS ERYTHEMATOSUS: LYMPHOCYTE SUBSETS OF PATHOPHYSIOLOGICAL FEATURES
Authors: Ning Yan, Jie Liang, Fangyuan Hu, Chong Gao, LI Xiaofeng, Caihong Wang
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is an autoimmune disease involving multiple systems. It is mainly characterized by abnormal activation of T and B lymphocytes and the production of a large number of autoantibodies. Blood system involvement is a common clinical manifestation. The occurrence of lymphopenia is very common, easy to merge infection and primary immunodeficiency<sup>[1-3]</sup>. <h3>Objectives</h3> To study the distribution characteristics of peripheral blood lymphocyte cell subsets in patients with newly diagnosed SLE and to explore the possible mechanism of lymphocyte reduction. <h3>Methods</h3> Sixty-six female patients with initial SLE. The diagnosis was consistent with the 1997 revised American College of Rheumatology (ACR) SLE classification criteria, and no glucocorticoids and immunosuppressive agents were used. According to the absolute value lymphocytes with SLE, 40 patients were divided into lymphopenia group(LA)(LY&lt; 1.0×10<sup>9</sup>/L), and 26 patients were normal lymphocytes group(LN). 30 female healthy controls. The absolute numbers of lymphocyte cell subsets and T subsets (total T, CD4<sup>+</sup>T, CD8<sup>+</sup>T, T helper 1 (Th1), T helper 2 (Th2), T helper 17 (Th17) and CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>T regulatory (Treg) cells) in peripheral blood were measured by Flow Cytometer (FCM). <h3>Results</h3> In the lymphopenia group, the absolute counts of T cell subsets and NK cells were significantly reduced, but the percentage of B cells and Th1 cells and the ratio of Th1/Th2 cells were significantly increased (Figure 1). The absolute number of CD4+ T cells and CD8+ T cells was significantly positively correlated with C3 levels(Figure 2). <h3>Conclusion</h3> Decresed T cell subsets and NK cells may be key pathophysiological features, as risk factor for development of severe infections and primary immunodeficiency in patients lymphopenia with SLE. Meanwhile, decreased CD4+ T cells and CD8+ T cells and increased B cells may cause auto- antibodies production leading to lymphopenia with SLE. Further studies are needed to assess profound lymphopenia and require specific management. <h3>References</h3> [1] MartinM, GuffroyA, ArgemiX,eta1.Systemic lupus erythematosus and lymphopenia: Clinical and pathophysiological features[J].Rev Med Interne. 2017 Sep;38(9):603-613. [2] Chen D, Li H, Xie J,etal. Herpes zoster in patients with systemic lupus erythematosus: Clinical features, complications and risk factors[J]. Exp Ther Med. 2017 Dec;14(6):6222-6228. [3] Merayo-Chalico J, Gómez-Martín D, Piñeirúa-Menéndez A,etal. Lymphopenia as risk factor for development of severe infections in patients with systemic lupus erythematosus: a case-control study[J]. QJM. 2013 May;106(5):451-7. <h3>Disclosure of Interests</h3> None declared
What will it take to stop the tobacco epidemic?
Authors: Navjoyt Ladher
Journal: BMJ (2019)

It’s almost 70 years since Richard Doll and A Bradford Hill published their landmark paper in The BMJ linking smoking to lung cancer (doi:10.1136/bmj.2.4682.739). In the intervening years we’ve learnt more about the range of lethal harms to health from tobacco and about the industry’s predatory practices. We also know more about the measures that successfully reduce and prevent smoking: taxation, smoke free laws, marketing restrictions, and smoking cessation services.

Yet tobacco remains a leading cause of …
Cellular and gene therapy
Authors: Rose Ann Padua
Journal: HemaSphere (2019)

Learning goals Those who attend this session will be updated on 2 (Checkpoint inhibitors and NK cells) of the exciting areas in immunotherapy. Insights into how invariant NK cells can merge with CART-based therapies will be given. Introduction The Education session has focused on 2 areas in which immunotherapy has delivered and touches on future developments. The first speaker, Pedro Berraono (Spain), presenting on “Mechanisms of action for different checkpoint inhibitors” will focus on checkpoint inhibitors CTLA-4, PD-1/PD-L1 monoclonal antibodies. The second speaker, Anastasios Karadimitris (United Kingdom) will talk on the “ Biology and therapeutic applications of invariant Natural Killer T (iNKT) cells in allogeneic stem cell transplantation and blood cancers” focusing on pre-clinical and clinical evidence to supports a critical role of donor iNKT cells in protection from aGVHD and their potential for its prevention; these iNKT cells may provide an optimal platform for chimeric antigen receptor (CART)-based immunotherapy of blood cancers The third speaker, Harry Dolstra (The Netherlands) will review where we are with “Stem cell derived NK cell therapy”.
The neuropeptide receptor calcitonin receptor-like (CALCRL) is a potential therapeutic target in acute myeloid leukemia
Authors: Linus Angenendt, Eike Bormann, Caroline Pabst, Vijay Alla, Dennis Görlich, Leonie Braun, Kim Dohlich, Christian Schwöppe, Stefan K. Bohlander, Maria Francisca Arteaga, Klaus Wethmar, Wolfgang Hartmann, Adrian Angenendt, Torsten Kessler, Rolf M. Mesters, Matthias Stelljes, Maja Rothenberg-Thurley, Karsten Spiekermann, Josée Hébert, Guy Sauvageau, Peter J. M. Valk, Bob Löwenberg, Hubert Serve, Carsten Müller-Tidow, Georg Lenz, Bernhard J. Wörmann, M. Christina Sauerland, Wolfgang Hiddemann, Wolfgang E. Berdel, Utz Krug, Klaus H. Metzeler, Jan-Henrik Mikesch, Tobias Herold, Christoph Schliemann
Journal: Leukemia (2019)
FRI0233 MORTALITY IN SLE PATIENTS COMPARED TO POPULATION CONTROLS IN FINLAND IN YEARS 2000–2015
Authors: Pia Elfving, Hannu Kautiainen, Lauri Virta, Oili Kaipiainen-Seppänen, Kari Puolakka
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> It is well established from a variety of studies that systemic lupus erythematosus (SLE) patients have a shortened life expectancy. The literature on SLE has highlighted the impact of cardiovascular diseases (CVD) on increased mortality <sup>1,2</sup>. However, there is lack of studies comparing results to the background population. <h3>Objectives:</h3> Aim of the study was to clarify, whether incident SLE patients have an excess mortality compared to population controls. <h3>Methods:</h3> The study included all adult (age ≥ 17 years), incident SLE patients who were entitled to a special reimbursement for SLE medication in years 2000 – 2014 in Finland. For each patient, the Population Register Centre identified 3 population controls matched for age, sex and place of residence. Comorbidities at baseline were obtained from the Care Register for Health Care of the National Institute for Health and Welfare. Data on education at baseline and deaths until the end of 2015 were retrieved from the Statistics Finland. <h3>Results:</h3> A total of 1006 incident SLE patients (84% females) and 3005 population controls were found. During the follow-up (mean 8.6 years), 98 patients (mean age at death 70±14 years, 65% females) died. The 5 -, 10-, and 15-year survival rates in SLE patients were 95.0% (95%CI 93.3-96.2%), 88.8% (86.2-91.0%) and 82.1% (77.6-85.8%), respectively. The number of deaths among controls was 187. Crude hazard ratio (HR) was 1.61 (95% CI: 1.26 to 2.06), p&lt;0.001, adjusted for education- and comorbidities 1.14 (95% CI: 0.88 to 1.48) p=0.32. Main causes of deaths in patients were CVDs (33%), malignancies (27%) and neurological diseases (10%). Ten-year cumulative mortality rate due to CVD was in SLE patients 3.3% (95CI 2.2 to 4.9%) and in controls 2.6% (2.0-3.3) and 15-year rate 6.7% (95C% CI 4.2 to 9.9) and 4.9% (3.6 to 12.0), respectively. Crude HR for CVD deaths was 1.28 (95% CI: 0.85 to 1.93), p=0.24, adjusted 0.88 (95% CI: 0.56 to 1.39), p=0.58. <h3>Conclusion:</h3> SLE patients had a slightly increased risk for overall and cardiovascular related mortality compared to population controls. After adjusting for education and comorbidities, the difference was not statistically significant. <h3>References:</h3> [1] Bernatsky S, et al. Mortality in systemic lupus erythematosus. Arthritis Rheum 2006;54:2550-7. [2] Björnådal L, et al. Cardiovascular disease a hazard despite improved prognosis in patients with systemic lupus erythematosus: results from a Swedish population based study 1964-95. J Rheumatol 2004;31:713-9. <h3>Disclosure of Interests:</h3> Pia Elfving Speakers bureau: Mylan Finland Oy, Abbvie Oy, UCB Pharma Oy Finland, Hannu Kautiainen: None declared, Lauri Virta: None declared, Oili Kaipiainen-Seppänen Speakers bureau: Boehringer Ingelheim, Kari Puolakka: None declared
Breast pectoral muscle segmentation in mammograms using a modified holistically-nested edge detection network
Authors: Andrik Rampun, Karen López-Linares, Philip J. Morrow, Bryan W. Scotney, Hui Wang, Inmaculada Garcia Ocaña, Grégory Maclair, Reyer Zwiggelaar, Miguel A. González Ballester, Iván Macía
Journal: Medical Image Analysis (2019)
OP0252 NEUROPATHIES IN SYSTEMIC LUPUS ERYTHEMATOSUS: RESULTS FROM AN INTERNATIONAL, INCEPTION COHORT STUDY
Authors: John Hanly, LI Qiuju, LI Su, Murray B Urowitz, Caroline Gordon, Sang-Cheol Bae, Juanita Romero-Diaz, Jorge Sanchez-Guerrero, Sasha Bernatsky, Ann E Clarke, Daniel J Wallace, David Isenberg, Anisur Rahman, Joan T Merrill, Paul Fortin, Dafna D Gladman, Ian N. Bruce, Michelle A Petri, Ellen M Ginzler, M.A. Dooley, Kristjan Steinsson, Rosalind Ramsey-Goldman, Asad A Zoma, Susan Manzi, Ola Nived, Andreas Jonsen, Munther Khamashta, Graciela S Alarcon, Ronald F van Vollenhoven, Elisabet Svenungsson, Cynthia Aranow, Meggan Mackay, Guillermo Ruiz-Irastorza, Manuel Ramos-Casals, S. Sam Lim, Murat Inanc, Kenneth C Kalunian, Soren Jacobsen, Christine Peschken, Diane L Kamen, Anca Askanase, Chris Theriault, Vernon Farewell
Journal: Annals of the Rheumatic Diseases (2019)

Asian patients were the youngest, had the lowest complement levels and the highest rate of ENA & DNA consistent with high disease activity.Low complement, but not DNA, was relatively common in Europe.LA patients, like Asians, had high rates of serologic activity but less incidence of low C3/C4, suggesting that this population may have intrinsic disease severity without being as acutely active.*Mann-Whitney Rank Sum **Chi-square # One-way ANOVA on ranks; Med-median p-p value C-comparator ns-not significant; Data not corrected for multiple comparisons Conclusion: SLE patients entering studies from North America are strikingly less likely to have markers of active disease than other regions, raising concerns for their suitability for trials.This appears to be associated, at least in part, with age, although more aggressive treatments cannot be ruled out.Asian subjects have the greatest prevalence of autoantibodies and low complement.Latin American patients have high prevalence of ANA!1:640 and other autoantibodies, but less evidence of low complements.These findings may help to explain regional differences in treatment/placebo responses and emphasize the importance of geographical stratification and improved methods to screen out patients unsuitable for SLE trials.
Scientists urge US Congress to reconsider bill that could allow genes to be patented
Authors: Owen Dyer
Journal: BMJ (2019)

Nine Nobel prize winners are among 83 leading scientists and physicians who have written to US legislators urging them not to rush through changes to patent law that could lead to the patenting of genes—and even of laws of nature.1

The scientists’ letter echoes concerns expressed in a previous letter sent to Congress two weeks ago from 170 organisations, including many US scientific and clinical societies.2

Both groups are alarmed by proposed changes that would rewrite section 101 of the Patent Act. The purpose of that clause is to prevent abuse of the patent process by people who …
Re: HRAS1 rare minisatellite alleles and breast cancer in Australian women under age forty years [2] (multiple letters)
Authors: T. G. Krontiris, J. L. Hopper, F. A. Firgaira, G. S. Dite, G. G. Giles, M. R.E. McCredie, M. C. Southey, D. J. Venter, R. Seshadri, C. R.E. McEvoy
Journal: JNCI Journal of the National Cancer Institute (2000)
MUTATIONS ON COHESIN COMPLEX ARE ASSOCIATED TO A POOR PROGNOSIS IN LOW-RISK MYELODYSPLASTIC SYNDROMES PATIENTS
Authors: M. Martín-Izquierdo, F. López-Cadenas, Sánchez J. del Real, A. Hernández-Sánchez, J. M. Hernández-Sánchez, K. Janusz, E. Lumbreras, M. Díez-Campelo, M. Tormo, M. Megido, C. Olivier, A. Madinaveitia-Ochoa, G. Martín-Nuñez, J. Dávila, C. Aguilar, J. N. Rodríguez, J. M. Alonso, M. Sierra, M. Vargas, S. Santos-Mínguez, C. Miguel-García, R. Benito, J. M. Hernández-Rivas, F. Ramos, M. Abáigar
Journal: HemaSphere (2019)
SP0031 NEWS IN THE WORLD OF REHABILITATION
Authors: Ann Bremander
Journal: Annals of the Rheumatic Diseases (2019)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease requiring long-term treatment with regular monitoring of the ongoing therapeutic process by a rheumatologist to achieve good health outcomes and prevent negative disease impacts.Objectives: The RheVITAL App is the product of a new and multilayered concept of treatment.A combination of a team of rheumatologists, physiotherapists, IT specialists and research partners from the German League against Arthritis have all contributed to the development of this research project.Methods: The presentation will show how this monitoring system improves the treatment of RA individually, monitors the patients on their way to self-empowerment and promotes participative collaboration between patients and rheumatologists.Results: The patients play an active role in the whole system.The patients are trained about their diseases, their treatment and the medicine they are taking.Furthermore they are given much more information about the German patient organisation.Conclusion: My talk will consider the function and management of the app, the difficulties as well as the efforts of data security and the role of the patient organisation as a research partner involved in this project.
Is Acute Myeloblastic Leukemia in Children Under 2 Years of Age a Specific Entity? A Report from the FRENCH ELAM02 Study Group
Authors: S. Blais, H. Boutroux, M. Pasquet, T. Leblanc, O. Fenneteau, V. Gandemer, Y. Bertrand, S. Ducassou, G. Michel, B. Nelken, A. Petit, W. Cuccuini, E. Gouache, Marceau-A. Renaut, A. Baruchel, H. Lapillonne, G. Leverger
Journal: HemaSphere (2019)

Abstract The clinical and biological characteristics of children under 2 years (infants) with acute myeloid leukemia (AML) are different from those of older children. We aimed to describe the specific characteristics of this population and the potential factors that influence the prognosis. We analyzed data concerning 438 children with newly-diagnosed AML treated in the ELAM02 protocol between March 2005 and December 2011, of which 103 were under 2 years old at diagnosis. The evaluation criteria were overall survival (OS) and event-free survival (EFS) of infants vs older children. The clinical and biological features were secondary criteria. Infants presented more frequent extra-medullary presentation than older children. They had a significantly higher proportion of skin lesions and central nervous system involvement (15% vs 3%, p &lt; 0.0001 and 26% vs 12%, p = 0.0005, respectively). The global incidence of KMT2A rearrangements was nearly 55% for infants vs 11% for older children (p &lt; 0.0001). Median 5-year OS was 70.4% for infants vs 71.4% for older children (p = 0.83). Five-year EFS was 67% for infants vs 58% for older children (p = 0.27). Infants with AML represent a cohort of patients with specific clinical and biological features. These remarkable differences had no significant impact on their outcome in the ELAM02 protocol.
Impact of Pneumococcal Vaccination on Multiple Myeloma
Authors: Loïc Renaud, Susanna Schraen, Guillemette Fouquet, Stephanie Guidez, Hélène Demarquette, Morgane Nudel, Claire Bories, Thomas Systchenko, Valentine Richez, Niels Moya, Cécile Gruchet, Deborah Desmier, Zoe Van De Wyngaert, Benjamin Carpentier, Anthony Levy, Antoine Machet, Florence Sabirou, Arthur Bobin, Salomon Manier, Thierry Facon, Stephen Harding, Xavier Leleu
Journal: Blood (2017)
PS1583 BONE MARROW TRANSPLANT AND VENOUS THROMBOEMBOLIC DISEASE, A POTENTIALLY PREVENTABLE CAUSE OF MORTALITY AND MORBILITY
Authors: E. Morente Constantín, M. Rivas Luque, A. Nuñez García, M.A. García Ruiz, A.B. Rivera Ginés, M. Jurado Chacón
Journal: HemaSphere (2019)

Background: Abstract Thrombotic events are frequent in patients undergoing HSCT, being an important cause of morbidity and mortality. The highest incidence occurs three months after the transplant. There are several risk factors, which add to those already known for VTE: neoplasia, central venous catheters, immobilization, chemotherapy, infections, GVHD. In the series described, the frequencies are variable, between 0.5 and 23.5%, with an overall incidence of 5%. In patients with GVHD, this incidence increases, with up to 35% of events. Aims: . Methods: METHODS A retrospective observational study that includes patients transplanted in our Unit between 2014 and 2017 has been conducted, with the objective of analyzing the incidence of VTE peri-TPH. Likewise, we have analyzed if it is associated to catheter, presence of CVRF, if there was a known medical history of thrombophilia, number of platelets at time of thrombosis, the heparin used and whether anticoagulation was maintained indefinitely or not. Results: RESULTS Out of the 235 patients included in our series, 130 underwent an autologous transplant and 105 an allogeneic transplant. 18 thrombotic events occurred (9 men and 9 women, aged between 18 and 65 years), which means 7.5% (14 occurred between days 0–100, 12 in patients undergoing autologous hematopoietic stem cell transplantation). Three of them had thromboembolism and the rest deep vein thrombosis, 4 of which with catheter. The platelet count at the time of the event ranges from 21 to 409,000 / mm3. Regarding the heparin used, 2 were treated with Tinzaparin and the rest with Bemiparin. Only 1 of the patients presented prior VTE. Among the patients, there were some with CVRF and others without relevant medical history. Just in one patient, a family thrombophilia study had been performed prior to his hematological diagnosis, resulting in a deficit of protein S. In 8 of the patients, anticoagulation was maintained indefinitely with LMWH in the post-transplant period. Summary/Conclusion: CONCLUSIONS Our incidence approaches the literature, albeit the series of published cases are heterogeneous and with variable differences. Although the incidence of thrombosis in these patients is a cause of marked morbidity and mortality, the risk of bleeding also increases, therefore routine prophylaxis is not recommended in all patients. We must undergo an exhaustive analysis of the data to identify individually which patients may be candidates for prophylaxis, with the aim of reducing the incidence without raising the hemorrhagic risk of our patients.
PB2369 THE METHOD OF STORAGE OF AUTOLOGOUS PERIPHERAL BLOOD HEMATOPOIETIC STEM CELLS
Authors: G. Rysev, A. Kuzyaeva, S. Voloshin, V. Shuvaev, A. Schmidt, A. Garifullin, A. Kuvshinov, M. Mikhaleva, S. Linnikov
Journal: HemaSphere (2019)

Background: High‐dose chemotherapy (HDCT) followed by autologous transplantation of hematopoietic stem cells (auto‐HSCT) is an important component of treatment in multiple myeloma (MM). There is a standard method of controlled cryopreservation of HSC suspension. We found that the storage of native HSC suspension with temperature fluctuations from +3 °C to +5 °C for 5 days does not significantly affect the content of CD34+ cells in the product, the index 7AAD– (7‐AAD (7‐aminoactinomycin – D) is a fluorescent marker that penetrates damaged cell membranes and binds to double‐stranded DNA. Through 7AAD does not penetrate intact membranes, so living cells are not stained 7AAD with flow cytometry), and colony‐forming ability (CFA) of HSC, as well as the recovery time of hematopoiesis in MM patients after auto‐HSCT. Aims: To evaluate the effectiveness and safety of the method of storage of non‐cryopreserved peripheral blood stem cells. Methods: 26 patients with MM were included in this study(male/female ratio 1.36:1). All the patients get standard immunochemotherapy programs and were in remission at the time of auto‐HSCT. Patients were divided into two groups depending on the method of stem cell storage: group 1 – non‐cryopreserved (n = 10), group 2 – cryopreserved (standard) (n = 16). An effectivity and safety were evaluated in such parameters as the number of CD34+ and 7AAD‐ cells, CFA after apheresis and before reinfusion of HSC. Also we evaluated the number of platelet concentrate transfusions, the timing of engraftment of granulocytic and megakaryocytic blood sprouts, the length of hospital stay after auto‐HSCT, the number of complications. Results: The results are presented in the comparison table of evaluated parameters. Summary/Conclusion: Thus, the proposed method of storage of HSC is not inferior to the traditional method with cryopreservation on such parameters as CD34+, 7AAD–, CFA, the number of platelet concentrate transfusions, terms of hematopoiesis restoration, length of hospital stay after HSCT, the number of complications. image
FRI0003 THE FUNCTION OF IRF7 SNP ON THE PRODUCTION OF TYPE I INTERFERON
Authors: Ye Zhizhong, Yin Zhihua, Zhou Haibo
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Type I IFN plays a significant role in the pathogenesis of Systemic Lupus Erythmatosus (SLE). IRF7 is a critical transcriptional factor for the production of type I interferons (IFN). <h3>Objectives</h3> To explore potential mechanisms for the SLE related IRF7 SNP on type I IFN production, which might indicate new theoretical basis for genetic therapeutic strategy. <h3>Methods</h3> We constructed different genotypes of SLE relevant SNP cell lines by Crispr/Cas9 technology, and confirmed them by sequencing. After TLR-ligand stimulation,the mRNA expression of IFNα was detected by real-time qPCR. The levels of IFNα, TNFα and IL-6 were detected by ELISA kit. The protein expression of IRF7/p-IRF7 was detected by western blot.The binding ability of endogenous IRF7 with typeIIFN promoter was studied by chromatin immunoprecipitation. <h3>Results</h3> We got IRF7 SNP rs1131665 GG/AA cell lines by gene editing technique. After TLR-ligand stimulation, IRF7 SNP rs1131665 AA cell line showed higher IFNα expression than GG, which indicated statistical significance. IRF7 SNP rs1131665 AA cell line showed higher p-IRF7 expression than GG detected with western blot. Endogenous IRF7 in IRF7 SNP rs1131665 AA cell line showed stronger binding ability with IFNα promoter than GG, which indicated statistical significance. <h3>Conclusion</h3> The missense variant of G to A in IRF7 SNP rs1131665, increased the production of typeIIFN, which indicated that IRF7 G to A missense variant increased the susceptibility of type I IFN associated diseases. <h3>References</h3> [1] Lin LH, Ling P, Liu MF.The potential role of interferon-regulatory factor 7 among Taiwanese patients with systemic lupus erythematosus.J Rheumatol. 2011,38(9):1914-1919. [2] Xu WD, Zhang YJ, Xu K, et al. IRF7, a functional factor associates with systemic lupus erythematosus. Cytokine. 2012,58(3):317-320. [3] Miyagawa F, Tagaya Y, Ozato K, et al.Essential Requirement for IFN Regulatory Factor 7 in Autoantibody Production but Not Development of Nephritis in Murine Lupus.J Immunol. 2016,197(6):2167-2176. <h3>Disclosure of Interests</h3> None declared