bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Vascular Outcomes in Patients with Atrial Fibrillation,
Authors: Gallagher Arlene M , Murray-Thomas Tarita , Clemens Andreas , Diana Ackermann , Bartels Dorothee B 
Published: October 2019

Abstract
Abstract 4223

Objective:
To describe the characteristics of patients with recently diagnosed atrial fibrillation (AF) and to estimate the incidence of vascular outcomes in patients with AF.

Methods:
A cohort study in newly diagnosed AF patients (2005–2010) without heart valve replacement/problems was performed in the General Practice Research Database (GPRD), UK. Linked data to the Hospital Episode Statistics (HES) and death certificates from the Office of National Surveillance (ONS) were included. Current vitamin K antagonists (VKA) treatment was defined as a valid prescription/INR measurement during the last 28 days, recent as a treatment period from 28 to 90 days after the last prescription/INR measurement, and past treatment as more than 90 days after last treatment/INR measurement. No treatment was the time between diagnosis of AF and first prescription/INR measurement, or the whole follow-up for patients that have never been treated. Vascular outcomes – first ever recorded – were assessed as primary hospital admission diagnosis recorded in HES, i.e. myocardial infarction (MI), stroke, and systemic peripheral arterial embolism (SPAE).

Results:
Data from 16,513 AF patients could be linked; 48% were female, the mean age (std) was 74 (12) years, the median duration of follow-up was 1.7 years (range 0–5). According to CHADS2 score 21% were at low risk, 65% at moderate and 14% at high risk for stroke. Overall 55.8% of the patients had at least one period of VKA use.
Overall, 1,151 vascular events were recorded (403 MIs, 716 strokes, 68 SPAE). The incidence (per 100 patient years (95% CIs)) of vascular events was 3.8 (3.5 – 4.0), 1.3 (1.2 – 1.4) for MI, 2.3 (2.1 – 2.5) for stroke and 0.2 (0.2 – 0.3) for SPAE. Stratification by period of VKA use resulted in incidences for current, recent, past and non users for MI of 0.7 (0.6 – 0.9), 0.7 (0.4 – 1.2), 1.1 (0.8 – 1.5), 1.9 (1.7 – 2.1), for stroke of 0.9 (0.8 – 1.1), 2.2 (1.6 – 2.9), 2.4 (1.9 – 2.9), 3.4 (3.1 – 3.7), and for SPAE of 0.2 (0.2 – 0.3), 0.2 (0.1 – 0.3), 0.3 (0.1 – 0.6), 0.2 (0.1 – 0.3), 0.2 (0.2 – 0.3).

Conclusion:
In this cohort study, a trend towards lower incidences of vascular events, specifically stroke and MI, was detected during VKA use compared to past/no use. No causal conclusions can be drawn from these crude incidence estimates, but the trends are in line with the clinical expectations of anticoagulation in AF patients.

Disclosures:
Clemens: Boehringer Ingelheim Pharma GmbH & Co. KG: Employment. Diana:Boehringer Ingelheim GmbH: Employment. Bartels:Boehringer Ingelheim GmbH: Employment.
Lenalidomide Followed with Donor Lymphocytes Infusion (DLI) After Allogeneic Stem-Cell Transplantation (Allo-SCT) with Reduced-Intensity Conditioning in Patients with High Risk Multiple Myeloma
Authors: El-Cheikh Jean , Crocchiolo Roberto , Ladaique Patrick , Furst Sabine , Castagna Luca , Faucher Catherine , Granata Angela , Oudin Claire , Lemarie Claude , Calmels Boris , Stoppa Anne Marie , De Colella jean Marc schiano , Duran Segolene , Chabannon Christian , Blaise Didier 
Published: October 2019

Abstract
Abstract 4310

Purpose:
Relapse remains the main issue after allogeneic stem cell transplantation (Allo-SCT) in high risk Multiple Myeloma (MM) patients. The aim of this study is to assess the anti-myeloma effect of lenalidomide followed by donor lymphocyte infusion (DLI) as adoptive immunotherapy after transplantation.

Patients and methods:
Twelve patients with refractory and high risk myeloma were analyzed. Median age at transplantation was 56 years (46–64); 6 patients (50%) received lenalidomide before Allo-SCT. All patients received a RIC including Fludarabine 30 mg/m2 5 days, ATG 2,5 mg/kg for 2 days and Busilvex 3.2 mg/kg/day (3 days in 6 patients and 2 days in 6 patients). All but one received peripheral blood stem cells (PBSC). Donor was HLA id in 6 patients and matched unrelated in 6 patients. It is our standard long term practice to consider post-transplant DLI in patients with progressive or persistent disease after day 100 if no GVHD signs were evident. In 2010, we introduced the use of lenalidomide after day 100 in patients with MM presenting the same characteristics. Doses ranged from 10 to 25 mg/day. Lenalodomide treatment could be completed with DLI, administered afterward, at least after 2 cycles.

Results:
The median time between Allo-SCT and lenalidomide was 10 months (3–38). The median initial dose of lenalidomide was 15 mg (10–25). Patients received a median of 6 cycles (1–10). Nine patients (60%) received an escalating dose of DLI; 1 × 107/Kg of CD3+cells for the first DLI and 1 × 108/Kg of CD3+cells for the second DLI. One patient with GVHD (after tapering of the cyclosporine A and only after 10 days of lenalidomide) and two patients with progressive disease after lenalidomide did not receive DLI.
The toxicity related to lenalidomide was mainly haematological (grade II in 4 patients (33%) and grade I in 3 patients (25%); 7 patients (58%) had moderate asthenia. One patient developed a reversible renal insufficiency after 10 cycles of lenalidomide, none of our patients developed thrombo-embolism under treatment.
At the last follow up, 9 patients are alive and all of them are under ongoing treatment. Four patients achieved complete remission (CR) and five patients partial remission at last evaluation. The 1 and 2 years probability of the progression-free survival (PFS) was 75% and 50% and overall survival (OS) was 83 % and 69% respectively. The median OS was not reached and the median PFS was 23 months.

Conclusions:
These data show that lenalidomide has an acceptable toxicity. Combination with DLI should be further evaluated in a larger cohort of patients.

Disclosures:
No relevant conflicts of interest to declare.
Adding AB Plasma Units to Emergency Release O Negative Red Blood Cells (RBC) Issued to the Emergency Department (ED)
Authors: Andrews Jennifer C. , Weiss Susan , Viele Maurene , Goodnough Lawrence T 
Published: October 2019

Abstract
Abstract 4333

Background:
Recent studies have shown improved mortality and decreased early coagulopathy in trauma patients with administration of RBCs, platelets and fresh frozen plasma in a 1:1:1 ratio (Shaz BH et al. Transfusion 2010;50:493–500). As a result, massive transfusion protocols (MTP) have become common at large academic institutions with level I trauma programs. Our institution recently added 2 units of AB plasma to our standard ED trauma cooler which contains 2 units of O negative RBCs and which is ordered by ED staff upon notification of an incoming trauma patient. The treating physicians can escalate blood component support by ordering an MTP if indicated. The purpose of this study was to assess the use and wastage of plasma and RBCs in the ED trauma cooler.

Methods:
Orders received for the trauma cooler from January 1 2011 to June 30 2011 at a large academic Trauma I center were reviewed retrospectively. Transfusions of RBC and plasma for each order were assessed as well as wastage of plasma or RBCs not transfused. Patients may have used more blood products than initially issued in the ED trauma cooler.

Results:
Ninety one orders were received for an ED trauma cooler during the 6-month period assessed. Fifteen (16%) of 91 orders resulted in transfusion of RBCs. Nine (10%) of 91 orders resulted in transfusion of plasma. Five of 182 (3%) plasma units issued were wasted because temperature parameters were exceeded before return to the transfusion service (TS). No untransfused RBC units were wasted and all were returned to available inventory. See table. The 15 O negative RBC units transfused from the ED trauma cooler during this time period represent 0.8% (15/1891) of our medical center's transfused O negative RBC units, and the 14 AB plasma units transfused or wasted from the ED trauma cooler represent 2% (14/573) of the AB plasma units transfused by the TS.

Conclusion:
Of the 48 academic hospitals participating in the 2009 University Health System Consortium (UHC) Efficient Blood Management Benchmarking Project, the published mean wastage of plasma was 3.36% (range 0.36% – 9.44%). Our 3% wastage rate for AB plasma in the ED trauma cooler was within this range. The addition of 2 units of AB plasma to the ED trauma cooler with 2 units of O negative RBCs was feasible at our institution with acceptable wastage of plasma and no undue strain on our supply and inventory of donor O negative RBC and AB plasma.

Disclosures:
No relevant conflicts of interest to declare.
The Burden of Blood Transfusion: A Utilization Analysis - A Pilot Study
Authors: Reitan John , Kudrik Fred J. , Fox Kayleen , Shreay Sanatan , van Breda Arletta , Corey-Lisle Patricia 
Published: October 2019

Abstract
Abstract 4342

Purpose:
The primary objective of this pilot study is to evaluate the burden of blood transfusion on the institutional outpatient transfusion center. The burden of blood transfusion will be characterized by quantifying time and personnel resources associated with the administration of blood transfusions.

Methods:
This pilot study is a retrospective chart review (starting July 1, 2010, working backwards until 100 evaluable patients are accrued) that evaluated time and resources of blood transfusions at a single local institutional transfusion center located in the US. The record review currently includes 80 RBC transfusions. The mean and standard deviation (SD) were calculated for patient’s age, pre-transfusion Hgb level and other transfusion related activities.

Results:
The mean (SD) patient age was 59 (12) years, and the mean pre-transfusion Hgb was 8.0 (0.8) g/dL. The majority of RBC units administered were 2 units (n =66) with one unit received by n=8 and three units received by n=6. Mean (SD) times to administer the first, second and third units were 102 (12) minutes, 101 (19) minutes and 93 (14) minutes, respectively. The mean (SD) duration of a patient visit to the transfusion center was 313 (59) minutes, with a range of 135 – 448 minutes. When one, two and three units were administered, mean (SD) visit duration was 203 (40) minutes, 321 (46) minutes and 375 (25) minutes, respectively.

Conclusions:
In this preliminary analysis when transfusion is administered, the majority of patients received 2 units of RBCs and the mean time to administer these 2 units was about 3.3 hrs. The duration of patient visits on average was 5.2 hrs which could be a considerable burden on cancer patients. The cost and labor quantification of mean time of administering RBC transfusion would elicit burden to the transfusion center.

Disclosures:
Reitan: Amgen: Research Funding. Shreay:Amgen: Employment. Corey-Lisle:Amgen: Employment.
Platelet Usage Trends-Could It Be Less?
Authors: Kocak Ulker , Belen Fatma Burcu , Okur Arzu , Kulali Ferit , Egritas Odul , Yenicesu Idil 
Published: October 2019

Abstract
Abstract 4343
Thrombocytopenia as a risk factor for major bleeding is a life threatening complication of critical disease situations. Prophylactic or therapeutic platelet transfusions are widely used for hemorrhagic problems.
The aim of this study was to find out the indications, the threshold for platelet transfusion for the pediatric patients in a tertiary care hospital throughout one year to determine the optimal platelet transfusion practice.
The study was conducted upon the records of the hospital's blood bank and the files of the patients were retrospectively reviewed.
A total of 378 platelet units were used in 104 patients with an age range of 0–18 years. The majority (48.1 %) of the transfusions were in mainly leukemia patients in the hematology department. Transfusions per patient were higher in hematology (mean 4.8 ± 7.4 transfusions) and neonatology (mean 4.8 ± 7.6 transfusions) (p > 0.05) departments.
256 (67.7 %) of the transfusions were single donor apheresis whereas 122 (32.3 %) were random donor platelet products. About 1/3 of the apheresis products were given when the platelet count was below 10 × 109/L and 1/3 were given when the platelet count was between 10–20 × 109/L. 118 (31.2 %) of the transfusions were used for prophylaxis in hematology and oncology departments when the platelet levels were below 10×109/L (mean platelet count of 9.8 ± 7.7 × 109/L and 8.8 ± 5.2 × 109/L). These levels are lower than other departments (p < 0.001). 59 % of the apheresis units were preferred for therapeutic reasons. The highest platelet levels were observed when platelet concentrates were used for treatment of bleeding or prior to any procedure (Table 1).
Platelet usage shows a discrepancy between the departments of pediatrics. Hematology and oncology patients were the major consumers of the platelet concentrates. Although it is known that when given in appropriate dosage no difference was observed between the platelet concentrates in terms of increasing the platelet counts, there was a tendency for using apheresis products which are the most expensive (188.61 dollars) among all. This practice could be abandoned by continuous education. Besides the guidelines should be reviewed periodically to remind the physicians the dilemma of transfusion; life saving on one hand and the risks on the other.

Disclosures:
No relevant conflicts of interest to declare.
Efficacy of Baxter’s Longer Acting rFVIII (BAX 855) in Mouse Models of Hemophilia A
Authors: Schiviz Alexandra , Barbara Eder , Lawo John-Philip , Ehrlich Hartmut J. , Scheiflinger Friedrich , Turecek Peter L , Schwarz Hans Peter , Muchitsch Eva-Maria , Hoellriegl Werner 
Published: October 2019

Abstract
Abstract 4350
Factor VIII (FVIII) is a critical component of the intrinsic coagulation pathway. FVIII concentrates are used in patients with hemophilia A to provide a hemostatic FVIII level sufficient to treat and prevent bleeding episodes. Multiple prophylactic administrations per week are necessary to maintain a FVIII level of at least 1% of normal to effectively prevent or reduce spontaneous bleeding episodes. A longer acting FVIII concentrate would reduce the frequency of infusions. Baxter and Nektar have developed a longer-acting PEGylated variant (BAX 855) of Baxter’s recombinant FVIII (ADVATE process). The aim of the presented studies was to evaluate the efficacy of BAX 855 in two primary pharmacodynamics in hemophilia A mice: a tail-tip bleeding model (TTBM) and a carotid occlusion model (COM).
BAX 855 was tested at a dose of 200 IU/kg rFVIII. ADVATE™ served as the active reference item, and formulation buffer as the negative control item. Mice received intravenous treatment with either BAX 855 or ADVATE™ 12–40h prior to the experiment. Buffer was administered 5–15min prior to the experiment.
Animals were anesthetized using ketamine and xylazine. In the TTBM (n=16) the tip of the tail was cut off and total blood loss [mg] was assessed over 60 minutes. In the COM study (n=10) the left carotid artery was exposed and the endothelium was denuded by topical application of FeCl3. Time to occlusion [min] was assessed.
Buffer-treated animals had a median blood loss of 951 mg in the TTBM and did not show vessel occlusion within 30 min in the COM. In the TTBM, a prophylactic effect of ADVATE™ could be observed for up to 18 h, leading to a reduction in blood loss to 121 mg after this treatment interval. Prophylactic efficacy after treatment with BAX 855 could be observed for up to 40 h with a median blood loss of 73 mg after 30 h and 436 mg after 40 h. In the COM, treatment with ADVATE™ 12 h before the experiment shortened the time to occlusion to 3.8 min. With BAX 855, a similar efficacy could be observed for up to 24 h after administration (5.2 min).
In summary, the results of our studies show that BAX 855 is efficacious in these two mouse models of hemophilia A and that the efficacy of BAX 855 is prolonged compared with an unmodified rFVIII. Furthermore, the intravenous injection of BAX 855 was well tolerated in all animals across all treatment groups without any signs of acute toxicity.

Disclosures:
Schiviz: Baxter Innovations GmbH: Employment. Barbara:Baxter Innovations GmbH: Employment. Lawo:Baxter Innovations GmbH: Employment. Ehrlich:Baxter Innovations GmbH: Employment. Scheiflinger:Baxter Innovations GmbH: Employment. Turecek:Baxter Innovations GmbH: Employment. Schwarz:Baxter Innovations GmbH: Employment. Muchitsch:Baxter Innovations GmbH: Employment. Hoellriegl:Baxter Innovations GmbH: Employment.
Plasminogen Activator Inhibitor-1 and Vitronectin Levels in Children with Acute Lymphoblastic Leukemia, and Their Relationship with Risk Groups
Authors: Ayduran Semra , Devecioglu Omer , Unuvar Aysegul , Ekmekci Hakan , Karakas Zeynep , Ozturk Gulyuz , Anak Sema , Agaoglu Leyla , Kavakli Kaan 
Published: October 2019

Abstract
Abstract 4365
Fibrinolytic system plays a role in tumor growth, invasion and metastasis in cancer. High levels of plasminogen activator inhibitor-1 (PAI-1) which is a part of fibrinolytic system is a sign of poor prognosis in a number of cancer types. Acute lymphoblastic leukemia (ALL) is the most frequent malignant disease of childhood. Risk groups of ALL are used to determine treatment strategies in childhood ALL. In this study, we aimed to ascertain the prognostic and predictive roles of PAI-1 and vitronectin in children with ALL, and their relationship with risk groups of ALL. In the literature, there are few studies with PAI-1, but no study with vitronectin and ALL in children. In this study, we analyzed the plasma PAI-1 and vitronectin levels of 37 recently diagnosed ALL patients (age range: 9 months–17 years), and 25 age-matched healthy children as a control group by using the ELISA technique. The mean PAI-1 levels was 27.36±16.53 ng/ml, vitronectin levels 97.54±29.82% in the ALL group; and, 23.60±10.44 ng/ml, 85.50±20.85% in the control group, respectively. It was found that the plasma vitronectin levels of ALL group was high as nearly statistically significant (p=0.06). Although, the PAI-1 levels of ALL group was higher than the control group, there was no statistically significance (p=0.27). The ALL group was divided into three risk groups (standard, moderate, and high) according to the BFM protocol. When the standard and moderate-high risk groups are compared with control group, the vitronectin levels of standard risk group was higher than the control group (p=0.048), but no difference was found for PAI-1 levels (p=1.00). There was no significant difference for vitronectin levels (p=0.76), and PAI-1 levels (p=0.25) between moderate-high risk groups and the control group, although PAI-1 levels were higher in moderate-high risk groups. In conclusion, we could not find any relationship between the parameters of fibrinolytic system and ALL risk groups except the vitronectin levels of standard risk group, new studies are needed.

Disclosures:
No relevant conflicts of interest to declare.
Growth Inhibition and Induction of Apoptosis in K562 Human Chronic Leukemic Cells by abnobaVISCUM® flaxini, Mistletoe Extracts From Ash Tree: Involvement of Activation of Caspases, Mcl-1 Down-Regulation, and ER Stress
Authors: Do Young-Rok , Park Yu-Kyung , Jang Byeong-Churl , Kim Jin Young , Kwon Ki Young 
Published: October 2019

Abstract
Abstract 4418
Evidence suggests that extracts from mistletoe (Viscum album L.) have anti-cancer effects on many human cancers. Little is known about the relationship between mistletoe extracts and hematological malignancies. In this study, we investigated the effect of abnobaVISCUMÒ Flaxini, a commercially available mistletoe extracts from ash tree, on growth of K562 human chronic leukemic cells. Results of cell count and DNA fragmentation assays demonstrated that there was strong growth suppression and induction of apoptosis in K562 cells after treatment with abnobaVISCUMÒ Flaxini at 2 mg/ml for 8 h. Western blot and RT-PCR analyses revealed that abnobaVISCUMÒ Flaxini treatment also led to activation of caspase-9 and -3 and PARP cleavage, but had no effect on expression of death receptor (DR)−4 and −5 in K562 cells. Expression of Bak and Bax was not changed, but that of Mcl-1 protein was strongly repressed in abnobaVISCUMÒ Flaxini-treated K562 cells. Moreover, while treatment with abnobaVISCUMÒ Flaxini decreased phosphorylation of ERK-1/2 and PKB, it stimulated phosphorylationof JNK-1/2 and p38 MAPK in K562 cells. Importantly, pharmacological inhibition studies demonstrated that treatment with z-VAD-fmk (a pan-caspase inhibitor), but not SP600125 (a JNK-1/2 inhibitor) or SB203580 (a p38 MAPK inhibitor), suppressed abnobaVISCUMÒ Flaxini-induced loss of survival and apoptosis in K562 cells, and z-VAD-fmk also blocked abnobaVISCUMÒ Flaxini-induced Mcl-1 protein down-regulation. Induction of ER stress was also seen in abnobaVISCUMÒ Flaxini-treated K562 cells, as judged by increased phosphorylation of eIF-2a and expression of GRP78 and CHOP, three known ER stress sensors. Collectively, these findings provide the first evidence of abnobaVISCUMÒ Flaxini-mediated anti-survival and apoptosis inducing effects on K562 cells via activation of caspases, Mcl-1 down-regulation, and triggering ER stress.

Disclosures:
No relevant conflicts of interest to declare.
Alantolactone Induces Apoptosis in Imatinib-Sensitive and -Resistant CML Cells by Inhibiting NF-KappaB Signaling and Degrading Bcr/Abl Protein
Authors: Yan Hua , Wei Wei , Zhao Shan , Liu Chuanxu , Wu Ying-Li , Chen Guo-Qiang 
Published: October 2019

Abstract
Abstract 4419
Chronic myelogenous leukemia (CML) is characterized by the t(9;22) chromosomal translocation, which results in the generation of Bcr-Abl oncogene that encodes the chimeric Bcr-Abl protein with constitutive tyrosine kinase activity. Despite the great success of imatinib therapy in CML, not all patients, especially those in the accelerated or blastic phase, experience an optimal response to this drug or even to the more potent, second-generation TKIs. The emergence of resistance to TKIs has also become a significant problem implying that physiopathologically relevant cellular targets should be validated, such as NF-kappaB (NF-kB).
Here we describe the activity of alantolactone, a small natural compound and see its effect on K562-sensitive (K562s, sensitive to imatinib) and K562-resistant (K562r, resistant to imatinib) cells.

Results:
Firstly, we used CCK-8 assay to determine the cell viability and found that K562s were inhibited up to 64.5% after 48 hours of incubation of 10uM concentration of alantolactone, Annexin V+ cells were up to 68% which were confirmed by morphological observation, and apoptosis-related proteins were activated during the treatment, suggesting its inducing-apoptosis ability. Secondly, incubation of alantolactone could inhibit NF-kB signaling activity, proved by inhibition of IkBa phosphorylation and blockade of nuclear translocation of p65, while the luciferase assay further revealed the inhibited transcription of NF-kB dependent reporter gene, which was confirmed by immunofluorescence staining. Of note, Bcr-Abl protein was specifically and rapidly down-regulated as early as 6 hours after 10uM of alantolactone treatment. And alantolactone-induced Bcr-Abl down-regulation could be partially reversed by the autophagy inhibitor chloroquine but not by the proteasome inhibitor MG132 or bortezomib, indicating that autophagy may contributes to Bcr-Abl reduction. Furthermore, similar concentration of alantolactone could also induce apoptosis in K562r cells and inhibited the growth of primary CD34+ leukemic cells from CML patients.
Collectively, our results primarily demonstrated that alantolactone could induce apoptosis in CML cells, regardless of imatinib-sensitive or -resistant, by inhibiting NF-kB signaling and depleting Bcr/Abl through a unique mechanism. Alantolactone could be used as a probe for deciphering the mechanism of Bcr-Abl destruction and NF-kB inhibition, and this agent may be a promising candidate for treating CML patients.

Disclosures:
No relevant conflicts of interest to declare.