tbuckley/cabot-search huggingface dataset:
Software tools for visualizing Hi-C data
Authors: Galip Gürkan Yardımcı, William Stafford Noble
Journal: Genome biology (2017)

High-throughput assays for measuring the three-dimensional (3D) configuration of DNA have provided unprecedented insights into the relationship between DNA 3D configuration and function. Data interpretation from assays such as ChIA-PET and Hi-C is challenging because the data is large and cannot be easily rendered using standard genome browsers. An effective Hi-C visualization tool must provide several visualization modes and be capable of viewing the data in conjunction with existing, complementary data. We review five software tools that do not require programming expertise. We summarize their complementary functionalities, and highlight which tool is best equipped for specific tasks.
Ibrutinib plus fludarabine, cyclophosphamide, and rituximab as initial treatment for younger patients with chronic lymphocytic leukaemia: a single-arm, multicentre, phase 2 trial
Authors: Matthew S Davids, Danielle M Brander, Haesook T Kim, Svitlana Tyekucheva, Jad Bsat, Alexandra Savell, Jeffrey M Hellman, Josie Bazemore, Karen Francoeur, Alvaro Alencar, Leyla Shune, Mohammad Omaira, Caron A Jacobson, Philippe Armand, Samuel Ng, Jennifer Crombie, Ann S LaCasce, Jon Arnason, Ephraim P Hochberg, Ronald W Takvorian, Jeremy S Abramson, David C Fisher, Jennifer R Brown
Journal: The Lancet Haematology (2019)
PS1151 PHASE 2 STUDY OF ACALABRUTINIB IN IBRUTINIB‐INTOLERANT PATIENTS WITH RELAPSED/REFRACTORY CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: K. Rogers, P.A. Thompson, J.N. Allan, M. Coleman, J.P. Sharman, B.D. Cheson, R. Izumi, M.M. Frigualt, C. Quah, R.K. Raman, M.H. Wang, T.J. Kipps
Journal: HemaSphere (2019)

Background: In patients with chronic lymphocytic leukemia (CLL) treated with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib, intolerance was the most common reason for discontinuation (50% to 63%; Mato AR, et al. Haematologica. 2018). Aims: This Phase 2 trial evaluated acalabrutinib, a highly selective, potent, covalent BTK inhibitor, in ibrutinib‐intolerant patients with relapsed/refractory CLL. Methods: Patients with relapsed/refractory CLL (≥1 prior therapy) who discontinued ibrutinib due to Grade 3/4 adverse events or persistent/recurrent Grade 2 adverse events and had progressive disease after ibrutinib discontinuation were eligible. Acalabrutinib was given orally at 100 mg twice daily in 28‐day cycles until progressive disease or unacceptable toxicity. The primary endpoint was overall response rate (ORR). Results: Sixty patients were treated. The median age was 70 years (range, 43 to 88). Patient characteristics included bulky disease ≥5 cm (33%), Rai stage III/IV (47%), del17p (28%), del11q (23%), and unmutated IGHV (79%). Fifty‐two of 55 patients (95%) with available baseline samples were wild type for BTK and PLCG2 . The median number of prior therapies was 2 (range, 1 to 10). The median duration of prior ibrutinib therapy was 6 months (range, &lt;1 to 55); common adverse events that led to ibrutinib discontinuation were atrial fibrillation/flutter (25%), diarrhea (12%), arthralgia (10%), and rash (12%). At a median follow‐up of 19 months (range, 1 to 31), 67% of patients remain on acalabrutinib; discontinuations were mostly due to progressive disease (13%) and adverse events (10%; pneumonia [n = 2], diarrhea, headache, ascites, arthralgia, subdural hematoma [all n = 1]). Efficacy outcomes are in the Table . Common adverse events (any grade) were diarrhea (48%), headache (40%), contusion (35%), and dizziness (32%). Serious adverse events (≥2 patients) were pneumonia (10%), anemia (3%), and syncope (3%). Atrial fibrillation occurred in 3 patients (5%; all Grade 1/2) and major hemorrhage in 2 (3%; Grade 3 hematuria and Grade 2 subdural hematoma). Grade 5 adverse events were pneumonia (n = 2), bronchopulmonary aspergillosis (n = 1), and ventricular fibrillation (n = 1); all were considered not related to treatment. Summary/Conclusion: Acalabrutinib is tolerable and effective in ibrutinib‐intolerant patients, providing a viable strategy for continuing BTK inhibitor therapy. image
THU0529 WHOLE BODY MAGNETIC RESONANCE IMAGINGIN JUVENILE DERMATOMYOSITIS. A LONGITUDINAL STUDY
Authors: CAPPELLO Carla, Eduardo Bronzatto, Sergio Dertkigil, Roberto Marini, Simone Appenzeller
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> Juvenile dermatomyositis (JDM) is a rare multisystem connective tissues disorder of unknown aetiology. Assessment of disease activity is a chalange in clinical practice. <h3>Objectives:</h3> To compare whole-body MRI (WB-MRI) with clinical examination in the assessment of disease activity in JDM. <h3>Methods:</h3> We included consecutive JDM patients followed in the rheumatology unit. All patients were submitted to clinical and laboratory evaluation. WB-MRI images were obtained using a 1.5 T MRI scanner and short T inversion recovery sequences (STIR). Muscle, peripheral inflammation and subcutaneous inflammations signal abnormalities were scored in 42 muscular groups. Muscle inflammation was classified as: 0 = absent; 1 = Mild to moderate/involvement less than 50% of muscle extension and 2 = Accentuated/greater than 50%. Peripheral and subcutaneous inflammations were classified as: 0 = absent; 1 = present; and on proximal and distal extremities. WB-MRI and clinical assessments were performed concurrently and results compared. Evaluation was repeated after 12 months. Statistics was performed according to the nature of the variable. <h3>Results:</h3> WB-MRI revealed muscle inflammation in 6 (31.6%) at study entry. We observed grade 2 muscle inflammation of the right and left scapular girdle (1/19 patients), right and left pelvic girdle (2/19 patients) and right and left tight (1/19 patients). Grade 1 inflammation was observed in peripheral right and left arm (2/19 patients), peripheral right and left thigh (1/19 patients). Grade 1 subcutaneous inflammation was observed in right and left thigh (1/19 patients) and left leg (1/19 patients). Additionally we observed sacroiilitis (1/19 patients), spinal cord infarction (21%) and osteonecrosis (5.2%). All patients were treated with standardized treatment. After 12 months 13/19 (68.4%) patients repeated the WB-MRI. Five (38.4%) patients had new/worsening of muscle and subcutaneous inflammation, one (7.7%) patient had tibial medullary infarction. Correlations between WB-MRI muscle score and disease activity measures were excellent (Manual Muscle Test: r=−0.88, Childhood Myositis Assessment Scale: rs=−0.81). Patients with subcutaneous inflammation developed clinically evident subcutaneous calcifications during follow-up. <h3>Conclusion:</h3> WB-MRI provides additional information to clinical evaluation and represents a promising tool to determine the grade of muscle inflammation to additional peripheral and subcutaneous tissue inflammation. <h3>References:</h3> [1] Malattia C, Damasio MB, Madeo A, et al. Ann Rheum Dis 2014;73:1083–1090 <h3>Disclosure of Interests:</h3> None declared
PB2415 HYDROXYUREA AN EFFECTIVE THERAPY TO AVOID SPLENECTOMY IN SICKLE CELL DISEASE AND THALASSEMIA: 15 YEARS EXPERIENCE IN SAUDI ARABIA
Authors: S. Al Jaouni
Journal: HemaSphere (2019)

Background: Background and Purpose: Spleen plays an important part in the immune system which helps the body fight infection and have a major role in children. Splenectomy have been decline in hemoglobin disorders in recent years. Aims: To assess the role of hydroxyurea if can eliminate the risk of splenectomy in sickle cell disease (SCD) and thalassemia in our medical center. Methods: Total of 84 patients enrolled in the study between 2003 to 2018 at King Abdulaziz University Hospital, Faculty of Medicine, King Abdulaziz University, Jeddah, Kingdom of Saudi Arabia, 24 sickle cell disease (SCD), 28 thalassemia major (TM) were suboptimal transfusion dependents and hypersplenism, 22 thalassemia inter media (TI). Results: Risk of splenectomy have been avoided in 23/24 SCD, 27/28 in TM and 22/22 in TI. Summary/Conclusion: Hydroxyurea is an effective and safe therapy can eliminate risk of splenectomy in SCD and thalassemia. Recent studies and meta analysis showed that hydroxyurea is safe and non‐carcinogenic.
PS955 FEASIBLE OUTCOME OF BLINATUMOMAB FOLLOWED BY ALLOGENEIC HEMATOPOIETIC CELL TRANSPLANTATION FOR ADULTS WITH RELAPSED OR REFRACTORY PHILADELPHIA-NEGATIVE ACUTE LYMPHOBLASTIC LEUKEMIA
Authors: J.-H. Yoon, S.Y. Yoon, J. Lee, C. Kim, K.-S. Eom, H.-J. Kim, J.W. Lee, S. Lee
Journal: HemaSphere (2019)

Background: Additional salvage regimens are burdensome for relapsed/refractory acute lymphoblastic leukemia (ALL) patients (pts) due to therapy-associated toxicities, which may affect quality of life with poor efficacy. In INO-VATE (Kantarjian et al, NEJM 2016), pts receiving inotuzumab ozogamicin (InO) vs standard chemotherapy (SC) had significantly greater remission rates and longer overall survival; after study treatment discontinuation, overall fewer subsequent induction/salvage therapies (STs, mainly burdensome chemotherapies) were used in the InO group vs SC. Aims: To investigate the treatment of InO on the time to the first ST (TST) in the INO-VATE trial. Methods: Study design was published. Adults with CD22+ ALL who were due to receive 1st or 2nd salvage treatment were randomized 1:1 to InO (n = 164) or SC (n = 162). TST was time from randomization to the start of the first ST. Pts who did not receive any ST were censored. Data cutoff: Jan 4, 2017. Results: Fewer InO pts had ST vs SC pts (Table). Among the censored pts, 83/108 (76.9%) in the InO vs 54/69 (78.3%) in the SC group died, 23/108 (21.3%) vs 5/69 (7.2%) were alive at the end of the study, and 2/108 (1.9%) vs 10/69 (14.5%) were no longer being followed for survival. TST was longer in pts receiving InO vs SC. Overall median (95% CI) TST was 18.8 (14.7–NA) vs 3.9 (2.4–5.1) months; hazard ratio (HR) = 0.34, 97.5% CI: 0.23–0.49, 1-sided P < 0.0001. For pts (InO: 85, SC: 126) who never received hematopoietic stem cell transplantation (HSCT) on study, fewer InO pts had ST vs SC pts; TST was significantly longer in InO vs SC. For pts (InO: 70, SC: 18) who had HSCT directly after salvage, TST was extended in InO vs SC.Summary/Conclusion: In this study, treatment with InO provided the benefit of extended TST, effectively allowing patients a longer time period until an ST was needed in both patients who proceeded to as well as those who did not proceed to HSCT.
Abstract 14109: Statin Eligibility Among Young Adults Prior to Myocardial Infarction
Authors: Avinainder Singh, Bradley Collins, Amber Fatima, Arman Qamar, David Biery, Julio Baez, Mary Cawley, Ankur Gupta, Josh Klein, Jon Hainer, Jorge Plutzky, Christopher P Cannon, Khurram Nasir, Marcelo F Di Carli, Deepak L Bhatt, Ron Blankstein
Journal: Circulation (2017)

Introduction: Current treatment guidelines suggest young adults have a low risk of atherosclerotic cardiovascular disease (ASCVD). We aimed to evaluate statin eligibility based on 2013 ACC/AHA guid...
SP0121 DEBATE: ILC AS INNOCENT BYSTANDER
Authors: Mikael Ebbo
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Innate lymphoid cells (ILC) are recently (10 years ago) described tissue-resident lymphoid populations [1]. They lack adaptive antigen receptor (generated by the recombination of genetic elements) and are innate counterparts of T lymphocytes. Indeed ILC1s, ILC2s, and ILC3s mirror CD4<sup>+</sup> T helper (Th)1, Th2, and Th17 cells, respectively, in terms of transcription factor expression and cytokine production. In this lecture, an overview of the different protective immunological functions of these helper ILC will be provided, in particular their role for maintenance of gut homeostasis, for control of parasitic, bacterial or viral infections, for anti-tumor immune responses, for metabolism, or for tissue repair mechanisms. The concept of ILC plasticity, which represents the capacity of these cells to change their phenotype and functional capacities in response to diverse microenvironment stimuli, will be also addressed. It directs the heterogeneity of these cells in the tissues, and may be important for their effective immune responses. In this context, targeting ILC for therapeutic use, for example in the battle against autoimmune or inflammatory diseases in which they may also play roles [2], could be associated with deleterious consequences. However, recent data concerning patients with a profound and selective ILC deficiency and no susceptibility to disease will be also presented here. This last observation suggests that most protective functions mentioned above may be redundant and potentially dispensable for human health, at least in modern conditions of hygiene and medicine, when T cell and B cell functions are preserved. <h3>References:</h3> [1] Innate Lymphoid Cells: 10 Years On. Vivier E, et al. Cell. 2018 Aug 23;174(5):1054-1066. [2] Innate lymphoid cells: major players in inflammatory diseases. Ebbo M, et al. Nat Rev Immunol. 2017 Nov;17(11):665-678. 3] . Evidence of innate lymphoid cell redundancy in humans. Vély F, et al. Nat Immunol. 2016 Nov;17(11):1291-1299. <h3>Disclosure of Interests:</h3> None declared
PB2182 OUTCOME OF FIRST‐LINE THERAPY FOR PATIENTS WITH SYSTEMIC LIGHT‐CHAIN AMYLOIDOSIS: MONOCENTRIC ANALYSIS
Authors: R. Fernández, A. Silva Soto, F. Cepeda, A. González, V. Robles, E. Fonseca, S. Sanchez, J. Torres, M. Sarasa, P. Chamorro, A. Álvarez, T. Arias, A. Bobes, A. Fernández, C. Fernández, S. González, M. E. González
Journal: HemaSphere (2019)

Background: Systemic light‐chain amyloidosis (AL) is characterised by deposition of misfolded immunoglobulin light chains within organs. Melphalan or cyclophosphamide with dexamethasone in combination with bortezomib are currently recommended first‐line therapy regimens. Aims: To describe the clinical presentation and outcomes for newly diagnosed AL amyloidosis patients. Methods This single‐centre retrospective study included all patients diagnosed with AL amyloidosis in our hospital area (300,000 inhabitants) between March 2012 to March 2018. Data regarding demography, diagnosis, treatment and follow‐up were extracted from the clinical history (HC). Survival curves were constructed according to the Kaplan‐Meier method and compared by logarithmic ranking. Time to progression (TTP) was defined as the time from the date of diagnosis or the start of a treatment for a disease until the disease worsens. Results: We analysed 24 patients (15women, 9 men) with newly diagnosed AL amyloidosis. Median age was 66 years (range 42‐82), and 6 pts were considered ASCT candidates. Involvement of kidney, peripheral nerve, heart, liver and other organs were found in 14 (35%), 13 (32.5%), 11 (24.5%), 1 (2.5%) and 1 (2.5%) cases, respectively. According to Mayo Stage 2012: stage 2: 25%, stage3: 33.33% and stage 4: 41.66% First‐line treatments were: regimens based on bortezomib CyBordex (cyclophosphamide, bortezomib and dexamethasone) n = 12, VTD (bortezomib, thalidomide and dexamethasone) n = 2, VMP (bortezomib, melphalan and prednisone) n = 2, BD (bortezomib and dexamethasone) n = 6, MP (melphalan and prednisone) n = 2 and CP (cyclophosphamide and prednisone) n = 1. Haematological responses of CyBordex, VTD, VMP, BD were 33.33%, 100% and 100% and 16.66% respectively. The haematological responses were: RC 25%, VGPR 33.33%, RP 8.33%, NR (no response) 33.33% The organ responses were 45.83% (n = 11). Median follow‐up of 19 months (95% CI 0‐49.9). Median PTT of 19 months (95% CI 0‐41.9). The rate of premature death within the first six months was 29.16%. Summary/Conclusion: Regimens based on bortezomib in newly diagnosed AL amyloidosis show results that seem comparable to those previously published in the literature. Almost a third of patients show no response, and premature death in six months is significative. To improve these outcomes, it is necessary to better define the role of proteasome inhibitors the role of new therapies. Educational interventions are important to optimize the diagnostic process and to reduce the rate of early deaths.
Abstract 14095: Role of Echocardiography for Screening of Pulmonary Hypertension in Patients With Advanced Lung Disease
Authors: Myriam Amsallem, David Boulate, Zoe Kooreman, Roham Zamanian, Guillaume Fadel, Ingela Schnittger, Elie Fadel, Gundeep Dhillon, Michael V McConnell, Olaf Mercier, Francois Haddad
Journal: Circulation (2016)

Introduction: The screening performance of right heart metrics for pulmonary hypertension (PH) among patients with advanced lung disease (ALD) is not well established. Hypothesis: We hypothesize th...
Immune Checkpoint Inhibitor Outcomes for Patients With Non–Small-Cell Lung Cancer Receiving Baseline Corticosteroids for Palliative Versus Nonpalliative Indications
Authors: Biagio Ricciuti, Suzanne E. Dahlberg, Anika Adeni, Lynette M. Sholl, Mizuki Nishino, Mark M. Awad
Journal: Journal of Clinical Oncology (2019)

PURPOSE Baseline use of corticosteroids is associated with poor outcomes in patients with non–small-cell lung cancer (NSCLC) treated with programmed cell death-1 axis inhibition. To approach the question of causation versus correlation for this association, we examined outcomes in patients treated with immunotherapy depending on whether corticosteroids were administered for cancer-related palliative reasons or cancer-unrelated indications. PATIENTS AND METHODS Clinical outcomes in patients with NSCLC treated with immunotherapy who received ≥ 10 mg prednisone were compared with outcomes in patients who received 0 to &lt; 10 mg of prednisone. RESULTS Of 650 patients, the 93 patients (14.3%) who received ≥ 10 mg of prednisone at the time of immunotherapy initiation had shorter median progression-free survival (mPFS) and median overall survival (mOS) times than patients who received 0 to &lt; 10 mg of prednisone (mPFS, 2.0 v 3.4 months, respectively; P = .01; mOS, 4.9 v 11.2 months, respectively; P &lt; .001). When analyzed by reason for corticosteroid administration, mPFS and mOS were significantly shorter only among patients who received ≥ 10 mg prednisone for palliative indications compared with patients who received ≥ 10 mg prednisone for cancer-unrelated reasons and with patients receiving 0 to &lt; 10 mg of prednisone (mPFS, 1.4 v 4.6 v 3.4 months, respectively; log-rank P &lt; .001 across the three groups; mOS, 2.2 v 10.7 v 11.2 months, respectively; log-rank P &lt; .001 across the three groups). There was no significant difference in mPFS or mOS in patients receiving ≥ 10 mg of prednisone for cancer-unrelated indications compared with patients receiving 0 to &lt; 10 mg of prednisone. CONCLUSION Although patients with NSCLC treated with ≥ 10 mg of prednisone at the time of immunotherapy initiation have worse outcomes than patients who received 0 to &lt; 10 mg of prednisone, this difference seems to be driven by a poor-prognosis subgroup of patients who receive corticosteroids for palliative indications.
PF794 DETECTION OF ANTIBODIES DIRECTED AGAINST DOMAIN 1 OF BETA 2 GLYCOPROTEIN I IN PATIENTS WITH ANTIPHOSPHOLIPID SYNDROME
Authors: A. Kerényi, G. Nagy, P. Antal‐Szalmás, J. Kappelmayer
Journal: HemaSphere (2019)

Background: Antiphospholipid syndrome (APS) is an acquired thrombophilia caused by antiphospholipid autoantibodies (aPL). Diagnosis of APS is based on laboratory and clinical criteria (thrombosis or pregnancy‐related complications). The detection of lupus anticoagulant (LA), IgG and/or IgM isotype anti‐cardiolipin (ACA) and anti‐β2 glycoprotein I antibodies (aβ2GPI) constitutes the laboratory tests of APS. The β2GPI protein consists of 5 domains and an association of thrombosis with the presence of antibodies directed against domain 1 (aD1β2GPI) was suggested in the literature. Aims: The aim of this study was to investigate the presence of IgG isotype aD1β2GPI and its association with thrombosis in our patient cohort. Methods: Using a chemiluminescence immunoassay (INOVA QUANTA Flash β2GPI‐Domain I, ACL Acustar) we have measured aD1β2GPI titer in 51 patients having IgG isotype aβ2GPI (APS with thrombosis: n = 21; APS with pregnancy loss: n = 7; other autoimmune disease: n = 18; aPL positive asymptomatic patients, n = 5). Results: In patient samples the concordance between the presence of IgG isotype aD1β2GPI and aβ2GPI was 67% and the correlation between these antibody titers was high (r = 0.71). We have found that the level of IgG isotype anti‐β2GPI was significantly higher in thrombotic APS patients compared to all other patient groups. The aD1β2GPI titer was the highest in thrombotic patients however, there was no significant difference in the antibody titer among the patient groups. The IgG isotype aβ2GPI and aD1β2GPI titers were significantly higher in triple positive patients (LA, ACA and aβ2GPI positive) than in double positive patients (ACA and aβ2GPI positive). In the aD1β2GPI positive group 47% of patients had thrombosis, while in the aD1β2GPI negative group this figure was only 29%, however, the association of aD1β2GPI positivity with thrombosis was non‐significant. Summary/Conclusion: This study provides further evidence that the large majority of IgG isotype aβ2GPI is directed against domain 1. Since the concordance between the two antibody positivity was not 100% and aD1β2GPI negative patients can present with thrombosis, we conclude that monitoring aD1β2GPI cannot replace detection of aβ2GPI in the laboratory diagnosis of APS.