tbuckley/cabot-search huggingface dataset:
PF324 RITUXIMAB DOSE ASSOCIATED WITH OVERALL SURVIVAL IN DIFFUSE LARGE B CELL LYMPHOMA
Authors: J.H. Kong, H.S. Kim, J.Y. Lee, S.Y. Hyun
Journal: HemaSphere (2019)

Background: The outcome of diffuse large B cell lymphoma ( DLBCL ) improved significantly, due to the addition of rituximab ( R ) to CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) chemotherapy. However, significant range of patients showed relapse or refractory to R‐CHOP, and the role of body surface area (BSA) or body mass index (BMI) to overall survival (OS) was not known or still controversial. Aims: We evaluated effects of rituximab dose, BSA or BMI on OS using National Health Information Database. Methods: This study included patients 5,332 patients who were diagnosed with DLBDL and received R‐CHOP as a frontline therapy between 2006 and 2014. The exclusion criteria were as follows;1) age &lt;20 years 2) R‐CHOP was given less than 4 times or over 8 times 3) R‐CHOP 2 months after diagnosis 4) Interval between two consecutive R‐CHOP injection was over 60 days. We extracted age, sex, prescribed medication list, and date of death from NHID. Weight and height of patients who had national general health examination before 1 st cycle of R‐CHOP was collected. Results: Median age was 58(20–92) years, and 57%(n = 3021) of them were male. Thirty‐eight % of patients (n = 2019) received R‐CHOP 4–5 times, and 62% (n = 3303), 6–8 times. Median dose of injected rituximab was total 7200(1,600–16,800) mg, and median mean dose of rituximab per each cycle was 600(400–1,000) mg. A total 2,523 patients (47.4%) were treated at medical institution in capital (Seoul) area. About 72% of patients (n = 3813) had national health examination before chemotherapy. Their median weight and height were 63(31–121) kg and 163(131–196) cm, respectively. Median BSA and BMI were 1.69m 2 and 23.9 kg/m 2 . With median 66(24–144) months of follow up, estimated 5‐year and 10‐year overall survival was 37.1% and 25.6% respectively. Log‐rank test for 10‐year OS, age≤60 (vs age&gt;60), female (vs male), 6–8 times of R‐CHOP injection (vs 4–5 times of R‐CHOP), total R dose≥7200 mg (vs &lt;7200), mean R dose≥600 mg, and medical institution in Seoul (vs others) were associated OS, significantly ( p &lt; 0.05). However, total R dose did not affect OS in multivariate analysis (p = 0.152). Among 3813 patients who had national health examination before R‐CHOP, patients whose BSA &lt;1.69m 2 had worse OS than BSA≥1.69m 2 . But BMI did not differentiate OS. Summary/Conclusion: With 66 (24–144) months of median follow up, estimated OS at 5‐year and 10‐year of DLBCL patients were 37.1% and 26.5%, respectively. Mean rituximab dose ≥600 mg showed better OS than &lt;600 mg. High BSA showed favorable OS, but BMI did not affected OS significantly. image
Noncontrast Magnetic Resonance for the Diagnosis of Cardiac Amyloidosis
Authors: Andrea Baggiano, Michele Boldrini, Ana Martinez-Naharro, Tushar Kotecha, Aviva Petrie, Tamer Rezk, Maurizio Gritti, Cristina Quarta, Daniel S. Knight, Ashutosh D. Wechalekar, Helen J. Lachmann, Stefano Perlini, Gianluca Pontone, James C. Moon, Peter Kellman, Julian D. Gillmore, Philip N. Hawkins, Marianna Fontana
Journal: JACC. Cardiovascular imaging (2019)
Cigarette consumption estimates for 71 countries from 1970 to 2015: systematic collection of comparable data to facilitate quasi-experimental evaluations of national and global tobacco control interventions
Authors: Steven J Hoffman, Jessica Mammone, Susan Rogers Van Katwyk, Lathika Sritharan, Maxwell Tran, Safa Al-Khateeb, Andrej Grjibovski, Elliot Gunn, Sara Kamali-Anaraki, Ben Li, Mathura Mahendren, Yasmeen Mansoor, Navneet Natt, Ejike Nwokoro, Harkanwal Randhawa, Melodie Yunju Song, Kelsey Vercammen, Carolyne Wang, Julia Woo, Mathieu JP Poirier
Journal: BMJ (2019)

To collect, appraise, select, and report the best available national estimates of cigarette consumption since 1970.Systematic collection of comparable data.71 of 214 countries for which searches for national cigarette consumption data were conducted, representing over 95% of global cigarette consumption and 85% of the world's population.Validated cigarette consumption data covering 1970-2015 were identified for 71 countries. Data quality appraisal was conducted by two research team members in duplicate, with greatest weight given to official government sources. All data were standardised into units of cigarettes consumed per year in each country, a detailed accounting of data quality and sourcing was prepared, and all collected data and metadata were made freely available in an open access dataset.Cigarette consumption fell in most countries over the past three decades but trends in country specific consumption were highly variable. For example, China consumed 2.5 million metric tonnes (MMT) of cigarettes in 2013, more than Russia (0.36 MMT), the United States (0.28 MMT), Indonesia (0.28 MMT), Japan (0.20 MMT), and the next 35 highest consuming countries combined. The US and Japan achieved reductions of more than 0.1 MMT from a decade earlier, whereas Russian consumption plateaued, and Chinese and Indonesian consumption increased by 0.75 MMT and 0.1 MMT, respectively. These data generally concord with modelled country level data from the Institute for Health Metrics and Evaluation and have the additional advantage of not smoothing year-over-year discontinuities that are necessary for robust quasi-experimental impact evaluations.Before this study, publicly available data on cigarette consumption have been limited; they have been inappropriate for quasi-experimental impact evaluations (modelled data), held privately by companies (proprietary data), or widely dispersed across many national statistical agencies and research organisations (disaggregated data). This new dataset confirms that cigarette consumption has decreased in most countries over the past three decades, but that secular country specific consumption trends are highly variable. The findings underscore the need for more robust processes in data reporting, ideally built into international legal instruments or other mandated processes. To monitor the impact of the WHO Framework Convention on Tobacco Control and other tobacco control interventions, data on national tobacco production, trade, and sales should be routinely collected and openly reported.
H3K27me3 Signal in the <i>Cis</i> Regulatory Elements Reveals the Differentiation Potential of Progenitors during <i>Drosophila</i> Neuroglial Development
Authors: Xiaolong Chen, Youqiong Ye, Liang Gu, Jin Sun, Yanhua Du, Wen-Ju Liu, Wei Li, Xiaobai Zhang, Cizhong Jiang
Journal: Genomics Proteomics & Bioinformatics (2019)

Abstract Drosophila neural development undergoes extensive chromatin remodeling and precise epigenetic regulation. However, the roles of chromatin remodeling in establishment and maintenance of cell identity during cell fate transition remain enigmatic. Here, we compared the changes in gene expression, as well as the dynamics of nucleosome positioning and key histone modifications between the four major neural cell types during Drosophila neural development. We find that the neural progenitors can be separated from the terminally differentiated cells based on their gene expression profiles, whereas nucleosome distribution in the flanking regions of transcription start sites fails to identify the relationships between the progenitors and the differentiated cells. H3K27me3 signal in promoters and enhancers can not only distinguish the progenitors from the differentiated cells but also identify the differentiation path of the neural stem cells (NSCs) to the intermediate progenitor cells to the glial cells. In contrast, H3K9ac signal fails to identify the differentiation path, although it activates distinct sets of genes with neuron-specific and glia-related functions during the differentiation of the NSCs into neurons and glia, respectively. Together, our study provides novel insights into the crucial roles of chromatin remodeling in determining cell type during Drosophila neural development.
PF666 LOW JAK2 V617F ALLELE BURDEN PHI‐NEGATIVE CHRONIC MYELOPROLIFERATIVE NEOPLASMS MAY ASSOCIATE WITH ADDITIONAL CALR OR MPL MUTATIONS
Authors: T. Makarik, A. Odilov, A. Abdullaev, E. Nikulina, S. Treglazova, E. Stepanova, I. Soubortseva, A. Kovrigina, A. Melikyan, A. Sudarikov
Journal: HemaSphere (2019)

Background: Jak2 (Janus kinase 2) V617F, CALR (Calreticulin) exon 9 and MPL (receptor for thrombopoietin) exon 10 mutations are associated with the vast majority of Phi‐negative chronic myeloproliferative neoplasms (MPNs). These mutations affect sequential stages of prolipherative signal transduction and therefore after the emergence of one type of mutation another types basically should not have any selective advantages for clonal expansion. However simultaneous findings of these mutations have been reported by different investigators in up to 10% of MPN cases. Aims: To analyze cases with combined mutations in Russian cohort of MPN patients Methods: Study includes 3267 samples, directed for genetic analysis to the National Research Center for Hematology between 2014 and 2019 from the patients with clinical evidence of MPN. DNAs and RNAs were extracted from blood using reagent kit from Interlabservice (Russia). Jak2 V617F mutation was quantitated by real‐time PCR kit from Syntol (Russia) according to manufacturers instructions. CALR exon 9 deletions/insertions were analyzed by fragment analysis (sensitivity &gt; = 3%). MPL W515L/K mutations were assessed by in‐house allele specific PCR. All cases were tested for phi‐negativity using BCR‐ABl p210 PCR kit from Interlabservice (Russia). Results: In 406 of 3267 cases (12.5%) CALR mutations were detected. In 24 of these 406 cases (6%) Jak2 V617F mutation was found in addition to CALR mutation. Matched measures were obtained at least twice at different time points during the course of disease for these cases. In 19 from 24 (80%) cases with combined CALR and Jak2 mutations V617F allele burden was lower than 3%. Also combination of Jak2 V617F with MPL W515L/K was observed in 3 out of 3267 cases only. Two of them had V617F allele burden lower than 3% (Tabl.1). Summary/Conclusion: Additional mutations may coexist over low background of JAK2 V617F allele. Therefore cases of MPNs with low initial JAK2 V617F allele should be further tested for CALR (and possibly MPL) mutations to ensure correct disease and treatment monitoring. Further dynamic observation studies are required to assess the value of additional mutations for MPN disease progression and treatment outcome. image
SP0102 US FOR SYNOVIAL BIOPSIES – CLINICAL RELEVANCE AND SAFETY + DEMO
Authors: Andrew Filer
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background:</h3> The introduction of ultrasound guidance to access synovial tissue samples has facilitated a rapid growth in tissue-related research. Ultrasound guidance enables operators to use less invasive approaches compared to a gold standard direct vision arthroscopy procedure while maintaining the quality of samples obtained. Patients find the procedures easy to tolerate and are willing to undergo repeat biopsy, facilitating the analysis of tissue samples in clinical trials and experimental medicine studies. Advanced analytic techniques including single cell analytics are now being used to exploit the tissue samples obtained in order to provide dramatic leaps in understanding of synovial pathology. <h3>Objectives:</h3> In this session the key aspects of the dominant techniques in use will be presented, including safety, patient tolerability and quality of output. The research and clinical utility of synovial biopsy will be discussed. Sonographic approaches to the major techniques will then be illustrated through video demonstrations, and competencies required to undertake training will be discussed alongside current EULAR initiatives for training. Finally, examples of research outputs generated through synovial biopsy will be explored alongside the logistics required to deliver such clinical studies. <h3>Disclosure of Interests:</h3> None declared
PS1109 DENTAL HEALTH STATUS IN PATIENTS WITH HEMOPHILIA. SINGLE CENTER EXPERIENCE IN ROMANIA
Authors: C.E. Ursu, M. Serban, O. Clevet, A. Traila, E. Boeriu, C. Jinca, E. Boia, S. Arghirescu
Journal: HemaSphere (2019)

Background: Shortage of replacement therapy in haemophilia is responsible for the devastating consequences of uncontrolled bleeds, with unfavourable impact on the quality of life, strongly dependent on oro‐dental health. Aims: The objective of our study was to analyse the dental status in persons with haemophilia (PwH) in our treatment conditions, characterised by the introduction of on demand replacement in 1997 and of prophylaxis in 2014‐2015. Methods: This descriptive non‐interventional cross‐sectional study was conducted on 47 PwH (12 children, 35 adults), all with severe form of disease and on a control matched group of 47 persons. For each PwH were recorded laboratory data and history of replacement therapy. Oral health status evaluation was performed according to the criteria suggested by World Health Organization (WHO). Results: We assessed a very bad dental status in PwH with very high values for the majority of the parameters. In haemophilic children comparable to matched control group there were significant differences regarding the D index and PL index (p = 0.04, p = 0.01). Concerning the domain of decayed teeth in children we observed the existence of an age correlation (r = 0.47/0.81), unfortunately with a lowering appeal for dental care in children with haemophilia, the F index (0.2 ± 0.4) being decreased compared to the children from control group (2.2 ± 2.2), with significant difference (p = 0.003). The dental indexes in adult haemophiliacs were found high, significantly higher in the field of D and F than those belonging to the control group. F index was found significantly higher in the control group than in PwH, proving the low addressability for dental care in haemophiliacs. All these results, with the exception of Missing teeth and DMFT index (r = 0.63/r = 0.65), were not correlated with the age. Adult PwH, with mean age of 34.8 ± 9.81 years, had a dismal dental profile, only 7/35 had a complete denture, 7/35 missing 25%, and 3/35 missing more than 50% of their teeth. Summary/Conclusion: Lack of access to treatment or a low consumption, especially in young age, can influence and have a decisive impact on oral health status in PwH. Our results highlight the importance of an accessible dental care for this vulnerable group of patients in the frame of a comprehensive haemophilia care, including preventive dental treatment and an adequate replacement therapy.
PF372 INHIBITION OF BROMODOMAIN AND EXTRA‐TERMINAL (BET) PROTEINS INCREASES SENSITIVITY TO VENETOCLAX IN CHRONIC LYMPHOCYTIC LEUKEMIA
Authors: G. Carrà, M.F. Lingua, B. Maffeo, A. Guerrasio, G. saglio, R. Taulli, A. Morotti
Journal: HemaSphere (2019)

Background: The development of drugs able to target BTK, PI3k‐delta and Bcl2 has dramatically improved Chronic Lymphocytic Leukemia therapies. However, resistant cases to these drugs have already been reported due to non‐recurrent changes in oncogenic pathways and genes expression signatures. Aims: In this study, we investigated thecooperative role of Venetoclax and the JQ1 inhibitor in order to prevent and eventually overcome the development of resistance to Bcl‐2 inhibitor. Methods: MEC‐1/EHEB cells lines and primary CD19 positive lymphocytes from CLL patients were treated with BET inhibitor JQ1 and venetoclax. Cell lines were screened for cell viability upon treatment with Venetoclax, JQ1and the combination of the two. Responses were measured as apoptosis induction (Annexin V), cell growth arrest and cell‐cycle accumulation. Furthermore, Western Blot analysis RT‐PCR and Immunofluorescence were used to determine expression of Brd members and BCL‐2 pathway components. Results: We demonstrated that treatment with BCL2 inhibitor is associated with a rapid emergence of resistant clones. Compared with each agent alone, cotreatment with JQ1 and venetoclax improved apoptosis in CLL cell lines and of the in vitro isolate primary CD19 + lymphocytes. Additionally, cotreatment could prevent the development of resistant clones. Lastly, JQ1 is also able to restore sensitiveness to venetoclax in venetoclax‐resistant CLL cell lines. Summary/Conclusion: Our findings indicated that cotreatment with JQ1 and BCL2 inhibitor synergistically induced apoptosis and eventually, prevent the development of resistant clones. Further knowledge is key to development of combinatorial treatment strategies with this two drugs.
PB1681 OUTCOME OF PATIENTS WITH PHILADELPHIA CHROMOSOME POSITIVE ALL IN SOUTHERN TUNISIA: ABOUT 13 CASES
Authors: Y. Fakhfakh, I. Frikha, H. Sannenna, S. Mnif, M. Chaari, S. Hdiji, M. Mdhaffar, O. Kassar, M. Ghorbel, M. Charfi, A. Saad, T. Benothmen, H. Elleuch, M. Elloumi
Journal: HemaSphere (2019)

Background: Since the era of therapy targeted by tyrosine kinase inhibitors (TKIs), the prognosis of acute lymphoblastic leukemia (ALL) in adult Philadelphia chromosome positive (Ph +) has been significantly improved. Aims: We evaluate in this study the outcome of adult Ph + ALL treated with TKI associated with chemotherapy. Methods: Our study is retrospective, including cases of de novo Ph + adult ALL diagnosed in the Hematology Department of Hedi Chaker Hospital of Sfax from January 2009 to March 2018. Cytogenetic analysis and research Bcr‐Abl transcript was performed for all patients. They were treated according to the GRAAPH 2005 protocol. TKI, Imatinib, was used at a dose of 600 to 800 mg/day. Bone marrow allograft has been indicated in patients younger than 50 years, in complete remission and with an HLA compliant intra‐familial donor. The current study reports the clinical features and treatment outcome of patients with Ph + ALL. Results: There were 13 patients diagnosed with Ph + ALL among 51 with ALL (25%). The median age at diagnosis was 44 years (range 20‐54 years) and the sex ratio was 0.62. The presence of t (9.22) was found in 8 cases, for all patients with a conclusive karyotype, 5 of them had additional abnormalities. Twelve had a positive Bcr‐Abl transcript. One patient had a positive Bcr‐Abl transcript but the cytogenetic study was not concluded. Complete remission (CR) was noted in 92% of cases. Eight patients (age &lt;50 years) were on allograft indications, seven of them had a compatible HLA donor. Of these, five patients had an allograft: four patients are alive in major molecular response after a mean follow‐up of 5 years (1‐7 years). One patient died in post‐transplant by acute GVH. For the 8 patients who did not have an allograft, 4 unfortunately died, the 4 others are alive in major molecular response after a mean follow‐up of 4 years (1‐7 years). Summary/Conclusion: Before the TKI era, adult Ph + ALL had a poor prognosis with unsatisfactory CR and survivals not exceeding 40%. Allogenic stem cell transplantation remains the only curative option for patients with suitable matched donors. Since the introduction of TKIs in chemotherapy regimens, the prognosis has been much improved, leading to a CR rate exceeding 80% in the literature, and an event‐free 5‐year survival rate exceeding 70%t, this was also found in our series.
A sandwich-type electrochemical aptasensor for Mycobacterium tuberculosis MPT64 antigen detection using C60NPs decorated N-CNTs/GO nanocomposite coupled with conductive PEI-functionalized metal-organic framework
Authors: Yuhan Chen, Xinzhu Liu, Shuliang Guo, Jun Cao, Jing Zhou, Jianli Zuo, Lijuan Bai
Journal: Biomaterials (2019)
Immune checkpoint blockade and CAR-T cell therapy in hematologic malignancies
Authors: Hao Wang, Gurbakhash Kaur, Alexander I. Sankin, Fuxiang Chen, Fangxia Guan, Xingxing Zang
Journal: Journal of Hematology & Oncology (2019)

Harnessing the power of the immune system to recognize and eliminate cancer cells is a longtime exploration. In the past decade, monoclonal antibody (mAb)-based immune checkpoint blockade (ICB) and chimeric antigen receptor T (CAR-T) cell therapy have proven to be safe and effective in hematologic malignancies. Despite the unprecedented success of ICB and CAR-T therapy, only a subset of patients can benefit partially due to immune dysfunction and lack of appropriate targets. Here, we review the preclinical and clinical advances of CTLA-4 and PD-L1/PD-1-based ICB and CD19-specific CAR-T cell therapy in hematologic malignancies. We also discuss the basic research and ongoing clinical trials on emerging immune checkpoints (Galectin-9/Tim-3, CD70/CD27, LAG-3, and LILRBs) and on new targets for CAR-T cell therapy (CD22, CD33, CD123, BCMA, CD38, and CD138) for the treatment of hematologic malignancies.
PB2371 CAN NELARABINE RESCUE THE GRAFT AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION IN T‐ALL ?
Authors: M. Kurt Yuksel, G. Cengiz Seval, S. Civriz Bozdag, S. K. Toprak, P. Topcuoglu, O. Arslan, O. Muhit, T. Demirer, H. Akan, M. Beksac, O. İlhan, G. Gurman
Journal: HemaSphere (2019)

Background: Adult ALL is a rare disease, T‐ALL accounts for nearly %20 of all ALL and T‐ALL is more common in adults than children. The use of pediatric intensive chemotherapy regimens in AYAs and nelarabine for relapsed and refractory diseases has improved outcomes. Still, allogeneic SCT remains an important component of treatment. Nevertheless relapse is inevitable. Aims: Aim of this study is to evaluate the effect of nelarabine as salvage therapy after HSCT, in terms of disease control, GVHD, PFS and OS. Methods: Between 2014‐2018 Nine (F/M = 1/8; median age = 28 years (21‐45)) patients,from one center are evaluated retrospectively. None of them received nelarabine, before HSCT. Transplantation characteristics are given in table 1 . Patients were treated at the time of relapse with nelarabine alone 1.5 g/M2/day on days 1, 3, 5 every 28 days. Results: Among the 9 patients 67% achieved hematologic remission during 8.2 months (range; 2.9‐19.2 mos) follow‐up. The features of nelarabine based salvage therapy are shown in table 2 . The main toxicity was neurological and involved 22% of patients. At 1 year, disease‐ free and overall survival rates were 66.7% and 50% respectively (Figure 1). Only one patient (11%) received DLI and MRD was lost. On the other hand patients who had MRD (4 (44%)) and received nelarabine had a stable MRD disease those did not transform to overt leukemia. Summary/Conclusion: The OS at 1 year for salvage treatment with nelarabine at first and secondary relapse is 28%, which is lower than nelarabin usage after HSCT (50%). There is no data about interaction between immune reconstitution, relapse prevention and nelarabine after HSCT. Nelarabine is a well‐tolerated drug with minimal toxicity and can be considered for maintenance therapy post HSCT in both MRD positive, bulky and CNS disease. Even though it does not show graft versus tumor effect, it can just prevent T‐ALL transform to an aggressive leukemia. image