bluuebunny/crossref_metadata_2025_split huggingface dataset:
Consultation for Thrombocytopenia in Hospitalized Patients
Authors: Boxer Michael 
Published: October 2019

Abstract
Abstract 4659
Thrombocytopenia is a frequent cause for hematologic consultation in an acute care hospital. During a 22 month period one hematologist assessed 93 patients with thrombocytopenia. Thrombocytopenia was the sole reason for the consultation. No previous thrombocytopenia had been recognized previously in any if these patients.
The cause for thrombocytopenia was liver diease in 21 patients, sepsis in 12, immune (ITP) in 12, antimetabolites or antiseizure medications in 7, heparin induced thrombocytopenia (HIT) in 6, platelet clumping in 4, thrombotic thrombocytopenic purpura (TTP) in 3, myelodysplasia (MDS) in 3, acute progranulocytic leukemia (APL) in 3, rhabdomyolysis in 2, viral infections in 2, systemic lupus (SLE) in 2, and intravenous antibiotics in 2.
The following conditions were each diagnosed once as the cause for thrombocytopenia:pregnancy, disseminated intravascular coagulation (DIC), post coronary bypass grafting, brain injury, acute myelogenous leukemia (AML-M5), antiphospholipid syndrome (APLS), and intra aortic ballon pump.
No diagnosis could be made in 13 patients. In 28 patients the initial diagnosis was incorrect. No diagnosis could be made in 13 patients. In 6 patients two causes for thrombocytopenia were present. One patient was admitted twice with two different causes for thrombocytopenia (sepsis and ITP).
Review of the peripheral smear is both necessary and mandatory. All three patients with APL were initially diagnosed with ITP, and the diagnosis of APL was not made until the smear was assessed. Smear review confirmed or made the diagnosis of TTP. Platelet clumping could not be made without reviewing the peripheral smear.
Primary hematologic diagnoses (ITP, HIT, clumping, TTP, MDS, APL, AML, APLS) were present in 33 patients. Secondary causes for thrombocytopenia were present in the majority of patients.
In summary thrmobocytopenia a frequent cause for hematologic consultation, and most patients will not have a primary hematologic etiology for the thrombocytopenia. Advanced liver disease is an underappreciated cause for thrombocytopenia and was never considered to be the cause for the thrombocytopenia by the referring physician.
Despite exhaustive testing the cause for thrombocytopenia could not be made in 13 patients. However in these patients the platelet count rarely was below 100,000.
The importance of reviewing the peripheral smear cannot be overemphasized.

Disclosures:
No relevant conflicts of interest to declare.
Nilotinib Exhibits an in Vitro Antiviral Activity Against Human Cytomegalovirus (HCMV): Potential Clinical Applications
Authors: Wolf Dana , Djian Esther , Beider Katia , Shimoni Avichai , Nagler Arnon 
Published: October 2019

Abstract
Abstract 4666
Chronic myeloid leukemia (CML) is a clonal disorder associated with chromosomal translocation t (9; 22), which produces the Philadelphia chromosome. The fusion gene encodes for the chimeric oncoprotein BCR-ABL, associated with deregulated constitutive tyrosine kinase (TK) activity, leading to leukemogenesis. Imatinib mesylate, the first potent selective inhibitor of BCR-ABL TK, has revolutionized the current management of CML. The second generation TK inhibitor (TKI) Nilotinib (Novartis, East Hanover, NJ) is an aminopyrimidine derivative of imatinib with an increased binding affinity to the chimeric p210 BCR-ABL. Nilotinib is active in imatinib-resistant or -intolerant patients in chronic phase, accelerated phase (AP), and blast crisis (BC) CML.
Allogeneic stem cell transplantation (SCT) is currently reserved for patients(pts) in CP after the failure of second line TKI or for patients in advanced phase disease.SCT remains the treatment of choice in patients with Ph+ALL. TKIs can be used successfully pre -SCT as a bridge to SCT in advanced disease and post-SCT in order to prevent disease recurrence. HCMV is one of the leading causes of morbidity and mortality post SCT in particular in pts transplanted for advance CML and pts with graft vs. host disease (GVHD) While preemptive antiviral therapy has reduced the occurrence of HCMV disease post SCT, the use of all currently available antiviral drugs is often limited by toxicity, low oral bioavailability, and drug resistance.
The mechanisms facilitating HCMV entry into the host cells are not clearly understood. Blocking of the platelet – derived growth factor receptor-α (PDGFRα) has been shown to inhibit HCMV internalization and gene expression. Recently, Imatinib have been shown to inhibit PDGFRα phosphorylation. As Nilotinib is a more potent PDGFR inhibitor, we assessed the in vitro antiviral activity of Nilotinib against HCMV. Nilotinib exhibited a significant dose-dependent inhibition of the virus upon pre-incubation with the drug. Moreover, Nilotinib demonstrated a ∼4.5-fold higher antiviral activity against HCMV when compared to imatinib, with IC50 values of 0.39 μM and 1.75 μM, respectively. No viral inhibition was found upon addition of the drugs after viral adsorption – compatible with inhibition of an early step of infection, involving viral binding/entry into the cell. These findings identify a promising new target for antiviral therapy, representing an alternative paradigm for treatment with compounds combining anti-cancer and antiviral activity. It remains to be determined if the anti-HCMV activity demonstrated for Nilotinib is of clinical relevance in patients undergoing SCT

Disclosures:
No relevant conflicts of interest to declare.
A Clinical Study of Bone Marrow Stromal Cell Therapy in Patients with Refractory Cgvhd by Down-Regulating the Jagged2 Gene
Authors: Weng Jianyu , Huang Xin , Geng Suxia , Luo Chengwei , Wu Suijing , Ling Wei , Guo Rong , Lu Zesheng , Deng Chengxin , Andy Pengxiang , Du Xin 
Published: October 2019

Abstract
Abstract 4673
Refractory chronic GVHD (cGVHD) is an important complication after allogeneic hematopoietic SCT and is prognostic of poor outcome. Bone Marrow Stromal Cells (MSCs) are involved in tissue repair and modulating immune responses in vitro and in vivo. MSCs as salvage treatment for refractory cGVHD have been reported in our previous study, however, the possible mechanism have yet not to be determined.
Between November 2006 and November 2010, 18 patients were diagnosed with refractory cGVHD, 8 patients were treated with in vitro expanded BM-derived MSCs as a compassionate treatment for refractory cGVHD, 10 patients that did not receive BMSCs treatment were control group. The median MSC dose given was 0.6×106/kg body weight. MSCs were harvested fresh from culture and administered to the patients by intravenous infusions over 30 minutes. The median time of MSC administrations was 3 (range, 2–6). The response was assessed monthly after BMSCs treatment, and the total follow-up period was 6 months. The organ response and the overall response were used to determine the therapeutic efficacies of MSC for refractory cGVHD. The expression of the Jagged2 gene of peripheral blood mononuclear cells in patients at the assessment points were analyzed using the TaqMan real-time polymerase chain reaction, with ABL mRNA expression levels as an internal reference.
After BMSCs treatment, a total of 6 patients (75%) had an overall response (PR n=6), and 2 patients had a minor partial response (mPR n=2). The expression levels of Jagged2 mRNA in these cases at the diagnosis of refractory cGVHD were significantly increased, compared with none cGVHD patients (23.94%±18.68% vs 3.76%±1.50%, P < 0.05), and the copies of Jagged2 mRNA in BMSC treatment responsed patients' peripheral blood were significantly reduced (5.15%±3.25%, P <0.05), while Jagged2 mRNA expression levels of the control group were no significant difference (P> 0.05).
Our pilot study showed that Jagged2 gene reproduction upregulated when the cGVHD is active, so, dynamic monitoring of Jagged2 mRNA expression may have the potential effect on predicting the activity of chronic graft-versus-host disease. Mechanism of Bone marrow stromal cells to treat refractory cGVHD may be related to down-regulation of donor T cells Notch ligand Jagged2 gene expression, which suppression of T cell Notch signaling pathway activation, thus inducing immune tolerance.

Disclosures:
No relevant conflicts of interest to declare.
Donor Lymphocyte Infusion for the Treatment and Prevention of Recurrence After Hematopoietic Stem Cell Transplantation
Authors: Liao Jianyun , Long Lina , Li Chunfu , Zhou Xiaohui , Liu Qifa 
Published: October 2019

Abstract
Abstract 4674
Background—Treatment and prevention of relapse and recurrence after HSCT is challenging. DLI from the same donor is an effective therapeutic clinical option for patients. Method—we retrospectively analyzed the data of 14 patients with diagnoses included ALL (n=3), AML(n=3), thalassemia (n=7), aplastic anemia(n=1), who received DLI after HSCT. We analyzed the relationship between the during of DLI to the occurrence of aGVHD. Results—A total of 25 infusions were given to 14 patients with a median infusion time of 116(44–620) days post-HSCT. acute graft-versus-host disease (GVHD) grade I occurred in 9 patients at a median day of 33.4(14–70) after DLI. GVHD prophylaxis (using CsA) reduced the incidence of aGVHD. Our data showed that the median time to DLI in patients with aGVHD was 206 (44–521) days, and aGVHD developed in about 50% of the patients receiving DLI less than 180 day post-transplantation, while GVHD occurred in 33.3% of the patients who received DLI over 180 day (p=). the risk of developing GVHD was also dependent on the dose of DLI, with 7 patients developing GVHD when the dose of infused cells is 1¡Á107 lymphocyte cells/kg however, ? patients. Conclusion—the response to DLI is dependent on the time post-transplant. It seems that it is more easy to develop GVHD to DLI less than 180 days post-transplantation and to receive a dose of 1¡Á107 lymphocyte cells/kg. GVHD would possibly occur in 4 weeks after DLI.

Disclosures:
No relevant conflicts of interest to declare.
Pancytopenia a Presentation of disseminated Histoplasmosis
Authors: Hussain Sakeer 
Published: October 2019

Abstract
Abstract 4687
A 70 year old female with diabetes mellitus, rheumatoid arthritis with worsening fatigue, intermittent shaking chills and fever for 2 weeks. She had been on oral prednisone 5 mg daily and methotrexate 15 mg every week for her rheumatoid arthritis. Vital signs were stable and physical examination was significant for 3+ lower extremity edema and pallor. The CBC showed pancytopenia, white cell count of 2.5×109/L (4.3–10.8×109/L), hemoglobin was 9.2g/dl (11.0–15.0g/dl), and platelet counts were 93 × 109/L (130–400 × 109/L). SHe had mildly elevated total bilirubin 1.7mg/dl (0.0–1.2mg/dl), elevated alkaline phosphate 1212U/L (38–126 U/L) liver enzymes, SGPT 83U/L (0–40U/L), SGOT 126U/L (0–35U/L), and elevated blood sugar of 260mg/dl. Blood cultures remain negative for bacterial growth for multiple days. Her SPEP, ANA, HIV, CMV, and EBV serology were negative. CT scan of the chest, abdomen and pelvis were consistent with hilar, mediastinal lymphadenopathy and upper abdominal lymphadenopathy with splenomegaly. A bone marrow aspiration and biopsy was consistant with histoplasma capsulatum infection. Patient was treated with IV amphotericin B for 4 weeks. Histoplasma capsulatum was identified from fungal culture from the bone marrow aspirate. Retrospectively urine analysis for histoplasma antigen was positive by ELISA. Subsequently patient recieved itraconazole for 6 months. Cytopenia and symptoms improved and lymphadenopathy regressed. Most patoents who develop disseminated histoplasmosis are immunosuppressed It often mimic the presentation of malignancy like lymphoma or infection like tuberculosis and inflammatory process like sarcoidosis. Misdiagnosis can lead to inappropriate and harmful therapy with glucocorticoides and cytotoxic chemotherapy. Diagnosis requires high index of suspicion and familiarity with clinical presentation and appropriate diagnostic test.

Disclosures:
No relevant conflicts of interest to declare.
Evaluating Conflicts of Interest in Academic Research On Erythropoietin Receptors in the Cancer Setting
Authors: Bennett Charles , vanSlooten Eleasa , Bialkowski Matthew , Trenery Alyssa , Byrne Ashlyn , Murday Alanna , Yarnold Paul , Qureshi Zaina Parvez , Sartor A. Oliver 
Published: October 2019

Abstract
Abstract 4695

Background:
We previously reported that among preclinical cancer articles published prior to 2008, academic researchers without financial conflicts of interest were significantly more likely than academic researchers with financial conflicts or researchers employed by erythropoiesis stimulating agent (ESA) manufacturers to identify erythropoietin (Epo)-induced cancer-related signaling events and Epo-induced changes in functions of cancer cells.(Arch Int Med 2010) In 2007, the National Cancer Institute convened a workshop on Epo-receptors for 14 academic researchers and six researchers employed by ESA manufacturers. We update our analysis following this workshop.

Methods:
Articles identified in MEDLINE and EMBASE databases (1989–2012) investigating preclinical ESA findings were reviewed. Outcomes included Epo-receptors, Epo-induced signaling events, Epo-induced cellular function events, and qualitative conclusions among reports published since the 2007 meeting. Recent publications before versus after the NCI workshop according to source of research funding were analyzed. Outcomes were reported according to academic investigators without financial conflicts of interest (26 publications post-2008; 64 publications pre-2008), academic investigators with financial conflicts (5 versus 7 publications) and investigators employed by ESA manufacturers (2 versus 3 publications).

Results:
Since 2008, academic investigators without financial conflicts of interest and academic investigators with financial conflicts differed from researchers employed by ESA-manufacturers with respect to identifying the following EPO-induced events: signaling associated with tumor promotion (86%, 100%, versus 0%; p=0.06), cellular function changes associated with tumor growth/metastases (86%, 67%, and 0%; p=0.06). We qualitatively concluded that preclinical findings raised concerns that ESAs could be harmful clinically (77%, 40%, and 0%, p=0.03). Prior to 2008, academic investigators without financial conflicts of interest differed from academic investigators with financial conflicts and researchers employed by ESA manufacturers for these same outcomes (signaling events, 94%, 0%, and 0%, p=0.001; cellular changes (57%, 0%, and 0%, p=0.007), and qualitative conclusions regarding potential harm (57%, 0%, and 0%, p=0.007), respectively.

Conclusions:
The potential for conflicts of interest to affect preclinical research findings dissipated, following an NCI-convened workshop, for academic researchers with financial conflicts of interest, but not for researchers employed by ESA manufacturers.

Disclosures:
Bialkowski: Eli Lilly: family member employment Other. Sartor:Amgen: Consultancy.
Improving the Quality of Our Clinical Work for Coumadin Anticoagulation Therapy with Electronic Medical Record (EMR) Based System Redesign
Authors: Thomas-Hemak Linda , Thomas Lisa , Shi Qi , Sheth Jignesh , Praveen Etikala , Choudhary Gunjan , Abdelmalek Cherif , Muppidi Vijayadershan , Eikins Tiffany 
Published: October 2019

Abstract
Abstract 4714

Introduction:
Coumadin anticoagulation therapy is indicated in a variety of thromboembolic conditions. Close INR monitoring is required to maintain therapeutic range in order to decrease complications, emergency room visits, and medical costs associated with Coumadin therapy. To achieve this, tight quality control in primary health care systems is undeniably important. The purpose of this study is to assess the effects of a redesigned system for coumadin anticoagulation therapy in an outpatient setting. Our project includes: (1) Meaningful use of a new electronic medical record (EMR) based INR flow sheet; (2) Improved physician and staff efficiency using new EMR based protocol for INR tracking and clinical decision support, including drug interaction information, dose adjustment, per-procedure anticoagulation bridging, and an education/training program; (3) Improved patient education, including enhanced Coumadin educational materials. Vitamin K prescriptions will be given to the patients in the event of complications with coumadin.

Method and Materials:
INR data were collected from 55 patients receiving Coumadin therapy from 10/01/2009 to 10/31/2011 at an outpatient setting. Total blood tests for INR were 1679 samples. We summarized results from 55 patients twelve months before and after using our redesigned system.

Result:
Our data shows the new system helped to: (1) Increased the percentage of INRs (average) in the therapeutic range from 51.35% to 54.05% and the percentage of INRs (average) in extended therapeutic range (+/−0.2) from 63.78% to 70.43%; (2) Decreased the highest value from 15.4 to 10.2; (3)Decreased annual total number of INR checkups for all patients from 881 to 798; and (4)Decreased average number of INR checkups per month from 1.8 to 1.3 (average).

Conclusion:
Our clinical data shows that Our EMR based system redesign not only helps to increase efficiency and safety of Coumadin anticoagulation therapy, but also decreases the frequency of INR checks, thereby reducing medical expenditures.

Disclosures:
No relevant conflicts of interest to declare.
Interleukin-1 Beta Promotes the Expression of Prox-1 and Vascular Endothelial Growth Factor Receptor Type-3 in Adult Human Dermal Fibroblasts
Authors: Takuji Matsuo , Shirasaki Ryosuke , Tashiro Haruko , Oka Yoko , Yamamoto Tadashi , Akiyama Nobu , Kawasugi Kazuo , Shirafuji Naoki 
Published: October 2019

Abstract
Abstract 4738

Background and Aims:
We recently reported that human interleukin 1 beta (IL-1 beta) stimulates bone-marrow stromal myofibroblasts to express a hematopoietic stem cell marker, CD34 (16th EHA, and 53rdASH meeting). To characterize precisely the effects of IL-1 beta to the stromal cells, adult human dermal fibroblasts (HDF) were cultured with IL-1 beta, and the morphological changes and molecular expressions were observed.

Materials and Methods:
HDF were purchased, and cultured in knockout DMEM medium with 15% KSR with or without recombinant human IL-1 beta for 3 weeks. The morphological changes and the expression of specific hematopoiesis-related genes were analyzed time-dependently. The concentration of hematopoietic growth factors in the culturing supernatants was also measured.

Results:
When HDF were cultured with human IL-1 beta for 3 weeks, the cellular morphology changed to the filamentous appearance. RT-PCR analyses revealed that cells expressed Prox-1, a master molecule for lymphatic duct neogenesis, and also vascular endothelial growth factor receptor (VEGFR) type-3. Smad7 and PAI1 were also expressed; however, LYVE1, a marker for lymphatic vascular endothelial cell, was not induced. VEGF-C production was also demonstrated at RNA and protein levels, and VEGF-C and VEGFR type-3 system played an important role in morphological changes and cell-proliferation.

Discussion:
We previously reported that when HDF were cultured in DMEM/F12 medium with IL-1 beta and EPO, hematopoietic markers were induced. When HDF were cultured in knockout DMEM, a condition for immature cell-growth at ES cell levels, and IL-1 beta, lymphatic duct neogenesis-related genes were activated, and HDF converted their morphology without an introduction of any genes externally. We are now making clear the precise action of IL-1 beta to HDF using microarray analysis.

Disclosures:
No relevant conflicts of interest to declare.
Derivation of Hematopoietic Progenitor Cells From Vector-Free Human Induced Pluripotent Stem Cells
Authors: Schuening Friedrich , Zaboikin Michail , Zaboikina Tatiana , Srinivasakumar Narasimhachar 
Published: October 2019

Abstract
Abstract 4746
Induced pluripotent stem cells (iPSCs), due to their self-renewal and differentiation capability, have tremendous potential in regenerative medicine. Differentiation of IPSCs in vitro to obtain sufficient number of hematopoietic stem cells (HSCs) and their progenitors (HPCs) from iPSCs for therapeutic purposes is a holy grail of cellular therapy. To this end, we are comparing different in vitro differentiation approaches for generation of HSCs/HPCs from IPSCs.
We have generated iPSCs from human adult dermal fibroblasts using two different reprogramming methods: 1) Transduction with retroviral vectors encoding human Klf4, Oct3/4, Sox2 and cMyc or 2) Electroporation with Epstein–Barr virus (EBV) based episomal plasmid vectors encoding Klf4, Oct3/4, Sox2, L-Myc and p53 targeting shRNA. The transduced/electroporated cells were reprogrammed on SNL5 mouse feeder cells. Putative iPSC-like colonies were cloned and adapted to grow under feeder-free conditions on Matrigel (BD) in mTeSR1 (Stem Cell Technologies) medium. From over 30 individual clones isolated, six were further characterized for: 1) expression of pluripotency markers (Tra-1–60, SSEA-3, SSEA-4, Nanog and Oct3/4) by immunofluorescence; 2) endogenous and total mRNA expression by quantitative real-time reverse-transcriptase PCR (RT-qPCR) for Klf4, Oct3/4, Sox2 and cMyc to distinguish between cellular and vector derived expression of reprogramming factors; 3) RT-qPCR to determine expression of other markers of pluripotency such as Nanog and DNA methyl transferease; 4) karyotype analysis to determine chromosomal anomalies. The vector-free IPSC clones were also tested for residual integrated EBV plasmid DNA by qPCR. Trilineage differentiation ability of the clones was determined through embryoid body formation in suspension cultures, and subsequent staining of resulting embryoid bodies after adherence to gelatin coated dishes for makers of ectoderm, mesoderm and endoderm.
HSCs/HPCs were obtained from IPSCs by 1) coculture with OP9 stromal cells, or 2) step-wise differentiation in feeder-free conditions on Matrigel under defined conditions in the presence of appropriate growth factors [Niwa A et al. PLoS One. (2011); 6(7):e22261.]. The resultant HSCs/HPCs were subjected to colony forming assays in semi-solid medium containing hematopoietic cytokines. Both erythroid and myelomonocytic colonies could be readily identified. The influence of ambient oxygen concentration on the HSC/HPC derivation procedure is being investigated. The results of these studies will be presented.

Disclosures:
No relevant conflicts of interest to declare.