bluuebunny/crossref_metadata_2025_split huggingface dataset:
Incidence of Pulmonary Embolism with Concomitant Deep Vein Thrombosis at an Urban Community Teaching Hospital
Authors: Goldberg Uri , Nasiri Wazhma , Alibakhiet Mohamed , Jean Henry , Mukherji Rajat , Kalavar Madhumati 
Published: October 2019

Abstract
Introduction
Though venous thromboembolism (VTE) is thought to be under-diagnosed, roughly 900,000 people are estimated to be affected by VTE each year in the U.S. According to CDC figures, VTE accounts for roughly 60,000 to 100,000 annual deaths. Recent research has demonstrated that the risk of mortality in patients with pulmonary embolism (PE) who were found to have concomitant deep vein thrombosis (DVT) was higher in comparison to patients with PE who did not have concomitant DVT (Beccatini et al. Chest 2015). We have sought to evaluate the risk of concomitant DVT among patients diagnosed with PE in our hospital population.
Methods
This is an ongoing retrospective cohort study examining the incidence of PE with concomitant DVT among patients admitted to an urban community teaching hospital between January 2011 and March 2015. Radiological findings for patients who underwent computed tomography angiography (CTA) and venous duplex ultrasound were reviewed. Patients found to have PE were sub-divided into two groups: those with concomitant DVT and those without concomitant DVT. Mortality risk, correlation with inferior vena cava (IVC) filter placement, and association with other comorbidities continue to be evaluated.
Results
Results of 1,777 CTAs were reviewed of which 160 demonstrated a positive finding of PE: 103 women (64.4%) and 57 men (35.6%). Patient age ranged from 19 to 97 years old. The mean and median ages for all PE-positive patients were 61.9 and 63,respectively. Several patients demonstrated multiple emboli; to wit, 273 distinct PEs were noted among the 160 individual patients. Of the 160 patients with PE, 81 were found to have concomitant DVT (50.6%).
Discussion
The combination of high mortality and rapid-though often overlooked-onset make VTE a uniquely vexing condition. Though the nature of the relationship between DVT and the increased mortality risk among patients with PE is unclear, the correlation has been convincingly demonstrated by prior research and may signal the need for more aggressive management for patients with concomitant thromboemboli. Our findings, consistent with the literature, suggest that the prevalence of concomitant PE and DVT may be substantial in the hospitalized population.

Disclosures
No relevant conflicts of interest to declare.
Radiosensitivity of Fancd2-/- mouse Bone Marrow Stromal Cells Is Altered By Abrogation of TGF-β Signaling
Authors: Chen Katherine , Franicola Darcy , Shields Donna , Epperly Michael W. , Zhang Xichen , Greenberger Joel S. 
Published: October 2019

Abstract
Both marrow-transplanted and non-transplanted Fanconi Anemia (FA) patients are often radiosensitive. Due to an increased risk of developing secondary malignancies, these patients require dose and volume modification during radiotherapy. To determine whether abrogation of TGF-β signaling alters the radiation sensitivity of Fancd2-/- mice, cell lines derived from double knockout (DKO) (SMAD3-/- Fancd2-/-) mice were compared with those from Fancd2-/-, SMAD3-/-, and wild-type mice for ionizing irradiation sensitivity.
Bone marrow stromal cell lines were derived from long-term bone marrow cultures of DKO, Fancd2-/-, SMAD3-/-, and wild-type SMAD3+/+ (129/Sv) X Fancd2+/+ (B6) F1 mice. Radiation sensitivity was determined using clonogenic irradiation survival curves. There was no significant difference in radiosensitivity comparing DKO cells (Do = 1.95 ± 0.06 Gy, ň = 4.3 ± 0.7) to the wild type SMAD3+/+ (129/Sv) X Fancd2+/+ (B6) F1 cell line (Do = 2.00 ± 0.11 Gy, and ň = 5.1 ± 0.7, p = 0.7003 and 0.4820, respectively). The Fancd2-/- cell line was more radiosensitive with a Do of 1.37 ± 0.09 Gy compared to 1.95 ± 0.07 and 2.00 ± 0.11 for DKO and wild type cells (p = 0.0063 and 0.0360, respectively. In contrast, the SMAD3-/- cell line was more radioresistant with an increased shoulder on the irradiation survival curve (ň = 12.1 ± 2.9) compared to the DKO or wild type SMAD3+/+ (129/Sv) X Fancd2+/+ (B6) F1 cell lines (ň = 4.335 ± 0.7 or 5.1 ± 0.7, p = 0.00277 or 0.0426, respectively). This confirms and extends results with SMAD3-/- mouse derived cell lines on another background strain (C57BL/6J) (Epperly, et al., Radiation Research, 165:671-677, 2006). TGF-β signaling was abrogated in both DKO and SMAD3-/- mouse cell lines (measured by TGF-β inhibition of fresh marrow CFU-GEMM in vitro), confirming the phenotype of altered TGF-β signaling.
Therefore, radiosensitivity associated with the Fancd2-/- genotype was abrogated by interruption of the TGF-β signaling pathway in the same cells.
Supported by research grant NIAID/NIH, U19A168021.

Disclosures
No relevant conflicts of interest to declare.
Association of the RUNX1/AML1 Gene Mutation and Familial MDS/AML: A Case Report and Review of Literature
Authors: Chen Wancheng , Li Hongbo 
Published: October 2019

Abstract
Myelodysplastic syndrome (MDS) and Acute Myeloid Leukemia (AML) are mostly sporadic hematopoetic malignancies, which generally thought inheritable, though specific gene abnormalities may play a role in the progression of myelodysplasia. Recently, many reports have revealed that mutations in the RUNX1/AML1 gene are involved in defective hematopoiesis. Moreover, patients with such mutations have a significant poorer prognosis than cases without RUNX1 mutations. Since familial occurrence of MDS/AML is rare, there are few reports about the relationship between RUNX1 mutations and familial MDS/AML. In the study of a familial MDS/AML, we found a61-year-old male with MDS who developed into AML later. He had a history of leukocytopenia and thrombocytopenia for decades before developing into pancytopenia. We identified a RUNX1mutationin this patient through sequencing. Furthermore, the same mutation was present in his son (II-1) who suffered from MDS as well as his granddaughter. Intriguingly, II-1 was 10years old when diagnosed with MDS, nearly 50 years earlier than his father. Myelodysplastic features in bone marrow sections of these two patients were not obvious in the early stage. They mainly showed active erythrocyte proliferation, together with an increased mean corpuscular volume, which can indicate inflection points in MDS progression. To date, patients with familial MDS had no antecedent hematological abnormalities in the early stage. In this study, we found a new inheritable mutation of the RUNX1 gene in the familial MDS which is frequently deregulated in hematological malignancies. As RUNX1 was present in the early stage of familial MDS, this genetic mutation may serve as an early diagnostic marker and contribute to the treatment of MDS/AML.

Disclosures
No relevant conflicts of interest to declare.
Single Cell RNA-Seq Reveals Clonal Consistency and Differential Malignancy in Extramedullary Plasmacytoma of Multiple Myeloma
Authors: Geng Shuang , Wang Jing , Chen Mingyi , Wang Wenming , Pang Yuhong , Liu Yuanyuan , Huang Yanyi , Jing Hongmei 
Published: October 2019

Abstract
Extramedullary Plasmacytoma (EMP) is a minor yet devastating metastatic form of Multiple Myeloma (MM), shortening patients' survival from 10 years to 6 months on average. Genetic cause of EMP in MM is yet to be defined. Transcriptome difference between EMP+ patients and EMP- patients is studied here on single cell level by RNA Sequencing (RNA-Seq). We sorted CD38+CD138+ malignant plasma cells from bone marrow and peripheral blood samples by flow cytometry, then picked up single malignant plasma cell and performed single cell RNA-Seq with SmartSeq2 protocol followed by Tn5-based library preparation from bone marrow, peripheral blood and extramedullary tissue of EMP patients. From the single cell RNA-Seq results, in bone marrow we found differential gene expression between EMP+ and EMP- samples, such as CTAG2, STMN1 and RRM2. By comparing circulating malignant plasma cells in PBMC and malignant plasma cell from the sample EMP+ patient, we observed metastatic clone in blood with the same VDJ immunoglobulin heavy chain as in bone marrow. Several genes' expression of these metastatic cells are down-regulated than in bone marrow, such as PAGE2, GTSF1, DICER1. These genes may correlate with egress capability of MM cells into peripheral to become circulating plasma cells (cPCs), and EMP eventually.

Disclosures
No relevant conflicts of interest to declare.
5-Azacitidine Remolds the Methylation Status and Inhibits Growth in Multiple Myeloma
Authors: Wang Wenming , Wang Jing , Chen Mingyi , Liang Yaoxian , Li Zhengqian , Zhang Zhe , Jing Hongmei 
Published: October 2019

Abstract
Multiple myeloma (MM) is a malignant disorder characterized by the proliferation of a single clone of plasma cells derived from B cells. Previous studies have demonstrated that both gene-specific hypermethylation and global hypomethylation characterizes the multiple myeloma epigenome. 5-azacytidine as a DNA methylation inhibitor has therapeutic efficacy in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Nevertheless,the effects of 5-azacytidine on MM remains unclear. We used RT-PCR to detect the expression of PTPL1 and used MS-PCR to determine the methylation status of PTPL1 in MM cell lines and after 5-azacytidine treatment. ELISA-like reaction was used to detect global DNA methylation level. The cytotoxic activity of 5-azacytidine was tested using cell viability and apoptosis assays. Flow cytometry was used to detect cell cycle after 5-azacytidine treatment. Our experiments discovered that the PTPL1 gene was hypermethylated in the U266 and H929 cell lines, and the expression of PTPL1 mRNA could be re-inducible by 5-azacytidine. 5-azacytidine also inhibited the proliferation of multiple myeloma cell lines U266 and H929 in a time- and dose-dependent manner, induced G2/M cell cycle arrest and caspase-dependent apoptosis. But in our study 5-azacytidine increased the methylation level for both cell lines. Our study showed that PTPL1 was epigenetically regulated in MM which can be reversed by 5-azacytidine, and highlights 5-azacytidine is a potential therapeutic candidate for MM, but additional studies are needed to determine the effects of genome-wide methylation changes in MM.

Disclosures
No relevant conflicts of interest to declare.
MDR1 polymorphisms Have an Impact on the Prognosis of Chinese Diffuse Large B Cell Lymphoma Patients
Authors: Kourong Miao , Zhengrui Xiao , Ying Ni , Guangli Yin , Li Jianyong 
Published: October 2019

Abstract
MDR1 (multidrug resistance 1) encodes an adenosine triphosphate (ATP) dependent efflux transporter that plays a fundamental role of transport harmful compounds outside cells to maintain optimal health. The present study aimed to investigate whether the MDR1 gene single nucleotide polymorphisms (SNPs) were associated with the prognosis of diffuse large B-cell lymphoma (DLBCL). Three common SNPs, including C1236T, G2677T/A and C3435T were focused on and a total of 150 DLBCL patients from Jiangsu Han population were successively genotyped by polymerase chain reaction-allele specific primers (PCR-ASP) method or DNA direct sequencing. At locus C1236T, patients carrying T allele (genotype CT and TT) had a prolonged overall survival (OS) when compared with patients with CC genotype (2-year OS 82.6% vs. 60.0%, respectively; HR=0.1, 95% CI 0.01-0.6, p =0.016). At locus C3435T, complete remission/ complete remission unconfirmed (CR/CRu) rate in C allele group was significantly higher than T allele group (66.7% vs. 51.9%, respectively; p=0.009). The progression-free survival (PFS) curves of with T (genotype CT and TT) and without T (genotype CC) were significantly different (2-year PFS 46.4% in with T group vs.73.7% in without T group, respectively; HR=1.9, 95% CI 1.0-3.6, p=0.045). At locus G2677T/A, the age for genotypes AG and AT groups were significantly younger than the other genotypes (51.1±12.6 years vs. 57.7±13.4 years, respectively; p=0.033). In the haplotype analysis of loci 1236-3435, compared with T-C group, the C-T group displayed an inferior PFS rate (2-year PFS 23.0% vs. 50.6%, respectively; HR=7.8, 95% CI 1.9-32.6, p=0.005), while C-C and T-T groups showed an intermediate PFS rate. Our findings demonstrate that genotype CT+TT at locus C1236T, allele C and genotype CC at locus C3435T might contribute to a relatively superior prognosis in DLBCL, as well as haplotype of T-C in loci 1236-3435. Besides, genotypes at locus G2677T/A might affect age at diagnosis, which has important prognostic value for DLBCL. These results could provide evidence that the MDR1 SNPs may influence the biologic feature and prognosis of DLBCL and shade new lights in disease association studies.

Disclosures
No relevant conflicts of interest to declare.
Dental Problems in Adult Patients with Sickle Cell Disease
Authors: Master Samip , Walton Jacqueline , Mansour Richard Preston 
Published: October 2019

Abstract
Introduction
Previous studies of children with SCD have shown developmental problems occurring in the enamel and dentin. Mucosal pallor, delayed eruption, dental hypoplasia, and radiographic changes are also common oral finding in patients with SCD. Preventive dental therapy is the ideal approach for management of patients with SCD. We surveyed a sample of our adult patients with SCD to determine the prevalence of patient reported dental problems, including existing "bad tooth", and tooth. We also investigated the prevalence of dental insurance that pays for regular dental exams.
Methods:
We have surveyed 74% of the IRB approved 100 patient sample and gathered the above mentioned information. We collected data on dental insurance, last dental exam, number of adult teeth removed, and patient self-assessment of bad teeth, tooth abscess and number of past episodes of either.
Results
Mean age was 33 years. There were 34 males and 40 females. Seventy percent (52/74) did not have dental insurance. Forty-two percent (31/74) have not had a dental exam within the last 12 months. Twenty-two percent (30/74) of patient had two or more adult teeth removed. 46 % reported that they currently have bad tooth and 31 %( 23/74) have now or have had a tooth abscess. 11 patients reported one episode, 9 patients reported 2 episodes and 4 patients reported three or more episodes of tooth abscess.
Conclusion
In our surveyed population of adult patients with SCD, we find a high number of self-reported advanced dental disease and failure to obtain regular dental care. 70 percent of these patients do not have dental insurance for preventive or advanced dental care. We conclude that adequate preventive dental care is an unmet need for the majority of this special population.

Disclosures
No relevant conflicts of interest to declare.
Clinical Profile of Langerhand Cell Histiocytosis- Single Center Experience
Authors: Al Jassmi Abdulrahman M. 
Published: October 2019

Abstract
Background/Objectives:
Dubai hospital is one of the three main centers which carters for the management of children presenting with benign and malignant blood disorders in the United Arab Emirates. This study is to demonstrate the varied clinical profile of children with Langerhans cell histiocytosis (LCH) who presented to Dubai hospital since 2012.
Methods/Design:
A Prospective analysis of children with LCH treated at our center was done. Complete history, physical examination, relevant laboratory and radiological investigations were studied for all children suspicious to have LCH. Diagnosis was confirmed by obtaining tissue from biopsy of involved areas. Once histopathology confirmed the diagnosis, extent of disease was evaluated and chemotherapy started based on the LCH-IV protocol.
Results:
A total of 10 children presented to Dubai hospital with LCH from 2012 to 2016. The age at diagnosis ranged from 5 months to 5 years. Diagnosis was confirmed by positive CD1a and S100 immuno-markers of involved tissue (100%). These children had varied presentations like respiratory distress, recurrent chest infections, chronic diarrhea, abdominal pain, back pain, inability to walk, lymphadenopathy and buccal mucosa swelling. Median time of diagnosis once the children reached to our center was between 15 days to 1 month. Five children (50%) had multisystem LCH with risk organ involvement. Four children (40 %) had single system involvement and one child had single system multifocal involvement. Osteolytic lesions were present in six children (60%) leading to an early diagnosis.
Good response to Induction I therapy (Prednisolone, Vinblastinefor 6 weeks) of Stratum I, LCH-IV protocol was seen in sevenchildren (70%). Two children were upgraded to Stratum II chemotherapy, LCH-IV protocol at the end of Induction II of stratum I chemotherapy (total 12 weeks of prednisone and Vinblastine) because of either poor response or progressive disease. One child was started on salvage chemotherapy, (Cladiribine, Cytarabine) during Induction therapy because of no response. There has been no mortality in our cohort.
Conclusion:
There should be high index of suspicion for LCH. One needs to be well acquainted to varied presentations of LCH for quickerdiagnosis. Induction therapy with Prednisolone and Vinblastine is a good prognostic marker for children with LCH in our study. It should still be considered the first line therapy for all children with LCH requiring chemotherapy because of lower toxicity profile and good response in the majority. Poor response to Initial Induction of 6 weeks with Vinblastine and Prednisolonewas salvageable with second line therapy in our cohort.

Disclosures
No relevant conflicts of interest to declare.
Venous and Arterial Thromboembolism Related Hospitalizations Among Patients with Gastrointestinal Malignancy in United States - Data from Nationwide Sample
Authors: Puligondla Chaitanya , Kumar Rachit , Parasa Sravanthi 
Published: October 2019

Abstract
Introduction:
Patients with underlying malignancies are at high risk for developing venous thromboembolism (VTE). We sought to characterize the risk and risk factors for developing VTE (both deep vein thrombosis (DVT) and Pulmonary embolism (PE)) and arterial thromboembolism among patients with underlying Gastrointestinal(GI) malignancies.
Methods:
We used the Nationwide Inpatient Sample (NIS) database to perform a cross-sectional study. The study group was defined as all hospitalized patients with GI malignancies above 18 years included in the NIS 2011 database with a primary discharge diagnosis of thromboembolism (Venous or arterial), as per the International Classification of Diseases - Clinical Modification, 9th revision (ICD-9-CM) codes. This VTE and arterial embolism population's demographics and outcomes were compared to the remainder of inpatient GI cancer patients without the diagnosis. All analyses were performed using STATA MP 12.VTE and Arterial embolism, identified by the ICD-9-CM codes, were studied comprehensively for their association with GI cancers and the risk factors were using multivariate logistic regression analysis. Odds ratios were calculated adjusting for relevant patient comorbidities.
Results:
Based on the location of GI cancer, there were a total of 37,872 patients hospitalized with underlying diagnosis of esophageal cancer, 97020 patients with pancreatic cancer, 45669 patients with gastric cancer and 267756 patients with colorectal cancer. The rates of VTE were highest among patients with pancreatic cancer (3.3%) followed by esophageal cancer 2.2%; gastric cancer 1.9%; colorectum (1.4%).
In multivariate analysis, risk of VTE diagnosis was highest among pancreatic cancer patients, adjusted Odds ratio (aOR) - 2.8; 95% CI (2.53 - 3.09) after adjusting for active chemotherapy status, race, age, gender and comorbidities as determined by Deyo - Charlson comorbidity index. aOR for risk of VTE among Esophageal cancer patients was 1.73 , 95% CI (1.49-2.01) ; Colorectal cancer 1.18; 95% CI (1.09-1.27) and gastric cancer 1.52, 95% CI(1.30-1,78). The risk of PE was higher than DVT among patients with VTE. Underlying GI cancer was not associated with increased risk of arterial embolization, acute cerebro vascular events or acute myocardial infarction. The number of death associated with a principal discharge diagnosis code of VTE were not significantly high.
Conclusion:
Patients with pancreatic cancer have the highest risk of hospitalization for VTE among patients with underlying GI malignancies. Underlying GI malignancy is not associated with increased risk of arterial embolization, acute cerebro vascular events or acute myocardial infarction.

Disclosures
No relevant conflicts of interest to declare.
An Active Intervention Has Reduced RBC Transfusion Number: A Single Center Expierience
Authors: Kirgner Ilya , Hareuveni Mara , Sagy Yael , Weiss-Meilik Ahuva , Oster Howard S , Avivi Irit , Barabash Gabriel , Mittelman Moshe 
Published: October 2019

Abstract
Background: "Choosing wisely" strategies have been applied in Tel Aviv Sourasky Medical Center (TASMC). Limiting red blood cell (RBC) transfusions according to the 1999/2005 guidelines, without compromising patient care, has been selected as a major goal. Our preliminary single center experience is described.
Methods : We initiated a program including physician education, inspection and feedback. We retrospectively reviewed the inpatient charts and the hospital RBC transfusion data from 2011-2015.
Results: Approximately 80,000 non-surgical patients are admitted yearly to TASMC, primarily to the Department of Medicine (350 beds). The percentage of transfused patients declined from 4.6% in 2011 to 4.2% in 2013. Most transfused patients were older than 80 years with cardiovascular disease or other co-morbidities. The % of patients requiring RBC transfusions who had pre-transfusion Hb ≥ 9 g/dL was reduced from 23.8% (2011) to 21.9% (2012) and 14.4% (2013). Those with pre-transfusion Hb ≥ 8g/dL declined from 62.9% (2011) to 59.6% (2012) and 51.8% (2013). The total number of RBC units transfused declined from 2982 in 2012 to 2404 in 2015, a 19.4% reduction.
Summary : An active policy including education, awareness, and feedback from blood bank to physician, using a lower Hb threshold, resulted in a dramatic reduction of RBC transfusions.

Disclosures
Kirgner: Tel Aviv Sourasky Medical Center: Consultancy. Avivi:Tel Aviv Sourasky Medical center: Consultancy, Other: consultancy to :BMS Roche.