bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of Lengths of Stay for Inpatients with Immune Thrombocytopenia Treated with Anti-Rh(D), Intravenous Immunoglobulin, and Steroids
Authors: Melinscak Hrvoje , Shapira Ilan , Varma Mala 
Published: October 2019

Abstract
Abstract 4646

Rationale:
Anti-Rh(D) is an effective treatment for acute immune thrombocytopenia [ITP]. It has a faster onset of action (1 day) vis a vis corticoids (3 days) and intravenous immunoglobulin [IVIG] (4 days). A direct comparison of length of stay for adult inpatients receiving these therapies has hitherto not been performed. We hypothesized that the length of stay would be shortest for patients treated with anti-Rh(D).

Methods:
A retrospective chart review was conducted to assess length of stay in relation to treatments proffered for ITP. The defining diagnosis of ITP [coded 287.31] was rendered from the computerised record at St. Luke's-Roosevelt Hospital Center and identified 303 patients, of which 147 received treatments for active ITP within a period spanning 01SEP2005 through 29FEB2012. Treatments consisted of prednisone alone, dexamethasone alone, anti-Rh(D) alone, IVIG alone, and combinations of corticoids and the latter two. An average length of stay was tabulated for each treatment regimen. Age and gender were also recorded.

Results:
A total of 147 hospitalisations for ITP were noted and the analysis of variance statistical calculation applied thus. The median age was 48 years and the male:female ratio was 1.1:1. Eleven groups were delineated and the means for length of hospital stay with confidence intervals derived. The groups were as follows: Prednisone, Dexamethasone, Methylprednisolone, Anti-Rh(D), IVIG, Prednisone and Anti-Rh(D), Dexamethasone and Anti-Rh(D), Prednisone and IVIG, Dexamethasone and IVIG, Methylprednisolone and IVIG, and Anti-Rh(D) and IVIG or Dexamethasone, Anti-Rh(D), and IVIG. The overall p-value for length of stay was 0.0016 (Table 1). The shortest stays were recorded for the corticoid alone groups; however, the mean stay for anti-Rh(D) was shorter than that of IVIG, both in sole and combined modality treatments.

Conclusion:
Anti-Rh(D) is favourable with respect to hospital stay duration. Although corticoids result in still shorter lengths of stay, anti-Rh(D) demonstrated a shorter length of stay compared with IVIG. Combined with its single dosing and relative cost savings, anti-Rh(D) is an excellent alternative to IVIG.

Disclosures:
No relevant conflicts of interest to declare.
Platelet Apoptosis in Uremic Patients
Authors: Li Ming , Ma Tongling , Lu Guoyuan , Deng Kun , Yan Rong , Dai Kesheng 
Published: October 2019

Abstract
Abstract 4647

Introduction:
Apoptosis, which serves for the regulation of cell lifespan and is long attributed exclusively to nucleated cells, has been well-documented in anucleate platelets. Diverse cell-external chemical and physical stimuli have been reported to induce transformation of resting platelets to apoptotic state. Uremia, a clinical syndrome associated with retention of various solutes that would normally be excreted by the kidneys, is frequently accompanied by bleeding tendency, and the mechanism remains unclear. The aim of the present study is to investigate whether platelet apoptosis occurs in uremia patients.

Methods:
Venous blood was drawed from 13 patients with end stage renal disease (ESRD) who exhibited uremia syndrome and 13 health controls. Platelet-rich plasma (PRP) was prepared and then was detected for apoptotic events including depolarization of mitochondrial inner membrane potential (ΔΨm), phosphatidylserine (PS ) exposure, variations of apoptotic Bcl-2 family proteins, activation of caspases-3 by Flow cytometry or Western-blot. Furthermore, normal washed platelets were incubated with the poor- platelet plasma (PPP) from uremic patients, and then were detected for apoptotic events. The comparisons of the data were made using paired Student's t-test.

Results:
Compared with controls, ΔΨm significantly depolarizated in platelets from uremic patients (P<0.05). Furthermore, Bax was up-regulated, Bcl-2 and Bcl-XL were down-regulated, and caspase-3 was activated in platelets from uremic patients. However, there was not significant difference in PS exposure and P-selectin expression between the platelets from uremic patients and health contols (P>0.05). Next, PPP from uremic patients was incubated with normal platelets, and the platelets presented ΔΨm depolarization, up-regulation of Bax, down-regulation of Bcl-2 and Bcl-XL, and caspase-3 activation.

Conclusion:
The data demonstrate that platelets are incurred apoptosis in uremia patients. The finding might suggest a novel pathogenic mechanism for bleeding tendency in uremic patients.

Disclosures:
No relevant conflicts of interest to declare.
Surface Expressions of Platelet Glycoprotein Ibα, GpIIb/IIIa, and P-Selectin Are Elevated in Lung Cancer Patients
Authors: Zhang Jiansheng , Zhao Lili , Huang Jianan , Zhang Pingping , Dai Kesheng 
Published: October 2019

Abstract
Abstract 4655

Objective:
Thromboembolic events are common symptoms in patients with cancer, and the mechanisms are not totally understood. The platelet adhesion moleculars play important roles in the process of thrombus formation. The aim of the current study is to investigate the surface expression of platelet glycoprotein (GP) Ibα, GPIIb/IIIa, and P-selectin in patients with lung cancer.

Method:
Platelets were isolated from patients with lung cancer and normal volunteers, and then the surface expressions of platelet GP Ibα, GPIIb/IIIa, and P-selectin were measured by Flow cytometry. The glycocalicin (GC) fragments in the peripheral blood of patients with lung cancer were tested by Western blot. The surface expression of GP Ibα on normal volunteers' platelets incubated with the platelet-poor plasma (PPP) of patients with lung cancer was measured by Flow cytometry and Western blot.

Results:
The surface expressions of platelet GP Ibα, GPIIb/IIIa, and P-selectin were obviously increased in patients with lung cancer compared with that of normal volunteers, and the GC fragments in PPP were also increased in patients with lung cancer. Incubation of control platelets with the PPP from cancer patients resulted in the elevation of the surface expression of GP Ibα in control platelets. Furthermore, the expressions of GP Ibα, GPIIb/IIIa, and P-selectin on platelets from patients with advanced stage of lung cancer (III-IV stage) were significantly higher than those with early stage (I-II stage) (P<0.05). However, there were not significantly difference in the surface expressions of GP Ibα, GPIIb/IIIa, and P-selectin among the pathological types of lung cancer (squamous cell carcinoma, adenocarcinoma, small cell lung carcinoma, large cell lung carcinoma) (P>0.05).

Conclusion:
The surface expressions of platelet GP Ibα, GPIIb/IIIa, and P-selectin were obviously elevated in patients with lung cancer, and the plasma from cancer patients is responsible for the elevations. These findings provide a new view to understand the pathogenic mechanisms of thromboembolic events in the patients with lung cancer.

Disclosures:
No relevant conflicts of interest to declare.
Pulmonary Endothelial Cell Irradiation Damage Signaling Initiates Late Fibrosis
Authors: Kalash Ronny , Houghton Frank , Zhang Xichen , Wang Hong , Epperly Michael W. , Greenberger Joel S. 
Published: October 2019

Abstract
Abstract 4682
Thoracic irradiation of C57BL/6NHsd mice produces an acute lung inflammatory period (0 to 30 days after irradiation), followed by a stable latent period (30 to 100 days), followed by a delayed fibrosis reaction (100 –150 days). Fibrosis involves migration of bone marrow derived mesenchymal stem cells (fibroblast progenitors) into the lung. The molecular mechanisms which initiate migration and homing of fibroblast progenitors are unknown. Increased pulmonary TGF-β expression has been correlated with the onset of fibrosis. To identify the cells and genetic pathways involved, C57BL/6NHsd female mice were irradiated with 20 Gy to the thoracic cavity and sacrificed at serial time points including days 0, 2, 14, 28, 50, 75, 100, 110, 125, 150, and 200, lungs were removed and RNA extracted from either whole lung or purified cell populations. Real Time Polymerase Chain Reaction (RT-PCR) was used to quantitate gene expression.
In whole lung tissue, when compared to un-irradiated lungs, a significant elevation in expression of multiple inflammation and chemotaxis associated genes (including TGF-β, TNF-α,and MnSOD) and stress response genes (including NFkB, AP-1, SP-1,and Nrf2) was detected both during the acute inflammatory phase (p= 0.0112, 0.0037, 0.0245 and p= 0.0001, < 0.0001, =0.0010, =0.0181 respectively) and late-onset fibrosis phase (p= 0.0079, 0.0459, 0.0001, and p < 0.0001, = 0.0006, =0.0128, < 0.0001 respectively), but were either not elevated or significantly decreased during the latent period ( p< 0.0001, = 0.3785, 0.8123, and p=.0243, < 0.0001, < 0.0001, < 0.0001 respectively). In contrast, increased expression of endothelial cell associated genes including: vWF, VEGF, CTGF, FGF1 and CCL13 was detected during the latent period, as well as during the acute and chronic reaction phases. Purified lung endothelial, but not epithelial cells, showed stable vascular gene elevations of vWF, VEGF, CTGF, FGF1 and CCL13 during the entire time course including day 7 (p < 0.0001, < 0.0001, =0.0035, =0.0009, =0.0056), day 75 (p=.00263, 0.0104, 0.0284, 0.0038, and 0.0007), and day 150 (p < 0.0001, < 0.0001, =0.0005, =0.0039, =0.0014 respectively). The data supports a significant role of vascular gene expression in the activation and recruitment of cells involved in radiation induced late pulmonary fibrosis.
Further analysis of lung endothelial cells may elucidate the mechanisms involved in the late effects of thoracic irradiation, and identify new targets for drug development to prevent irradiation pulmonary fibrosis.

Acknowledgments:
This project was supported by NIH-2R01CA119927-08A1.

Disclosures:
No relevant conflicts of interest to declare.
Rapid Increase of CD8+ T Cell Count in Peripheral Blood of Pediatric Patients After HLA-Identical Stem Cell Transplantation for African Sickle Cell Anemia
Authors: Isgrò Antonella , Marziali Marco , Sodani Pietro , Gaziev Javid , Fraboni Daniela , Paciaroni Katia , Simone Maria Domenica , De Angelis Gioia , Alfieri Cecilia , Gallucci Cristiano , Roveda Andrea , Torelli Fabio , Cardarelli Luisa , Ribersani Michela , Lucarelli Guido 
Published: October 2019

Abstract
Abstract 4769

Background.
Sickle Cell anemia (SCA) remain a disease with high risk of morbidity and early death, especially in African patients. Allogeneic haematopoietic stem cell transplantation (HSCT) is the only curative treatment for SCA. To analyze immunohematological reconstitution after transplant, we report our experience concerning 12 geno-identical HSCT for SCA-patients prepared with the same myeloablative conditioning regiment consisting of Busulfan and Cyclophosphamide.

Patients and Methods.
Twelve patients with a median age of 12 years (range, 2–16), affected by sickle cell anemia (SCA), received hematopoietic stem cell transplantations from HLA-identical, related donors following a myeloablative conditioning regimen. To analyze the mechanisms involved in immunological reconstitution post transplant, we analyzed T cell subsets by flow cytometry at + 60 post transplant.

Results.
All patients had sustained engraftment and remained free of any SCA-related events after transplantation. Sixty days after the transplant, the patients had significantly lower CD4+ T cells in comparison to the controls (15.6 ± 5.9 % vs. 47.5 ± 6% respectively), whereas CD8+ T cells were the first lymphocytes to repopulate the peripheral blood with up to 45% of these cells being CD8+ T cells (in mean 48.5 ± 14.3 % vs. 20 ± 7%). All patients displayed reduced numbers of B cells versus normal value, and 10/12 patients had only 0% to 1% of control levels of CD19+ cells. CD3-CD56+bright NK cells were 18.6 ± 12.2 %, whereas CD3-CD16+ (with cytotoxic functions) were 16.7 ± 11.8 %.

Conclusion.
Our primary finding include the following: 1) rapid increase of lymphocytes in peripheral blood after transplant; 2) rapid expansion of CD8+ T cell but not CD4 T cell counts. Probably reactivation of cytomegalovirus (CMV) infection, observed in 11/12 patients on the early stages of T-lymphocyte recovery after transplant, might induce a dramatic increase in CD8 but not in CD4 T-cell counts.

Disclosures:
No relevant conflicts of interest to declare.
The Revised High-Dose Regimen of Beacop in the Primary Treatment of the Advanced Hodgkin's Lymphoma: A Interim Report
Authors: LIU Peng , Shi Yuankai , Wang Zhao 
Published: October 2019

Abstract
Abstract 4783

Objective
In the study, we compared the efficacy between the revised high-dose and standard-dose of the revised BEACOP regimen (Bleomycin, Etoposide, Epidoxorubicin, Cyclophophamide, Vincristine, Prednisione) in the treatment of the advanced Hodgkin's lymphoma (HL).

Patients and methods
Patients with HL of Stage III/IV were 1:1 randomized into either the standard-dose BEACOP regimen (the same to the BEACOPP regimen in GHSG-HD9 study except procarbazine) in the control arm or the revised high-dose BEACOP regimen (different from BEACOPPesc regimen in GHSG-HD9 study, excluding procarbazine, increasing the dose of cyclophophamide and doxorubicin, with the standard-dose of etoposide, and without the preventive G-CSF support) in the experimental arm. Patients with large tumor or residual tumor after 6 to 8 cycles chemotherapy would be received local radiotherapy. All patients were evaluated by imaging examination every 2 cycles during treatment and were followed up every 3 months from the end of the treatment.

Results
33 cases with advanced HL completed whole cycles chemotherapy and were followed-up a medium time of 12 months. The interim analysis showed that, patients received revised high-dose BEACOP had better response than those with standard-dose BEACOP. After 2 cycles chemotherapy, 2/17 cases had complete response (CR), and 8/17 cases had reduced more than 75% in the tumor size in the experimental arm; while none of 16 cases in the control arm achieved the similar response. After 6 cycles chemotherapy, 13/17 cases in the experimental arm achieved CR/CRu, compared with 8/16 cases in the control arm. Simultaneously, adverse drug reactions, such as neutropenia, nausea and vomiting, were observed significantly increased in the experimental arm. However, no related death and SAE occurred. All the patients showed good tolerance in the study.

Conclusions
In the HD9 study, asian patients received with BEACOPPesc were not tolerated enough to complete the whole chemotherapy, because of the serious toxicity such as long-term bone marrow suppression. In our study, we demonstrated that revised high-dose BEACOP in the primary treatment of the advanced HL would achieved the more high rate of CR/CRu compared with standard-dose BEACOP, and patients with revised high-dose BEACOP showed good tolerance and controllable acute hematotoxicity, even without the preventive use of G-CSF. Therefore, the revised high-dose BEACOP regimen might be a potential choice for Asian patients with advanced HL. However, more cases and long-term follow-up should be needed in the future to evaluate the long-term overall survival (OS) rate, efficacy and toxicity.

Disclosures:
LIU: Research Project of Cancer Hospital, CAMS: Research Funding.
Prognostic Significance of Minimal Residual Disease in Adult Patients with B-Lineage Acute Lymphoblastic Leukemia by 8-Color Flow Cytometry
Authors: Weng Xiang-Qin , Shen Yang , Sheng Yan , Chen Bing , Wang Jing-han , Li Jun-ming , Zhu Yong-Mei , Chen Sai-Juan 
Published: October 2019

Abstract
Abstract 4789
Monitoring of minimal residual disease (MRD) in patients with acute lymphoblastic leukemia (ALL) by immunophenotyping and/or molecular techniques provides a way to precisely evaluate early treatment response and predict relapse. In this study, we have investigated the prognostic significance of MRD in adult patients with B-lineage acute lymphoblastic leukemia (B-ALL) by 8-color flow cytometry. A cohort of 106 patients with B-ALL who had achieved a complete remission (CR) and at least 1 LAIP characteristics were enrolled to perform MRD assessment at the end of induction and 1 cycle of consolidation. LAIPs were identifiable in 96% of the patients by 8-color flow cytometric assay, in which, most cases (90.6%) containing 2 or more LAIPs had a sensitivity as high as identifying 1 leukemic blast among 1×105 BM nucleated cells. MRD negative status could clearly predict a favorable 1 year relapse free survival (RFS) and 2 year overall survival (OS) when a cut-off level of 0.01% was used to define MRD positivity at the point of achieving CR (P=0.000 and 0.000, respectively) and after 1 cycle of consolidation (P=0.000 and 0.000, respectively), respectively. In multivariate analysis including cytogenetic abnormalities, clinical factors and MRD status, late CR (P=0.046), MRD status at the points of obtaining CR (P=0.016) and 1 consolidation (P=0.007) were associated with RFS independently, while only MRD status after 1 course of consolidation was independent prognostic factor for OS (P=0.000). Of note, in exploring the fewer patients with MRD negative status experienced recent relapse, we have identified that most of such patients had a MRD level of 10−4−10−5 comparing to undetectable MRD level. Furthermore, our evidences showed that MRD assessed by flow cytometry and by RQ-PCR assay targeting to BCR-ABL fusion gene yielded concordant results in the vast majority of cases (90%). In conclusion, immunophenotypic evaluation of MRD by 8-color flow cytometry could work as an important tool to assess the treatment response and prognosis precisely in adult B-ALL.

Disclosures:
No relevant conflicts of interest to declare.
A Novel Non-Genetic Photostable Approach to Labelling Acute Myeloid Leukemia and Bone Marrow Cells with Quantum Dots
Authors: Zheng Yanwen , Mao Zhengwei , Yin Bin 
Published: October 2019

Abstract
Abstract 4818
Acute myeloid leukemia (AML) is a detrimental disease with difficult diagnosis and treatment. Understanding the biology of AML at the molecular and cellular levels would be essential to successful management of the disease. However, the notoriously known difficulty in manipulation of leukemia cells has long hindered the dissection of AML pathogenesis. The advent of CdSe/ZnS quantum dots (QDs) represents an important advancement in the research field of nanotechnology, which have recently also been applied for imaging of live cells. Here, we have introduced a non-genetic approach of marking blood cells, by taking advantage of QD technology. We compared QDs complexed with different vehicles, including a peptide Tat (QDs-Tat), cationic polymer Turbofect (QDs-Tf) and liposome Lipofectamine 2000 (QDs-Lip), in their abilities to mark cells. QDs-Tat showed the highest efficiency in delivery into hematopoietic cells, among the three vehicles. We then examined QDs-Tat labelling of leukemia cell lines, and found that QDs-Tat could label 293T, bone marrow (BM) cells, THP-1, MEG-01 and HL-60 with a decreasing efficiency. The efficiency of QDs-Tat delivery was dependent on the concentration of QDs-Tat applied, but not the length of incubation time. In addition, more uniform intracellular distributions of QDs in 293T and leukemia cells were obtained with QDs-Tat, compared with the granule-like formation obtained with QDs-Lip. Clearly, QD fluorescence was sharp and tolerant to repetitive photo excitations, and could be detected in 293T for up to one week following labelling. In summary, our results suggest that QDs have provided a photostable, non-genetic and transient approach that labels normal and malignant hematopoietic cells in a cell type-, vehicle-, and QD concentration-dependent manner. We expect for potentially wide applications of QDs as an easy and fast tool assisting investigations of various types of blood cells in the near future.

Disclosures:
No relevant conflicts of interest to declare.
Peripheral Regulatory B Cell Phenotype in Multiple Sclerosis Patients
Authors: Habib Jakob , Deng Jiusheng , Pennati Andrea , Lava Neil , Galipeau Jacques 
Published: October 2019

Abstract
Abstract 4843
Regulatory B cells (Bregs) are a unique CD5+/CD1d+/IL10+ B cell subtype which has novel immunosuppressive capabilities. It remains to be determined if subjects suffering from autoimmune ailments such as multiple sclerosis (MS) display a defect in number or function of Bregs in association with their disease. Our hypothesis is that total B cell number, and Breg subset in particular, is distinct when comparing peripheral blood B cell populations from MS to healthy controls (HC). This study herein focuses on establishing a phenotypic baseline of the peripheral B cell profile. The total number of CD19+ B cells in HC is 892±816 cells/μL (average ±SD, n=28), of which CD5+/CD1d+ Breg subset is 4.6±5.6 cells/μL. We found a greater number of B cells in MS subjects, 1441±1011 cells/μL (n=22, p<0.05, Student's t-test). However, the number of Bregs in MS patients is not significantly different from HC, 7.5±7.6 cells/μL (p=0.13). We further interrogated the phenotype of B cells in MS subjects and found that there is an increased number of CD27−IgD+ naïve/intermediate phenotype in MS, 1041±794 cells/μL, versus HC, 624±606 cells/μL (p<0.05). Our findings demonstrate that MS is not associated with a deficiency in the absolute number of CD5+/CD1d+ Bregs but rather a 60% increase in CD27−IgD+ B cells. We hypothesize that altered B cell distribution may be functionally associated to the underlying immune disease process of MS. This finding may inform the design of clinical trials examining B cell depletion strategies for treatment of MS.

Disclosures:
No relevant conflicts of interest to declare.
Clinical Features, Treatment and Prognosis of Extranodal NK/T Cell Lymphoma, Nasal Type: A Retrospective Analysis of 88 Cases From a Single Institution in China
Authors: Xuemei Wang , Xu Juan , JIngjing Wen , Zhibin Liu 
Published: October 2019

Abstract
Abstract 4848

Background and Objective:
Extranodal NK/T Cell Lymphoma, nasal type (NKTCL), a rare malignancy in western countries, behaves distinct clinicopathologic features. Patients are generally refractory to conventional chemotherapy. No standard therapy regimen has been established yet. Prognosis of this highly aggressive disease is usually dismal. As it is relatively prevalent in the southwest China, the analysis will provide useful information on the clinical characteristics, treatment options and survival.

Methods:
Hospitalized patients newly diagnosed as NKTCL according to the WHO classification in our institution from January 2000 to December 2010 were surveyed. 88 cases were retrospectively analyzed. Patients were treated by different regimens: chemotherapy-alone, radiotherapy-alone or radio-chemotherapy. All patients had thorough baseline and follow-up assessments. The median observation time was 28 months (range 3∼96).

Results:

Conclusions:
NKTCL occurs most often in young or middle aged adults with a male predominance and has a strong association with Epstein-Barr virus (EBV) infection. Patients with advanced stage disease usually have a poor prognosis. Better response and higher survival chances are expected by radiotherapy or combined radio-chemotherapy.

Disclosures:
No relevant conflicts of interest to declare.