bluuebunny/crossref_metadata_2025_split huggingface dataset:
Markers of Coagulation and Angiogenesis Can Serve As Surrogate Biomarkers for Disease Activity and Survival in Cancer Patients
Authors: Beleva Elina Angelova , Deneva Tanya , Popov Veselin , Grudeva Janet G. 
Published: October 2019

Abstract
Based on observations of the link between hemostatic system and malignancy it is plausible to consider that plasma coagulation factors could serve as easily accessible markers for detection of malignant state and monitoring of cancer patients. Therefore, we hypothesized that tissue factor (TF), angiopoietin-2 (Ang-2) and soluble urokinase plasminogen activator receptor (suPAR) might perform as diagnostic and predictive biomarkers for the presence of malignancy as well as for the development of cancer-related events: metastatic progression and death.
To analyze their performance TF-associated microparticle activity (MPTF), tissue factor antigen (TFAg), Ang-2 and suPAR were determined in 128 cancer patients with various cancer types receiving chemotherapy by sequential measurements (up to four times) at prespecified time points incorporated into interim and end-of-treatment analysis. MPTF activity was measured with Zymuphen MPTF kit, TFAg, suPAR and ANG-2 were quantitated by ELISA. Patients were followed up for progression free survival (PFS) from therapy initiation until occurrence of a combined event defined as either metastatic progression or death. In order to determine the predictive ability of hemostatic biomarkers for a PFS event Log-rank (Mantel-Cox) test was applied. ROC analysis was used to determine the cut off values for detection of an event, cut off values were transformed into binary variables and Kaplan-Meier curves were constructed. Cox regression analysis was applied to explore quantitatively the effect on the risk of progression.
Results: Cut off values for the occurrence of an event were MPTF < 0.5 pg/ml (AUC 0.591), TFAg (√ pg/ml) > 8.28 (AUC 0.603), Ang-2 > 302.3 pg/ml (AUC 0.615) and suPAR (√ pg/ml) > 2.83. Shortened PFS was associated with decreased MPTF procoagulant activity and elevated plasma levels of TFAg, Ang-2, suPAR. As significant predictors for PFS were determined only TFAg (RR 4.57, p=0.038), Ang-2 (RR 2.138, p=0.031) and suPAR (RR 2.238, p=0.049).
Conclusion: TFAg, Ang-2 and suPAR might be identified as significant adverse predictors of metastatic progression or death in cancer patients and risk is increased with elevated plasma levels.

Disclosures
No relevant conflicts of interest to declare.
Mechanism of Action of Hydroxychloroquine in the Antiphospholipid Syndrome
Authors: Müller-Calleja Nadine , Manukyan Davit , Ruf Wolfram , Lackner Karl 
Published: October 2019

Abstract
Objective. The antiphospholipid syndrome (APS) is characterized by thromboembolic events and/or recurrent abortions in the presence of pathogenic antiphospholipid antibodies (aPL). Hydroxychloroquine (HCQ) is recommended for thromboprophylaxis in patients with systemic lupus erythematosus and aPL. We aimed at identifying mechanisms responsible for the beneficial effects of HCQ in the APS.
Methods. Monocytic cells were stimulated with human aPL in vitro and expression of tissue factor (TF) and tumor necrosis factor (TNFα) was quantified by qRT-PCR. For intracellular ROS detection, cells were stained with OxyBurst and analyzed by flow cytometry. Live cell imaging was performed by confocal laser scanning microscopy to show translocation of NADPH oxidase 2 (NOX2) and TLR8 on stimulation. Finally, the effect of HCQ was tested in an in vivo model of venous thrombosis.
Results. HCQ prevents the induction of TF and TNFα by aPL in MonoMac1 cells, by blocking the activation of endosomal NOX2. This latter effect is not mediated by direct interference with the previously described uptake of aPL into the endosome but by inhibiting the recruitment of the catalytic subunit of NOX2 (gp91phox) into the endosome. Furthermore, HCQ protects mice from aPL induced and NOX2 mediated thrombus formation in vivo.
Conclusion. We propose that interference with the assembly of endosomal NOX2 is a major effect of HCQ responsible for its antithrombotic effect in the APS. Since most if not all APS patients harbor aPL that activate endosomal NOX2 this probably explains the well established efficacy of HCQ in APS patients.

Disclosures
No relevant conflicts of interest to declare.
Insight into Donor Deferral Pattern Based on Peripheral Blood Counts: An Experience from Southern Pakistan
Authors: Irfan Syed Mohammed , Sultan Sadia , Abbas Syeda Alia , Ashar Sana 
Published: October 2019

Abstract
Introduction:
American association of blood banking (AABB) recommends screening of all potential donors by a copper sulphate technique, but this method has chances of false acceptance as well as false deferral. Additionally others valuable blood parameters remain undetermined. Yet this is practically applicable in developed countries with low prevalence of anemia and community infections. In Pakistan anemia's secondary to nutritional deficiency or infectious diseases are much common. It makes the application of this crude method questionable. With this background we determined the whole peripheral blood counts by automated hematology analyzers in all prospective blood donors.
This is to provide the pre-donation deferral rate of the healthy blood donors based on peripheral blood counts. The basic knowledge about frequency, types and severity of anemia among donors will help to plan a strategy to promote donor recruitment and overall national health.
Methods:
Prospective records of all the reported donors were collected from January-2014 to December-2015 at Liaquat National Hospital, Karachi.
Results:
Overall 36954 potential donors reported to the blood bank, out of which 33853 were selected and 3101 were deferred, which makes the deferral rate of 8.39%. Of total, 264 (0.71%) donors were excluded based on history whereas 174 (0.47%) donors were excluded due to examination findings while majority [n=2663 (7.20%)] of donor were deferred based on complete blood counts.
Based on peripheral blood counts; anemia (91.8%) represents the major cause of deferral, followed by raised total leukocytic count (3.7%) and polycythemia (3.3%) respectively and thrombocytopenia (1.0%) was the least potential cause. Microcytic-hypochromic anemia was found in 58.5% donors followed by normocytic and macrocytic anemias in 38.9% and 2.4% respectively. Mild anemia was seen in 78.2% followed by moderate and severe anemias in 20.5% and 1.18% respectively.
Conclusion:
In view of frequently anemic donors in the present study, it is strongly recommended to have a full blood counts rather to rely on semi-quantitative methods which led to acceptance of anemic donors.
High prevalence of anemia among Pakistani blood donors signifies deteriorating health status not only in donor population but also in general population as well. Astonishingly high TLC (sub clinical infections) turned out as second important cause of deferral. This situation recalls for strenuous efforts to overcome as it entails that we will likely to face more dearth of donors in future.

Disclosures
No relevant conflicts of interest to declare.
Prognostic Significance of IDH1 and IDH2 mutations in Older Patients with Primary Cytogenetically Normal Acute Myeloid Leukemia
Authors: Wang Jinghan , Ma Zhixin , Wang Qinrong , Yu Mengxia , Yin Xiufeng , Li Xia , Suo Shanshan , Shen Dan , Wang Yungui , Huang Xin , Pan Hanzhang , Wang Huanping , Chen Zhimei , Huang Jiansong , Mao Liping , Yu Wenjuan , Wei Juying , Qian Wenbin , Mai Wenyuan , Meng Haitao , Tong Hongyan , Chen Suning , Marcucci Guido , Chen Saijuan , Jin Jie 
Published: October 2019

Abstract
IDH1 and IDH2 mutations are frequently identified in older patients with AML.With the development and application of IDH inhibitor, the prognostic significance of these mutations in old patients is of primary importance. To assess the impact on clinic outcome, we analyzed 224 older (> 60 years) patients with primary cytogenetically normal acute myeloid leukemia (CN-AML) similarly treated with intensive induction chemotherapy. Our analysis identified IDH1 and/or IDH2 (IDH1/2), IDH1 or IDH2 mutations in 63(28%), 29(12.9%) and 35(15.6%) patients, respectively. In general, IDH1 and IDH2 mutations were mutually exclusive, with only one patient having both IDH1 R132C and IDH2 R140Q mutations. IDH2 R172 mutations were exclusive with all other mutations analyzed (NPM1, CEBPA, DNMT3A, IDH1 and FLT3-ITD). There was a strong interaction between IDH2 mutation and NPM1 mutational status. Concurrent presence of IDH2 R140 and NPM1 mutations was independently associated with longer overall survival (OS; P=0.038, HR=0.42) and event free survival (EFS; P=0.034, HR=0.46) compared to the wild type counterpart in multivariable analyses. In contrast, IDH1 mutations were independently associated with shorter OS (P=0.004, HR=1.98) and EFS (P=0.014, HR=1.72) in multivariable analyses. Notably, IDH1 R132 mutations harbored higher levels of total 2-hydroxyglutarate compared to IDH2 R140Q mutations. Patients with IDH1 mutations or IDH2 R140 and NPM1 mutations harbored also distinct miRNA-expression signatures. Future studies will establish whether these difference between IDH1 and IDH2 mutations will be relevant with respect to response of the respective subsets of patients to the emerging therapies with IDH1 and IDH2 inhibitors.

Disclosures
No relevant conflicts of interest to declare.
Early Deaths in Pediatric Acute Leukemia; A Challenge in Developing Countries
Authors: Hafez Hanafy Ahmed , Solaiman Rawaa , Bilal Dalia , Shalaby Lobna m 
Published: October 2019

Abstract
Background and objectives: The survival rates of children with acute leukemia is consistently improving, due to the lower relapse rates in addition to reducing treatment-related mortality, which is mainly a result of infectious causes. The aim of the study is to describe the incidence and risk factors associated with early deaths (first 42 days in treatment) among children with acute leukemia. Methods: This is a retrospective study included newly diagnosed patients with acute leukemia who presented to the National Cancer Institute, Cairo University between Jan. 2011 to Dec. 2013. Patients' data were collected from their files and analyzed for the total and early death rates and proposed causes of death. Results: The study included 370 patients, 253 with acute lymphoblastic leukemia (ALL), 100 with acute myeloid leukemia (AML) and 17 with mixed phenotypic acute leukemia (MPAL). The total death rate among the whole group was 40.5% (n=150) and induction death rate was 19.2% (n=71). AML was accompanied with higher rates of total and induction deaths as they were 58% and 25% respectively, compared to 33.6% and 17.4% in ALL. These early deaths were attributed mostly to infection 64.7% (n=46) and cerebrovascular accidents 18.3% (n=13). Early deaths were significantly higher in patients with age below 2 years old (p. value=0.008), and in those with poor response to therapy (p. value= 0.001). Using enhanced supportive care measures as better infection control, appropriate antibiotic guidelines and available intensive care unit during 2013 had significantly reduced the overall and induction mortality rates (27.8% and 13.8% respectively in 2013 versus 45% and 20.3% in 2011 and 49% and 25% in 2012). Conclusion: Induction deaths in pediatric acute leukemia remain a major challenge in developing countries and constitute an increasing fraction of all deaths. Accordingly, using a well equipped cancer centers with better supportive care guidelines is essential to further improve the survival in these group of patients.
Key words: Acute Leukemia- Pediatrics- Early Death- Infection

Disclosures
No relevant conflicts of interest to declare.
Clinical Significance of Myeloblasts Percentage in the De Novo Acute Myeloid Leukemia with Erythroid Hyperplasia
Authors: Qiu Shaowei , Wei Hui , Lin Dong , Zhang Guangji , Wei Shuning , Zhou Chunlin , Liu Kaiqi , Wang Ying , Liu Bingcheng , Liu Yuntao , Gong Benfa , Gong Xiaoyuan , Feng Sizhou , Mi Yingchang , Han Mingzhe , Wang Jianxiang 
Published: October 2019

Abstract
Objects: Investigate the clinical significance of myeloblasts percentage in the de novo acute myeloid leukemia(AML) with erythroid hyperplasia from a single center of China
Methods: We retrospectively collected information regarding clinical characteristics and survival data from de novo101 patients with newly diagnosed AML with erythroid hyperplasia (> 50% erythroid cells) from 2002-2016. The total patients were divided into two groups according to the myeloblasts percentage in total marrow cells. Cases with<20% total myeloblast was defined as low-blast group while cases with>20% total myeloblast was defined as high-blast group. Median follow-up of patients was 10.03 months.
Results:1.A total of 101 patients were diagnosed as de novo acute myeloid leukemia with erythorid hyperplasia according to WHO2008 criteria, 70 patients was classified as low-blast group, 31 patients was classified as high-blast group. Compared with high-blast group, in the low-blast group, the median age was older (39.8 vs 33.3, p=0.044), male was predominant (71.4% vs 48.4%, p=0.01). But complete remission (CR) after induction chemotherapy was lower in high-blast group(44.4% vs 57.4%, p=0.019).There were no difference in the white blood count(WBC), chromosome karyotype and incidence of various gene mutations.
2. The median survival time in the low-blast group and high-blast group was 39.19 months and 23.43 months respectively. 3-year overall survival(OS) was 53.1% and 43.4%(p=0.668), 3-year disease free survival(DFS) was 71.4% and 47.8% (p=0.297).
3. Univariable analysis showed that OS of 101 AML patients was correlated with prognosis subtype, remission of induction chemotherapy, transplant and relapse, and not related with myeloblast percentage exceed 20% of total morrow cells or not, WBC, age, gender and induction regimens. DFS of the all patients was correlated with the remission of induction chemotherapy and prognosis subtype. Multivariable analysis showed that OS was only correlated with remission of induction chemotherapy and transplant, DFS was only correlated with remission of induction chemotherapy.
Conclusions: In the AML patients with erythroid hyperplasia with<20% total myeloblast, the age was older and CR was higher than that with >20% total myeloblast, but the survival was similar in both patients regardless of myeloblast percentage. The patients who attained CR after induction chemotherapy and received transplantation would get better outcome.

Disclosures
No relevant conflicts of interest to declare.
Monitoring AML Disease Status with Next Generation Sequencing
Authors: Liu Zach , Dimov Nikolay 
Published: October 2019

Abstract
Recent advance in next generation sequencing (NGS) have confirmed that AML is a heterogeneous malignancy harboring may many genetic mutations. These mutations have been studied for leukemia genesis, diagnosis and therapeutic targets. Monitoring minimal residual diseases has also been studied recently. We summarized our experience with NGS in morning AML disease status.
NGS data during 2014 and 2016 from patient with newly diagnosed or AML and/or AML follow-up patients along with bone marrow biopsy, FISH/cytogenetics, flow cytometric results were reviewed. Targeted sequencing was performed with customized panel (34 genes) on Ion PGM platform from Life Technology Inc.
41 AML patients with complete bone marrow work-up with bone marrow morphology, flow cytometry, FISH/cytogenetics (MFFC) and NGS were collected. At least one sample with complete work-up for each patient was included. Majority of the patients had several studies (2-8 samples). 15 out of 41 (36.6%) has complete remission based on bone marrow morphology, flow cytometry, FISH/cytogenetic studies. No mutations were detected among these 15 patients. 17 patients (41%) showed concordant result with other technologies, i.e. when the patient was in remission based on MFFC, No mutations were detected. When patient had recurrent AML or residual disease, mutations were detected. It worth to point out that 2 patients showed positive mutation without detectable increase in myeloblasts. These 2 patients had relapsed AML within 3 months. Different subclones were detected at different intervals in 1 patient. 2 (0.5%) patients (1 with newly diagnosed AML and 1 with early recurrent AML) showed no detectable mutations. Mutations were detected in 5 patients (12%) with AML remission by MFFC, additional follow-up is need for these patients. The most common mutations included TET2, ASXL1, DNMT3A, RUNX1, IDH1 and TP53.
NGS is valuable to assess the AML status despite of heterogeneous genetic abnormalities. Although the NGS results were concordant with bone marrow morphology, FISH/cytogenetics and flow cytometry in most of the cases (87.5%), persistent mutations may be detectable in cases without detectable residual AML by other modalities, which may be associated with minimal residual disease or early relapse, and need further evaluation. Clonal evaluation may occur at molecular level occasionally.

Disclosures
No relevant conflicts of interest to declare.
Fusion Protein Ompc-CD154 Inhibits Proliferation and Induces Apoptosis in B-NHL Cell Lines By a Mechanism That Involves MAPK P38 and TRAF2 Activation
Authors: Pantoja-Escobar Gerardo , Romo-Dorantes Laura , Morales-Martinez Mario , Vega Gabriel G , Martinez-Maza Otoniel , Huerta-Yepez Sara , Vega Mario I. 
Published: October 2019

Abstract
CD40 is a member of the TNF super family, which is expressed mainly in B cells, dendritic cells and macrophages, and the interaction with its ligand CD154 is essential for the development of the immune response. The activation or selective inhibition of this pathway is part of various therapeutic strategies for the treatment of diseases with inflammatory or immune origin, as well as various types of tumors. The fusion protein OmpC-CD154 expresses 10 amino acids of CD154 (Ser149-Trp140) and is capable of binding to CD40, inducing apoptosis and inhibiting proliferation in NHL cell lines. In this study we demonstrate that the fusion protein OmpC-CD154 induced apoptosis and inhibition of proliferation in several B-NHL cell lines. In addition, we analyzed the mechanisms involved in the induction of apoptosis and the inhibition of proliferation. Our results by Western blot demonstrate that OmpC-CD154 induced degradation of Bcl-6 by a MAPK p38 activation dependent mechanism. Pre-treatment of Ramos and Raji cell lines with a specific chemical p38 inhibitor reverted the effect of OmpC-CD154 in proliferation. Our results showed that the fusion protein can also inhibit the constitutive activation of both the canonical and non-canonical NF-kB pathways, and this inhibition was associated with the activation of the TRAFs pathway, as it promotes TRAF2 phosphorylation, and the decreasing of the expression of TRAF3. All these effects were greater than those observed with recombinant human CD154 on B-NHL cell lines. The present findings establish that a CD154 peptide fused with a protein exhibits significant cytotoxicity on B-NHL cells. Current studies are evaluating fusion proteins with CD154 peptide that are not antigenic in vivo and that have significant anti-tumor effects, both direct and on the host immune response, with minimal toxicity.

Disclosures
No relevant conflicts of interest to declare.
Prognostic Significance of Serum LDH in B Cell Chronic Lymphoproliferative Disorders: A Single-Institution Study of 829 Cases in China
Authors: Liu Huimin , Xiong Wenjie , Li Heng , Lv Rui , Liu Wei , Yi Shuhua , Li Zengjun , Qiu Lugui 
Published: October 2019

Abstract
Background: B-cell chronic lymphoproliferative disorders (B-CLPD) comprise several indolent lymphoma subtypes with similar characteristics but also difference and heterogeneity. Several prognostic systems had been established for separate subtypes, such as Rai/Binet stage system for CLL, FLIPI for follicular lymphoma. Here, we want to explore the prognostic role of some common clinical characteristics in each lymphoma subtype, such as serum LDH.
Materials and methods: The clinical data of 829 patients with B-CLPD including clinical features, LDH expression level, cytogenetic abnormalities and therapeutic outcome were analyzed retrospectively in department of lymphoma & myeloma, Institute of hematology & Blood disease hospital from April 1990 to August 2013, and the prognosis of B-CLPD patients with different expression levels of LDH was compared, including overall survival (OS) and progression-free survival (PFS) rates.
Results: 829 patients were divided into three groups, including 426 (51.4%) patients with chronic lymphocytic lymphoma (CLL), 307 (37.0%) patients with non-CLL B-CLPD and 96 (11.6%) patients with BLPD-U. Elevated serum LDH at diagnosis was detected in 112 (26.3%), 85 (27.7%) and 23 (24.9%) of CLL, non-CLL B-CLPD and BLPD-U group, respectively. Patients with elevated LDH B-CLPD had poorer 5-year overall survival rate (CLL: 63.8% vs 83.0%; non-CLL B-CLPD: 62.2% vs 78.1%; BLPD-U: 47.4% vs 88.6%) and 5-year progression-free survival rate (CLL: 52.0% vs 78.2%; non-CLL B-CLPD: 40.8% vs 75.6%; BLPD-U: 48.9% vs 89.5%) than LDH normal patients. Univariate analysis showed that LDH expression, hemoglobin level, platelet count, B symptoms, P53 deletion were prognostic factors for CLL patient survival, while LDH expression, platelet count, albumin level affected non-CLL B-CLPD patient survival significantly and LDH expression, albumin level, ECOG PS scores for BLPD-U patient survival. Multivariate analysis showed that elevated LDH was an independent significant prognostic factor for overall survival (P<.001) and progression-free survival (P<.001) in all three groups.
Conclusion s: Based on these data, we conclude that elevated serum LDH at diagnosis is an unfavorable prognostic factor in patients with B-CLPD.

Disclosures
No relevant conflicts of interest to declare.