bluuebunny/crossref_metadata_2025_split huggingface dataset:
Venous Thromboembolism Prophylaxis in Acute Medically Ill Patients: A Retrospective Cohort Study
Authors: Gafter-Gvili Anat , Drozdinsky Genady , Zusman Oren , Kushnir Shiri , Leibovici Leonard 
Published: November 2019

Background and Aims
Venous thromboembolism (VTE) is considered as a preventable cause of death for hospitalized patients. Current guidelines recommend pharmacologic prophylaxis for medical patients considered high risk for VTE, despite failure of studies to show reduction in mortality. We aimed to assess the benefit and safety of VTE prophylaxis in acutely ill medical patients hospitalized in internal medicine wards.
Methods
Retrospective cohort study of all patients admitted to the internal medicine and acute geriatric departments, with an admission lasting more than 48 hours, during 2012-2018. Patients who received pharmacologic prophylaxis were compared to those who did not. The primary outcome was 30-day mortality. Secondary outcomes were the 90 day incidence of pulmonary embolism (PE), symptomatic deep vein thrombosis (DVT), and major bleeding. Propensity-weighted logistic multivariable analysis was performed.
Results
A total of 18890 patient-unique episodes were included in the analysis. Of them 3206 (17%) received prophylaxis. A total of 1309 (6.9%) died. 540/1309 (41.3%) of those who received VTE prophylaxis died and 769/1309 (58.7%) of those who did not receive prophylaxis died. VTE Prophylaxis was not associated with a reduction in mortality, multivariate-adjusted OR 0.99 (95% CI 0.84-1.14). One hundred and forty two patients (0.7%) developed VTE. The frequency of VTE among patients who received VTE prophylaxis was 31% (44/142) compared with 69% (98/142) in patients who did not receive prophylaxis. The frequency of VTE in patients who had a Padua score ≥4 and received VTE prophylaxis, was 1.9% (30/1573) compared with 1.6% (44/2797) in those with a Padua score ≥4 who did not receive prophylaxis. 74/142 (52.1%) of patients with VTE had a Padua score ≥4, 44/1309 (1.4%) of those who received VTE prophylaxis and 98/15864 (0.6%) of those who did not. VTE Prophylaxis was not associated with reduction in VTE in the whole cohort, multivariable-adjusted OR 1.09 (95% CI 0.52-2.29). VTE prophylaxis was associated with an increase in major bleeding (multivariable-adjusted OR 1.24, 95% CI 1.04-1.48)
Conclusion
The current practice of routinely administering VTE prophylaxis to medically ill patients considered at high risk for VTE, resulted in a high risk for bleeding a without clear clinical benefit, and should be reassessed.

Disclosures
No relevant conflicts of interest to declare.
An Evaluation of Major Comorbidities and Treatment Patterns of Newly Diagnosed Acute Myeloid Leukemia Patients: A Retrospective Analysis of Electronic Medical Records from US
Authors: Tu Nora , Islam Zahidul , Fliss Albert E , Salas Maribel 
Published: November 2019

Background: There is limited data available on patient characteristics and treatment patterns for patients diagnosed with acute myeloid leukemia (AML) particularly from electronic medical record (EMR) database in US.
Objective: Our goal was to examine comorbidities and treatment patterns among newly diagnosed AML patients in US.
Methods: We conducted a retrospective cohort study using fully adjudicated data provided by IQVIA from the EMR database including patient data from January 2012-July 2018 across the US. ICD-9/10-CM codes were used to identify newly diagnosed AML (excluding APL) patients. Initial AML diagnosis codes which indicated relapse or remission were excluded from the newly diagnosed population. Demographics and comorbidities at baseline as well as AML
treatments received after initial diagnosis were examined.
Results: A total of 3387 patients who had an AML diagnosis were retrieved. 2879 were newly diagnosed with mean age of 65.9 and median age at 70 (ranged from 17 to 85) and 54.8 % were male. Prior to the first AML diagnosis record (i.e. index date), 18.7% had other prior malignant solid tumors and 13.5% had antecedent Myelodysplastic Syndrome (MDS), while 71.2% were AML de novo.
Cardiovascular diseases (18.7%) and diabetes (4.6%) were the most common comorbidities occurred before or after initial AML diagnosis. After index date, 38.2% of the newly diagnosed patients received FDA approved drugs for AML and 18% received supportive care only. 2.3 % received hematopoietic cell transplant. Among the FDA approved drugs for AML, hypomethylating agents (37.4% Decitabine and 35.3% Azacitidine), cytarabine based treatments (21.8%) were the most commonly used first line treatment. 25% switched to other AML drugs later in the treatment. Filgrastim (49.6%) and Azoles (37.4%) were the most frequently used supportive care.
Conclusions: Among newly diagnosed AML patients, most had AML de novo. Cardiovascular disease and diabetes are the most common comorbidities and monotherapy was predominantly used as first line therapy. Low percentage of hematopoietic cell transplant observed in this population needs further investigation.

Disclosures
Tu: Daiichi Sankyo, Inc.: Employment. Islam:Daiichi Sankyo, Inc.: Employment. Fliss:Daiichi Sankyo, Inc.: Employment. Salas:Daiichi Sankyo, Inc.: Employment.
The Net Clinical Benefit of Thrombolysis in the Management of Submassive Pulmonary Embolism: Systematic Review and Meta-Analysis
Authors: Alcedo Pedro , Rojas Hernandez Cristhiam Mauricio , Garcia Perdomo Herney Andres 
Published: November 2019

Background: Benefit of thrombolytic therapy in patients with massive pulmonary embolism (PE) has been proven. Evidence supporting benefit in clinical outcomes of this approach in the subgroup of patients with submassive PE is lacking.
Objective: The primary objective was to determine the impact of thrombolysis on overall survival in patients with submassive PE. Secondary outcomes included bleeding, thrombotic complications, improvement on parameters of right ventricular strain and all cause-mortality.
Methods: A search strategy was conducted in MEDLINE (OVID), EMBASE, LILACS and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception to nowadays. Search was also conducted in other databases and unpublished literature. Clinical trials were included without language restrictions. The risk of bias was evaluated with the Cochrane Collaboration's tool. We performed a meta-analysis with a fixed effect model according to the heterogeneity. PROSPERO registration number is CRD42019128229.
Results: Twelve studies were included in the qualitative and quantitative analysis. 2,564 patients were found among the twelve studies. Risk of bias was assessed mostly as low or unclear risk among the study items. The risk ratio (RR) for all-cause mortality was 1.00 95% CI (0.77 to1.30). The RR of total bleeding and major bleeding were 2.72 95% CI (1.58 to4.69) and 2.17 95% CI (1.03 to4.55), respectively, finding higher risk in thrombolytic therapy. For stroke the RR was 2.22 95% CI (0.17 to28.73), and for recurrent PE the RR was 0.56 95% CI (0.23 to1.37), finding no differences regarding these outcomes. Unfortunately, there were no results reported about overall survival in any of the studies.
Conclusion: In patients with submassive PE, the risk of bleeding is higher when thrombolysis is used. There is no significant difference between thrombolysis and anticoagulation in recurrence of PE, stroke, and all-cause mortality
Figure

Disclosures
No relevant conflicts of interest to declare.
Dose Adjusted R-EPOCH Does Not Improve Outcomes in High Grade B Cell Lymphoma with Double Expressor Status or Gain of MYC/BCL2
Authors: Hardefeldt Prue , Moore John , Milliken Sam , Fay Keith , Orly Lavee , Mayson Eleni , Withers Barbara , Hamad Nada 
Published: November 2019

Introduction:
Diffuse large B cell lymphoma is a heterogenous disease with prognosis known to vary based on histological changes including immunohistochemistry and gene rearrangements by florescence in situ hybridisation (FISH). Both immunohistochemical overexpression as well as gene rearrangements in MYC, BCL2 and BCL6 are thought to contribute to poor prognosis. The benefit of high dose chemotherapy is unclear for those with high grade B cell lymphoma with double hit status (DHL) by FISH , double expressor status (DEL) or gain of MYC/BCL2. The purpose of this study was to retrospectively analyse the effect of escalated chemotherapy in this population over a 5 year period.
Methods:
All patients with DLBCL treated between 2012-2017 were screened retrospectively for inclusion in the study based on immunohistochemistry and FISH at time of initial diagnosis. Immunohistochemistry was assessed on formalin fixed, paraffin embedded specimens with BCL2 and MYC considered positive at over 40% and 50% respectively. FISH was assessed using dual colour break apart probe.
Results:
135 patients were diagnosed with DLBCL of which 53 patients had immunohistochemistry and FISH at diagnosis confirming either, DEL or gain of MYC/BCL2 status. The mean age was 65 years and median follow up 21 months. The overall response rate in DH treated with DA-R-EPOCH was 57%. There were insufficient cases treated with R-CHOP for comparison. Overall response rates in DEL were 94% for DA-R-EPOCH and 93% for R-CHOP. Overall survival (OS) and disease free survival (DFS) in DHL was 6 months and 2 months respectively when treated with DA-R-EPOCH. There was no significant difference in OS or DFS in DEL treated with DA-R-EPOCH compared with R-CHOP (OS: 42 months vs 38 months respectively (p=0.962), DFS 36 months vs 30 months (p=0.931)). Gain of MYC/BCL2 did not affect OS (p= 0.539) or DFS (p=0.439) when comparing treatment regimen.
Conclusion: DA-R-EPOCH did not improve treatment response rates OS or DFS in patients with double expresser lymphoma or gain of MYC/BCL2. This study also confirms the previously reported poor outcomes associated with DHL

Disclosures
No relevant conflicts of interest to declare.
Safety of Doacs in Patients with CNS Malignancies
Authors: Swartz Andrew , Drappatz Jan 
Published: November 2019

Background: Neuro-oncology patients, like all cancer patients, are at a high risk for thromboembolic complications and frequently require treatment with anticoagulation. DOACs have emerged as a less burdensome treatment for cancer associated thrombosis with comparable safety and efficacy to LMWH. Unfortunately, there is a paucity of data to support the use of DOACs in patients with primary and metastatic brain tumors and there is concern in the medical community for increased risk of intracranial hemorrhage. Objectives: The purpose of this study is to better understand the safety profile of anticoagulants in brain tumor patients, with a particular interest in the safety and efficacy of DOACs. Our hypothesis is that DOACs are as safe and effective as LWMH in this patient population. Methods: This study was conducted through retrospective chart review of patients with primary and metastatic brain tumors on anticoagulation. Our outcomes of interest were major bleeding (as defined by ISTH guidelines), with particular interest in Intracranial hemorrhage as well as minor bleeding and recurrent thrombosis. Radiographic images of all patients were reviewed for evidence of ICH and CTCAE v5 criteria were used to grade severity of ICH cases with range from 1 (asymptomatic imaging finding) to 5 (death). Results and Conclusions: A total of 130 patients with brain tumors were evaluated (69% primary brain tumor, 15% CNS lymphoma, 16% metastatic disease). Out of this population, 62 were on LMWH and 52 were on DOACs. The incidence of major bleeding was 20.9% in the LMWH group vs. 9.6% in the DOAC group (P =0.1, 95% CI -2.45 - 24.1). The incidence of ICH was 14.5% in the LMWH group and 5.8% in the DOAC group (P =0.13 95% CI -3.23 - 20.2). The severity of ICH in both groups was low with median CTCAE v5 scores of 2 in LMWH group and 3 in the DOAC group. The incidence of minor bleeding was 16.1% in LMWH group and 21.1% in the DOAC group (P = 0.49 CI -9.2 - 19.7). Recurrent thrombosis in both groups occurred in <5% of cases. Our conclusion is that in patients with primary and metastatic brain tumors, DOACs are not associated with an increased incidence of major bleeding or ICH compared to LMWH and are a safe and effective option in this patient population.

Disclosures
No relevant conflicts of interest to declare.
Next Generation CRISPR Gene-Edited and Off-the-Shelf Virus-Specific T-Cells for the Immunocompromised Patient
Authors: Basar Rafet , Daher May , Uprety Nadima , Gokdemir Elif , Alsuliman Abdullah Saleh , Mendt Mayela Carolina , Kerbauy Lucila , Shanley Mayra , Ozcan Gonca , Ensley Emily , Cortes Ana Karen Nunez , Li Li , Lu Junjun , Kaplan Mecit , Nandivada Vandana , Bdaiwi Mustafa , Li Ye , Garcia Luciana Melo , Liu Enli , Ang Sonny , Banerjee Pinaki P , Champlin Richard E. , Shpall Elizabeth J. , Rezvani Katayoun 
Published: November 2019

Introduction: A number of Clinical trials have demonstrated the feasibility, safety and efficacy of cell and gene therapy for cancer, autoimmune disorders and infectious disease. Strategies that enhance the function and survival of immune cells are critical for the success of immunotherapy. We have developed a strategy for the ex vivo expansion of off-the-shelf viral-specific T cells (VSRs) from healthy donor buffy coat which have been extremely effective in eradicating refractory cytomegalovirus (CMV), polyomavirus and adenovirus infections in immunocompromised patients. Glucocorticoids commonly used to treat graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplantation (HSCT) are a common cause of iatrogenically-induced immunosuppression and contribute the risk of life-threatening viral-infections. To render VSTs resistant to the lymphocytotoxic effect of glucocorticoids, we have developed a novel strategy to silence the expression of the glucocorticoid receptor using RNA-guided endonucleases CRISPR (clustered regularly interspaced short palindromic repeats) and CRISPR-associated (Cas) 9 gene editing..
Methods: The technique involves the expansion from donor blood of CMV, BKV or adenoviral-specific T cells using peptide libraries from the immunodominant viral proteins followed by CRISPR knockout of exon 2 of the GR gene on chromosome 5 of the human NR3C1 gene. Cells are electroporated with the RNP (Cas9 plus guide RNA) complex (IDT pre-designed alt-R crispr Cas9 platform) using Neon electroporation and the Amaxa 4-D nucleofector system.
Results: GR knockout efficiency in ex vivo expanded virus-specific T cells was consistently > 90%. In vitro experiments confirmed the resistance of VSTs to corticosteroid treatment as assessed by annexin V assay. GR KO VSTs maintained potent antiviral activity as assessed by their ability to proliferate and release effector cytokines in response to viral antigens.
Conclusions: CRISPR gene-editing to knock-out the glucocorticoid receptor gene in viral-specific T cells can preserve the activity of VSTs in the presence of corticosteroid-induced immunosuppression. Engineering runs using GMP-compliant Cas9 protein and gRNA are underway in anticipation of a clinical trial.

Disclosures
Champlin: Sanofi-Genzyme: Research Funding; Actinium: Consultancy; Johnson and Johnson: Consultancy.
Comparison of Two Different ELISA Methods for Heparin-Induced Thrombocytopenia (HIT) Screening on an Automated ELISA Platform
Authors: Mardovina Tatsiana , Chromczak John G , Riley Paul W 
Published: November 2019

BACKGROUND:
Heparin-induced thrombocytopenia (HIT) is an adverse complication of unfractionated and low molecular weight heparin caused by antibodies recognizing platelet factor 4-heparin (PF4/hep) complexes leading to platelet activation. The diagnosis of HIT is based on the combination of the clinical picture, using the 4T score along with screening and confirmatory methods to detect platelet activating anti‐PF4/H antibodies.
OBJECTIVES:
Performance was evaluated for two enzyme linked immunosorbent assays (ELISAs), 1) Asserachrom HPIA , Diagnostica Stago Inc., Parsippany, NJ, USA and 2) LIFECODES PF4 Enhanced, Immucor, Inc., Norcross, GA, USA for screening-based detection of PF4/hep antibodies.
METHODS:
ELISA assays were run per manufacturer recommendations and adapted for automation on a Dynex DS2 automated ELISA platform. Performance characteristics of the two immunoassays were assessed, including sensitivity, specificity, concordance with serotonin release assay (SRA), positive predictive value (PPV) and negative predictive value (NPV). 21 samples were used in the study.
Results:
Both assays, Asserachrom HPIA and LIFECODES PF4 Enhanced demonstrated 100% sensitivity and NPV, confirming both assays' reliability to detect and rule out HIT (see table). The diagnostic specificity was significantly higher for Asserachrom HPIA vs. LIFECODES PF4 Enhanced (77.8% vs 31.6%). Asserachrom HPIA showed fewer false positive results, with PPV of 42.9% for Asserachrom HPIA vs. 13.3% for LIFECODES PF4 Enhanced. No false negative results were found for either assay. Asserachrom HPIA demonstrated 81.0% concordance with SRA, vs. 38.1% for LIFECODES PF4 Enhanced.
CONCLUSIONS:
HIT is a life-threatening disorder, with diagnosis depending on clinical findings using the 4T score along with laboratory evaluation. Combining the 4T score with PF4/hep antibody screening increases the accuracy of excluding HIT. Our observations indicate Asserachrom HPIA provides results with high sensitivity and specificity, minimizing false positivess, allowing use of alternative anticoagulants more selectively in at risk patients, to potentially improve patient management while minimizing costs.

Disclosures
Mardovina: Diagnostica Stago, Inc.: Employment. Chromczak:Diagnostica Stago, Inc.: Employment. Riley:Diagnostica Stago, Inc.: Employment.
The Clinical Impact of Modified Barthel Index in Elderly Patients over 60 Years with Diffuse Large B-Cell Lymphoma
Authors: Ogura Shinji , Akimoto Masahiro , Sakurai Aki , Ito Chisako , Fujita Yuriko , Aisa Yoshinobu , Nakazato Tomonori 
Published: November 2019

[Introduction]Modified Barthel Index (MBI) is widely used to measure performance in activities in daily living (ADL), especially in elderly patients. MBI consists of 10 items: feeding, personal hygiene (grooming), bathing, dressing, toilet transfer, bladder control, bowel control, chair/bed transfers, stair climbing, and ambulation. A total score ranges from 0 to 20. MBI has been studied in several types of cancer which is correlated with prognosis. However, the prognostic role of MBI in diffuse large B-cell lymphoma is still unknown. The study aims to investigate the predictive role of MBI in elderly patients over 60 years with DLBCL.
[Methods]This retrospective study included elderly DLBCL patients over 60 years treated at our institution between 2009 and 2018. MBI score of each patient was evaluated at diagnosis. Receiver operator characteristic (ROC) curve was used to generate a cut off value for MBI. Kaplan-Meier method and univariate, multivariate analysis by Cox proportional hazards model were performed to assess the prognostic influence of the factors including Stage, Revised International Prognostic Index score (R-IPI), Performance status (PS), Extra-nodal Site Involvement (ESI), Lactate Dehydrogenase (LDH), Soluble Interleukine-2Receptor (sIL-2R), Albumin, B symptoms and MBI. The study protocol was approved by the Institutional Review Board of Yokohama Municipal Citizen's Hospital, and it was carried out in accordance with the Declaration of Helsinki.
[Results]A total of 187 patients were included in the analysis. There were 102 males and 85 females, with a median age of 77 (range: 61-93). The median follow-up time was 39 months. The optimal MBI cutoff value for predicting 3-year survival was determined by ROC analysis to be 14.Patients with low MBI scores (< 14) had significantly shorter overall survival (OS) than those with high MBI scores (≥ 14) (3-year OS, 14.2 % vs. 65.2 %, p < 0.001). Among 163 patients receiving chemotherapy, patients with low MBI scores had shorter OS than those with high MBI scores (3-year OS, 21.2 % vs. 66.4 %, p < 0.001). In multivariate analysis, parameters having independent adverse significance for OS were: Low MBI (< 14) (p < 0.001, HR 2.49), PS ( ≥ 2) (p=0.04, HR 1.84).
[Conclusion]In the present study we demonstrated that Low MBI was deeply associated with poor outcome in elderly patients with DLBCL. In particular, our data proved that a low MBI is an independent prognostic factor for survival in elderly patients with DLBCL. These results suggest that Low MBI may have an important role in DLBCL and may be also a useful prognostic marker. Since our results are based on a small-sized analysis, further large prospective studies are warranted to verify this conclusion.

Disclosures
No relevant conflicts of interest to declare.
Mutation Status and Burden Can Improve Prognostic Prediction of Patients with Lower-Risk Myelodysplastic Syndromes
Authors: Jiang Lingxu , Luo Yingwan , Jin Jie , Tong Hongyan 
Published: November 2019

Patients with lower-risk myelodysplastic syndromes (LR-MDS) as defined by the International Prognostic Scoring System (IPSS) have more favorable prognosis in general, but significant inter-individual heterogeneity exists. In this study, we examined the molecular profile of 15 MDS-relevant genes in 159 patients with LR-MDS using next-generation sequencing. In univariate COX regression, shorter overall survival (OS) was associated with mutation status of ASXL1 (P=0.001), RUNX1 (P=0.031), EZH2 (P=0.049), TP53 (P=0.016), SRSF2 (P=0.046), JAK2 (P=0.040), and IDH2 (P=0.035). We also found significantly shorter OS in patients with a TET2 variant allele frequency (VAF) ≥18% versus those with either a TET2 VAF <18% or without TET2 mutations (median: 20.4 vs. 47.8 months; P=0.020; HR=2.183, 95%CI: 1.129-4.224). After adjustment for the IPSS, shorter OS was associated with mutation status of ASXL1 (P<0.001; HR=4.306, 95%CI: 2.144-8.650), TP53 (P=0.004; HR=4.863, 95%CI: 1.662-14.230) and JAK2 (P=0.002; HR=5.466, 95%CI: 1.848-16.169), as well as a TET2 VAF ≥18% (P=0.008; HR=2.492, 95%CI: 1.273-4.876). Also, OS was increasingly shorter as the number of mutational factors increased (P<0.001). A novel prognostic scoring system based on the IPSS and the presence/absence of the 4 independent mutational factors further stratified LR-MDS patients into three prognostically different groups (P<0.001).The newly developed scoring system re-defined 10.1% (16/159) of patients as higher-risk group, who could not be predicted by the currently prognostic models. In conclusion, integration of IPSS with mutation status/burden of certain MDS-relevant genes may improve the prognostication of patients with LR-MDSand could help identify those with worse-than-expected prognosis for more aggressive treatment.
Figure

Disclosures
No relevant conflicts of interest to declare.