tbuckley/cabot-search huggingface dataset:
SP0158 CON SESSION: PREPARE YOUR DATA COLLECTION WELL: IMPUTATION DOES NOT REPLACE ‘REAL DATA”
Authors: Dougados Maxime
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The recently proposed sophisticated statistical methods to impute missing data are very attractive. For the clinical researchers in charge of data collection, it might be tempting to “neglect” the quality of data collection in favor of the time spent by one database manager/statistician to impute missing data. This presentation will be a plea in favor to make all the possible efforts to collect appropriately the data in clinical research studies/trials. In particular, emphasis will be placed on the importance of writing a specific section in any research protocol describing the technics used to avoid these missing data and also the a priori decided technic that will be used to manage the missing data. One point of importance in this section: to specify in advance the maximum percentage of missing data over which no imputation can be made. Two different situations: - Cross-sectional studies. Any item (for example HLA B27, MRI SIJ inflammation positivity) should be considered as mandatory or not before running the study. - Longitudinal studies: any longitudinal protocol should include a section detailing the technic to appropriately follow the patients in order to avoid the “lost of follow-up patients”. This is particularly important in longitudinal follow-up of patients suffering from a recent onset disease (e.g. early synovitis cohorts, early inflammatory back pain cohorts) since it is well known that the “lost of follow-up” have specific baseline characteristics suggesting a less severe disease. It is also important to decrease at a minimum level the “lost of follow-up” patients participating at a therapeutical trial/registry since the reason of “lost of follow-up” might be related to a specific drug effect. <h3>Disclosure of Interests:</h3> maxime dougados Grant/research support from: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma, Consultant for: Eli Lilly and Company, Pfizer, AbbVie, and UCB Pharma
Measuring progress in health in China and its provinces
Authors: Gonghuan Yang, Xia Wan
Journal: The Lancet (2019)

In The Lancet, Maigeng Zhou and colleagues1 present a systematic analysis for the Global Burden of Disease Study (GBD) 2017 on mortality, morbidity, and risk factors in China and its provinces, from 1990 to 2017. Their report is, to our knowledge, the first comprehensive subnational assessment of health in the Chinese population after previous GBD China 2010 on mortality, morbidity, combined health loss, and risks at the national level2 and GBD China 2013 on mortality at the national and province level.
PS956 A MULTICENTER, RETROSPECTIVE STUDY TO EVALUATE EFFICACY AND SAFETY OF BUSULFAN/FLUDARABINE CONDITIONING FOR ALLOGENEIC STEM CELL TRANSPLANTATION IN ADULT PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: S.-S. Lee, S.-H. Jung, M.H. Heo, D.S. Kim, J.H. Lee, H.-S. Park, Y.J. Lee, J.H. Yi, K.-W. Kang, Y. Koh, H.-Y. Yhim, J.-C. Jo, Y.-C. Mun, W.-S. Lee, D.-H. Yang, S. Lee
Journal: HemaSphere (2019)

Background: In adult patients with relapsed or refractory (R/R) Philadelphia chromosome-negative (Ph-negative) acute lymphoblastic leukemia (ALL), CR rates are much lower and survival outcomes are very poor. For safe salvage and bridge to allogeneic hematopoietic cell transplantation (allo-HCT), several immune-based treatments have been tried. We analyzed the treatment outcomes and prognostic factors of blinatumomab. Aims: In this study, we analyzed the treatment outcome of blinatumomab and prognostic factors in adult patients with R/R Ph-negative BCP-ALL. Methods: From 2016 to 2018, 32 adult patients with R/R Ph-negative ALL were treated with blinatumomab. All received uniform prephase dexamethasone 20 mg/day for 4 days. Urgent allo-HCT was planned in patients with complete remission (CR). At the time of blinatumomab treatment, 9 patients (28.1%) were primary refractory, 10 (31.2%) had relapsed during/after consolidation chemotherapy, and 13 (40.6%) had relapsed after first (n = 11) or second (n = 2) allo-HCT. Results: Overall, 23 patients (71.9%; 100% for primary refractory, 70% for relapsed patients during/after consolidation chemotherapy, 53.8% for relapsed patients after allo-HCT) achieved CR but 3 of them relapsed – thus, 20 (62.5%) finally underwent allo-HCT in CR following blinatumomab. CR rate was lower in poor-risk karyotype (33.3% vs. 87.0% ; p = 0.005). After median follow-up of 11.9 months (range 6.7 to 23.6), 1-year OS of all patients was 55.4% with a median survival of 14.5 months. The 1-year OS and relapse rate of 20 patients who underwent allo-HCT was 77.8% and 5.6%, repectively, while 1-year OS for patients who failed to blinatumomab was 12.0% (p < 0.001). In addition, extramedullary relapse (EMR, 14.3% vs. 68.4%, p = 0.007) and high peripheral blood blast count (26.7% vs. 59.8%; p = 0.026) were related with poorer 1-year OS. Summary/Conclusion: Blinatumomab is a feasible choice for salvage chemotherapy for adult patients with R/R Ph-negative ALL which showed a good CR rate at any time of salvage and showed a good bridge to allo-HCT. However, the role in patients with poor-risk karyotype, EMR, or high tumor burden should be evaluated in future trials.
THU0119 SUCCESSFUL PSYCHOPHARMACOTHERAPY OF ANXIETY AND DEPRESSIVE DISORDERS IMPROVES RHEUMATOID ARTHRITIS REMISSION RATE AT FIVE YEARS FOLLOW-UP
Authors: Anton Abramkin, Tatiana Lisitsyna, Dmitry Veltishchev, Olga Seravina, Oksana Kovalevskaya, Svetlana Glukhova, Evgeny Nasonov
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> Anxiety and depressive disorders (ADD) affect rheumatoid arthritis (RA) disease activity and remission rate. Psychopharmacotherapy (PPT) of ADD attempts to improve the remission rate. <h3>Objectives</h3> To determine factors associated with RA remission rate. <h3>Methods</h3> 128 RA-patients (pts) were enrolled, 86% were women with a mean age of 47,4±11,3 (M±SD) yrs. All pts met the full ACR criteria for RA. Remission was defined as DAS28&lt;2,6. Mean RA activity by DAS28 was high (5,27±1,78) at baseline. 69,4% RA-pts were already taking prednisone (9 [5; 10] mg/day (Me (25%; 75%)), 84,4% - conventional disease-modifying antirheumatic drugs (cDMARDs), 7,8% - biologic DMARDs (bDMARDs) - anti-TNF-α – 6,3%, rituximab – 1,6%. ADD were diagnosed in 123 (96,1%) of RA-pts in accordance with ICD-10 in semi-structured interview. Severity of depression and anxiety was evaluated with Montgomery–Asberg Depression Rating Scale (MADRS) and Hamilton Anxiety Rating Scale (HAM-A). RA-pts with ADD were divided into the following treatment groups: 1 – cDMARDs (n=39), 2 – cDMARDs + PPT (sertraline or mianserine) (n=43), 3 – cDMARDs + bDMARDs (n=32), 4 – cDMARDs + bDMARDs + PPT (sertraline or mianserine) (n=9). Biologics treatment duration varied from 1 to 6 years, antidepressants – from 6 to 96 weeks. Logistic regression analysis was conducted to determine factors associated with RA remission rate. <h3>Results</h3> At 5-yrs endpoint in 83 RA-pts remission rate was 22,9% (8,3%, 34,5%, 19,0% and 33,3% in groups 1, 2, 3 and 4, respectively). Significantly higher proportion of patients achieved remission in cDMARDs + PPT group vs cDMARDs group (34,5% vs 8,3%, RR 1,8 (95%CI 0,35 – 9,2), p=0,024). By univariate logistic regression, male sex, younger age, shorter RA duration, RF and ACPA negativity, lower baseline DAS28 and HAQ, absence of extraarticular RA manifestations and depression at the beginning of the study, and remission of anxiety and depressive symptoms at the end of the study were significantly associated with RA remission (table 1). These variables were subjected to multivariate stepwise logistic regression. Only lower baseline DAS28 (OR 0,636 (95%CI 0,515 – 0,785), p&lt;0,001) and remission of anxiety and depressive symptoms at 5-yrs endpoint (OR 6,89 (95%CI 1,8 – 26,29), p=0,005) were independently associated with RA remission at 5-years follow-up. <h3>Conclusion</h3> Lower baseline DAS28 and remission of anxiety and depressive symptoms at 5-yrs endpoint are associated with higher rheumatoid arthritis remission rate at five years follow-up. <h3>Disclosure of Interests</h3> None declared
PF706 OCCULT BLEEDING IN CHILDREN WITH IMMUNE THROMBOCYTOPENIA: RELATION TO LABORATORY PARAMETERS &amp;ITP HEALTH QUALITY OF LIFE
Authors: A. Tantawy, N. Elsherif, K. Aboulfotouh, M. Kenny
Journal: HemaSphere (2019)

Background: Occult hemorrhage can occur in any internal organ in ITP patients. Four sites of occult hemorrhage deserve special attention including microscopic hematuria, fecal occult blood, retinal hemorrhage, and silent intracranial hemorrhage. Aims: The aim of this study was to investigate for the frequency of subclinical bleeding in Egyptian children with ITP and its relation to different clinical and laboratory parameters of the disease including bleeding score and health quality of life. Methods: This cross sectional study included 40 ITP patients recruited from the Pediatric Hematology&amp;Oncology unit, Children Hospital, Ain Shams University. Occult blood in stools and urine analysis, fundus examination, and non‐contrast brain MRI, for brain microbleed, were done Results: The total number of patients with occult bleeds was eleven. Two patients had occult blood in stool, five had microscopic hematuria, one had retinal bleeds and three patients had brain microbleeds. Their mean age was 10.23 ± 4.18 and their mean initial bleeding score was 2.55 ± 0.82. Nine patients with occult bleeding were chronic, one persistent and one acute ITP patients. There was no significant differences between patients with occult bleeding and those without as regards the initial bleeding score, the platelet counts &amp; hemoglobin level, as well as the mean platelet counts &amp; mean hemoglobin level over the disease duration. Although the scoring of the effect on the parent's life, Child and parents quality of life was low in 3 out of 11 patients with occult bleeding, we did not find a significant difference between patients with occult bleeding and those without as regards the ITP health quality of life items Summary/Conclusion: Our results suggest that subclinical bleeding is a potential risk in children with ITP, more commonly chronic ITP patients. We could not demonstrate a significant relation of occult bleeding to the laboratory findings, bleeding score, and the ITP health quality of life; nevertheless, the significance of the routine assessment of occult bleeding in ITP and the identification of high‐risk patients require additional studies.
Abstract 18298: Genomic Classification of Permanent versus New-onset Postoperative Atrial Fibrillation Using Atrial Myocardial Gene Expression Profiling
Authors: Martin I Sigurdsson, Nathan H Waldron, Michael W Manning, Quintin J Quinones, Joseph P Mathew, Mihai V Podgoreanu
Journal: Circulation (2017)

Introduction: To evaluate molecular mechanisms governing initiation versus perpetuation of atrial fibrillation (AF), we compared myocardial transcript abundance in two cohorts of patients undergoin...
PS1211 CD22 CAR T-CELL THERAPY IN 34 REFRACTORY OR RELAPSED B ACUTE LYMPHOBLASTIC LEUKEMIA PATIENTS
Authors: J. Pan, B. DENG, S. Liu, T. Wu, Z. Gao, Y. Lin, Y. Zhao, Y. Zhang, X. Tan, A.H. Chang, C. Tong
Journal: HemaSphere (2019)

Background: Autologous CAR-T cell therapy is now a proven breakthrough technology in the treatment of B cell malignancies and holds promise in the therapy of all types of cancer. However, autologous CAR-T cell therapy does have significant challenges relating to logistics and product consistency. Allogeneic CAR-T therapeutic products could allow treatment of multiple patients with cells from the same healthy donor, increasing product consistency, likely reducing manufacturing costs and avoiding the time delay required to generate an autologous T cell product. Aims: Allogeneic CAR-T cell therapy is dependent upon eliminating the activity of the endogenous T Cell Receptor (TCR) within the engineered T cell, thereby preventing the induction of a graft versus host response and resultant potentially life-threatening toxicity. We have explored RNA interference to modulate the TCR and to assess the potential of short hairpin RNA (shRNA) as a platform technology for Allogeneic CAR T cell therapy. Methods: shRNAs targeting the CD3ε and CD3ζ chains of the TCR complex were expressed in primary T cells where the efficacy of the individual shRNAs to downregulate the CD3 component and subsequent impact upon TCR expression assessed. The optimal shRNAs were tested in a head to head fashion against the state-of-the-art gene editing technology, CRISPR-Cas9, in vitro for response against mitogenic stimulation and in animal models for control of xenoGvHD. Results: shRNAs specific for CD3ε and CD3ζ reduced the transcriptional expression of their relevant targets, as well as the cell surface expression of the TCR. Downregulation of TCR expression and inhibition of the in vitro mitogenic response when challenged with anti-CD3 antibodies was similar between shRNAs and CRISP-Cas9 targeting CD3ζ. Importantly, in vivo experiments with T cells adoptively transferred to NSG mice showed that shRNAs targeting CD3ζ protected animals from GvHD, while T cell persistence was significantly higher compared to T cells genetically engineered with CRISP-Cas9 targeting CD3ζ. Summary/Conclusion: This work demonstrates that the expression of shRNA in a standard retroviral vector provides a one-step solution to produce cells suitable for Allogeneic CAR T cell therapy. Our testing continues, involving the examination of the anti-tumor potency of such shRNA-Allo CAR-T cells. Importantly, this approach provides a one vector solution that offers an alternative to strategies such as gene editing to eliminate the TCR, while also requiring no major alteration to current CAR-T cell manufacturing, that should enable the rapid adoption of the approach into clinical testing.
Abstract 14638: Stent-type at Percutaneous Coronary Intervention and Long-term Outcomes in Relation to Renal Function: Data From 103.747 Patients in the SCAAR-registry
Authors: Robert Edfors, Stefan James, Karolina Szummer, Marie Evans, Juan-Jesus Carrero, Jonas Spaak, Tomas Jernberg, Bo Lagerqvist
Journal: Circulation (2015)

Objective: To evaluate the risk of hard clinical endpoints of different types of PCI stents in relation to renal function. Methods: During 2007 and 2013, 103.747 patients enrolled in the Swedish Coronary Angiography &amp; Angioplasty Registry (SCAAR) with a known serum creatinine were treated with PCI using new generation drug eluting stents (n-DES) (n=32.440), old generation drug eluting stents (o-DES) (n=17.363) or bare metal stents (BMS) (n=53.974). Renal function groups were derived from creatinine estimated glomerular filtration rate (eGFR) and expressed in ml/min/1.73 m2. The hazard risk (HR) of the combined endpoint (all-cause mortality or myocardial infarction readmission) was estimated using Cox landmark analyses (≤1 year and &gt;1 year to 3 years). Adjustments were made for year, hospital, extent of coronary artery disease, indication for PCI, use of multiple stents, periprocedural antithrombotic treatment, number of stents, stent dimensions, diabetes, age, gender, risk factors and history of cardiovascular disease. Results: N-DES was associated with a significantly lower up-to 1 year risk compared to BMS in patients with eGFR &gt;60. These associations were attenuated and not significant in patients with eGFR &lt;60. Adjusted HR comparing o-DES and BMS were not statistically different (≤1 year). There was no significant difference between n-DES and BMS after 1 year. Compared to BMS, o-DES had significantly higher risks in patients with eGFR ≥60 and in patients with eGFR 30-59 HR was similarly but not significantly elevated. Conclusion: In this large national registry we found that in patients with normal renal function, n-DES was associated with a lower up to 1-year risk of MI readmission or all-cause mortality, whereas o-DES was associated with a higher risk after 1 year. A similar trend was seen for patients with moderately reduced renal function but not for patients with severely reduced renal function.
S1644 ASSOCIATION OF SYSTEMIC CYTOKINE LEVELS WITH RISK OF VENOUS THROMBOEMBOLISM IN PATIENTS WITH GLIOMA
Authors: P. Mir Seyed Nazari, F. Moik, C. Marosi, J. Riedl, A.‐S. Berghoff, M. Preusser, J.A. Hainfellner, I. Pabinger, G. Zlabinger, C. Ay
Journal: HemaSphere (2019)

Background: Venous thromboembolism occurs frequently in patients with primary brain tumors. Aims: Given the strong interplay between inflammation and haemostasis, the aim of the current study was to investigate the association of serum cytokine levels and risk of VTE development in patients with glioma. Methods: Within the framework of the Vienna Cancer and Thrombosis Study (CATS), a prospective and observational cohort study of patients with active cancer, we conducted an exploratory analysis. Patients were recruited at the time of cancer diagnosis or progression of disease after remission and followed for two years. Primary endpoint was symptomatic and objectively confirmed VTE. At study entry, a single blood draw was performed. Several cytokines (e.g. Interleukin (IL)‐1b, IL‐4, IL‐6, IL‐8, IL‐10, IL11, CCL3, TNF‐a, VEGF‐a) were measured in serum samples with the xMAP technology developed by Luminex. Results: In this study, 128 glioma patients were analyzed. Of those, 98/128 (76.6%) were diagnosed with glioblastoma (WHO grade IV), 24/128 (18.8%) with anaplastic glioma (WHO grade III) and 6/128 (4.7%) with diffuse glioma (WHO grade II). In total, 22/128 (17.2%) glioma had an IDH1 mutation. During follow‐up, 14/128 (10.9%) patients developed VTE. In univariable Cox‐regression analysis, CCL3 levels were significantly associated with risk of developing VTE (hazard ratio [HR] per 10 units increase: 0.629 [95% CI: 0.407–0.0.972], p = 0.037 ), while there was no significant association between the risk of VTE and serum levels of IL‐1b, IL‐4, IL‐6, IL‐8, IL‐10, IL‐11, TNF‐aand VEGF‐a, respectively. In multivariable analysis, adjusting for potential confounders (sex, age, glioblastoma), the association of CCL3 with the risk of VTE remained statistically significant (adjusted HR: 0.628 [0.397–0.992], p = 0.046 ). Cumulative incidence of VTE in reverse Kaplan‐Meier estimates was 22.8% in patients with low CCL3 serum levels (≤ 25 th percentile = 1.95 pg/ml) and 9.1% in patients with higher CCL3 serum levels (&gt; 25 th percentile) (log‐rank, p = 0.017 ). (Figure 1) Summary/Conclusion: One out of 10 patients with glioma developed VTE in our study and low serum levels of CCL3 were associated with an increased risk of VTE. In conclusion, CCL3 might be useful as a potential biomarker for prediction of risk of VTE in patients with glioma. image
Detecting Long-Term Balancing Selection Using Allele Frequency Correlation
Authors: Katherine M. Siewert, Benjamin F. Voight
Journal: Molecular Biology and Evolution (2017)

Balancing selection occurs when multiple alleles are maintained in a population, which can result in their preservation over long evolutionary time periods. A characteristic signature of this long-term balancing selection is an excess number of intermediate frequency polymorphisms near the balanced variant. However, the expected distribution of allele frequencies at these loci has not been extensively detailed, and therefore existing summary statistic methods do not explicitly take it into account. Using simulations, we show that new mutations which arise in close proximity to a site targeted by balancing selection accumulate at frequencies nearly identical to that of the balanced allele. In order to scan the genome for balancing selection, we propose a new summary statistic, β, which detects these clusters of alleles at similar frequencies. Simulation studies show that compared with existing summary statistics, our measure has improved power to detect balancing selection, and is reasonably powered in non-equilibrium demographic models and under a range of recombination and mutation rates. We compute β on 1000 Genomes Project data to identify loci potentially subjected to long-term balancing selection in humans. We report two balanced haplotypes-localized to the genes WFS1 and CADM2-that are strongly linked to association signals for complex traits. Our approach is computationally efficient and applicable to species that lack appropriate outgroup sequences, allowing for well-powered analysis of selection in the wide variety of species for which population data are rapidly being generated.
PB1954 DETECTION OF COMPLEX VARIANT T(9;22) CHROMOSOME TRANSLOCATIONS IN NEWLY DIAGNOSED CASES OF CHRONIC MYELOID LEUKAEMIA
Authors: N. Fareed, N.M. somroo, M.S. Quraishy, S. Rafiq
Journal: HemaSphere (2019)

Background: Chronic myeloid leukemia (CML) is a stem cell clonal disease characterized by the acquisition of a fusion protein, BCR‐ABL1 oncogene, which leads to uncontrolled proliferation of myeloid elements in all stages of differentiation. However, a small proportion of patients with CML have simple or complex variants of this translocation, involving various breakpoints in addition to 9q34 and 22q11. Aims: Detection of complex variant t(9;22) chromosome translocations in newly diagnosed cases of Chronic Myeloid Leukaemia which help us to choose therapy modalities. Methods: This study was conducted for a time period of 05 years from 2012 to 2017 in the department of Oncology/ Hematology of Civil hospital, Karachi. Between April 2012 and April 2017, 88 CML patients were diagnosed in our Department. Informed consent was obtained from the patient in accordance with the Declaration of Helsinki. Diagnosis was done on the morphological basis and BCR‐ABL mutation by PCR/FISH. Conventional cytogenetic analysis was performed on unstimulated 24‐hour culture of a bone marrow (BM) specimen. The cells were cultured and processed by conventional methods, and the chromosomes were stained with trypsin‐Giemsa banding (GTG‐banding). Results: A total of 88 patients were Philadelphia‐positive CML, out of which 53(60.2%) were males &amp; 35(39.7%) were females. Mean age was 48 yrs ± 11.43. Out of them, the group of 9 (10.2%) patients with complex cytogenetics were consisted of 5 females and 4 males, ranging in age at diagnosis from 32 to 66 yrs. All the patients were in chronic phase at presentation. Cytogenetic analysis by G‐banding revealed the presence of 9 reciprocal three‐way variant translocations of the classical t(9;22)(q34;q11). The chromosome breakpoints involved in these complex variant translocations were the following: 1p13, 1q21, 1p22, 2q31, 3q21, 3p21, 11q13, 15q24 and Xp11.2 Summary/Conclusion: In our study 09 patients had complex variants of t(9;22).The presence of these complex variants at diagnosis and during the TKI treatment may announce treatment failure and/ or transformation to advanced stage (accelerated or blast). Early identification of these abnormalities may help in choosing therapy modalities.