tbuckley/cabot-search huggingface dataset:
PB1980 IMPROVING HEALTHCARE PROVIDERS’ KNOWLEDGE REGARDING THE PRINCIPLES OF GENE THERAPY FOR HEMOPHILIA THROUGH ONLINE EDUCATION
Authors: S. Hurst, C. Warren, H. Kadkhoda, E. VanLaar, G. Pierce
Journal: HemaSphere (2019)

Background: Gene therapy offers the hope of a functional cure for hemophilia. To prepare healthcare providers (HCPs) for this potential paradigm shift in care, National Hemophilia Foundation (NHF), European Haemophilia Consortium (EHC), the World Federation of Hemophilia (WFH), and Medscape Education collaborated to develop a multi‐modal, online, continuing medical education (CME) curriculum. Aims: The current study assessed the ability of online CME to improve HCPs knowledge regarding the scientific principles underlying gene therapy overall and its study in hemophilia. Methods: A 15‐minute, CME‐certified video commentary with synchronized slides was developed and launched online on 8/3/2018. Educational effectiveness was assessed with a repeated‐pairs pre‐/post‐assessment study design, in which each individual served as his/her own control. Responses to 3 multiple‐choice, knowledge questions and 1 self‐efficacy confidence question were analyzed. A chi‐squared test assessed changes pre‐ to post‐assessment. P values &lt;0.05 are statistically significant. Effect sizes were evaluated using Cramer's V (&lt;0.05 modest; 0.06‐0.15 noticeable effect; 0.16‐0.26 considerable effect; &gt;0.26 extensive effect). Results: To date, 1634 HCPs (958 physicians) have participated in this activity. This analysis presents data from the subset of hematologists/oncologists (n = 77; hem/oncs) and pediatric oncologists (n = 69) who answered all pre‐/post‐assessment questions during the initial analysis period of 8/3/18‐9/5/18; data collection is ongoing. Significant improvements were observed overall (hem/oncs: P = .0007; V = .156) and in the following areas, ‐ Correct identification of transient transaminitis as the most common adverse event observed in gene therapy trials: hem/oncs: 45% vs 73% (62% relative increase), P = 0.0006, V = .277; and pediatric hematologists: 26% vs 43% (% relative increase), P = .032, V = .181 ‐ Recognition of the relatively low homology between the adeno‐associated virus (AAV) vector used in gene therapy trials for hemophilia A (AAV5) and other primate AAVs: hem/oncs: 36% vs 55% (53% relative increase), P = 0.023, V = .182 ‐ Pediatric hematologists exhibited a small increase in knowledge, but this change was not statistically significant: 33% vs 41% (24% relative increase), P = NS ‐ Both of hem/oncs (39%) and pediatric hematologists (32%) indicated increased confidence in their understanding of the science underlying gene therapy in hemophilia Lastly, the findings uncovered educational needs, such as the understanding of the FIX construct currently under study in hemophilia B trials. Summary/Conclusion: Participation in this online activity significantly improved knowledge among hem/oncs and pediatric hematologists with regard to the adverse events, viral vectors, and gene constructs in current clinical trials for gene therapy in hemophilia.
Do the salivary glands of patients with systemic sclerosis show ultrasonographic modifications suggestive of Sjögren's syndrome?
Authors: Marion Couderc, Anne Tournadre, Sylvain Mathieu, Bruno Pereira, Martin Soubrier, Jean Jacques Dubost
Journal: Annals of the Rheumatic Diseases (2019)

The paper by Ferdowsi et al , reported a 23-item composite damage index to quantify organ damage in systemic sclerosis (SSc).1 In this index, sicca symptoms (item 3) play an important role (weight score=3). Actually, sicca symptoms are frequently reported by patients with SSc (7.5%–68%) and could be due to a fibrosis process of the salivary glands (SGs).2–4 In recent years, ultrasonography (US) of the parotid and submandibular glands has been widely used for identifying SG modifications in patients with primary Sjogren’s syndrome (pSS). In order to assess modifications in the SG echostructure in patients with SSc and compare them with those of patients with pSS or controls with sicca symptoms, we prospectively enrolled patients with SSc fulfilling the American College of Rheumatology/European League against Rheumatism (ACR/EULAR) 2013 classification criteria, patients with pSS according …
Исследование показателей качества жизни по данным SF-8 у пациентов с функциональными гастроинтестинальными заболеваниями
Authors: A.E. Dorofeiev, T.Ye. Kuhler, A.Yu. Butova
Journal: GASTROENTEROLOGY (2020)

Исследование качества жизни (КЖ) — весьма важный метод, который может способствовать улучшению контакта между врачом и пациентом, выявлению влияния заболевания на физическое, психологическое и социальное благополучие пациента, повышению эффективности проводимой терапии и разработке реабилитационных программ. Целью работы было исследовать психосоматические особенности и КЖ больных с синдромом раздраженного кишечника (СРК) и функциональной диспепсией (ФД). Данное исследование являлось кросс-секционным. В него были включены 80 пациентов с диагнозом ФД и 93 пациента с диагнозом СРК согласно Римским критериям III, а также группа контроля из 30 здоровых добровольцев. Проводилась оценка КЖ, связанного со здоровьем, по стандартной 4-недельной форме опросника SF-8. При сравнении показателей уровня КЖ пациентов с ФД и СРК было выявлено значительное ухудшение в сравнении с группой контроля, однако не было статистически значимых отличий между ними (p &lt; 0,05).
Cell death–mediated cytokine release and its therapeutic implications
Authors: David E. Place, Thirumala-Devi Kanneganti
Journal: The Journal of Experimental Medicine (2019)

Targeting apoptosis to treat diseases has seen tremendous success over the past decades. More recently, alternative forms of regulated cell death, including pyroptosis and necroptosis, have been described. Understanding the molecular cascades regulating both pyroptosis and necroptosis will yield even more targets to treat diseases. These lytic forms of cell death are distinct from apoptosis due to their characteristic lysis and release of cellular components that promote disease or direct a beneficial immune response. In this review, we focus on how pyroptosis and necroptosis, which release potent immune cytokines such as IL-1 and IL-18, contribute to various diseases. We also consider the important role that the executioners of these cell death pathways, GSDMD and MLKL, play in the progression of inflammatory diseases. Crosstalk between the different cell death pathways likely plays a major role physiologically. New therapeutic strategies targeting these specific molecules hold enormous potential for managing inflammatory diseases.
Genome-wide stability of the DNA replication program in single mammalian cells
Authors: Saori Takahashi, Hisashi Miura, Takahiro Shibata, Koji Nagao, Katsuzumi Okumura, Masato Ogata, Chikashi Obuse, Shin-ichiro Takebayashi, Ichiro Hiratani
Journal: Nature Genetics (2019)
AB0365 EFFICACY OF TOCILIZUMAB FOR CORTICOSTEROID AND METHOTREXATE SPARING IN RHEUMATOID ARTHRITIS
Authors: Panagiotis Athanassiou, Marina Gatsiou, Lambros Athanassiou, Pavlos Tsakiridis, Aikaterini Tzanavari, Eirini Devetzi, Charoula Katsavouni, Ifigenia Kostoglou-Athanassiou
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Successful management of rheumatoid arthritis (RA) depends on the early administration of DMARDs and biologic DMARDs. The biologic agent tocilizumab, an interleukin-6 receptor inhibitor, has been used for the management of RA. <h3>Objectives</h3> The aim was to describe a cohort of RA patients treated with tocilizumab and the effect of this treatment on the other DMARDs used, namely methotrexate and corticosteroids. <h3>Methods</h3> In a cohort of 80 patients with rheumatoid arthritis the biologic agent tocilizumab was administered in combination with methotrexate administered sc and 10 mg prednisolone. Within this cohort, 26 patients were on tocilizumab administered iv 8 mg/kg/4wks (maximum dose 800 mg) and 54 were on tocilizumab administered sc 162mg/wk. As corticosteroid administration is characterized by adverse effects, such as osteoporosis and diabetes mellitus, in the course of the disease, in all patients an effort was made to reduce and, if possible, withdraw corticosteroids. An effort was also made to reduce methotrexate dosage. After a year, prednisolone was either significantly reduced or withdrawn. The final dosage of prednisolone was either 2.5-5 mg or complete withdrawal. The successful reduction of methotrexate dosing schedule was also achieved. The final methotrexate dose was either 12.5 mg sc or complete withdrawal. After a period of 52 weeks in this cohort 42 of 80 patients (52.5%) were on monotherapy with tocilizumab. <h3>Results</h3> In a cohort of 80 patients with RA the administrations of tocilizumab, either iv or sc, proved safe and effective. Remission or low disease activity of RA was achieved. Corticosteroid dosage was reduced. Methotrexate dosage was also reduced. After 52 weeks within the group of RA patients on treatment with tocilizumab, in 42 complete withdrawal of corticosteroids and methotrexate proved feasible. Patients on tocilizumab monotherapy remained in remission. <h3>Conclusion</h3> It appears that tocilizumab is safe and effective for the treatment of RA. Tocilizumab treatment may permit withdrawal of both corticosteroids and methotrexate in patients with RA. The management of active RA initially with low dose corticosteroids in combination with methotrexate sc and, in the case of failure to achieve remission, with the addition of the biologic agent tocilizumab had as a result either significant corticosteroid reduction or complete withdrawal and reduction of methotrexate dosage, the disease remaining in remission. <h3>Disclosure of Interests</h3> None declared
PF568 INVESTIGATING MECHANISMS OF ELOTUZUMAB AND LENALIDOMIDE THERAPY IN MULTIPLE MYELOMA
Authors: K.J. Richardson, M. Robbins, N.A. Bezman, H. Quach, S.J. Harrison, M.H. Prince, D.S. Ritchie, M.R. Jenkins, P.A. Beavis, P.K. Darcy, P.J. Neeson
Journal: HemaSphere (2019)

Background: Multiple myeloma (MM) is currently incurable. To investigate new treatment options, patients with refractory relapsed (RR) MM were treated with combination of Elotuzumab (Elo, anti‐SLAMF7 antibody) and Lenalidomide (Len, IMiD) and had a 84% objective response rate. We hypothesized this Elo+Len clinical efficacy was due to repair of NK dysfunction in MM patient NK cells. Aims: To explore the mechanisms whereby Elo+Len rescued MM patient NK cell function. Methods: We co‐cultured MM patient PBMCs with myeloma cells and drug combinations in vitro, and compared changes in NK cell activation, cytotoxicity, cytokine/chemokine levels, and adhesion molecule expression between healthy donor (HD) and MM patient cohorts. We also used a humanized MM model to explore the in vivo efficacy of the Elo+Len combination. Results: We showed that Elo engaged NK cell FcγRIIIa, initiated anti‐myeloma cell cytotoxicity and NK cell secretion of pro‐inflammatory cytokines (IFNγ, TNFα) and chemokines (CCL3, CCL4, CCL5), suggesting recruitment of other immune effector cells to the tumour. Elo+Len treatment significantly enhanced in‐vitro Elo‐induced cytotoxicity of healthy donor (HD) and newly diagnosed MM (NDMM) patient PBMCs. In contrast, RRMM patient NK cells had divergent responses to Elo+Len treatment, including impaired cytotoxicity (7/11 patients), and normal cytotoxicity (4/11 patients) ( Fig 1A ). Len significantly increased the chemokine secretion of HD PBMCs and to a lesser extent, NDMM and RRMM patient PBMCs, with the exception of CCL5 which was upregulated similarly between all groups. Interestingly, both MM‐derived NK cells and OPM2 myeloma cells upregulated CD54 following Elo and Len therapy, strongly correlated with myeloma cell killing (P = 0.002, R 2 = 0.76). This was most evident on the 4 responding RRMM patient PBMCS and their OPM2 targets ( Fig 1A‐B , data points highlighted in red). Surprisingly, NK cell CD107a was upregulated equally on all groups in response to Elo, regardless of killing activity. This suggests MM patient dysfunctional NK cells are sufficiently activated to degranulate, but are unable to kill myeloma cells due to inefficient adhesion and synapse formation. We also found that Elo induced in‐vivo therapeutic efficacy of human NK cells against RPMI8226.huSLAMF7 (RPMI8226 cells engineered to express human SLAMF7) multiple myeloma tumors, this was further enhanced with Len co‐treatment (Fig 1C) . Summary/Conclusion: Our data suggests that Len improved Elo‐induced tumor control via increased cytotoxicity, chemotactic recruitment of effector cells and enhanced NK‐target synaptic adhesion. These data also suggest that monitoring an increase in CD54 expression on MM patient myeloma cells and NK cells may be a useful biomarker that tracks with Elo+Len efficacy. image
Abstract 13749: Importance of Multiple Biomarker Approach in Patients With Cardiac Sarcoidosis
Authors: Takatoyo Kiko, Akiomi Yoshihisa, Yusuke Kimishima, Yu Sato, Shunsuke Watanabe, Yuki Kanno, Makiko Tatsumi, Satoshi Abe, Takamasa Sato, Satoshi Suzuki, Masayoshi Oikawa, Atsushi Kobayashi, Takayoshi Yamaki, Hiroyuki Kunii, Kazuhiko Nakazato, Shu-ichi Saitoh, Takafumi Ishida, Yasuchika Takeishi
Journal: Circulation (2017)

Background: Sarcoidosis is a systemic, granulomatous disease of unknown origin that has variable clinical courses and affects multiple organs, including the heart (cardiac sarcoidosis, CS). It has ...
AB1413-HPR FACTORS AFFECTING ACTIVITIES OF DAILY LIVING IN WOMEN INDIVIDUALS WITH SCLERODERMA
Authors: Serap Acar, Nazenin Hande Sezgin, Sema Savci, Aylin Tanriverdi, Buse Ozcan Kahraman, Aydan Koken Avsar, Ahmet Merih Birlik
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Scleroderma is a multisystemic chronic disease with hand involvement in many patients and responsible for marked disability. Patients with scleroderma have reduced ability to perform activities of daily living (ADL) and several factors may be associated with difficulties in ADL and impairment of upper extremity functions. <h3>Objectives</h3> Aim of this study was to indicate the relationship among activities of daily living and pain, fatigue, disease severity, upper extremity strength and functional disability in patients with scleroderma and to identify the factors affecting activities of daily living in individuals with scleroderma. <h3>Methods</h3> Thirty five women individuals with scleroderma with mean age 56.46 10.45 were included into the present study. The activities of daily living was evaluated with Milliken ADL questionnaire, pain with visual analog scale (VAS), fatigue with fatigue severity scale (FSS), disease severity with modified Rodnan score (MRS), upper extremity strength with handgrip strength and functional disability with Health Assessment Questionnaire (HAQ). The relationships among the variables were analyzed by the Spearman correlation test. Correlation coefficients between Milliken ADL and other variables were determined by linear regression. The statistics were analyzed by SPPS 23.0 version. <h3>Results</h3> The Milliken ADL did not significantly correlated with MRS and VAS (p &gt; 0.05), whereas Milliken ADL did significantly correlated with handgrip strength (r = 0.680, p = 0.001), FSS (r = - 0.729, p = 0.001), HAQ (r = - 0.867, p = 0.001). Additionally, handgrip strength, fatigue severity scale and HAQ were significant and independent determinants for activities of daily living, accounting for 95.0% of the variance in Milliken ADL in patients with scleroderma. <h3>Conclusion</h3> The findings of this study show that scleroderma patients daily life is affected by the disease at different levels. Impaired hand function and difficulties in the performance of ADL are common in scleroderma and may influence an individuals functional disability. Therefore, provide therapeutic interventions at the optimal time it is important to follow the development of these factors in the early stages of the disease. <h3>References</h3> [1] G. Sandqvist, R. Hesselstrand &amp; K. Eberhardt (2009) A longitudinal follow-up of hand involvement and activities of daily living in early systemic sclerosis, Scandinavian Journal of Rheumatology, 38:4, 304-310, DOI: 10.1080/03009740802695466 [2] Kemal EROL, Kevser GOK, Gizem CENGIZ and Salih OZGOCMEN Hand functions in systemic sclerosis and rheumatoid arthritis and influence on clinical variables International Journal of Rheumatic Diseases2018; 21: 249252 <h3>Disclosure of Interests</h3> None declared
Single Cell Transcriptomics, Mega-Phylogeny, and the Genetic Basis of Morphological Innovations in Rhizaria
Authors: Anders K. Krabberød, Russell J.S. Orr, Jon Bråte, Tom Kristensen, Kjell R. Bjørklund, Kamran Shalchian-Tabrizi
Journal: Molecular Biology and Evolution (2017)

The innovation of the eukaryote cytoskeleton enabled phagocytosis, intracellular transport, and cytokinesis, and is largely responsible for the diversity of morphologies among eukaryotes. Still, the relationship between phenotypic innovations in the cytoskeleton and their underlying genotype is poorly understood. To explore the genetic mechanism of morphological evolution of the eukaryotic cytoskeleton, we provide the first single cell transcriptomes from uncultured, free-living unicellular eukaryotes: the polycystine radiolarian Lithomelissa setosa (Nassellaria) and Sticholonche zanclea (Taxopodida). A phylogenomic approach using 255 genes finds Radiolaria and Foraminifera as separate monophyletic groups (together as Retaria), while Cercozoa is shown to be paraphyletic where Endomyxa is sister to Retaria. Analysis of the genetic components of the cytoskeleton and mapping of the evolution of these on the revised phylogeny of Rhizaria reveal lineage-specific gene duplications and neofunctionalization of α and β tubulin in Retaria, actin in Retaria and Endomyxa, and Arp2/3 complex genes in Chlorarachniophyta. We show how genetic innovations have shaped cytoskeletal structures in Rhizaria, and how single cell transcriptomics can be applied for resolving deep phylogenies and studying gene evolution in uncultured protist species.
The Opportunity of CBD — Reforming the Law
Authors: Pieter A. Cohen, Joshua Sharfstein
Journal: New England Journal of Medicine (2019)

Interview with Dr. Pieter Cohen on the legal status of cannabidiol and an opportunity to strengthen the FDA's approach to safety requirements for new dietary ingredients. (07:42)Download Recently, the FDA has taken the position that cannabidiol cannot be legally sold in either supplements or foods. As many manufacturers defy the FDA, this moment may provide an opportunity to improve the oversight of supplement ingredients and food additives.
PB2153 MENTAL HEALTH AND QUALITY OF LIFE IN PATIENTS WITH RELAPSED/REFRACTORY MULTIPLE MYELOMA TREATED WITH ELOTUZUMAB PLUS LENALIDOMIDE AND DEXAMETHASONE
Authors: Y. Hiramatsu, S. Kubonishi, T. Inomata, N. Motizuki, R. Ueda, Y. Goto
Journal: HemaSphere (2019)

Background: Elotuzumab plus lenalidomide and dexamethasone (ELd) is an important treatment option for the management of patients with relapsed/refractory multiple myeloma (RRMM). This, combined with the well-established long-term safety and tolerability profile, supports this regimen as a valuable treatment option offering long-term benefits to patients with RRMM. Current therapies aim to maintain health-related quality of life (HRQoL) while prolonging survival. In the ELOQUENT-2 study, improvements in PFS and ORR were achieved without compromising pain control or diminishing HRQoL, pain scores and HRQoL remaining unaffected over time. However, in clinical practice, there are few reports confirming the influence of the patient's mental state on quality of life while continuing ELd therapy. Aims: The aim of this study was to evaluate the patient's mental state before and after ELd therapy as a mediator of health-related quality of life. Methods The study population was 15 RRMM patients who would be treated with ELd as a clinical practice. Data were collected from a self-administered questionnaire and patients’ medical records. We developed an original questionnaire called M-QoL8 to confirm the patient's condition in clinical practice, not for clinical research. The module comprises eight questions: burden or suffering of visit, the treatment feels effective, want to continue treatment, improve the quality of life, having hope for living, better than pretreatment and feeling that they are healthy. After obtaining informed consent, we assessed QoL of the baseline and 4th cycle after study enrolment. We also assessment of HRQoL using the EORTC QLQ-C30, QLQ-MY20. Results: A total of 16 RRMM patients receiving ELd therapy were enrolled between June 2018 and March 2019. Completed questionnaire were received from 15 patients. The median age was 76 years (range;66-87), and male was dominant (n = 13,81%). We summarized the 11 cases that we could evaluate for the second time and update it at the time of presentation. In the first questionnaire after ELd therapy, the average score of feeling that they are healthy was as high as 8.3 (5-10) compared with the average score of 6.7 (0-10) for the treatment feels effective. This tendency was similar in the questionnaire after the addition of 4th cycle, and the average score of hope of continuation of ELd therapy was maintained at 7.8 to 8.2. Summary/Conclusion: In RRMM patients who cannot expect cure, an important goal for continuing treatment is to maintain quality of life, with patients feeling that they are healthy, and having hope for living. As a result of comparison before and after the start of ELd therapy, many patients report that they are maintaining their health. Using simple questions in the M-QoL8 to evaluate mental and emotional quality of life, it is possible to evaluate these important aspects of health before and after ELd treatment.