bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cerebral Venous Thrombosis Case Series at a Tertiary Care Hospital: Exploring Treatment Safety and Efficacy of Direct Oral Anticoagulants
Authors: Alsheef Mohammed Abdullah , Alomar Mukhtar , Zaidi Abdul Rehman Z. , Kullab Ghaydaa Juma , AlHazzaa Mohammed , Bafaraj Asaad , Badahman Abdullah 
Published: November 2019

Background:
Cerebral venous thrombosis (CVT) is an uncommon cause of stroke that mainly affects young adults and children. Initial treatment with heparin followed by wafarin is the mainstay of treatment. Only insufficient experience is available for direct oral anticoagulants (DOACs).
Aims:
The study aims to demonstrate the efficacy and safety of DOACs such as (Rivaroxaban and Dabigatran) in patients with objectively confirmed CVT.
Methods:
Data of 46 cases of CVT collected using a standardized case report form. Inclusion criteria were patients diagnosed with CVT, confirmed by CT or MRI imaging.
Results:
The total number of patients was 46 (9 males and 37 females). The mean age of the patients was 35.2± 5 years. The most common clinical manifestations among our patients were headache followed by seizure. 52% of cases were unprovoked, while 48% were provoked by pregnancy and oral contraceptive pills. Superior sagittal sinus (55%) and transverse sinus (44.9%) were the most common sites. Involvement of more than three venous sinuses was 34.8%. Thrombophilic abnormality was detected in 21.7% of patients. Initiation of anticoagulation (AC) was mostly low molecular weight heparin (LMWH) (80%), followed by unfractionated heparin (UFH) (17.7%) and fondaparinex (2%). Maintenance AC with Rivaroxaban after heparin (LMWH/UFH) was in 63% of our patients, the rest were switched from Warfarin to Rivaroxaban (34.8%), and one was treated by Dabigatran (2%). CVT recurrence was observed in one patient. Major bleeding (according to ISTH criteria) was not reported in our case series.
Conclusions:
DOACs demonstrated good safety and efficacy profile and can potentially replace warfarin in CVT patients.

Disclosures
No relevant conflicts of interest to declare.
Combined Thalidomide and Recombinant Human Interferon-α-1b and Interleukin-2 for Acute Myeloid Leukemia of Various Disease Status: A Multi-Center Prospective Study
Authors: Mi Ruihua , Chen Lin , Wei Xudong , WANG Xiaojiao , Song Yongping 
Published: November 2019

AML (acute myeloid leukemia) patients with relapsed refractory diseases or in poor physical conditions have very limited choices of appropriate treatment regimens, and most alternative options are costly. Here, we reported that an affordable regimen with combined recombinant human interferon-α-1b (IFN-α1b), thalidomide, and recombinant interleukin-2 (IL-2) (the ITI regimen) achieved varying degrees of therapeutic effects in AML patients of various disease status and vulnerabilities. ITI regimen was administrated as follow: a subcutaneous injection of IFN-α1b 60 μg qod, IL-2 1 million unit qod, and 200mg thalidomide tablet orally taken every night before sleep.
Group A Sixty-eight patients who were with relapsed or refractory AML were enrolled, sixty finished at least one course, a response rate (CR+CRi) of 16.7% (10/60) was observed, and, and 7 (11.7%) patients achieved partial remission.(Table 1)
Group B Eighteen patients with morphologically complete remission and consistently positive MRD were enrolled, each patients underwent ITI regimen for 2 months at least. According to the criteria of the WHO risk stratification, 7 were with a favorable risk, 8 were with a intermediate risk, and 3 were with a high risk. Patients with FLT3-ITD mutations were treated with oral sorafenib during early induction and consolidation treatment. These 18 patients received conventional dosage of ITI regimen. Seven patients had a negative MRD after 1 or 2 months. The MRD levels of 3 patients significantly decreased after one or two months. Five patients suffered a Morphological relapse. Another 3 patients failed to the conventional dosage of ITI regimen with an increased MRD rate, but it decreased after we made a modification of IFN-α1b and IL-2 administration daily. The response rate of the 18 patients in Group B was 72.2%, where MRD < 0.01% was defined as the negative threshold. (Table 2)
Group C Eighty-eight patients with MRD-negative AML after consolidation were enrolled. Among the 88 patients with initial CR, 11 (12.5%) relapsed during the maintenance period (Figure 1). All these 11 patients relapsed within 2 years, with a median recurrence period of 20 months, of which 2, 4, and 5 patients, respectively, were with favorable, intermediate, and high risk. The indicated that this regimen effectively reduced the relapse rate.(Table 3)

Disclosures
No relevant conflicts of interest to declare.
An Institutional Survey of Thrombophilia Evaluation in the Setting of Venous Thromboembolism (VTE)
Authors: Garrahy Ian , Pawar Tushar , Donato Anthony , Stevenson Amber , Forman Daniel 
Published: November 2019

Introduction:
There has been increasing recognition of various laboratory markers of thrombophilia that are associated with increased risk of thrombosis either through hereditary (i.e. Factor V Leiden, prothrombin G20210A mutation, and protein C, S, and antithrombin deficiencies) and/or acquired means (i.e. antiphospholipid antibodies) over the past decades. Availability of thrombophilia biomarkers has the potential to lead to inappropriate testing and treatment.
Methods:
An online anonymous questionnaire was sent to all providers in the Tower Health System asking them about their practice, specialty, degree, years in practice, and basic questions regarding their comfort and frequency of prescribing anticoagulants. The questionnaire also asked the providers how they would manage ten various clinical scenarios related to anticoagulation management. One question specifically asked whether a hereditary thrombophilia panel should be ordered for a 65-year-old with provoked VTE and no concerning family history of VTE. Analysis of variance was used to compare the scoring means between groups while linear regression and Pearson's correlation coefficient measured the relationship between years of practice and test scores.
Results:
Out of 404 responders, 170 (42.1%) inappropriately ordered a hereditary thrombophilia panel on the question (see Figure 1) that addressed this topic. 53.6% and 35% of the outpatient and inpatient physicians answered the question incorrectly which was statistically significant (p value 0.026).
Conclusion:
This project suggests a professional practice gap in which overtesting might be ordered. In particular, this study found a statistically significant difference between inpatient and outpatient providers in the ordering of a thrombophilia panel. Whether just-in-time reminders or other educational interventions could close this gap is a matter for further study.
Figure 1

Disclosures
No relevant conflicts of interest to declare.
Development of a Low-Cost Electrical Impedance-Based Microflow Cytometer
Authors: Dieujuste Darryl , Liu Jia , Du E. , Alvarez Ofelia A. 
Published: November 2019

Sickle Cell Disease (SCD) is a genetic condition caused by a mutated hemoglobin molecule (HbS) found in red blood cells (RBCs). HbS polymerizes in low oxygen environments and contribute to painful vaso-occlusion in patients. Laboratory diagnosis of SCD is typically made by detection of the presence of sickle cells by peripheral blood smear, and presence of HbS by electrophoresis and high-performance liquid chromatography. Recently, flow cytometry technique in companion with sickling assays has demonstrated the capability in quantitative measurements of sickle cells at single-cell level, using software algorithm for cell-imaging analysis (Van Beers et. al. American Journal of Hematology 2014), and electrical impedance (Liu et. al. Sensors and Actuators B: Chemical 2018). Here, we show a portable, cost-efficient electrical impedance-based sensor and its capability to be used in conjunction with microfluidics-based sickling assay for microflow cytometry of sickle cells.
The impedance microflow cytometer is based on a commercially available integrated circuit (IC), the AD5933. Using a microcontroller and additional circuitry on a custom designed printed circuit board, we are able to produce sinusoidal signals of up to 100kHz in frequency and sample up to 200 data points per second, at a cost under $60 in materials to create. The impedance measurement range is optimized to work in companion with microfluidic chips in general. In order to measure sickle cells, the impedance microflow cytometer is used in companion with our unique Polydimethylsiloxane (PDMS) microfluidic cell sickling assay (Du et. al. PNAS 2014). Cells are suspended in phosphate buffered saline (PBS) medium and move in the microchannel using a pressure driven flow. Impedance measurement is achieved using two Ti/Au electrodes embedded in the microchannel as cells flow past the electrodes. Data is captured and made available for post processing using a customized MATLAB script. RBCs from healthy donors and SCD patients were used to demonstrate the capability of the developed system. The results showed that our system can separate between normal RBCs and sickle cells, as well as between sickled and unsickled cells. The performance in detection of sickle cells is comparable to a commercial impedance analyzer. This proof-of-concept design aims to minimize the physical space needed for cytometry as well as bring affordable and reliable cytometry results within its given limitations.
Figure

Disclosures
Alvarez: Forma Therapeutics: Consultancy; Novartis: Consultancy.
Clinical Efficacy of L-Annamycin, a Liposomal Formulated Non-Cross-Resistant and Non-Cardiotoxic Anthracycline in Relapsed/Refractory AML Patients
Authors: Gil Lidia , Shepard Robert C. , Silberman Sandra L , Zak Ewa Maria , Priebe Waldemar 
Published: November 2019

Introduction: An anthracycline combined with cytarabine remains the backbone for induction therapy in the treatment of AML. De novo and acquired multidrug resistance (MDR) limits efficacy of clinically used anthracyclines. L-Annamycin, a novel anthracycline formulated in multilamellar liposomes, has been shown to overcome MDR in preclinical in vitro and in vivo doxorubicin resistant models as well as in clinical studies. Furthermore, preclinical toxicology studies comparing L-Annamycin to doxorubicin determined that the drug displayed dramatically reduced cardiotoxicity. These promising properties justified initiation of Phase I/II clinical trials in both the US and Europe using L-Annamycin for the treatment of R/R AML.
Aims: The aim of the Phase I component is to determine the recommended Phase 2 dose (RP2D) of L-Annamycin for the treatment of R/R AML. The expansion Phase IIa studies are designed to assess L-Annamycin efficacy leading to a Phase II registration study for accelerated approval.
Methods: The Phase I component is a standard 3+3 design to determine the RP2D. An additional 21 patients expansion phase will be enrolled at the RP2D to confirm efficacy. A DMC will monitor all data and decide if the study should continue and if any changes to the protocol are needed. Cardiotoxicity is being closely studied with stress 2-D echocardiography and biomarkers such as troponin.
Results: This study is ongoing in both Europe and the USA. Even at a relatively low starting dose, two patients had sufficient response from a single 3-day course of L-Annamycin to qualify for a potentially curative bone marrow transplant. In total, 11 patients have completed at least one course of L-Annamycin with no signs of cardiotoxicity. Adverse events included one instance of Grade 2 mucositis, which resolved quickly.
Summary/Conclusion: Despite progress in the treatment of AML most patients will relapse and die from refractory disease. Properties of L-Annamycin, including the ability to overcome MDR, a critical mechanism of resistance, and the lack of cardiac toxicity, are highly promising and fully justify a Phase II clinical study designed to demonstrate L-Annamycin efficacy in all patients with R/R AML agnostic of mutational status.

Disclosures
Shepard: Moleculin Biotech Inc: Employment, Equity Ownership. Silberman:Trovagene: Consultancy; Moleculin Biotech: Employment. Priebe:MOLECULIN BIOTECH INC: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties.
A 19-Year Retrospective Analysis of Venous Thromboembolism Trends in Chemotherapy-Induced Anemia: Red Blood Cell Transfusion Versus Erythrocyte Stimulating Agent Administration
Authors: Bryer Emily , Kallan Michael , Chiu Ting-Shaun , Scheuba Katerina , Henry David H. 
Published: November 2019

Introduction: Anemia is a common and unfortunate consequence of chemotherapy; patients receiving a variety of chemotherapy regimens often develop chemotherapy-induced anemia (CIA), which contributes to poor outcomes including increased mortality. Prompt and effective treatment of CIA is essential to prevent fewer chemotherapy dose delays and reductions. Optimal therapy of CIA is controversial and involves the solitary and combined use of intravenous iron, red blood cell (RBC) transfusions, and erythropoietin stimulating agents (ESAs). Despite the baseline coagulopathies present in patients with malignancy, administration of both RBC transfusions and ESAs is independently associated with venous thromboembolism (VTE). It remains unknown whether the risk of VTE in patients with CIA is greater among patients who receive RBC transfusions or ESAs.
Methods: A retrospective study analyzed 13,334 patients in the University of Pennsylvania Health System with malignancies of various type, stage, and histopathology who developed CIA between 1998-2017. Using multivariate Cox regression, we determined adjusted hazard ratios (and corresponding 95% confidence intervals) of VTE development after adjusting for RBC and ESA intervention (all during the 90 days following CIA diagnosis).
Results: (Table 1) Among the 13,334 patients with CIA, 10,948 patients did not receive any therapy during the 90-day period for their anemia (neither RBC nor ESA), 1,892 received RBC transfusion, 368 received ESA, and 126 patients received both. Among all patients, 2,620 (19.7%) developed a VTE within the 90-day period. VTE risk following RBC transfusion (HR=2.18, 95% CI 1.98-2.39, p<0.001) was approximately four-fold the VTE risk following ESA administration (HR=0.55, 95% CI 0.42-0.72, p<0.001).
Conclusion: While both RBC transfusion and ESA administration are associated with VTE, our data suggests a greater risk of VTE development with RBC transfusion as compared with ESA administration.

Disclosures
No relevant conflicts of interest to declare.
A Comprehensive Analysis of Rhoa Mutation Positive and Negative Angioimmunoblastic T-Cell Lymphomas By Targeted Deep Sequencing, Expression Profiling, and Single Cell Digital Image Analysis
Authors: Butzmann Alexandra , Sridhar Kaushik , Jangam Diwash , Kumar Jyoti , Sahoo Malaya K , Shahmarvand Nahid , Warnke Roger A , Rangasamy Elumalai , Pinsky Benjamin A , Ohgami Robert S. 
Published: November 2019

Angioimmunoblastic T-cell lymphoma is a uniquely aggressive mature T-cell neoplasm. In recent years, recurrent genetic mutations in RHOA, TET2, DNMT3A and IDH2 have been identified which characterize this disease. However, a deep molecular study assessing both DNA mutations and RNA expression profile, combined with digital image analysis is lacking.
We designed a study to assess the significance of molecular and morphologic features by high resolution digital image analysis in cases of AITL. Eighteen separate tissues from ten patients with AITL were identified and analyzed in this study.
Our results confirm recurrent mutations in RHOA, TET2, DNMT3A, and IDH2, and demonstrate increased DNA mutations in coding, promoter and CTCF binding sites in RHOA mutated AITLs versus RHOA non-mutated cases as well as increased overall survival in RHOA mutated patients. In addition, single cell computational digital image analysis morphologically characterized RHOA mutated AITL cells as distinct from cells from RHOA mutation negative patients. Computational analysis of single cell morphological parameters revealed RHOA mutated cells have reduced eccentricity (more circular) compared to RHOA non-mutated AITL cells.
Overall, this study expands our understanding of AITL and demonstrates that there are specific cell biologic and morphologic manifestations of RHOA mutations in cases of AITL.
KeyPoints:
1) RHOA mutated AITL show distinctly increased and more deleterious mutations than RHOA unmutated cases
2) RHOA mutated T-cells have distinct morphologic features from RHOA unmutated T-cells

Disclosures
Ohgami: Agilent technologies: Other: received support/funding.
Complementary Transplantation Improved Results of Both Peripheral Blood Stem Cells and Unrelated Cord Blood Transplants in Thalassemia: A Multi-Center Study from China
Authors: Li Chunfu , Liu Sixi , He Yuelin , Wang Xiaodong , Liao Jianyun , Li Shan , Zheng Xiaolin , Wu Xuedong , Li Changgang , Feng Xiaoqin , Wen Feiqiu , Liu Huaying , Zhou Xiaohui , Peng Zhiyong , He Lan , Bu Chaoke , Wing Leung 
Published: November 2019

Background: Unrelated cord blood (UCB) transplant (UCBT) is not recommended in patients with thalassemia major (TM) so far. Post-transplant (PT) Cyclophosphamide (PTCy) with long pre-transplant immunosuppression therapy have improved haploidentical peripheral blood (PB) stem cell transplant (haplo-SCT) survival in TM patients but with 2/31 primary rejection. So, we designed a novel dual transplantation of UCBT following haplo-SCTwith PTCy(NF-14-TM-CT protocol).
Aim:To improve results of haplo-SCT and UCBT in patients with TM.
Patients and method: NF-14-TM -CT protocol was termed as double-insurance dual transplantsincluding a haplo-SCT and an UCBT, in which conditioning regimen consisted of ATG (at -10 to -8 day), Cy (-7), Fludarabine (-6 to -2), Busulfan (-6 to -4) Thiotepa (-3), haplo-PB (0), PTCy (+3, +4) and UCB (+6). PTCy serve as GVHD prophylaxes after haplo-SCT and as conditioning before UCBT. In total 131 patients with TM from three pediatric center in China received NF-14-TM-CT protocolfrom June, 2014 to April, 2019, with a median follow-up of 13 (2-59) months and a median age of 8 (3.5-17) years.
Results Final haplo-PB engrafted(group1)in 76 patients with mean PBSC-MNCof 22.49 (±5.36) x108/kgand UCB nuclear cells (NC) of 5.95 (±3.39) x107/kg and final UCB engrafted (group 2) in 55 patients with mean PBSC-MNC of 21.78 (±5.68) x108/kg and mean UCB-NC of. 5.43 (±2.32) x107/kg. The 4-year overall survival (OS), thalassemia-free survival (TFS), graft rejection (GR), and transplant related mortality (TRM) were 97.6%, 96.0%, 1.5%, and 2.4%, respectively (Fig. A), in total. The corresponding rates for group 1 were 98.3%, 96.9%, 1.7% and 1.8% and for group 2 were 95.5%, 93.8%, 4.5% and 1.4%, respectively. No statistic significant difference was found in OS, TFS, GR and TRM, respectively, when comparing group 1 with group 2 (Fig. B. C, D, E).The incidence of grade II-IV acute GVHD, III-IV acute GVHD, mild chronic GVHD, moderate/severe chronic GVHD, VOD, PT cystitisand PT hemolysis of the entire cohort was 16.8%, 6.87%, 9.92%, 1.52%, 4.60%, 31.3% and 14.5, respectively.
Summary:Current study proved that the novel CT improved the results of haplo-SCT and UCBT in patients with TM.

Disclosures
Wing: Miltenyi Biotec: Employment.
1q21 Gain May Challenge the Role of t(4;14) As an Adverse Prognostic Marker of Multiple Myeloma
Authors: Du Chenxing , Gang An , Xu Yan , Mao Xuehan , Yan Yuting , Liu Jiahui , Fan Huishou , Sui Weiwei , Deng Shuhui , Zengjun Li , Li Chengwen , Yi Shuhua , Hao Mu , Zou Dehui , Zhan Fenghuang , Tai Yu-Tzu , Anderson Kenneth C. , Qiu Lugui 
Published: November 2019

In the era of bortezomib, traditional prognostic markers in multiple myeloma (MM) may be suspect. The outcome of patients with t(4;14) is largely improved by bortezomib based treatment. Whether the outcome of patients with t(4;14) is still homogeneously inferior remains unknown. In this long follow-up non-randomized clinical trial, we observed no significant difference in the PFS and OS of t(4;14) positive or negative patients in the bortezomib arm. Interestingly, t(4;14) was highly correlated with the presence of 1q21 gain. In t(4;14)-positive patients, the median OS of patients with and without 1q21 gain was 38.8 and 57.2 months (P=0.034), respectively. In t(4;14)-negative patients, the median OS of the two subgroups was 43.0 and 89.4 months (P<0.001), respectively. In contrast, no statistical difference in PFS or OS was observed in 1q21 gain patients with versus without t(4;14) aberration. We then discovered that 1q21 gain facilitated the acquisition of new chromosome abnormalities and contributed to the genomic instability, evidenced by the strong correlation between 1q21 gain and complex karyotypes or the acquisition of more than two cytogenetic aberrations. Moreover, 1q21 gain and/or del(17p) were powerful enough to discriminate the high-risk patients. The combination of 1q21 gain with International Staging System (ISS) was useful to divide MM patients with respect to their survival. Finally, although bortezomib might benefit patients with 1q21 gain, it could not completely overcome its adverse effects, suggesting the necessity of more effective therapies for these patients.
Figure

Disclosures
Zhan: BIPHARM LLC: Consultancy, Other: % Allocation of Profit. Anderson:Gilead Sciences: Other: Advisory Board; Janssen: Other: Advisory Board; OncoPep: Other: Scientific founder ; Sanofi-Aventis: Other: Advisory Board; C4 Therapeutics: Other: Scientific founder .
Epidemiology, Diagnosis and Management of Neonatal Thrombosis
Authors: Shaik Mohammed , Patel Dhiman , Mihir Bhatt , Chan Anthony K.C. , Paes Bosco 
Published: November 2019

Introduction:
Current research on neonatal thrombosis is limited. It relies heavily on individual case reports and much of the data is extrapolated from the adult scientific literature. The aim of this descriptive study is to review the epidemiology, diagnosis and management of neonatal thrombosis at a single tertiary care institution.
Methods:
This is a retrospective study of apatients admitted to McMaster Children's Hospital, neonatal intensive care unite from 2005 to 2018. Data on patient demographics, diagnostic imaging, thrombophilia testing, co-morbidities, treatment, outcomes were collected from health records.
Results:
A total of 242 neonatal patients were included. The distribution of 251 thrombotic episodes was: 144 portal vein, 15 cerebral sino-venous, 12 cardiac, 2 pulmonary embolisms, 5 renal vein, 40 extremity and central venous and 13 arterial. Additionally, 20 cases categorized as miscellaneous, consisted of clots in sites such as the basilic vein or umbilical artery, among other locations. Male and female percentages were 55% and 45%, respectively. Preterm to term infant ratio was 1.5:1. The average age at diagnosis was 13.2 days. 70% of thrombotic episodes were line-related, while infection and surgery were associated with 19% and 12% of episodes, respectively. 52% of the patients were blood group O. 30% of the patients received initial anticoagulation treatment, while the rest were managed conservatively. There was a trend towards higher rate of complete clot resolution in patients who received anticoagulation (48%) compared to those who did not (40%).
Conclusion:
This is one of the largest, single institution, epidemiologic studies of neonatal thrombosis. In our group of patients, portal vein thrombosis was most prevalent compared to other sites of thrombosis and catheterization was the commonest risk factor. There was a trend towards improved resolution with anticoagulation. Further prospective studies are required to confirm these findings.

Disclosures
No relevant conflicts of interest to declare.