bluuebunny/crossref_metadata_2025_split huggingface dataset:
"Part of the Ritual": a Qualitative Study of Patient and Physician Perspectives on the Use of Anticoagulation for Improving Pregnancy Outcomes in Obstetrical Antiphospholipid Syndrome
Authors: Skeith Leslie , Rodger Marc A. , Bates Shannon M. , Gonsalves Carol , Taylor Taryn S. 
Published: October 2019

Abstract
INTRODUCTION: Antiphospholipid syndrome is an acquired thrombophilia associated with recurrent pregnancy loss. Treatment with low-molecular-weight heparin (LMWH) and/or aspirin (ASA) during pregnancy to prevent future loss is based on limited trial data with mixed results. Given the clinical equipoise, we sought to understand how patients and physicians navigate the decision-making process for use of antepartum LMWH and/or ASA. This research is needed to inform the feasibility of future research that seeks to resolve the question of treatment efficacy in this patient population.
METHODS: Following constructivist grounded theory (CGT) methodology, we interviewed 10 patients and 10 thrombosis physicians in Ottawa, Canada from January 2017 to March 2018. Patients were drawn from women included in the TIPPS (Thrombophilia in Pregnancy Prophylaxis Study) screening logs and from consecutive women attending a specialty Thrombosis Clinic who met the revised Sapporo/Sydney laboratory criteria and had at least 1 prior late loss or 2 early losses (<10 weeks gestation). Data collection and analysis occurred iteratively, in keeping with CGT methodology.
RESULTS: Our analysis generated three predominant themes, present across both patient and physician interviews, which captured a patient-led decision-making experience: (1) Accepting Uncertainty, (2) Focusing on Safety and (3) Managing High Stakes. Many patients accepted the uncertainty of their situation; they felt hopeful but were also reluctant to expect a better pregnancy outcome. This was echoed in the physician interviews, which emphasized the uncertainty of LMWH/ASA in improving outcomes when counselling patients on their options. Both groups focused on the low-risk nature and safety of these medications. Patients focused on safety to the fetus, with little concern for maternal risk. Finally, patients and physicians acknowledged the high emotional burden and what was at stake: avoiding further pregnancy loss. Patients responded to their situation by taking action (i.e. using LMWH injections became a "ritual") whereas physicians reacted by removing themselves from the final decision and "[leaving] it up to the patient".
CONCLUSION: In this setting of clinical equipoise and in the absence of serious safety concerns, decision-making around antepartum LMWH/ASA was largely directed by informed patient choice. These findings should be considered when designing future research on the role for LMWH/ASA in this population, as it suggests that the perceived benefits of treatment go beyond improving pregnancy rates. Rather, patients seem to derive psychological benefit from the process of taking action, even in the absence of a guaranteed good outcome.

Disclosures
Skeith: Leo Pharma: Honoraria; CSL Behring: Research Funding. Rodger:Biomerieux: Research Funding.
Association of 30 Day Readmission between Psychosocial, Behavioral and Epidemiological Factors in Adult SCD Patients
Authors: Saha Aparna , Poojary Priti , Pandya Dishita , Kumar Abhishek , Nadkarni Girish , Kaur Supreet 
Published: October 2019

Abstract
Background: Sickle-cell disease (SCD) has been identified as a major public health problem by the World Health Organization (WHO) and is one of the most common hematological genetic diseases. In United States, there are approximately 100,000 admissions per year attributed to SCD. Our objective is to provide nationally representative rates for unplanned 30-day readmissions in SCD patients as well as identify reasons for, characteristics and predictors of these readmissions.
Methods: We performed retrospective analysis using the 2013 Nationwide Readmissions Database (NRD) of the Healthcare Cost and Utilization Project (HCUP) from AHRQ. We used chi-square tests, t tests, and Wilcoxon rank-sum tests for descriptive analyses and survey logistic regression to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations with readmissions adjusting for confounders.
Results : Of the 46,842 hospitalizations with SCD as the primary diagnosis for the index admission, 11,787(25.2%) had at least one 30-day unplanned readmission and 30% of these readmissions were within the first week after discharge. Among 11,787 readmissions, 83% of the readmissions were attributed to SCD, including 81.5% due to acute painful crisis. Patients who got readmitted were likely to be younger, with more comorbidity burden including chronic kidney disease, asthma, drug abuse and hypertension. Predictors of readmissions included: age 18-29 years (aOR 1.5, 95% CI 1.3 - 1.6; P<0.01), chronic kidney disease (aOR 1.3, 95% CI 1.1 - 1.6, P <0.01), depression (aOR 1.2, 95% CI 1.1 - 1.4, P<0.01), drug abuse (aOR 1.2, 95% CI 1.1 - 1.4, P 0.04), and discharge against medical advice (AMA) (aOR 1.8, 95% CI 1.5-2.1, P<0.01. AMA discharges and depression were responsible, respectively, for 76% and 23% increases in the odds of 30-day readmission.
Conclusion: About a quarter of patients admitted with SCD get re-admitted within a month of discharge. This calls for identification of modifiable risk factors and timely intervention with safe hospital discharge which is critically important for patient care and national health expenditure.

Disclosures
No relevant conflicts of interest to declare.
VWF Mediates Platelet Activation and Secretion to Promote Osteosarcoma Metastasis
Authors: Zhao Yiming , Wang Qi , Jiang Miao , Ruan Changgeng 
Published: October 2019

Abstract
[Background] As a multimer protein that mediates the adhesion of platelets to vascular surface, VWF has been found to participate in tumor metastasis, and may also be involved in the interaction between platelets and tumor cells. We observed in our clinical studies that the expression of VWF in lung metastatic osteosarcoma tumor is significantly higher than that of in primary osteosarcoma. Based on these observations, we speculate that VWF and platelets may contribute to promoting osteosarcoma metastasis. Thus, this study is to explore the effects of VWF-mediated platelet activation and secretion on the migration and invasion ability of SAOS2 cells with VWF-expressing osteosarcoma cell line SAOS2 as a model, as well as the inhibition of the interaction between VWF and platelets by specific antibodies.
[Methods] SAOS2 cells were stimulated with inflammatory factor PMA and resulted in increased expression of vWF. Then the adhesion of labeled platelets to SAOS2 cells was evaluated under static and flow conditions, respectively. The above processes were intervened with SZ-2(anti-GPIb), SZ-123(anti-VWF) and AVW3 (anti-VWF) mAbs which specifically blocked the vWF-GPIbα pathway. Transwell assay was used to explore the effect of vWF-mediated migration and invasion ability of SAOS2 cells. PDGF-BB, TGF-β and VEGF that could be secreted by platelets to promote tumor cells growth in the co-culture system of platelets and SAOS2 cells were detected by ELISA.
[Results] Under static and flow conditions, SAOS2 cells treated with PMA exhibited significantly higher platelets-adhesion capacity compared to the cells untreated with PMA, and the adhesion could be partially inhibited by SZ-2 and AVW3 mAbs. Furthermore, platelets significantly promoted the migration and invasion ability of SAOS2 cells, and PDGF-BB and TGF-β secreted by platelets were also increased in these processes. Both of SZ-2 and AVW3 mAbs partially decreased the migration and invasion ability of SAOS2 cells.
[Conclusions] vWF were expressed highly in some kind of non-endothelial origin cancer cells, such as SAOS2, which mediates platelet activation and secreting factors such as PDGF-BB and TGF-β to promote tumor cells growth. Activated platelets have a significant promoted effect on the migration and invasion ability of SAOS2 cells and this process can be inhibited by antibodies that specifically block the pathway of VWF-GPIbα.

Disclosures
No relevant conflicts of interest to declare.
Home Care of Acute Leukemia Patients: From Active Therapy to End-of-Life and Palliative Care. a Three-Year Experience of a Single Centre
Authors: Capodanno Isabella , Alfieri Pierluigi , Tamagnini Enrica , Codeluppi Katia , Luminari Stefano , Merli Francesco 
Published: October 2019

Abstract

Purpose:
Since July 2012, the Haematological Home Care (HHC) program was activated in our Institution to improve quality of assistance of patients with haematological malignancies, both in the terminal phase of disease and during active chemotherapy.
Methods:
We conducted a retrospective study to describe the 3-year experience of our HHC program; its efficacy was measured for acute leukaemia patients only analysing number of hospitalizations, number of accesses to the Emergency department and place of death. Our study population was also compared with historical data from a small group of 17 patients with acute leukaemia assisted at home, by their general practitioner, in the previous 3 years, when the HHC program was not available.
Results:
The study group consisted of 44 patients, 36 of whom (82%) needed a palliative treatment, while 8 (18%) had an ongoing active chemotherapy. The mean number of hospitalizations was 0.64 (range 0-7) per patient and the number of emergency department visits was 0.82 (range 0-4) per patient. Place of death was home environment in 51.4% and hospital in 40.5% of patients.
When compared to data of the historical group, HCC program significantly reduced the number of hospitalizations (0.64 vs 2.53 per patient, range 0-9; P 0.001), significantly increased the number of patients who died at home (51.5% vs 6%; P=0.003) and reduced those who died in hospital (40.5% vs 65%; P 0.003).
Conclusions:
Home care for patients with acute leukaemia is feasible, decreases the number of hospitalizations, and increases the number of patients who die in their own home.
Figure. Figure.

Disclosures
Luminari: Servier: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Roche: Consultancy; Sandoz: Consultancy.
ELN Genetic Risk Stratification Not Affect the Mid-Term Survival in Childhood AML: Report from Southern China Childhood AML Group
Authors: Feng Xiaoqin , Li Jian , He Xiangling , Xu Honggui , Zheng Mincui , Wen Hong , He Yingyi , Liu Sixi , Ruan Yongsheng , Li Chunfu 
Published: October 2019

Abstract
OBJECTIVE: To evaluate the survival of children with acute myeloid leukemia (AML) in the ELN genetic risk stratification. To explore the precise treatment and efficacy in childhood AML.
Methods: The information of genetics of 151 newly diagnosed AML children enrolled in the Southern China Childhood AML Collaboration Group from December 2014 to June 2017 were retrospectively analyzed. These patients was divided into low-risk, intermediate-risk and high-risk groups according to the ELN genetic risk stratification. All cases were treated with the Southern China Childhood AML Collaborative Group protocol. The induction of remission was not randomized using FLAG-IDA and DAE regimens for 2 courses of treatment. The consolidation therapy was performed using HAE and MidAC regimens. 20 cases underwent hematopoietic stem cell transplantation. The mediate follow-up time was 18 months. Survival analysis and Log-Rank test were investigated by Graphpad Prism software.
RESULTS: Of 151 children with AML, AML1/ETO positive in 46(30.5%) cases, CBFβ/MYH11 positive in 12(7.9%) cases, MLL gene in 18(11.9%) cases (including MLLT3-KMT2A in 7 cases). There were mutation gene FTL3/ITD in 24(15.9%) cases, ASXL1 mutation In 10(6.6%) cases, NPM1 mutation in 3(2.0%) cases and CEBPA double mutation in 4(2.6%) cases. Chromosome -7 or 7q- was found in 5(3.3%) cases. According to the ELN genetic risk stratification, 60/151(39.7%), 52/151(34.4%) and 39/151(25.8%) of patients were classified as low-risk, intermediate-risk and high-risk respectively. In the cohort of DAE induction, the CR+CRi rate was 95%, 69% and 80% in the low-risk, intermediate-risk and high-risk group. In the cohort of FLAG-IDA induction, the CR+CRi rate was 100%, 95% and 100% in the low-risk, intermediate-risk and high-risk group. The significance of CR+CRi rate only were be seen in the intermediate-risk group( P=0.02). The 2 year overall OS and DFS were 82.56% and 75.74% respectively. The 2-year DFS of the FLAG-IDA and DAE groups were 85.38% and 53.72% respectively (P=0.0004). The 2-year DFS of the LR, IR, and HR groups in the FLAG-IDA group were 89.23%, 92.29%, and 91.67% respectively, and no statistical difference was found among the groups (P=0.909). The 2-year DFS of the chemotherapy group and the hematopoietic stem cell transplantation group were 82.24% and 63.38%. There were no statistical differences between the groups.
Discussion: The FLAG-IDA induction group significantly improved DFS compared with the DAE group. Hematopoietic stem cell transplantation failed to improve the survival of children with AML in the short period in our multicentre study. Our mid-term results show that the ELN genetic risk stratification had not a significant impact on the prognosis of newly diagnosed childhood AML with high-intensity therapy.

Disclosures
No relevant conflicts of interest to declare.
Interrogation of the Coagulation Cascade Acute Coronary Syndrome Using Novel Elisa-Based Assays for Single Protease Quantification
Authors: Posma Jens , van Oerle Rene , Fens Diane , govers Riemslag Jose , Mueller Julia , Heitmeier Stefan , ten Cate Hugo , Spronk Henri M.H. 
Published: October 2019

Abstract
Background: Acute coronary syndrome (ACS), the main contributor to myocardial infarction, is a thrombotic complication of atherosclerosis. Growing evidence supports a role for the intrinsic coagulation cascade in various thrombotic diseases. To gain more inside in the contribution of the intrinsic coagulation cascade in an ACS, we developed novel, ELISA-based assays for the quantification of Kallikrein, activated factor XII (FXIIa), FXIa, FXa, FIXa, and thrombin in complex with a physiological inhibitor.
Methods: During this prospective cohort study, blood from patients with a first ACS (n=61) was collected upon admission (before heparin injection(t=0), and after 1(t=1) and 6 (t=2) months. Plasma levels of Kallikrein-C1inhibitor (K-C1inh), FXIIa-C1inh, FXIa-C1inh, FXIa-α1 anti trypsin, FXIa-antithrombin (AT), FIXa-AT, FXa-AT, and thrombin-AT(TAT) were measured using newly developed ELISA's and compared to apparently healthy controls (n=60). Methods were validated according to the EP5-protocol for within- and -between run variability.
Results: The inter coefficients of variability for K-C1inh is 11.9%, FXIa-α1-AT 14.4%, FXIa-AT 13.7%, FIXa-AT 4.9%, FXa-AT 2.6% and TAT 8.6 %. Levels of FXIa-α1-AT, FXI- ΑΤ, FIXa-AT and TAT were all significantly elevated in plasma from ACS patients at time of the acute event compared to healthy control: FXIa-α1 anti trypsin respectively 202.8 (IQR 156.6 - 283.4) vs 29.0 pM (IQR 0.00 - 101.0); FXIa-AT levels were respectively 35.9 pM (IQR 23.9 - 43.4) vs 28.0 pM (IQR 23.3 - 34.0); FIXa-AT respectively 102.0pM (IQR 87.4 - 123.0) vs 90.5 pM (IQR 83.2 - 104.3); TAT respectively 5.59 (IQR 3.91 - 9.85) vs 2.26 pM (IQR 1.78 - 2.71)(Fig1). Plasma levels of FXIa-α1-AT, FXIa-AT FIXa-AT, and TAT decreased during follow up. Additionally, FXIa-α1-AT, FXIa-AT FIXa-AT, and TAT were higher in patients with ST-elevated myocardial infarction (STEMI) compared to subjects with non-STEMI or angina pectoris.
Conclusion: Elisa based profiling of the coagulation proteases provide a highly sensitive and reproducible method used to distinguish the different activation states of single proteases in the coagulation cascade. With these novel assays we show that FXIa-α1-AT, FXIa-AT FIXa-AT, and TAT are significantly elevated in patients with ACS. Additionally, patients with STEMI have a more pronounced hypercoagulable state than non-STEMI and angina pectoris patients.
Figure 1. Figure 1.

Disclosures
No relevant conflicts of interest to declare.
Prevalence of Hepatitis B, Hepatitis C and HIV in Sickle Cell Disease Patients from Oman
Authors: Alkindi Salam , AL-Umairi Nada , Pathare Anil 
Published: October 2019

Abstract
Background and Purpose: Oman is a country with an intermediate prevalence of Hepatitis B (HBV) carriers (2.8-7.1%, 20101), while the prevalence of HBV infection was 5.8% (20142). Hepatitis C (HCV) prevalence reported from Oman was 0.41% (20163). Further, a total of 2394 Human Immunodeficiency (HIV) infections were identified among Omanis (20134). Unfortunately, there are no studies on the prevalence of HIV, HBV and HCV in sickle cell disease (SCD) patients from Oman.
Objectives: This study was therefore performed to estimate the prevalence of HBV, HCV and HIV among SCD patients from Oman.
Methods: In a retrospective cross-sectional cohort study, medical records of all patients with SCD and sickle cell trait (SCT) patients who received blood transfusions between 2006 to 2017 were retrieved from the hospital information system. Specifically, data on HIV, HBV and HCV exposure were recorded to study the prevalence, following approval for the study from the hospital medical research and ethics committee.
Results: Amongst a total of 1000 patient (491 males and 509 females), 126 (12.6%) had anti-HCV antibodies (anti-HCV) based on serology and amongst these 52(5.2%) were PCR positive. Genotype 1 was the most predominant (n=36), followed by genotype 3& 4(n=7 each) followed by genotype 2(n=2). 23 (2.3%) SCD patients showed positive serology for hepatitis B surface antigen (HbsAg) and amongst these 16 (1.6%) were PCR positive. None of the SCD patients showed positive serology for HIV. Liver Ultrasound was normal in 788 patients (78.8%), whereas, 208(20.8%) had hepatomegaly and 4(0.4%)had liver cirrhosis. Further, only 2 patients amongst the 36 patients who had died had a hepatic cause.
Conclusion: This study provides comprehensive data on the prevalence of HBV and HCV infection among SCD patients and raises concerns regarding the HCV prevalence in these patients with its impact on chronic liver disease. Reassuringly, no case with HIV was observed.

Disclosures
No relevant conflicts of interest to declare.
Suppression of CUL4B Induces G1 Cell Cycle Arrest through the Modulation of AKT Signaling Pathway
Authors: Li Ying , Zhang Ya , Zhou Xiangxiang , Wang Xin 
Published: October 2019

Abstract
Introduction
T-cell lymphomas (TCL) are a heterogeneous group and one of the more aggressive of non-Hodgkin lymphomas. Previous studies have illustrated the poor prognosis in major propotion of patients due to refractory and recurrent TCL. CUL4B, a member of the CUL4B-RING E3 ubiquitin ligase complex, has been demonstrated to be involved in tumorigenesis and correlated to poor survival, contributing to tumor progression via several mechanisms, including epigenetic silencing of tumor suppressors. Although CUL4B was recently identified as a novel oncogene in several solid malignancies, the potential functional role of CUL4B in TCL are poorly understood to data. Hence, the aim of this study was to determine the pro-tumor function and mechanism of CUL4B in TCL.
Methods
The paraffin-embedded lymph node samples were collected from 30 newly diagnosed cases of T-cell lymphoma and 20 normal lymph nodes with approval in our hospital. TCL samples and purified normal T cells (including CD4+, CD8+, HLA-DR+, and HLA-DR-cells) (Pier Paolo Piccaluga et al., 2007) were evaluated for CUL4B expression. Peripheral blood mononuclear cells (PBMCs) were isolated from healthy donors. Expression levels of CUL4B mRNA and protein in TCL cells was detected by RT-PCR and western blot assay. Lentiviral vectors were used to transfected TCL cells to stably silence CULB. To evaluate the effects of CULB on cell proliferation and cycle, cell counting kit-8 and Propidium iodide staining were assessed respectively.
Results
We found that the expression levels of CUL4B were elevated in TCL samples compared with purified normal T cells via analyzing previously published gene expression data (Pier Paolo Piccaluga et al., 2007) (Fig. 1A). IHC assay indicated that CUL4B was higher expressed compared to normal lymph nodes (Fig. 1B). Moreover, RT-PCR and western blotting assays confirmed the elevated expression level of CUL4B in TCL cells compared with PBMCs in agreement with ICH assay (Fig. 1C-D). The function of cell viability maintenance of CUL4B as well as correlation with poor outcome has been reported previously in solid tumor. In consistent with previous studies in solid malignancies, knockdown CUL4B in TCL cells inhibited cell proliferation, induced G1/S phase arrest (Fig. 1E). Additionally, loss-of-function assay showed that the expression of phosphorylated AKT were reduced in TCL cells. Besides, p21 and p27 were observed in TCL cells (Fig. 1F).
Conclusion
Our investigations firstly identified the elevated expression levels and the oncogenic role of CUL4B in TCL tumorigenesis. Expression of CUL4B was upregulated in TCL. Targeting CUL4B with shRNA interference exerted therapeutic potential in abrogating cell survival, inducing cell cycle arrest through regulating the AKT signaling pathway. Taken together, targeting the expression of CUL4B may provide a novel approach to TCL therapy.

Disclosures
No relevant conflicts of interest to declare.