bluuebunny/crossref_metadata_2025_split huggingface dataset:
Massive Pulmonary and Coronary Artery Thromboembolism in the Setting of Undetected Patent Foramen Ovale
Authors: Thomas Sarah , Braswell Diana , Stephenson Corinne 
Published: October 2019

Abstract
Invasive surgery brings with it a unique set of post-surgical risks that are directly dependent on various factors including the specific surgical approach used, pre-existing comorbidities and features such as gender and age. Pulmonary thromboembolism is one of the most feared complications following surgery, and diagnosis and treatment of this entity is a challenging task for the clinician. Here we describe a case of massive pulmonary thromboembolism and associated coronary artery thromboemboli status post spinal fusion surgery in a 68 year-old man with an undetected patent foramen ovale (PFO). Although the decedent was managed clinically with proper deep venous thrombosis prophylaxis protocols and physical rehabilitation, he went into cardiorespiratory arrest after experiencing acute oxygen desaturation and newly detected right bundle branch block. PFO can be incidentally found in 25% of the adult population. Several clinical syndromes including stroke, migraine headaches and obstructive sleep apnea have been associated in patients with PFO, the last two from which the decedent suffered. The pathology of this unique case of massive pulmonary thromboembolism resulting in coronary artery thromboemboli in the setting of an undetected PFO is discussed. The discovery of PFO in patients prior to surgery, if detected early, may improve post-surgical outcomes.
Figure 1. Massive pulmonary artery thromboembolism in situ, gross examination. Figure 1. Massive pulmonary artery thromboembolism in situ, gross examination. Figure 2. Histology, hematoxylin and eosin. A. Pulmonary thromboembolus at the bifurcation of the pulmonary arteries and pulmonary trunk. B. Hemorrhagic infarct and thromboemboli in varying stages of organization, right lower lobe, lung. C. Cross section of the proximal left anterior descending coronary artery with thromboembolus. D. Cross section of the posterior descending coronary artery with thromboembolus. Figure 2. Histology, hematoxylin and eosin. A. Pulmonary thromboembolus at the bifurcation of the pulmonary arteries and pulmonary trunk. B. Hemorrhagic infarct and thromboemboli in varying stages of organization, right lower lobe, lung. C. Cross section of the proximal left anterior descending coronary artery with thromboembolus. D. Cross section of the posterior descending coronary artery with thromboembolus. Figure 3. Patent foramen ovale, gross examination. Figure 3. Patent foramen ovale, gross examination.

Disclosures
No relevant conflicts of interest to declare.
Inpatient Thrombophilia Workup in Patients with Acute Venous Thromboembolism
Authors: Mehta Vivek Rashmikant , Khan Uzma , Basu Aparna , Jan Asif , Gbadamosi Bolanie , Chowdhury Junad , Parashar Kamesh , Khawaja Muznay , Kufile Oluwatoyin , Bhattarai Rajiv , Thobani Sanya , Korman Michael 
Published: October 2019

Abstract
Background
Any inherited or acquired condition that increases the risk of developing deep venous thrombosis or pulmonary embolism is considered a thrombophilic disorder. Some examples of inherited causes of thromboembolic disorders are Factor V Leiden mutation (FVL), Prothrombin gene mutation, Protein C deficiency (low or dysfunctional), Protein S deficiency (low or dysfunctional), Anti-thrombin (AT) deficiency (low or dysfunctional). Use of these studies in clinical practice has been questioned. We attempted to identify if there are populations of patients that undergo more inpatient screening for inherited causes of venous thromboembolism (VTE).
Methods
Retrospective chart review of patients admitted with PE or DVT in a community teaching hospital between May 2012 and December 2014. Only patients who had DVT confirmed with ultrasound or PE confirmed with CT angiogram or had high probability of PE on V/Q scan were included in the study. Individual charts were reviewed to see if thrombophilia workup was ordered.
Results
A total of 704 patients with acute venous thromboembolism were identified who met our inclusion criteria for the study. Of this 111 patients (15.76%) had one or more thrombophilia screening studies ordered. Risk factors related to venous thromboembolism were evaluated for all of the 704 patients. In our patient population, patients who were smokers (31% vs 20%), had history of sleep apnea (9% vs 3%), a past medical history (PMH) of VTE (37% vs 25%) or who had a family history (FH) of VTE (11% vs 4%) were more likely to have a thrombophilia workup ordered. Table 2 shows the frequency of individual thrombophilia studies ordered among the 111 patients who had testing performed and table 3 shows distribution of positive results.
Table. Test Result Abnormal Test Results ANA 1 Decreased AT III 10 Decreased Protein C 10 Decreased Protein S 7 Increased Homocysteine 6 Factor V Leiden 4 PT Gene Mutation 1 APLA 1
Conclusion
The largest numbers of positive test results were noted for Protein C, Protein S and Antithrombin III and these are known to be affected by acute thrombosis and therefore could be false positives. Our study shows that those patients with PMH or FH of VTE were more likely to have thrombophilia studies. There is no consensus opinion as to whether to perform thrombophilia screenings in acute care settings. Given this and the fact that personal or family history of VTE do not usually modify future treatment decisions and that there may be significant number of false positives we do not recommend routine screening in these patient populations.
Figure 1. Figure 1. Figure 2. Figure 2.

Disclosures
No relevant conflicts of interest to declare.
Early Outcomes Following Endoluminal Deep Venous Reconstruction Using Dedicated Venous Stents
Authors: Saha Prakash , Black Stephen A , Cohen Ander , Karunanithy Narayan , Hunt Beverley J , Breen Karen 
Published: October 2019

Abstract
Objectives
Evaluate early outcomes following endoluminal stenting using first-generation dedicated venous stents.
Methods
Patients undergoing deep venous reconstruction using venous stents between 2012-2015 were identified. Duplex ultrasonography was used to assess sent patency at 1d, 2wks, 3mths, 6mths and yearly following intervention. Venous Disability Scores (VDS) and Villalta Scores (VS) taken before and after intervention (6wks, 6mths, yearly) were calculated.
Results
347stents were inserted in 140pts (median age 39yrs, 80 female) with median follow-up 16mths (1-38mths). Overall 1yr primary, primary-assisted and secondary patency rates were 67%, 80% and 82% respectively. The 1yr re-intervention rate was 30% with 16% occurring within two-weeks.
57pts had stenting of residual stenoses after catheter-directed-thrombolysis for acute iliofemoral DVT. Median post-operative VDS and VS were 0 (P<0.001). 1pt developed an ulcer at 6mths.
81pts had stenting for chronic outflow obstruction after failed medical management. 77pts (95%) had occluded vessels prior to treatment. The median pre-operative VS was 14 (4-23) and 9pts had an ulcer. Following intervention, the median VS was 4 (0-22, P<0.001) and ulcer healing was achieved in 67% (n=6/9).
Conclusions
First-generation dedicated venous stents show promise at providing symptom relief in the short-term. Close surveillance is, however, required to maintain stent patency and factors that influence occlusion warrant further investigation. Long-term evaluation of these stents is required to investigate whether these encouraging early results can be maintained.

Disclosures
Saha: Bayer: Honoraria. Black:Veniti: Consultancy. Cohen:Bayer: Consultancy, Honoraria, Research Funding, Speakers Bureau; Boehringer Ingelheim: Consultancy, Honoraria, Research Funding, Speakers Bureau; Daiichi Sankyo: Consultancy, Honoraria, Research Funding, Speakers Bureau; GSK: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Johnson and Johnson: Consultancy, Honoraria, Research Funding; Mitsubishi Pharma: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Sanofi: Consultancy, Honoraria, Research Funding. Karunanithy:Cook: Honoraria.
Cost-Effectiveness Evaluation for the US of Fondaparinux Compared to Argatroban in the Management of Suspected HIT
Authors: Aljabri Ahmed , Gharaibeh Mahdi , Huckleberry Yvonne , Kutbi Hussam , Raz Yuval , Yun Seongseok , Abraham Ivo , Erstad Brian 
Published: October 2019

Abstract
Introduction. The relative efficacy and safety of fondaparinux and argatroban in the management of suspected heparin-induced thrombocytopenia (HIT) have been documented. We conducted a cost-effectiveness analysis of both agents in terms of cost and adverse events averted.
Methods. We developed a two-armed decision tree model to simulate a cohort of patients with suspected or confirmed HIT managed with argatroban or fondaparinux, using published efficacy data and probabilities of developing HIT-related VTE or major bleeding. The primary base case analysis considered our institutional cost while the secondary analysis used the Average Wholesale Price. Probabilistic sensitivity analysis (PSA) was performed to confirm findings and one-way sensitivity analysis to evaluate additional scenarios.
Results. In the primary base case analysis, fondaparinux dominated argatroban treatment as it was less expensive in managing suspected HIT ($154 vs. $2,064) and more effective in terms of adverse events averted (0.998878 vs. 0.995739). This was confirmed in PSA in terms of both cost ($154 vs. $1,999) and adverse events averted (0.9988711 vs. 0.9957212). Sensitivity analysis showed that the total costs of argatroban would never be less than fondaparinux based on our assumptions. In the secondary analysis, fondaparinux was less expensive ($362 vs. $3722) and more effective in terms of adverse event averted (0.998878 vs. 0.995739). The PSA confirmed these findings both in terms of cost ($343 vs. $3477) adverse events averted. (0.9988711 vs. 0.9957212).
Conclusions. The cost savings from a once-daily SC fondaparinux injection with limited laboratory monitoring are more advantageous than IV argatroban infusion that requires continuous titration.

Disclosures
Off Label Use: Fondaparinux is used as "off-label" for the management of patients with suspected or confirmed HIT.
Influence of Gender and Coagulation Factors on Efficacy and Safety of Rivaroxaban in Adolescents & Young Adults with Venous Thromboembolism
Authors: Krause Manuela , Limperger Verena , Henningsen Anna , Clausnizer Hartmut , Kenet Gili , Kowalski Dorothee , Nowak-Gottl Ulrike 
Published: October 2019

Abstract
Background: Venous thromboembolism [TE] is a multifactorial disease and antithrombotic therapy with Rivaroxaban [RIVA] is increasingly being administered for TE treatment in adults.
Aim: The objective of the present study was to evaluate efficacy and safety of standard RIVA administered as routine medication in an outpatient cohort of patients with TE.
Methods: In 212 consecutively admitted outpatients (14-<55 years; male:female ratio 1.5:1) with TE on standard RIVA medication (2x 15 mg followed by 20 mg) recruited between January 2013 and December 2014, monitoring of RIVA through (24h) and peak levels (Xa-based chromogenic substrate S-2732; Haemochrom Diagnostica) along with anti-factor-Xa-activities [Xa; Xa-based assay, Haemochrom Diagnostica], selected coagulation factors and biomarkers (factors II, V, VIII, Ristocetin-cofactor [RICO] was performed. Efficacy endpoints were defined i) as any TE or thrombus progression during treatment [TP], safety endpoints were defined as ii) significant bleeding [B] requiring any medical intervention, such as dose reduction, withdrawal of RIVA or death related to therapy. Descriptive analysis non-parametric statistics, Chi-square test and logistic regression were performed.
Results: Patients were followed over a median of 12 months. The median daily RIVA dose of 0.25 mg (0.1-0.52) in females was significantly higher compared to males with 0.21 mg (0.09-0.4; p<0.000). RIVA dose was clearly correlated to Xa (p<0.0001; rho=0.945). During the study period two out of 212 patients developed TP [0.94%] and a total of 46 clinical relevant B episodes [21.7%] were diagnosed in 38 females (hypermenorrhagia n=21: necessitating hysterectomy in 2 cases) and 8 males. In bleeders compared to non-bleeders median (min-max) RIVA dose per kgbw was significantly higher (0.26 mg [0.16-0.52] vs. 0.22 mg [0.09-0.52]; p=0.008). Multivariate analysis adjusted for gender, body mass index, RIVA dose, through levels and coagulation factors revealed and increased odds [95% CI] of 3.9 [1.5-9.6] in women to develop B. In addition, a gradual decrease of RICO per IU/ml was significantly associated with clinical relevant B (p=0.04).
Conclusion: Along with good efficacy results our data demonstrate a high bleeding rate of 36.9% in women on standard RIVA. Lower RISTO activities in fertile/premenopausal women contributed significantly to B.

Disclosures
Kenet: Bayer, LFB, NovoNordisk: Membership on an entity's Board of Directors or advisory committees. Nowak-Gottl:Bayer, LFB: Membership on an entity's Board of Directors or advisory committees.
Production of TGF-β Is Decreased in the Bone Marrow of Double Knockout (DKO) SMAD3-/- Fancd2-/- Mice
Authors: Falvello Virginia , Epperly Michael W. , Dixon Tracy , Franicola Darcy , Zhang Xichen , Greenberger Joel S. 
Published: October 2019

Abstract
Homologous deletion recombinant negative DKO mice, missing action of both Fancd2 and SMAD3 proteins were derived to test the hypothesis that abrogation of TGF-β signaling would reverse Fanconi Anemia (FA) stem cell sensitivity to TGF-β. To determine whether DKO mouse tissues demonstrated detectable differences in production of the ligand for TGF-β receptor, tissues from adult six - eight week old DKO mice were compared to those from Fancd2-/- (C57BL/6J background), SMAD3-/- (129/Sv genetic background), or wild type F1 mice (129/Sv X B6) for levels of TGF-β. Tissues examined included bone marrow, intestine, spleen, liver, muscle, and brain. Tissues were homogenized, and analyzed for bone marrow protein by Luminex analysis using a TGF beta 1 multispecies kit for Luminex Platform (Life Technologies).
The results demonstrated decreased but not significant production of TGF-β in the bone marrow of DKO mice (3068 ± 753 pg TGF-β/mg protein) compared to 5211 ± 1662 (p = 0.0761) for wild type F1 mice (129/Sv X B6), and 5192 ± 705 (0.1085) for Fancd2-/- mice. However, TGF-β production in DKO was significantly decreased compared to Smad3-/- (129/Sv) mice (9828 ± 1076, p = 0.0127). The lungs from DKO also had decreased TGF-β production compared to wild type F1 mice (436 ± 125 and 1159 ± 44 pg/mg, respectively, p= 0.0217). Decreased TGF-β production was also seen in the DKO liver compared to F1 wild type liver (13.2 ± 1.7 and 33.5 ± 3.6, respectively, p = 0.0072). Bone marrow stromal cell lines derived from long-term bone marrow cultures of each mouse strain were tested for production of TGF-β. SMAD3-/- bone marrow stromal cells also had an increased production of TGF-β (236 pg/mg) compared to wild type F1, Fancd2-/- and DKO cell lines (117, 136 and 144 pg/ml). Bone marrow CFU-GEMM from each mouse strain was tested for sensitivity to inhibition by increasing concentrations of TGF-β, and both fresh bone marrow from DKO and SMAD3-/- mice demonstrated no TGF-β mediated abrogation of colony formation. In contrast, fresh marrow from wild type and Fancd2-/- mice demonstrated TGF-β concentration dependent inhibition of CFU-GEMM colony formation in vitro. These data indicate that TGF-β production in DKO mice is decreased in bone marrow, lung and liver compared to that in F1 wild type, SMAD3-/- or Fancd2-/- mice, and suggest that the control of TGF-β production by abrogation of TGF-β signaling in the setting of deletion of Fancd2 may be modulated in an organ specific manner.
Supported by research grant NIAID/NIH, U19A168021.

Disclosures
No relevant conflicts of interest to declare.
DNA Cross-Linking Agent Sensitivity of Fanconi Anemia (FA) Cells Is Preserved in Double Knockout (DKO) SMAD3-/- Fancd2-/- Mouse Cell Lines
Authors: Chen Zean , Franicola Darcy , Shields Donna , Epperly Michael W. , Zhang Xichen , Greenberger Joel S. 
Published: October 2019

Abstract
Increased sensitivity to inhibition of hematopoiesis by TGF-β has been hypothesized to be a mechanism of hematopoietic failure in Fanconi Anemia (FA). To determine whether abrogation of TGF-β signaling rescued biologic parameters of hematopoiesis, we derived a novel DKO mouse strain (SMAD3-/- (129/Sv) Fancd2-/- (C57BL/6)) by breeding double heterozygote mice. The DKO mice were small at birth, but achieved normalized growth and development by six - eight weeks. Hematopoiesis in long-term bone marrow cultures derived from DKO mice, ceased generating day 14 CFU-GEMM hematopoietic progenitors by 18 weeks, similar to that observed with Fancd2-/- marrow cultures. In contrast, cultures from SMAD3-/- (129/Sv) demonstrated continuous hematopoiesis for over 30 weeks confirming results with marrow from SMAD3-/- (C57BL/6J) mice (Epperly, et al., Experimental Hematology, 33:353-362, 2005), and significantly longer than that in control 129/Sv X C57BL/6J F1 mouse long-term marrow cultures. Bone marrow stromal cell lines derived from long-term marrow cultures were tested for the diagnostic criterion of FA, increased sensitivity to DNA cross-linking agent, Mitomycin-C. Cells were incubated in Mitomycin-C at concentrations ranging from 0-20 ng/ml for four days and then plated in 4 well tissue culture plates, incubated for 7 days at 37o C in a CO2 incubator, stained with crystal violet, and colonies of greater than 50 cells counted. Similar to Fancd2-/- marrow stromal cells, DKO marrow stromal cells showed increased sensitivity to Mito-C, while marrow stromal cell lines from wild type or SMAD3-/- mouse marrow cultures were relatively resistant (p = 0.0086 comparing Fancd2-/- to control 129/Sv X C57BL/6J F1 cells, p = 0.0156 comparing DKO with control 129/Sv X C57BL/6J F1 cells, and p = 0.4676 comparing Smad3-/- cells to control 129/Sv X C57BL/6J F1 cells). Fresh bone marrow from DKO mice, similar to that from SMAD3-/- mice, demonstrated resistance to inhibition of hematopoietic cell colonies in vitro by increasing concentrations of TGF-β. Therefore, abrogation of TGF-β signaling in DKO cells did not alter the sensitivity of Fancd2-/- marrow stromal cells to Mitomycin-C.
Supported by research grant NIAID/NIH, U19A168021.

Disclosures
No relevant conflicts of interest to declare.
Carbonic Anhydrase IX Promotes the Tumorigenicity of Adult T-Cell Leukemia/Lymphoma-Derived Cells in NOG Mice
Authors: Nasu Kentaro , Yamaguchi Kazunori , Takanashi Yuka , Sugamura Kazuo , Harigae Hideo 
Published: October 2019

Abstract
Carbonic anhydrase IX (CA9) is a membrane-associated carbonic anhydrase that regulates pH through its extra-cellular catalytic domain and thereby fosters tumor cell survival, growth, and invasion. The expression of CA9 is induced by hypoxia via HIF-1α. CA9 overexpression is known to be closely associated with aggressive behaviors and poor prognoses in various types of human solid tumors. In particular, CA9 is a critical mediator of the expansion of breast cancer stem cells in hypoxic niches by sustaining the mesenchymal and 'stemness' phenotypes of these cells. However, as for hematological malignancies, there are few reports suggesting a relation between its tumorigenecity and CA9. Here we demonstrated that CA9 plays a crucial role in promoting the tumorigenicity of the ATL-derived cells.
Recently we established a highly tumorigenic subline, ST1-N6, from an ATL-derived cell line, ST1, by serial transplantation in immunodeficient NOG mice. ST1-N6 cells developed subcutaneous tumors under a shorter duration and smaller cell number than parental ST1 cells. DNA microarray gene expression analysis revealed an upregulated expression of CA9 in ST1-N6 cells as compared with ST1 cells. After serial sorting of ST1 cells by CA9 expression, we obtained ST1-CA9high and ST1-CA9low sublines. Like ST1-N6 cells, ST1-CA9high cells showed stronger tumorigenicity than ST1-CA9low or parental ST1 cells. Knockdown of CA9 expression with shRNAs suppressed the tumorigenicity of ST1-CA9high cells, whereas ST1 cells introduced with CA9 significantly showed enhanced tumorigenicity. Another ATL-derived cell line, TL-Om1 also showed increased tumorigenicity in NOG mice when introduced with CA9. These observations indicate that CA9 contributes to promoting the tumorigenic potential of ATL-derived cells in xenotransplantation.
To investigate CA9 expression on fresh ATL cells, we prepared peripheral blood from six acute ATL patients, and tested for quantitative expression of CA9 in sera of six ATL patients and three healthy donors by ELISA. The amounts of serum CA9 were 31.1~95.4 pg/ml in the healthy donors, while they were 175.6~1, 971.6 pg/ml in the ATL patients. We next prepared ATL tissues from nine ATL patients, and two of them contained a few CA9high cells, which were cells expressing CD25, suggesting that a part of ATL lymphoma cells expressed CA9. These results suggested that the amount of serum CA9 tends to be higher in ATL patients than healthy donors.
Based on these findings, we suppose that CA9 plays an important role in the malignant development of ATL.

Disclosures
No relevant conflicts of interest to declare.
Azatidine Treatment in Very Elderly Patients Diagnosed with Acute Myelogenous Leukemia (AML) or High Risk Myelodysplastic Syndrome (MDS)
Authors: Gutierrez Javier , Morales Elena , Gonzalez Matilde , Herrada Juan 
Published: October 2019

Abstract
Background: The use of azatidine (AZT) is the agent of choice for first line treatment of elderly (age >74 years) patients (pts) with high risk MDS or AML (2015 National Comprehensive Cancer Network Guidelines). The Hematology consultant is frequently involved in the care of very elderly (age >79 years) individuals. Our aim is to report our experience with 3 patient aged 80 or above that received treatment with AZT.
Methods: Retrospective review
Results: We reviewed the medical records of patients treated for high risk MDS or AML at our institution between July 2009 and March 2012. A total of 3 pts aged 80 or above were identified. All three pts were males, and all received AZT 100 mg/m2/day x 7 days subcutaneously in every cycle of 28 days. Patient 1 (aged 81) had 12 % of blasts in the bone marrow (BM), was diagnosed with Refractory Anemia with Excess Blasts-2 (RAEB-2) applying the 2008 World Health Organization Classification (WHO) of MDS. Patient 2 (aged 90) had AML with multilineage dysplasia and 38% blasts in BM. Patient 3 (aged 80) had AML with multilineage dysplasia and 30% blasts in BM. Pts characteristics and results are summarized in Table 1.
Conclusions: In pts diagnosed with high risk MDS or AML, advanced chronological age (> 79 years) alone should not preclude the use of effective and well tolerated therapy. Identification of pts in this geriatric subgroup who may benefit from AZT merits additional research.
Table 1. Diagnosis Age(years) Baseline laboratory Peripheral blood %Blast in Bone Marrow Number of AZT cycles received Response Survival(months) Patient 1 RAEB-2 81 Hb 14 g/dl Platelets 56x10e9/L Leucocytes 1.90x10e9/L (Neutrophils 0.81x10e9/L) 12 11 CR* in BM after 6 cycles 17 Patient 2 AML 90 Hb 8.06 g/dl Platelets 20x10e9/L Leucocytes 1.30x10e9/L(Neutrophils 0.64x10e9/L) 38 15 CR in BM after 7 cycles 22 Patient 3 AML 80 Hb 7.50 g/dl Platelets 30x10e9/L Leucocytes 6.00x10e9/L(Neutrophils 1.44x10e9/L) 30 19 CR in BM after 6 cycles 23 *CR: complete remission (<5% blast in aspirate with spicules)

Disclosures
No relevant conflicts of interest to declare.