tbuckley/cabot-search huggingface dataset:
THU0178 THE EFFECT OF TOLEROGENIC DENDRITIC CELLS IN PATIENTS WITH RHEUMATOID ARTHRITIS: A SMALL PILOT TRIAL
Authors: Yuliya Kurochkina, Tamara Tyrinova, Olga Leplina, Marina Tikhonova, Alexey Sizikov, Anna Sulutian, Oksana Chumasova, Alexander Ostanin, Elena Chernykh
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Dendritic cells (DCs) are known to contribute to the pathogenesis of rheumatoid arthritis (RA) through thepresentation of cartilage glycoprotein, production ofproinflammatory cytokines and activation of Th1/Th17 responses. Along with stimulating activity, DCs may exhibit suppressive functions via capacity to induce T cell apoptosis/anergy and to generate regulatory T cells. Since these DCs have potential to control autoreactive T-lymphocytes, utilization of tolerogenicDCs seems to be a promising immunotherapeutic toolto treat RA. <h3>Objectives</h3> The aim of our study is to evaluate the safety and tolerability of a single intra-articular injection(into the knee joint) of autologous monocyte-derived dendritic cells generated in the presence of IFN-α/GM-CSFand tolerized with Dexamethasone inRApatients. <h3>Methods</h3> DCs were generated by culturing blood monocytes for 5 days with GM-CSF and IFN-α in the presence dexamethasone, applied on third day. Azoximer bromides maturation stimuli was added on fourth day. Twelve RA patients with moderate and high disease activity and ultrasound-defined kneesynovitis were recruited in this study. All patients fullfield ACR/EULAR criteria (2010) and received methotrexate, leflunomide, sulfasalazine or their combination. The patients received intra-articular injections of1*10<sup>6</sup>, 3*10<sup>6</sup>, 5*10<sup>6</sup>,8*10<sup>6</sup>,10<sup>*</sup>10<sup>6</sup>DCs in knee joints. Safety was assessed by evaluation of adverse events (AE). Acceptability was assessed by questionnaire. DAS28 and HAQ were used for assessment of treatment efficiency. This trial registered on clinicaltrials.gov (ID:NCT03337165). <h3>Results</h3> DCs injections were safe and well tolerated. No one participants showed worsening of symptoms in targeting knee, fever, elevation of blood pressure or other AE within 7 days after injection. All patients, evaluated at 6 months follow-up showed a good EULAR response (improvement of DAS28-ESR &gt;1.2). The median DAS28-ESR decreased from 5.1to 3.1 (p=0.03). The median pain VAS score decreased from 52 (41-70) mm to 42 (15-55) mm; p=0.04. In addition, we detected median HAQ improvement (from 1.45 to1.0; p=0.04).The effect of treatment had been continued for 6 month and after that we indicated escape of effect. <h3>Conclusion</h3> The data obtained suggest that single intra-articular injection of autologous tolerogenic dendritic cells is safe, well tolerated, and have a potential not long term efficiency and requires the repeating of procedure. <h3>Disclosure of Interests</h3> None declared
Predictive factors for treatment-related mortality and major adverse events after autologous haematopoietic stem cell transplantation for systemic sclerosis: results of a long-term follow-up multicentre study
Authors: Sandra van Bijnen, Jeska de Vries-Bouwstra, Cornelia H van den Ende, Maaike Boonstra, Lucie Kroft, Bram Geurts, Miranda Snoeren, Anne Schouffoer, Julia Spierings, Jacob M van Laar, Tom WJ Huizinga, Alexandre Voskuyl, Erik Marijt, Walter van der Velden, Frank HJ van den Hoogen, Madelon C Vonk
Journal: Annals of the Rheumatic Diseases (2020)

<h3>Background</h3> Autologous haematopoietic stem cell transplantation (HSCT) improves survival in systemic sclerosis (SSc) with poor prognosis, but is hampered by treatment-related mortality (TRM). <h3>Objective</h3> To evaluate event-free survival (EFS), TRM, response to treatment, disease progression and patient characteristics associated with events. <h3>Methods</h3> All patients treated with HSCT for SSc in The Netherlands until 2017 (n=92) were included. Data on skin involvement (modified Rodnan skin score (mRSS), pulmonary function (forced vital capacity (FVC) and diffusion capacity of the lungs for carbon monoxide (DLCO)), extent of interstitial lung disease on high-resolution CT using Goh scores and left ventricular ejection fraction (LVEF) were collected at baseline, 1, 2 and 5 years. Occurrence of events, defined as death or major organ failure, were collected until 2019. As control, a comparison between patients treated with cyclophosphamide (CYC) and patients with HSCT who participated in the Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial was performed. <h3>Results</h3> Median follow-up was 4.6 years. EFS estimates at 5, 10 and 15 years were 78%, 76% and 66%, respectively. Twenty deaths occurred. Mean FVC, DLCO, mRSS and Goh scores all improved significantly. Disease progression occurred in 22 patients. Frequency of TRM decreased over time and occurred more often in males. Events were independently associated with male sex, LVEF &lt;50% and older age. In ASTIS, patients treated with HSCT (n=23) 7 events occurred versus 13 in the CYC group (n=22). <h3>Conclusion</h3> Our data confirm long-term efficacy of HSCT in improving survival, skin and lung involvement in SSc. Male sex, lower LVEF and older age at baseline were identified as risk factors for events.
Comment on Law et al. Suboptimal Nocturnal Glucose Control Is Associated With Large for Gestational Age in Treated Gestational Diabetes Mellitus. Diabetes Care 2019;42:810–815
Authors: Ninon Foussard, Sophie Cambos, Pauline Poupon, Marie Monlun, Laurence Blanco, Magalie Haissaguerre, Virginie Grouthier, Fritz-Line Velayoudom-Cephise, Kamel Mohammedi, Vincent Rigalleau
Journal: Diabetes Care (2019)

We were interested in the article by Law et al. (1), who reported that high nocturnal glucose, as recorded by continuous glucose monitoring (CGM), was associated with large for gestational age (LGA) newborns in women with gestational diabetes mellitus (GDM). The nocturnal hyperglycemia was not detected by fasting self-monitored blood glucose (SMBG), which argues for performing CGM in GDM.

The figure in the article nicely depicts how nocturnal hyperglycemia was missed by conventional SMBG: as underlined by the authors, the difference in nocturnal CGM glucose between mothers of LGA infants and those of normal-weight newborns was a peak displayed at 0200–0300 h, which then progressively declined to become nonsignificant when the women …
AB0174 CLINICAL SIGNIFICANCE OF THE URINARY CD11C+ MYELOID CELLS IN THE PATIENTS WITH LUPUS NEPHRITIS
Authors: Jihye Kim, Jae Hyung Jung, Jung Sun Lee, Ji Seon Oh, Wook Jang Seo, Yong-Gil Kim, Chang-Keun Lee, Bin Yoo, Seokchan Hong
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> It is known that various immune cell populations play important pathogenic roles in lupus nephritis (LN). Kidney-infiltrating myeloid cells are responsible for the pathology in murine model for LN. However, the characteristics of myeloid cells in patients with LN have not previously been investigated because of difficulties of access to affected tissue. Recent studies have reported that the urine has become an alternative substitute for kidney tissue to study renal pathology. <h3>Objectives</h3> Therefore, we investigated the characteristics and functions of urinary myeloid cells in patients with LN. <h3>Methods</h3> Within viable CD45+ cells, the frequency and absolute numbers of myeloid cells in the urine were examined after exclusion of lymphoid cells by expression of CD3, CD19 and CD56. Expression of phenotypic markers and production of pro-inflammatory cytokines were analyzed in urinary myeloid cells of patients with LN. <h3>Results</h3> Myeloid cells were identified by the expression of CD45+ and CD11c+ in the urine of patients with LN. The frequency and absolute numbers of myeloid cells were markedly increased in the urine of patients with proliferative LN than non-proliferative LN. In addition, titers of anti-dsDNA antibodies were correlated with the frequency or numbers of urinary CD11c+ myeloid cells. These urinary CD11c+ myeloid cells showed the phenotypes of infiltrated monocyte-derived cells rather than tissue-resident macrophage. In addition, CD11c+ myeloid cells were localized in tubulointerstitium and had capacity to produce pro-inflammatory cytokines including IL-6. Further, we found that there was a significant population of tubule cells in the urine, which is correlated with the frequency of CD11c+ myeloid cells. <h3>Conclusion</h3> Our results indicate that CD11c+ myeloid cells are present in the urine and contribute to tubulointerstitial inflammation in proliferative LN. <h3>Disclosure of Interests</h3> None declared
Educational and health outcomes of children treated for asthma: Scotland-wide record linkage study of 683 716 children
Authors: Michael Fleming, Catherine A. Fitton, Markus F.C. Steiner, James S. McLay, David Clark, Albert King, Daniel F. Mackay, Jill P. Pell
Journal: European Respiratory Journal (2019)

Background The global prevalence of childhood asthma is increasing. The condition impacts physical and psychosocial morbidity; therefore, wide-ranging effects on health and education outcomes are plausible. Methods Linkage of eight Scotland-wide databases, covering dispensed prescriptions, hospital admissions, maternity records, death certificates, annual pupil census, examinations, school absences/exclusions and unemployment, provided data on 683 716 children attending Scottish schools between 2009 and 2013. We compared schoolchildren on medication for asthma with peers, adjusting for sociodemographic, maternity and comorbidity confounders, and explored effect modifiers and mediators. Results The 45 900 (6.0%) children treated for asthma had an increased risk of hospitalisation, particularly within the first year of treatment (incidence rate ratio 1.98, 95% CI 1.93–2.04), and increased mortality (HR 1.77, 95% CI 1.30–2.40). They were more likely to have special educational need for mental (OR 1.76, 95% CI 1.49–2.08) and physical (OR 2.76, 95% CI 2.57–2.95) health reasons, and performed worse in school exams (OR 1.11, 95% CI 1.06–1.16). Higher absenteeism (incidence rate ratio 1.25, 95% CI 1.24–1.26) partially explained their poorer attainment. Conclusions Children with treated asthma have poorer education and health outcomes than their peers. Educational interventions that mitigate the adverse effects of absenteeism should be considered.
Author Correction: Control of tumor-associated macrophages and T cells in glioblastoma via AHR and CD39
Authors: Maisa C. Takenaka, Galina Gabriely, Veit Rothhammer, Ivan D. Mascanfroni, Michael A. Wheeler, Chun-Cheih Chao, Cristina Gutiérrez-Vázquez, Jessica Kenison, Emily C. Tjon, Andreia Barroso, Tyler Vandeventer, Kalil Alves de Lima, Sonja Rothweiler, Lior Mayo, Soufiene Ghannam, Stephanie Zandee, Luke Healy, David Sherr, Mauricio F. Farez, Alexandre Prat, Jack Antel, David A. Reardon, Hailei Zhang, Simon C. Robson, Gad Getz, Howard L. Weiner, Francisco J. Quintana
Journal: Nature Neuroscience (2019)
No CFH or ARMS2 Interaction with Omega-3 Fatty Acids, Low versus High Zinc, or β-Carotene versus Lutein and Zeaxanthin on Progression of Age-Related Macular Degeneration in the Age-Related Eye Disease Study 2
Authors: Freekje van Asten, Chi-Yang Chiu, Elvira Agrón, Traci E. Clemons, Rinki Ratnapriya, Anand Swaroop, Michael L. Klein, Ruzong Fan, Emily Y. Chew
Journal: Ophthalmology (2019)
PB2170 HEPATITIS C VIRUS-DRIVEN MULTIPLE MYELOMA IN STABLE COMPLETE REMISSION AFTER ANTIVIRAL TREATMENT
Authors: A. Rodríguez-García, M. Linares, R. Sánchez, R. Alonso, A. Pérez-Revilla, E. Bigot-Corbel, S. Hermouet, J. Martínez-López
Journal: HemaSphere (2019)

Background: Despite great advances in knowledge and treatment in past decades, multiple myeloma (MM) remains an incurable disease. Several studies suggest its association with infectious pathogens, such as hepatitis C virus (HCV) and Epstein Barr virus (EBV). Aims: In this study, we report on the case of a female MM patient in third relapse (after natural killer (NK) therapy with lenalidomide; bortezomib, lenalidomide, and dexamethasone (BLD); bortezomib, bendamustine, and dexamethasone (BBD) and the antiviral agents sofosbuvir and ledipasvir, who achieved stable complete response (CR) once HCV infection was successfully treated with antivirals, thus establishing a probable relationship between HCV infection and MM in this patient. Methods Serum samples from the patient were analyzed before and after antiviral treatment (Sofusbuvir + Ledipasvir). The HCV burden was determined by RT-qPCR. MRD was evaluated by cytology and MFC immunophenotyping, in bone marrow samples. The number of plasma cell clones and the tumor load were determined in bone marrow samples by next-generation sequencing. The patient's monoclonal immunoglobulin (mc IgG) was isolated by agarose gel electrophoresis and its purity was evaluated by isoelectric focusing. The reactivity to different microbial antigens was determined by means of the multiplex infectious-antigen microarray (MIAA) assay and the commercial kit INNO-LIA HCV score (Fujirebio). Results: The patient, age 59, presented with ISS IIA stage MM (5.7 g/dL mc IgG, 0.27 g/dL free lambda chains, 90% plasma cells in the bone marrow, without cytogenetic alterations, and osteolytic lesions). HCV infection, causing hepatic toxicity, was discovered in this patient before MM disease. The patient was in third relapse of MM treatment when she received anti-HCV treatment. After antiviral therapy, the HCV load in the patient's serum decreased to undetectable levels (Fig. 1A). Simultaneously, the patient achieved CR of MM, with minimal residual disease (MRD) negativity (Fig. 1B). Agarose gel electrophoresis of pre-HCV treatment samples showed one band of mc IgG, which disappeared after anti-HCV treatment (Fig. 1 C). The patient's mc IgG was purified and analysis of its specificity of recognition revealed that it targeted the HCV C1 (core) protein (Fig. 1D). Three years have now passed after HCV treatment, and the patient remains in stable CR of MM.Summary/Conclusion: In this case of refractory MM where the patient's mc IgG targeted HCV, successful HCV eradication with antivirals Sofosbuvir and Ledipasvir resulted in persistent complete remission of MM as well as of hepatitis C. These results suggest that for HCV-positive individuals, a causal relationship exists between HCV infection and the development of MM, and that MM patients infected with HCV benefit from early anti-HCV therapy.
FRI0151 THE RELATIONSHIP BETWEEN THE EFFECTIVENESS OF METHOTREXATE (MTX) IN RHEUMATOID ARTHRITIS (RA) AND MTX POLYGLUTAMATES LEVELS (MTXPGS) IN RED BLOOD CELLS BY TANDEM CHROMATOMASS SPECTROMETRY (PILOT STUDY)
Authors: Galina Gridneva, Yury Muraviev, Alexander Lila, Natalia Baymeeva
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Therapeutic control of the level of MTXPGs in erythrocytes may be an objective marker of its effective dose in RA treatment. <h3>Objectives</h3> To evaluate the relationship between the level of MTXPGs in erythrocytes and the effectiveness of the dose of MT used by RA patients. <h3>Methods</h3> The study included 60 random selected RA patients over the age of 18, 16 men and 44 women. The diagnosis in all cases met the criteria of ACR/EULAR 2010. All pts received MTX at a constant dose of at least 20 mg per week subcutaneously for at least the last 12 weeks. Patients were divided into 2 groups depending on the presence (group 1, n = 30) or absence (group 2, n = 30) of the therapeutic effect of MTX, according to the criteria of the EULAR response to therapy. The groups were comparable in age, sex, alcohol intake, smoking, body mass index (BMI), ACPP-positivity, incidence of unwanted reactions to MTX, single dose of MTX, duration of MTX treatment course. The groups differed in duration of the disease at the beginning of the current course of continuous therapy: 5.5 [2.0, 12.0] months in group 1 and 12.0 [3.0, 60.0] months in group 2; in group 2 patients received glucocorticoids (GK) orally 17 (57%) against 9 (30%) in group 1. Blood sampling was performed no later than 36 hours after the last administration of methotrexate. From each patient 2 ml of hemolysed blood were examined using an Agilent 6410 chromatograph (Agilent Technologies) - a quantitative measurement of methotrexate polyglutamate by liquid chromatography-spectrometry. <h3>Results</h3> It was established that the levels of total MTXPG and MTXPG1,2,3,5 in erythrocytes did not depend on the effectiveness of MTX, the dose of which was comparable in all patients. At the same time, the level of MTXPG4 was significantly higher (p = 0.023) in patients of group 1 (26.4 ± 6.1 nmol/l) compared with patients in group 2 (22.1 ± 6.8 nmol/l). Evaluation of the ROC curve showed that MTXPG4 values below 22.5 nmol/l corresponded to the absence of the therapeutic effect of MTX. The area under the curve was 0.672, (CI 95 0.536-0.808); p = 0.022. Sensitivity - 77%, specificity - 53.3%. <h3>Conclusion</h3> For effective treatment of RA patients, it is necessary to administer such doses of MTX so that the achieved level of MTXPG4 in erythrocytes is not less than 22.5 nmol/l. <h3> Disclosure of Interests: </h3> Galina Gridneva: None declared, Yury Muraviev: None declared, Alexander Lila Speakers bureau: Pfizer, Inc., MSD, Novartis, AbbVie Inc., Celgen Corporation, Biocad, Janssen, UCB, Inc., Natalia Baymeeva: None declared
The training in SHARE communication course by physicians increases the signing of do-not-resuscitate orders for critical patients in the emergency room (cross-sectional study)
Authors: Ya-Hui Cheng, Chih-Hung Chen, Fen-Ju Chen, Eng-Yen Huang, Po-Ming Liu, Chia-Te Kung, Hsien-Li Huang, Li-Hui Yang, Peng-Chen Chien, Ching-Hua Hsieh
Journal: International Journal of Surgery (2019)
Abstract 17224: Genetic Association Study of Circulating NT-proANP in the General Community Identifies a Novel Gene Cluster Associated With Stroke
Authors: Naveen L Pereira, Nirubol Tosakulwong, Christopher G Scott, Gregory D Jenkins, Naresh Prodduturi, Margaret M Redfield, Timothy M Olson, Richard J Rodeheffer, Richard M Weinshilboum, John C Burnett
Journal: Circulation (2013)

Background: Reduced N-terminal pro-atrial natriuretic peptide (NT-proANP) levels have been associated with development of hypertension, metabolic syndrome, heart failure and myocardial infarction. ...
Mechanisms of immune-related adverse events associated with immune checkpoint blockade: using germline genetics to develop a personalized approach
Authors: Zia Khan, Christian Hammer, Ellie Guardino, G. Scott Chandler, Matthew L. Albert
Journal: Genome Medicine (2019)

Personalized care of cancer patients undergoing treatment with immune checkpoint inhibitors will require approaches that can predict their susceptibility to immune-related adverse events. Understanding the role of germline genetic factors in determining individual responses to immunotherapy will deepen our understanding of immune toxicity and, importantly, it may lead to tools for identifying patients who are at risk.
PS1566 HEMATOPOIETIC STEM CELL GRAFTS AS A SOURCE FOR RECONSTITUTING INNATE LYMPHOID CELLS FOLLOWING STEM CELL TRANSPLANTATION
Authors: V. Van Hoeven, A. Kroeze, N. Haverkate, S. Omar, L. Jachimowski, Y. van Lier, S. Franken, S. Zeerleder, B. Blom, C. Voermans, M. Hazenberg
Journal: HemaSphere (2019)

Background: Graft‐versus‐host disease (GvHD) is a common and life threatening complication of allogeneic stem cell transplantations (ASCT), and is thought to be initiated by chemotherapy‐induced tissue damage. Innate lymphoid cells are involved in tissue remodeling and repair and may therefore have a protective role in the development of GvHD. Indeed, in a previous study we observed that relatively high frequencies of activated ILC3 s before and/or after ASCT were associated with a lower risk to develop GvHD. While rapid reconstitution of ILCs thus seems favorable, ILCs in fact recover slowly and do not reach normal levels within 6 months post‐ASCT. Aims: By investigating the composition of stem cell grafts and the ILC‐development potential of graft‐derived multipotent hematopoietic progenitor cells (HPCs), we here aim to gain more insight into how ILCs reconstitute from stem cell grafts. Methods: Peripheral blood‐mobilized stem cell grafts of healthy adult donors were thawed and ILCs were phenotyped by flow cytometry. Lineage − CD34 + CD45RA + HPCs were FACS‐sorted and cultured for a maximum of 4 weeks on JAG1‐expressing OP9 stromal cells in the presence of IL‐2, IL‐7, stem cell factor and Flt3‐ligand. This method was previously shown to support ILC development. Results: We detected mature ILC1 s, ILC2 s and ILC3 s in all grafts, and the median frequency of total CD127 + ILCs was 0.26% of the lymphocytes. The distribution of the ILC subsets differed substantially between stem cell grafts. HPCs isolated from human fetal liver successfully developed into ILCs within 4 weeks culture, however, HPCs derived from adult stem cell grafts did not have the capacity to develop into ILCs. We are currently investigating whether the age and the source of the isolated HPCs matters by testing the ILC developmental potential of cord‐blood and bone‐marrow derived HPCs. At the same time we are extending our graft and post‐ASCT analyses to be able to correlate our in vitro findings to in vivo ILC reconstitution. Summary/Conclusion: While mature ILCs present in stem cell grafts may be a good source for reconstituting ILCs, the ILC‐developmental potency of (adult) graft‐derived HPCs seems to be poor, possibly reflecting a decline in the potency of stem cells to develop into ILCs with increasing age. These results offer an explanation for the slow reconstitution of ILCs after ASCT. image