bluuebunny/crossref_metadata_2025_split huggingface dataset:
Utilizing the Predictive Value of the 4T Scoring System to Reduce Unnecessary HIT Panel Costs in the Community Hospital Setting
Authors: Potdar Rashmika , Gupta Sorab , Ng Jia Hwei , Robert Schoepe , Berson Andrew , Bansal Reena , Mohiuddin Kamran , Sy Go Mylene 
Published: October 2019

Abstract
Abstract
Study Objective-Heparin Induced Thrombocytopenia (HIT) is a life-threatening immunological response to heparin. The objectives for this study were to determine if the 4T scoring system was being utilized as a tool for predicting HIT, and to look at the costs associated with HIT panels.
Methods-This was a retrospective chart review of patients greater than 18 years of age who had HIT panels performed between January 2013 and June 2014 in a community hospital. Any duplicate HIT panels sent during the same admission period were excluded. Study investigators were trained in two 30-minute intervals in the area of data collection and retrospective calculation of 4T score.
Results- Of the 154 patients studied, 73 (47.4%) were male, and 81 (52.6%)were female. All patients had a 4T score calculated by study investigators during data analysis, and 1.29% (n=2) had a 4T score calculated before a HIT panel was sent by the team taking care of the patient. 62.3% (n=96) of patients had a low 4T score and 37. 7%( n=58) had an intermediate to high 4T score. Hematology was consulted on 57.7% (n=89) and anticoagulant administration was stopped on 74 % (n=114), while in 26 % ( 40/ 154) heparin was continued despite sending HIT. 25.4%(29/114) were started on alternate anti- coagulants after stopping heparin . Throughout the course of the study, 20 patients died, with only 1 of these patients being HIT positive.
If 100 unnecessary HIT panels were performed in a year, the hospital would be charged more than $20,000 by the diagnostic lab. Additional costs include the halting of Heparin administration and starting an alternate anticoagulant such as Argatroban. 24 hour administration of Argatroban costed $1,000 for continuous infusion. HIT panels have a turnaround time of 4-5 days, resulting in the additional charge of $5,000 just for Argatroban administration. A lengthened stay in the hospital due to HIT panel turnaround time is also a source of increased costs. Combined, the ordering of a HIT panel, alternate anticoagulant administration, and bed charges could amount to $40,000 over the course of four days. This time and money could be put to better use treating the underlying disease of the patient, instead of focusing on the testing for HIT.
Conclusion-Management of HIT in community hospital was sub-optimal. Lack of utilization of the 4T scoring system led to unnecessary ordering of HIT panels. This increased duration of hospital stay, elevated the cost of treatment, and resulted in the holding of prophylactic anticoagulants.

Disclosures
No relevant conflicts of interest to declare.
A New Dosing Model Based on Body Mass Index to Guide Factor VIII Dosing in Patients with Hemophilia A
Authors: Tiede Andreas , Goldmann Georg , Miljić Predrag S , Korsholm Lars , Matytsina Irina , Persson Paula , Lissitchkov Toshko Jelev 
Published: October 2019

Abstract
See attached image file

Disclosures
Tiede: Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Consultancy; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Honoraria; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Research Funding. Goldmann:Novo Nordisk and other companies: Honoraria; Novo Nordisk and other companies: Consultancy. Miljić:Novo Nordisk: Other: Investigator fees as a participant of the clinical trial. Korsholm:Novo Nordisk A/S: Employment; Novo Nordisk A/S: Other: Owns stocks. Matytsina:Novo Nordisk A/S: Other: Owns stocks; Novo Nordisk A/S: Employment. Persson:Novo Nordisk A/S: Employment; Novo Nordisk A/S: Other: Owns stocks. Lissitchkov:Novo Nordisk: Other: Investigator fees as a participant of the clinical trial.
Risk Factors and Outcomes of Deep Vein Thrombosis in Pediatric Osteomyelitis
Authors: Ahmad Maria , Knoll Christine M. , Shah Sanjay J. , Mirea Lucia 
Published: October 2019

Abstract
Background:
Estimates of the incidence of DVT in patients with osteomyelitis range widely from 5%-30%, however risk factors and outcomes of DVT in this cohort have not been thoroughly established.
Objective:
This study aims to estimate the incidence of DVT in patients with osteomyelitis, and to assess risk factors and outcomes of DVT.
Design/Method:
After IRB approval, a retrospective chart review was conducted for patients aged 0-18 years seen at Phoenix Children's Hospital between 2012-2016 with ICD 9/10 codes for osteomyelitis. Exclusion criteria included chronic recurrent multifocal osteomyelitis, and chronic DVT. Demographics, clinical factors and outcomes were compared between osteomyelitis patients with and without DVT using the Fisher-exact and Wilcoxon-rank sum tests, as appropriate for the data distribution.
Results:
A total of 179 study subjects with osteomyelitis had a mean (standard deviation) age of 8.4 (5.7) years. DVT was present in 14 (8% of 179) patients, and 4 (28%), 5 (36%) and 5 (36%) patients received anticoagulation for < 6, 6-12 and ≥12 weeks, respectively. Patients with vs without DVT were more likely to be male (86% vs 59%; p-value=0.05), and had significantly higher rates of bacteremia (64% vs 24%; p-value=0.003). Rates of central lines were comparable between DVT and non-DVT patients (71% vs 68%; p-value=1.00); however patients with DVT vs without DVT had significantly longer mean length of stay (18 vs 9 days; p-value <0.0001) and higher rates of ICU admission (71% vs 16%; p-value <0.0001).
Conclusion:
The incidence of DVT among osteomyelitis pediatric patients was estimated at 8%, with risk increased by male sex and bacteremia. Patients with DVT had significantly higher rates of ICU admission and longer length of hospital stay. Many of these patients had standard practice management of their DVT with 6-12 weeks of anticoagulation underscoring the need for future efforts targeting DVT prophylaxis.

Disclosures
No relevant conflicts of interest to declare.
Epigenetic Therapy Targets Th1/Th17 Polarization to Reversing Immune Evasion and Treating Leukemia Relapse Post Allogeneic Stem Cell Transplantation in Non-APL AML Patients
Authors: Yang Xi , Zheng Hong , Dai Jingying , Li Chenglong , Zhang Rong , WANG Xiaodong , Wang Chunsen , Huang Xiaobing 
Published: October 2019

Abstract
To reverse non-APL AML patients with post-transplantation relapse before hematological relapse(early-stage relapse), we investigated the safety and efficacy of a new epigenetic therapy(DNA methyltransferase inhibitors, Decitabine and histone deacetylase inhibitors, Chidamide, plus Thymalfasin simultaneously). Twenty-four patients were enrolled in this observational study. The most common adverse event was CTCAE grade 2 thrombocytopenia (20/24). No acute GVHD was observed in patients received this treatment regimen. Strikingly all 24 patients responded to this epigenetic therapy with minute residual disease(MRD) decreasing (ORR 100%). At the more than 3-year follow-up, overall survival rate is 87.5%(21/24), with relapse-free survival rate of 75%(18/24). With this epigenetic therapy for 3 months, Th1 cells and CD3+CD4-CD8+T cells increased gradually, and Th17 cells decreased. The status of Th1 and Th17 cells remained at the time of 3 months after discontinuation. Interestingly, the Th1/Th17 ratio was low in patients with relapse disease and then increased gradually during this treatment regimen, correlated with the down trend of MRD. Therefore, our new epigenetic therapy is safe and tolerable for non-APL AML suffering post-transplant early relapse. The polarization for Th1/Th17 and the significant elevated ratio of Th1/Th17 seemed to better reflect the epigenetic therapy-mediated immune effect, which maybe a good biomarker for the early relapse monitoring.

Disclosures
No relevant conflicts of interest to declare.
Increased Risk of Second Primary Hematologic and Solid Malignancies in Patients with Mycosis Fungoides
Authors: Goyal Amrita , O'Leary Daniel , Lazaryan Aleksandr 
Published: October 2019

Abstract
Importance: Mycosis fungoides (MF) is a rare, generally indolent non-Hodgkin T-cell lymphoma of the skin. It has previously been associated with increased risk of second hematologic malignancies and melanoma, but the association with second solid malignancies has not been well characterized.
Objective: This retrospective analysis seeks to assess the risk of developing a second primary hematologic or solid malignancy in patients with MF.
Design: We performed (1) an analysis of patients diagnosed with MF from 2000-2014 in the 18 population-based United States cancer registries of the Surveillance, Epidemiology, and End Results Program (SEER-18), and (2) a retrospective cohort study of patients with MF treated at the University of Minnesota (UMN) from 2005-2017 with a control group of patients with seborrheic dermatitis.
Setting: This study is a combination of population-based data and a single-center cohort.
Participants: SEER-18 consists of a population-based sample of patients across the United States with a diagnosis of MF (n=6196). The UMN cohort included a cohort of 172 patients with MF treated at the UMN from 2005-2017.
Results: In the SEER-18 cohort, relative risks were estimated using the standardized incidence ratios (SIR). Of the 6196 patients in the MF cohort there were 514 (8.3%) second cancer events (SIR 7.3, 95% confidence interval [CI] 6.7-7.9). Patients with MF were at substantially increased risk for both. non-Hodgkin (SIR 46.51, CI 39.16-55.0) and Hodgkin lymphoma (SIR 69.8, CI 34.8-124.9). MF patients were also at higher risk of melanoma (SIR 7.2, CI 4.5-10.9), lung (SIR 6.2, CI 4.8-7.8), female breast (SIR 8.0, CI 5.8-10.6), prostate (SIR 4.1, CI 3.1-5.2), bladder (SIR 3.6, CI 2.0-5.8), colon (SIR 5.2, CI 3.7-7.2) and renal (SIR 3.9, CI 1.8-7.3) cancers.
In the UMN cohort, patients with MF were significantly more likely to develop a second malignancy than patients with seborrheic dermatitis (relative risk [RR] 8.1, p<0.0005, CI 5.1-13.2). Patients with tumor stage MF were more likely to develop a second malignancy than those with patch/plaque stage disease (RR 3.2 p<0.01, CI 2.6-10.4). Similarly, patients with stage IIB or higher were significantly more likely than those with early stage disease (RR 3.0, p<0.003, CI 3.1-13.5) to develop a second malignancy. Analysis of treatments and imaging undergone by each patient revealed no significant difference in systemic, topical, radio- or phototherapy, or number of CT scans between patients who did and did not develop second malignancies.
Conclusions and Relevance: Patients with MF are at increased risk of developing second malignancies, particularly those with advanced stage disease or tumors. These findings warrant the development of targeted screening strategies for patients with MF.

Disclosures
No relevant conflicts of interest to declare.
The Impact of Selenium Deficiency on a Sickle Cell Disease Mouse Model
Authors: Jagadeeswaran Ramasamy , Lenny Hong , Zhang Helen , Afranie-Sakyi Jennifer , Molokie Robert E. , Lavelle Donald , Diamond Alan , Rivers Angela 
Published: October 2019

Abstract
Sickle cell disease (SCD) is caused by a mutation in the β-globin gene resulting in a disease that affects more than 100,000 Americans and millions worldwide. Though pain is the hallmark of SCD, patients also suffer damage to most organ systems. Sickle cell hemoglobin (HbS) polymerization occurs when deoxygenated, rendering red blood cells rigid and fragile. Production of excessive reactive oxygen species (ROS) and intracellular hypoxia in RBCs further accelerates the pathology associated with SCD. Recently, vaso-occlusive crisis (VOC) and organ damage were established to be strongly associated with oxidative stress in RBCs. This occurs when there is an increase in oxidants that exceeds the cellular anti-oxidant defenses. Excessive ROS can trigger a cascade of oxidative reactions that damage membrane lipids, and essential enzymatic antioxidants such as GPx-1, ultimately leading to hemolysis and multi-organ dysfunction. ROS generation in RBCs of SCD patients is due to factors such as HbS auto-oxidation and potentially aberrant mitochondrial function. We recently determined that red blood cells obtained from SCD mice and SCD patients retain their mitochondria compared to control subjects. Mitochondria retained SCD RBCs are also associated with elevated levels of ROS and hemolysis. Oxidative stress in the RBCs of SCD patients may be elevated by lower levels of antioxidant proteins such as the selenium-dependent enzyme GPX1. GPX1 was first described as an enzyme capable of protecting hemoglobin from ROS and has been reported to be lower in the RBCs in SCD. Selenium levels are lower among African Americans in the Chicago area and elsewhere. In this regard, it is notable that in the United States, African Americans represent the majority of those with SCD. To investigate the relationship between selenium levels and SCD, we have utilized a mouse model of SCD to examine the impact of a reduced intake of selenium on parameters associated with SCD pathology. SCD mice on a selenium-deficient diet (<0.01 mg/kg diet) were compared to mice fed with a selenium-adequate diet (0.1mg/kg). SCD mice in the selenium-deficient group exhibited an increase in mitochondria retaining RBCs (Se deficient: 26%±6.9%, n=3 vs. Se adequate: 5 % ± 3.5%, n=3, p<0.01), reduced Hb levels (Se deficient 5.7± 0.17 g/dl, n=3 vs. Se adequate 7.0± 0.83 g/dl, n=4 p<0.05), and an increased RBC oxygen consumption rate (OCR). These results support the hypothesis that low selenium status likely results in reduced levels of anti-oxidant selenoproteins and enhanced SCD severity.

Disclosures
Lavelle: Global Blood therapeutics: Research Funding.
Boosting Gamma Delta T Cells-Mediated ADCC By PD-1 Blockade in Follicular Lymphoma
Authors: Bezombes Christine , Rossi Cédric , Gravelle Pauline , Bordenave Julie , Decaup Emilie , Poupot Mary , Tosolini Marie , Franchini Don-Marc , Laurent Camille , Morin Renaud , Lagarde Jean-Michel , Ysebaert Loic , Savina Ariel , Klein Christian , Perez-Galan Patricia , Fournié Jean-Jacques 
Published: October 2019

Abstract
Follicular lymphoma (FL) is a common non Hodgkin's lymphoma subtype in which immune escape mechanisms are implicated in resistance to chemo-immunotherapy. Although molecular studies point to qualitative and quantitative deregulation of immune checkpoints, in depth cellular analysis of FL immune escape is lacking. Here, by functional assays and in silico analyses we show that a subset of FL patients displays a 'high' immune escape phenotype. These FL cases are characterized by abundant infiltration of PD1+ CD16+ TCRVgamma9Vdelta2 gamma delta T lymphocytes and high expression of gamma delta cytolytic markers. In a 3D co-culture assay (MALC), gamma delta T cells could mediate both direct and indirect (ADCC in the presence of anti-CD20 mAbs) cytolytic activity against FL cell aggregates. Importantly, PD-1, which is expressed by most FL-infiltrating gamma delta T lymphocytes with ADCC capacity, impaired these functions. In conclusion, we identify a PD1-regulated gamma delta T cell cytolytic immune component in FL. Our data provide a treatment rational by PD-1 blockade aimed at boosting gamma delta anti-tumor function in FL.

Disclosures
Morin: IMACTIV-3D: Employment. Lagarde:IMACTIV-3D: Employment. Savina:Institut Roche: Employment. Klein:F. Hoffmann-La Roche Ltd.: Employment, Other: stock, Patents & Royalties.
Lymphadenopathy in a TB-Endemic Region: Employing Focused Techniques in a Rapid Access Lymph Node Biopsy Clinic
Authors: Antel Katherine Rae , Verburgh Estelle , Louw Vernon J. , Oosthuizen Jenna , Malherbe Francois , Gary Maartens , Nicol Mark 
Published: October 2019

Abstract
Introduction
Lymphoma and extrapulmonary tuberculosis (EPTB) are common in HIV and may cause peripheral lymphadenopathy. EPTB can be difficult to diagnose and consequently, patients with lymphadenopathy in TB-endemic regions are frequently placed on empiric TB treatment. This may result in a missed or delayed diagnosis of lymphoma.
In the local setting, in Cape Town (South Africa), primary level doctors have difficulty accessing lymph node excision biopsies which rely on an over-burdened surgical service. Core-needle biopsy is not currently routinely performed for peripheral lymphadenopathy in the investigation of lymphadenopathy.
Methods
A prospective study of patients with peripheral lymphadenopathy >2cm was performed. A rapid access lymph node biopsy clinic examined the performance of three methods of investigation on a lymph node: the fine-needle aspirate for cytology (FNAC), the Xpert MTB/Rif Ultra (on both aspirate and tissue specimens), and the ultrasound-guided core-needle biopsy. In all patients a final histological diagnosis was sought, including referral for excision biopsy if core-needle histology was inconclusive. If >0.5ml of pus was aspirated this was tested with the Xpert MTB/Rif and a biopsy was not performed.
Results
Sixty-two patients including 48% HIV+ have undergone investigation. The final diagnosis is known for 56 patients: lymphoma in 34%, TB in 30%, cancer in 12%. Ultra had a 64% sensitivity on the aspirate (95% CI 31-89%), and 73% on tissue (95% CI 39-94). In both cases specificity was 100%. FNAC was diagnostic in 0% of lymphoma cases (reported atypical in 24%); it was diagnostic for TB (+AFBs) in 27% with TB; and diagnostic in 36% of disseminated cancer cases. The core biopsy was able to make a diagnosis in 83% of cases (including sub-typing in 89% of lymphoma cases).
Conclusion
The Ultra shows promising sensitivity and should routinely be performed for both HIV+ and -patients at the first visit in the investigation of unexplained lymphadenopathy in a TB-endemic region. If the Ultra is negative, a core-needle biopsy is the most appropriate next investigation. In a TB-endemic region, FNAC should be reserved for patients >50 years who are HIV negative. There is no role for empiric TB treatment for patients with peripheral lymphadenopathy in the era of new TB diagnostic tests, and the application of these investigations with early biopsy for patients with negative TB tests will result in earlier detection of lymphoma.

Disclosures
No relevant conflicts of interest to declare.
Genotypic Groups As Risk Factor for Cardiac MR Abnormalities and Complications in Thalassemia Major
Authors: Pepe Alessia , Meloni Antonella , Salvadori Stefano , Macchi Silvia , Vitucci Angelantonio , Murgia Mauro , Maggio Aurelio , Fiorenza Maria Flavia , Massei Francesco , Commendatore Francesca Valeria , Giuliano Pietro , Positano Vincenzo , Pistoia Laura 
Published: October 2019

Abstract
Introduction. Beta thalassemia major (β-TM) displays a great deal of genotypic heterogeneity, not fully investigated in terms of cause-effect. This prospective and multicentre study aimed to detect if different genotypic groups could predict the development of cardiovascular magnetic resonance (CMR) abnormalities and cardiac complications (CC).
Methods. We considered 708 β-TM patients (373 females, 30.05±9.47 years), consecutively enrolled in Myocardial Iron Overload in Thalassemia (MIOT) network. Data were collected from birth to the first CMR imaging scan. Myocardial iron overload was assessed by the multislice multiecho T2* technique. Biventricular function parameters were quantified by cine images. Late gadolinium enhancement (LGE) images were acquired to detect myocardial fibrosis.
Results. On the basis of the type of gene mutation, three groups of patients were identified: homozygotes β+ (N=158), compound heterozygotes β+ / β° (N=298) and homozygotes β° (N=252). Table 1 shows the effect of genotype group on the development of different cardiac outcomes. Compared to the milder genotype group homozygotes β+, the other two groups showed a significantly higher risk of myocardial iron overload (MIO) and left ventricular dysfunction. We recorded 90 (13.0 %) cardiac events: 46 heart failures (HF), 38 arrhythmias (33 supraventricular, 3 ventricular and 2 hypoinetic) and 6 pulmonary hypertensions (PH). No prospective association was detected between genotype group and HF and PH. The homozygous β° group showed a significantly higher risk of arrhythmias than the homozygous β+ group and at the limit of significance than the compound heterozygotes. Globally, homozygotes β° showed a significantly higher risk of CC than homozygotes β+.
Conclusion. Different genotypic groups predict the development of MIO, left ventricular dysfunction, arrhythmias and CC in β-TM patients. These data support the knowledge of the different genotypic groups in the clinical management of β-TM patients.
Table Table.

Disclosures
Pepe: Chiesi Farmaceutici S.p.A., ApoPharma Inc., and Bayer: Other: No profit support.
Metabolic Reprogramming Overcomes T Cell Inhibition By AML Cells
Authors: Uhl Franziska Maria , Chen Sophia , O'Sullivan David , Buck Michael , Büscher Jörg , Pfeifer Dietmar , Finke Jürgen , Duyster Justus , Bertz Hartmut , Shoumariyeh Khalid , Börries Melanie , Richter Gesa , Madl Tobias , Pearce Erika L. , Zeiser Robert 
Published: October 2019

Abstract

Allogeneic hematopoietic cell transplantation (allo-HCT) is the treatment strategy of choice for the majority of patients with acute myeloid leukemia (AML). However, about 40% of patients relapse, which is associated with a poor prognosis. Donor lymphocyte infusions (DLIs) induce remission only in a minority of relapsed AML patients.
In order to understand the impact of AML cells on T cell bioenergetics, we investigated the metabolic phenotype and immunological profile of CD8+ T cells isolated from AML patients at primary diagnosis, during remission and relapse after allo-HCT. At diagnosis, T cells exhibited robust metabolic activity and strong immune activation. In contrast, during relapse, T cells demonstrated reduced glycolytic and respiratory activity compared to their status at remission. The metabolic phenotype was accompanied by reduced cytotoxic ability. Metabolomics revealed lactate accumulation and substantial arginine depletion in the serum of these patients.
The results observed in the human setting could be reproduced in a murine graft versus leukemia (GVL) model where T cells isolated from AML bearing mice exhibited lower metabolic activity compared to control animals.
In vitro co-culture experiments enabled tightly controlled conditions for mechanistic studies. The metabolic impairment induced by AML cells was mediated by soluble factors, mirroring the major changes in serum metabolites of patients, and interfered with the crucial metabolic reprogramming in the priming phase of T cells. Well-known mechanisms such as nutrient deprivation could be excluded. Extensive transcriptomic and metabolomic analyses have been undertaken in order to identify the molecules responsible for the diminished metabolic activation.
Influencing mitochondrial architecture thereby boosting respiratory activity prior to infusion led to enhanced anti-leukemic activity of T cells in vivo. The pre-treatment favored an immunological memory phenotype essential for a potent GVL effect. Using metabolic stimuli as pre-treatment of DLIs could promote T cell resistance against tumor evasion and increase anti-tumor immunity. This could greatly improve the success of DLIs and other adoptive T cell transfer strategies in the treatment of AML relapse.

Disclosures
Finke: Neovii: Consultancy, Honoraria, Other: travel grants, Research Funding; Medac: Consultancy, Honoraria, Other: travel grants, Research Funding; Novartis: Consultancy, Honoraria, Other: travel grants, Research Funding; Riemser: Consultancy, Honoraria, Research Funding.