tbuckley/cabot-search huggingface dataset:
PS1206 TRANSCRIPTION FACTOR BOB1 IS ESSENTIAL FOR GERMINAL CENTER‐DERIVED B CELL MALIGNANCIES OFFERING AN ATTRACTIVE TARGET FOR TCR‐BASED THERAPY
Authors: R. Reijmers, M. Meeuwsen, C. Kweekel, M. Kop, A. Meringa, L. Jahn, F. Falkenburg, M. Heemskerk
Journal: HemaSphere (2019)

Background: Antigen‐loss tumor escape variants are a major concern when targeting cancer, while tumor‐specific targeting is crucial to prevent unwanted toxicity. Thus, targeting essential cancer‐ or lineage‐specific genes might represent attractive targets for antineoplastic therapies since antigen‐loss is less likely to occur, and toxicity is limited. Here, we describe B cell lineage‐specific transcriptional coactivator BOB1 to meet these important criteria. Interestingly, in our lab we have successfully identified several distinct T cell receptors (TCRs) that are BOB1‐specific with demonstrable preclinical efficacy. Aims: With this study we aimed to demonstrate that the transcriptional coactivator BOB1 is essential for survival of B cell malignancies with a germinal center origin, and that these neoplasms are recognized by our recently and newly identified BOB1‐specific TCRs in the context of HLA‐B ∗ 07:02 and HLA‐B ∗ 35:01, respectively. Methods: Using a CRISPR/Cas9 puromycin plasmid containing a sgRNA or by applying a doxycycline‐inducible system, we set out to target BOB1 in different B cell malignancies. Upon targeting, we selected puromycin resistant single‐cell clones or tracked cell growth upon induction, and used sanger‐sequencing to identify possible indel mutations. Besides single‐cell analysis, Tracking of Indels by DEcomposition (TIDE) was used to accurately quantify the editing efficacy and most prominent types of indel mutation in different pools of B cell tumors. Finally, we performed in vitro co‐cultures with BOB1‐specific TCR transduced CD8 T cells and a plethora of B cell malignancies, including myeloma and lymphoma, and assessed preclinical efficacy targeting myeloma in vivo . Results: Remarkably, for each type of B cell tumor used, we were unable to generate BOB1‐deficient clones, unveiling the importance for cell survival. In line, using the TIDE algorithm for easy detection of predominant types of indel mutations in targeted pools of distinct types of B cell malignancies, we found unmutated BOB1 sequences only (&gt;90%), while generally a mere 5% is expected to be unaltered for any irrelevant gene. Finally, we further established the essentiality of BOB1 in a broad panel of B cell malignancies containing inducible CRISPR/Cas9, which uniformly resulted in rapid cell death upon induction. Interestingly and importantly, using our recently and newly identified TCRs recognizing peptides derived from BOB1 in the context of HLA‐B ∗ 07:02 and HLA‐B ∗ 35:01, we observed highly specific and efficient targeting of a vast majority of B cell malignancies in vitro and in vivo . Summary/Conclusion: Altogether, we postulate BOB1 as an essential B cell lineage‐specific target, fortifying gene transfer of our unique TCRs into CD8+ cytotoxic T cells as an efficient therapeutic treatment option for a large variety of B cell neoplasms.
Chemiluminescence and Bioluminescence Imaging for Biosensing and Therapy: <i>In Vitro</i> and <i>In Vivo</i> Perspectives
Authors: Yongcun Yan, Pengfei Shi, Weiling Song, Sai Bi
Journal: Theranostics (2019)

Chemiluminescence (CL) and bioluminescence (BL) imaging technologies, which require no external light source so as to avoid the photobleaching, background interference and autoluminescence, have become powerful tools in biochemical analysis and biomedical science with the development of advanced imaging equipment.CL imaging technology has been widely applied to high-throughput detection of a variety of analytes because of its high sensitivity, high efficiency and high signal-to-noise ratio (SNR).Using luciferase and fluorescent proteins as reporters, various BL imaging systems have been developed innovatively for real-time monitoring of diverse molecules in vivo based on the reaction between luciferin and the substrate.Meanwhile, the kinetics of protein interactions even in deep tissues has been studied by BL imaging.In this review, we summarize in vitro and in vivo applications of CL and BL imaging for biosensing and therapy.We first focus on in vitro CL imaging from the view of improving the sensitivity.Then, in vivo CL applications in cells and tissues based on different CL systems are demonstrated.Subsequently, the recent in vitro and in vivo applications of BL imaging are summarized.Finally, we provide the insight into the development trends and future perspectives of CL and BL imaging technologies.
PB2173 OUTCOMES AFTER AUTOLOGOUS STEM CELL TRANSPLANTATION IN MULTIPLE MYELOMA: IMPACT OF RENAL FAILURE
Authors: R. El Fatmi, R. Ouerghi, E. Azza, S. Riahi, D. Belloumi, L. Torjemane, N. Abdeljelil, A. Lakhal, S. Ladeb, T. Ben Othman
Journal: HemaSphere (2019)

Background: Renal failure (RF) is a common complication of multiple myeloma found in 25% at diagnosis and in 50% during the course of the disease. RF persistence after induction treatment may constitute a factor of ineligibility for autologous stem cell transplantation (ASCT). However, its impact on toxicity and survival post-ASCT is still subject to discussion. Aims: We aimed to compare the toxicity and survival after ASCT in newly diagnosed multiple myeloma (NDMM) patients (pts) with or without RF at diagnosis Methods Retrospective comparative study of two groups of NDMM pts without RF at diagnosis (Group 1: G1) or with RF at diagnosis (Group 2: G2). These patients were treated according to the Tunisian national referential by dexamethasone, thalidomide +/- bortezomib and transplanted at the hematology department of the national center of bone marrow transplant between January 2011 and December 2016. The IMWG 2014 and IMWG 2016 response criteria were used to assess hematologic and renal response respectively. Results: Data from 134 patients were analyzed. Median age at ASCT was 54 years (range, 25-65). Sex ratio was 1.2. In all, 114 (85%) and 20 (15%) pts were included in G1 and G2 respectively. In G2, 13 pts (65%) had severe renal impairment at diagnosis; 2 of them required at least one dialysis session. After induction, renal response was complete (70%), partial (15%) or minor (15%). As a pre-transplant conditioning, all pts in G1 received melphalan (MEL) at the dose of 200 mg/m2. In G2, pts received either MEL 200 mg/m2 (85%) or MEL 140 mg/m2 (15%). The two comparative groups were matched with regards to preASCT patient's characteristics and hematological status. In G2 compared to G1, risk of grade ≥3 mucositis (100 vs 51%) was significantly higher, while no significant differences were found in duration of neutropenia (medians 6 vs 6 days), microbiologically documented infection (31 vs 26%), duration of hospitalization (medians: 23 vs 23 days), post-transplant response (ORR; 75 vs 87%), time to progression (median 20 vs 19 months), 5-year PFS (34vs 33%) and OS (61 vs 59%) Summary/Conclusion: Apart from mucositis, ASCT in MM with or without RF was associated with a comparable toxicity and survival rate
SP0062 CARDIOVASCULAR MORBIDITY AND GOUT – FROM EPIDEMIOLOGY TO THERAPY
Authors: Mariano Andrés
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> Gout is an independent cardiovascular risk factor. Patients suffering from gout show a higher incidence of all forms of the atherosclerotic disease, as well as cardiovascular and all-cause mortality. This associates with both comorbidities and urate crystal-led inflammation. Thus, gout, along with being the most common form of inflammatory arthritis in rich countries, carries with significant morbidity and mortality. Proper management is essential. The purpose of this lecture is to analyze the potential strategies aimed to control the cardiovascular risk in patients with gout. <h3>Disclosure of Interests:</h3> None declared
PS1253 MAGNIFY: PHASE IIIB INTERIM ANALYSIS OF INDUCTION #R2 FOLLOWED BY MAINTENANCE IN PATIENTS WITH RELAPSED/REFRACTORY INDOLENT NON‐HODGKIN LYMPHOMA
Authors: M.J. Rummel, D.J. Andorsky, M. Coleman, A. Yacoub, J.M. Melear, S.R. Fanning, K.S. Kolibaba, F. Lansigan, C. Reynolds, K. Foon, J. Li, M. Llorente, J. Sharman
Journal: HemaSphere (2019)

Background: There is a lack of standard treatment approaches for patients with relapsed indolent non‐Hodgkin lymphoma (iNHL). Current study results with PI3K inhibitors have reported a median PFS of &lt;1 y in the relapsed/refractory setting (R/R) for patients with iNHL. Lenalidomide, an immunomodulatory agent, enhances the activity of rituximab when combined into a regimen known as R 2 , which has recently reported a median PFS of 39.4 mo in patients with R/R iNHL patients from the phase III AUGMENT study (Leonard. ASH 2018:445). Aims: These analyses examine the interim primary endpoint of overall response rate (ORR; 1999 IWG) for induction R 2 in efficacy‐evaluable patients receiving ≥ 1 treatment and who have available baseline and post‐baseline assessments. Methods: The multicenter, non‐registrational phase IIIb MAGNIFY trial in patients with R/R follicular lymphoma (FL) grade 1–3a and marginal zone lymphoma (MZL) was designed to determine the optimal duration of lenalidomide (NCT01996865). R 2 treatment includes lenalidomide 20 mg/d, d1–21/28 plus rituximab 375 mg/m 2 /wk cycle 1 and q8wk cycles 3+ given for 12 cycles, and is followed by 1:1 randomization in patients with stable disease or better to continued R 2 vs rituximab maintenance. Results: 370 enrolled patients (80% FL grade 1–3a; 20% MZL) had a median age of 66 y, 83% stage III/IV disease, and a median of 2 prior therapies (95% prior rituximab‐containing). At a median 16.7 mo follow‐up, efficacy‐evaluable patients demonstrated a 73% ORR and 45% complete response (CR; Table). Similar efficacy results were shown for patients by histology. Overall, the median time to response (TTR) was 2.7 mo, median duration was response (DOR) was 36.8 mo, and median progression‐free survival (PFS) was 36.0 mo. According to their refractory status to rituximab at baseline, patients who were rituximab‐refractory and non‐refractory, respectively, had an ORR (CR) of 63% (40%) and 78% (47%), and median PFS of 18.1 mo and not reached. Of 370 patients who were randomized, 142 (38%) have entered the maintenance phase. The most common all‐grade adverse events were 48% fatigue, 40% neutropenia, 35% diarrhea, 30% nausea, and 29% constipation. Although the grade 3/4 adverse event neutropenia was 34%, all others were &lt;6%. Summary/Conclusion: R 2 therapy is an active treatment regimen in patients with R/R FL grade 1–3a and MZL, including patients refractory to rituximab, and with a tolerable safety profile. image
PB1758 CHILDHOOD ACUTE MYELOID LEUKEMIA IN SOUTHERN TUNISIA: ABOUT 52 CASES
Authors: O. kassar, R. mallek, Y. Fakhfakh, M. charfi, M. chaari, F. kallel, M. ghorbel, I. frikha, H. belaaj, M. mdhaffar, S. mseddi, M. Elloumi
Journal: HemaSphere (2019)

Background: Childhood acute myeloid leukemia (AML) represents 20% of childhood acute leukemia. Despite major improvement in outcome, the prognostic is pejorative compared with childhood acute lymphoblastic leukemia. Aims: We report the clinical features and treatment outcome of children de novo AML in southern Tunisia. Methods: Our study is retrospective including Children (age ≤ 20 years) affected by de novo AML between January 2005 and June 2018 treated in the department of hematology of CHU Hedi Chaker Sfax. Diagnosis has been established according to FAB classification confirmed by flow cytometry. Secondary leukemia and FAB M3 were excluded. Induction chemotherapy associated cytarabine 200 mg/m 2 for 7 days and daunorubicin 60 mg/m 2 for 3 days or mitoxantrone 12 mg/m 2 for 5 days. After induction, patients with an HLA‐matched sibling donor underwent allogeneic Bone Marrow Transplantation (allo‐BMT) in first complete remission (CR1). Patients without a matched sibling donor received in CR1 three or four courses of consolidation. We evaluated complete remission rate, overall survival (OS) and event‐free survival (EFS). The Kaplan‐Meier method was used to estimate OS and EFS. Results: We collected 52 cases of childhood AML, including 28 boys and 24 girls (sex ratio = 1.03). The median age at diagnosis was 12 years (1.5‐20 years). The median initial white blood cell and hemoglobin level were 76 G/L (extreme 0.9 G/L ‐ 900 G/L) and 6.5 g / dL respectively. The median count of platelet was 55000/mm 3 . Distribution according FAB classification was: 17% of AML0, 21% of AML1, 19% of AML2, 23% of AML4, 6%of AML5 and 2% of AML6, 6% of AML7 and 2% of AMLbipheno. Cytogenetic of bone marrow cells showed chromosomal abnormalities in 58% of cases, only 13 (25%) patients had favorable abnormalities. Thirty‐one patients (60%) achieved complete response after one cure and 34 patients (65 %) after one or two courses of chemotherapy. Failure rate and toxic death were respectively 8% and 27%. Hematopoietic stem cell transplant was indicated in 24 (46%) patients but only 8 underwent the procedure. Nine patients (17.3%) relapsed within 8 months from diagnosis. The 5‐year OS and EFS were 50% and 48% respectively. Summary/Conclusion: Our study is characterized by frequent leucocytosis forms and FAB type M2. The CR rate and our EFS and OS rates observed in our series remain lower than in international trials. These can be explained by the frequency of refractory forms and the small number of bone marrow transplantation. Intensification chemotherapy of induction as well as consolidation therapy with allo‐BMT can improve the outcome of our patients.
SP0139 WHAT WE ARE BRILLIANT AT; NURSING PERSPECTIVE
Authors: Ricardo Ferreira
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> The challenges confronting health care delivery systems worldwide are rapidly changing, and this calls for practice-defined competencies for nurses and other health care workers (Zhang, Luk, Arthur, &amp; Wong, 2001). The definition of competency or competence in nursing has been a subject of debate (Axley, 2008; Fukada, 2018; Zhang et al., 2001). Its clarification is important and still needed to establish a foundation for realistic working behaviours, for nursing education and management. Although there has been an extensive and valuable work in the definition of core competencies of nursing profession, which includes both autonomous and interdependent activities within the multidisciplinary team, little scientific research has been done to clarify the way in which nursing profession is unique. This presentation will address the following questions: What are nurses (collectively) really brilliant at? What leads them to develop unique characteristics? How do they bring into care, that matches or complements other health professions to result in better quality care? The presentation is informed by a scoping review, a survey of international nurse leaders and researchers. <h3>References:</h3> [1] Axley, L. (2008). Competency: a concept analysis. Nurs Forum, 43(4), 214-222. doi:10.1111/j.1744-6198.2008.00115. [2] Fukada, M. (2018). Nursing Competency: Definition, Structure and Development. Yonago Acta Medica, 61(1), 1-7. [3] Zhang, Z., Luk, W., Arthur, D., &amp; Wong, T. (2001). Nursing competencies: personal characteristics contributing to effective nursing performance. Journal of Advanced Nursing, 33(4), 467-474. <h3>Disclosure of Interests:</h3> None declared
Integrative Copy Number Analysis of Uveal Melanoma Reveals Novel Candidate Genes Involved in Tumorigenesis Including a Tumor Suppressor Role for <i>PHF10/BAF45a</i>
Authors: Hima Anbunathan, Ruth Verstraten, Arun D. Singh, J. William Harbour, Anne M. Bowcock
Journal: Clinical Cancer Research (2019)

Uveal melanoma is a primary malignancy of the eye with oncogenic mutations in GNAQ, GNA11, or CYSLTR2, and additional mutations in BAP1 (usually associated with LOH of Chr 3), SF3B1, or EIF1AX. There are other characteristic chromosomal alterations, but their significance is not clear.To investigate genes driving chromosomal alterations, we integrated copy number, transcriptome, and mutation data from three cohorts and followed up key findings.We observed significant enrichment of transcripts on chromosomes 1p, 3, 6, 8, and 16q and identified seven shared focal copy number alterations (FCNAs) on Chr 1p36, 2q37, 3, 6q25, 6q27, and 8q24. Integrated analyses revealed clusters of genes in focal copy number regions whose expression was associated with metastasis and worse overall survival. This included genes from Chr 1p36, 3p21, and 8q24.3. At Chr 6q27, we identified two tumors with homozygous deletion of PHF10/BAF45a and one with a frameshift mutation with concomitant loss of the wild-type allele. Downregulation of PHF10 in uveal melanoma cell lines and tumors altered a number of biological pathways including development and adhesion. These findings provide support for a role for PHF10 as a novel tumor suppressor at Chr 6q27.Integration of copy number, transcriptome, and mutation data revealed novel candidate genes playing a role in uveal melanoma pathogenesis and a potential tumor suppressor role for PHF10.
Accurate Estimation of Neural Population Dynamics without Spike Sorting
Authors: Eric M. Trautmann, Sergey D. Stavisky, Subhaneil Lahiri, Katherine C. Ames, Matthew T. Kaufman, Daniel J. O’Shea, Saurabh Vyas, Xulu Sun, Stephen I. Ryu, Surya Ganguli, Krishna V. Shenoy
Journal: Neuron (2019)
AB0251 ASSESSMENT OF CARDIOVASCULAR RISK IN RHEUMATOID ARTHRITIS AND ITS RELATION WITH LEPTIN AND INTERLEUKIN-6
Authors: Samar Goma, Eman El-Hakeim, Zeinab Abd Elhameed, Dina Mohareb, Rania Gamal, Fatma El Noby, Mohamed Raouf Abdel Razek, Salma Taha
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> In rheumatoid arthritis patients the risk of cardiovascular affection is 2–3 times higher than the general population (Hollan, Meroni et al. 2013), with increased morbidity and mortality(Perles, Sánchez et al. 2013). This is due to increase in the traditional and nontraditional risk factor(Skeoch and Bruce 2015). <h3>Objectives</h3> The aim of this study is to determine the cardiovascular risk in patients with RA using four established CV risk algorithms Framingham Risk Score (FRS), Systematic Coronary Risk Evaluation Score (SCORE], Reynolds Risk Score (RRS), Q II Risk Score and there relation with serum levels of leptin and interleukin-6 (IL-6). <h3>Methods</h3> Sixty seven RA patients were enrolled in this study. The 10-year CVR for RA patients were calculated using FRS, SCORE, RRS and Q II Risk Score. Serum leptin and IL-6 were estimated. <h3>Results</h3> The results showed a significant difference between higher leptin values and disease activity, obesity, positive RF and longer disease duration, On the other hand, we found a significant difference between higher IL-6 values and disease activity, and hypertriglyceridemia. As regarding correlations of IL-6 and Leptin with different cardiovascular scores, there were no significant correlations with exception of moderate significant correlation between IL-6 and RRS (r= 0.42, <i>P</i>&lt; 0.001). <h3>Conclusion</h3> New models of CVD risk prediction incorporating RA specific variables or imaging techniques are needed. <h3>References</h3> [1] Hollan, I., P. L. Meroni, J. M. Ahearn, J. C. Tervaert, S. Curran, C. S. Goodyear, K. A. Hestad, B. Kahaleh, M. Riggio and K. Shields (2013). "Cardiovascular disease in autoimmune rheumatic diseases."Autoimmunity reviews12(10): 1004-1015. [2] Perles, C. M., J. A. Sánchez, B. García-Magallón and C. S. Gómez (2013). "Artritis reumatoide (II)." Medicine-Programa de Formación Médica Continuada Acreditado 11(30): 1850-1855. [3] Skeoch, S. and I. N. Bruce (2015). "Atherosclerosis in rheumatoid arthritis: is it all about inflammation?" Nature Reviews Rheumatology11(7): 390. <h3>Disclosure of Interests</h3> None declared
Recombinant Porcine FVIII in Acquired Hemophilia: Decreased Product Usage When Used Upfront, Non-Utility of Baseline Porcine Bethesda Titer, and Confirmation of Dosing Algorithm
Authors: Patrick Ellsworth, Sheh-Li Chen, Nigel S. Key, Raj S. Kasthuri, Micah J. Mooberry, Alice D. Ma
Journal: Blood (2018)
SP0114 CASE 1 PRESENTER: IMMINENT FRACTURE RISK: ASSESSMENT AND DOES IT HELP CLINICAL MANAGEMENT
Authors: Nicholas Fuggle
Journal: Annals of the Rheumatic Diseases (2019)

<h3></h3> A 60 year old female was under long-term follow-up for rheumatoid arthritis, for which she took methotrexate. Ten years previously she had been found to have a single vertebral fracture and her fracture risk, assessed using The WHO Fracture Risk Assessment Tool (FRAX®), was calculated as a 13% risk of major osteoporotic fracture over the next 10 years. According to The National Osteoporosis Guideline Group (NOGG) recommendations, she underwent Dual X-ray Absorptiometry (DXA) which demonstrated a bone mineral density T-score of -1.7 at the femoral neck. Lifestyle, vitamin D and calcium intake were optimised and follow-up was arranged for 6 months. Prior to her next appointment she fell and sustained a fracture of the distal radius. On fracture liaison review her FRAX® risk of fracture was 14% (rising due to an increased year of age) despite the recent change in clinical circumstances. This case serves to emphasise the clinical conundra associated with imminent fracture risk (the 2 years after a fracture when the patient is at a significantly higher risk of fracture) and the difficulties with the decision to treat. <h3>Disclosure of Interests:</h3> None declared
Response to 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: Graham R. Law, Alia Alnaji, Lina Alrefaii, Del Endersby, Sarah J. Cartland, Stephen G. Gilbey, Paul E. Jennings, Helen R. Murphy, Eleanor M. Scott
Journal: Diabetes Care (2019)

We thank Foussard et al. (1) for their insightful comments on our recent article (2). We demonstrated that women with gestational diabetes mellitus who subsequently have a large for gestational age (LGA) infant run significantly higher glucose overnight, detectable by continuous glucose monitoring (CGM), at 32 weeks’ gestation than those women who do not go on to have an LGA infant (2). We speculate that there may be several reasons why this is observed.

Foussard et al. (1) suggest that, irrespective of the cause, NPH insulin administered in the evening should be considered the treatment of choice because its peak action coincides with the relative nocturnal hyperglycemia we demonstrated. Our own …
PB2203 IMPROVEMENT OF THE HEMATOLOGIC TOXICITIES OF RUXOLITINIB IN PATIENTS WITH MPN‐ASSOCIATED MYELOFIBROSIS USING A COMBINATION OF THALIDOMIDE, STANOZOLOL AND PREDNISONE
Authors: M. Duan, D. zhou
Journal: HemaSphere (2019)

Background: Anemia and thrombocytopenia are the most frequently reported adverse events of ruxolitinib in patients with MPN‐associated myelofibrosis (MPN‐MF). Although thalidomide, androgens and prednisone have previously demonstrated improvements in myelofibrosis‐associated anemia, it is unclear whether these drugs are effective in patients taking ruxolitinib. Aims: To evaluate the efficacy and tolerability of combination therapy with low dose thalidomide, stanozolol and prednisone (TSP) in patients with IPSS intermediate‐2 or high‐risk myelofibrosis (MF) who received ruxolitinib treatment. Methods: Sixty‐five patients with MPN‐MF who took ruxolitinib were enrolled in this retrospective study, of which 46 patients also took TSP while 19 did not take TSP (TSP and non‐TSP groups). Results: Within the first 24 weeks, the proportion of patients with anemia and platelet count ≥50 × 10 9 /L were 45.7% and 67.4% in the TSP group as compared to 0% and 10.5% in the non‐TSP group (p &lt; 0.001). The mean hemoglobin level in the non‐TSP group reached the nadir after approximately 12–16 weeks of therapy, but gradually increased in the TSP group. Summary/Conclusion: In summary, TSP regime can improve anemia and thrombocytopenia during ruxolitinib treatment in patients with MPN‐MF, and the associated adverse events were manageable. image