bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interim 18f-PDGPET for Aggressive Non-Hodgking's Lymphoma: A Systematic Review and Meta-Analysis
Authors: Caramazza Domenica , Dentali Francesco , Merli Michele , Saccullo Giorgia , Malato Alessandra , Quintini Gerlando , Iannitto Emilio , Passamonti Francesco , Siragusa Sergio 
Published: October 2019

Abstract
Abstract 5183

Background:
The advantage of using interim 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET) scan in the clinical work-up of patients with non-Hodgkin's lymphoma (NLH) is unclear. Data from meta-analyses are inconclusive, mainly because of the low number of patients evaluated and heterogeneity among studies. New clinical investigations, focused on this topic, have been recently published. We conducted an updated systematic review on the role of 18PDG-PET for the interim evaluation in patients with aggressive lymphomas.

Materials and Methods:
Medline, Embase, Scopus and Databases were searched for relevant studies through March 2011. We included studies that evaluated FDG-PET performed between the first and the fourth cycle of first-line chemotherapy. Patients were selected when they were evaluated for response assessment with interim 18FDG-PET. For each study, we constructed a 2 × 2 contingency table consisting of true positive (TP), false positive (FP), false negative (FN), and true negative (TN), where all patients were categorized according to whether they were PET positive or negative, and whether they experienced treatment failure. A meta-analysis of the prognostic accuracy was performed.

Results:
We selected 16 out of 46 studies, involving 1256 patients with aggressive NHLs (90% with Diffuse Large B-Cell Lymphoma); 1157 patients met our inclusion criteria and were considered for the final analysis. Interim18FDG-PET, performed after a median of 3 cycles of chemotherapy (range 1–6 cycles), gave true and false negative results in 641 (56 %) and 65 (6%) patients, respectively. Therefore, 18FDG-PET had an overall sensitivity of 0.80 (95% CI, 0.69 to 0.88) and a specificity of 0.84 (95% CI, 0.76 to 0.90) (figure). Heterogeneity among studies was substantial.

Conclusion:
Because of data heterogeneity, interim 18FDG-PET for aggressive NHL patients remains an unproven test for routine clinical practice. Its role should be further evaluated in clinical researches with homogeneous treatments and standardized imaging.

Disclosures:
No relevant conflicts of interest to declare.
Establishment and Characterization of a Novel Human Cell Line of Triple Hit Lymphoma, AMU-ML1, Carrying t(2;18)(p11.2;q21) and t(3;8;14)(q27;q24;q32) That Involve BCL2, BCL6 and MYC
Authors: Tsunekawa Norikazu , Hanamura Ichiro , Yamamoto Hidesuke , Nagoshi Hisao , Wakabayashi Motohiro , Sakamoto Natsumi , Horio Tomohiro , Gotoh Mineaki , Mizuno Shohei , Takahashi Miyuki , Suganuma Kazuto , Goto Mayuko , Hiramatsu Akihito , Watarai Masaya , Shikami Masato , Imamura Akira , Mihara Hidetsugu , Taki Tomohiko , Taniwaki Masafumi , Miwa Hiroshi , Nitta Masakazu 
Published: October 2019

Abstract
Abstract 5210
Mature B-cell lymphomas with both BCL2 and MYC translocations to IG loci are rarely identified and most of them are classified as B-cell lymphoma, unclassifiable, with features intermediate between diffuse large B-cell lymphoma and Burkitt lymphoma (IL) in the new World Health Organization classification.
In this study, we established a novel human lymphoma cell line, AMU-ML1, from pericardial effusion (PE) of a patient with IL before the initiation of chemotherapy and analyzed its characters. A 60-year-old male was admitted to our hospital because of PE and diagnosed as having IL from the atypical lymphocytes in PE. He was treated with rituximab plus hyper-CVAD and other regimens but died of lymphoma approximately 10 months after diagnosis without reaching complete remission.
The cells from patient's PE at diagnosis were cultured in RPMI 1640 supplemented with 20% heat-inactivated fetal bovine serum (FBS). After 5 months of culture, cell proliferation became continuous with 10% FBS and the cell line was designated as AMU-ML1 (Aichi Medical University, malignant lymphoma, no. 1) after confirmation that the cells began growing again after the conventional freeze-thaw procedure.
AMU-ML1 cells were positive for CD10, CD19, CD20, CD79a, HLA-DR and cytoplasmic lambda chain and negative for CD3, CD4, CD5, CD8, CD13, CD23, CD33 and CD56 by flow cytometry analysis and showed a complex karyotypes including t(2;18)(p11.2;q21) and t(3;8;14)(q27;q24;q32) by G-banding analysis. This profile is consistent with the profile of the patient's cells. Spectral karyotyping and fluorescent in situ hybridization analysis of AMU-ML1 cells revealed that t(2;18)(p11.2;q21) was IGL/BCL2 and t(3;8;14)(q27;q24;q32) was BCL6/MYC, MYC/IGH and IGH/BCL6.
Subcutaneous transplantation of AMU-ML1 cells into NOD/scid mice treated with anti-asialo GM1 antibody resulted in formation of primary tumors.
Thus, the AMU-ML1 cell line is useful for studying the biological consequences of IL with triple hit of BCL2, BCL6 and MYC, and possibly invasion to PE of lymphoma.

Disclosures:
No relevant conflicts of interest to declare.
Epidemiology of Mantle Cell Lymphoma: A Population-Based Study in France
Authors: Leux Christophe , Herry Aurélie , Maynadie Marc , Cabrera Quentin , Troussard Xavier , Le Guyader-Peyrou Sandra , Le Gouill Steven , Monnereau Alain 
Published: October 2019

Abstract
Abstract 5222

Introduction:
Mantle cell lymphoma (MCL) is an aggressive and rare B-cell lymphoma entity representing around 5–8% of non-Hodgkin's lymphomas in adults. To our knowledge no data is available on the epidemiology of MCL in France. We aimed to describe incidence, survival and main clinical characteristics of MCL in a French population.

Methods:
Patients diagnosed with MCL were identified in three administrative areas covered by an haematological malignancies registry: the Côte d'Or (from 1988 to 2008), the Basse-Normandie (from 1997 to 2006) and the Gironde (from 2002 to 2006). Main clinical features and management characteristics were collected. World age-standardised incidence rates, observed survival and relative survival were estimated for the period 2002–2006.

Results:
Mantle cell lymphoma was diagnosed in 213 patients over the whole period. Seventy percent of patients were males. Over the period 2002–2006, the age-standardised incidence rate of MCL (per 100,000) was 0.72 in men (n=100) and 0.17 in women (n=35). The median age at diagnosis was 72 years (range: 30–92). Late-stage (III-IV) MCL was diagnosed in 81.5% of patients. MCL international prognostic index (MIPI) was lower or equal to intermediate risk in 36% of patients. The median relative survival time was 41 months (95% confidence interval: 38–62) and was significantly higher in patients with a low or intermediate MIPI (74 months, CI95%: 53–91) than in patients with a high risk (38 months, CI95%: 30–49). Treatment included frontline chemotherapy in 85% patients and 54% patients received rituximab. Ten percent of patients participated in a clinical trial.

Conclusion:
Epidemiological characteristics of MCL in France were quite similar to epidemiological data reported in other industrialized countries. Incidence rates were characterized by a male-to-female ratio of 4:1. Median overall survival was less than 4 years.

Disclosures:
No relevant conflicts of interest to declare.
Thymic Retention of CD4+CD25hi+FoxP3+ T Regulatory (Treg) Cells Is Responsible for Peripheral Treg Deficiency and Platelet and Megakaryocyte Destruction in Active Immune Thrombocytopenia (ITP)
Authors: Semple John W. , Gebremeskel Simon , Aslam Rukhsana , Ni Heyu , Freedman John 
Published: October 2019

Abstract
Abstract 523
Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder in which antibodies and/or cytotoxic T cells are directed against an individual's own platelets and/or megakaryocytes and lead to enhanced platelet destruction in the periphery and reduced platelet production within the bone marrow. It is becoming increasingly clear that the immune dysregulation leading to ITP is primarily due to T cell disturbances and recently, many reports have demonstrated that active ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP that demonstrates both antibody and T cell-mediated platelet and megakaryocyte destruction, we analyzed the role that Tregs may play in active ITP. BALB/c CD61 knockout (KO) mice were immunized against wildtype (CD61+) platelets and 1.5×104 of their splenocytes were transferred ip into CB.17 severe combined immunodeficient (SCID) mice and their platelet counts, phenotype and percentage of CD4+CD25hi+FoxP3+ Tregs were enumerated in various lymphoid tissues at various times after transfer. Results showed that within 2 weeks post-transfer, 16 of 30 transferred mice became thrombocytopenic (<300×109 platelets/L) whereas the remaining mice did not. Bleeding diatheses and mortality occurred in 4 of the 16 thrombocytopenic mice. Of interest, compared with control SCID mice transferred with naïve BALB/c splenocytes or the non-thrombocytopenic SCID mice, the thrombocytopenic mice had significant elevations in thymic weights and percentages of CD4+CD25hi+FoxP3 Tregs by 2 weeks post transfer. Splenic weights in the thrombocytopenic mice increased but at the same rate as control mice, however, the proportion of Tregs in the spleens were significantly less than control non-thrombocytopenic mice. Treatment of the thrombocytopenic mice with 2g/kg intravenous gammaglobulin (IVIg) raised the platelet counts, reduced thymic weights and normalized both the thymic and splenic Treg populations compared with controls. The results suggest that active ITP in this mouse model is associated with a peripheral (splenic) Treg deficiency due to thymic retention of the Tregs. It proposes a new mechanism of Treg deficiency in ITP; Tregs are withheld from the periphery by thymic sequestration.

Disclosures:
No relevant conflicts of interest to declare.
Venous Thromboembolism Following Major Surgery and Risk of Recurrence: A Population-Based Cohort Study
Authors: Kondal Dimple , Kahn Susan R. , Tagalakis Vicky 
Published: October 2019

Abstract
Abstract 5243

Background:
Venous thromboembolism (VTE) which includes deep vein thrombosis (DVT) and pulmonary embolism (PE) is a common complication of major surgery. Little is known of the risk of recurrent VTE following postoperative VTE.

Objectives:
We used the administrative health claims (RAMQ) and hospital discharge (MED ECHO) databases of Quebec, Canada to conduct a population-based retrospective cohort study to describe the time to VTE following general surgery and to assess the risk of VTE recurrence among patients with surgery-provoked VTE.

Methods:
Using a previously defined cohort of individuals who had a first-time discharge diagnosis of VTE between January 1996 and December 2004 in MED ECHO, which systematically records information on all hospital admissions in the province of Quebec, we identified patients who had undergone major surgery in the 3 months prior to the VTE. Subjects were followed from the time of incident VTE until first VTE recurrence, death, or end of study (December 31, 2005).

Results:
Our study population consisted of 9629 patients with new VTE up to 3 months following major surgery. The mean age was 63.9 years (SD=15.2) and 53% were female. General surgery (32%) was the most common procedure. The mean time to VTE after surgery was 29.5 days (SD=62.6) with 30% of events diagnosed after discharge. The 5-year adjusted cumulative risk of recurrence was 7.9%. Patients with VTE diagnosed after discharge had an adjusted relative risk of recurrence of 1.43 (95% confidence interval (1.21, 1.69)) compared to patients with VTE diagnosed before discharge.

Conclusions:
Our results suggest that surgery-provoked VTE occurs frequently after discharge and is associated with an elevated risk of recurrence, and that patients with post-discharge VTE are at a higher risk of recurrence than patients with VTE diagnosed before discharge. Thromboprophylaxis strategies post-discharge should be considered in this population.

Disclosures:
Tagalakis: Sanofi Aventis: Research Funding; Pfizer: Research Funding.
The Phenotypic Expression of Homozygous and Compound Heterozygous Factor V R506Q (Factor V Leiden, FVL) and Factor II A20210G: Ten Years Experience At a Referral Center
Authors: Al-Mondhiry Hamid A B , Nifong Thomas P , Eyster Mary Elaine 
Published: October 2019

Abstract
Abstract 5252
Heterozygous Factor V Leiden, the most common inherited thrombotic disorder with an estimated incidence of about 5% in Caucasian population, poses a moderate risk of first venous thromboembolic (VTE) event. The homozygous and compound heterozygous states are comparatively rare but are thought to be associated with high risk of recurrent VTE. This report describes ten years experience with homozygous and compound heterozygous FVL and Factor II A20210G at a major referral center in central Pennsylvania, USA. Between January 2000 and December 2010, 31 homozygous F VL patients, 2 homozygous FII A20210G, 10 compound heterozygous FVL and F II A20210G and 6 compound heterozygous F VL and protein C (PC), protein S (PS) or antithrombin (AT) deficiency were encountered. The reasons for referral were personal or family history of VTE or a first degree relative diagnosed with any of these conditions. Among these patients, 5 homozygous F VL, 1 compound heterozygous F VL and F II A20210G, and 1 compound heterozygous factor VL and PC deficiency remained free of VTE at age 17–64 years, even though they were exposed to prothrombotic conditions, e.g., surgery, hormones or pregnancy. Two compound heterozygous F VL and PS deficient patients suffered ischemic strokes, one at age 3 ½ years and the other at age 45 years, but no VTE. The other patients suffered lower extremity deep vein thrombosis and/or pulmonary embolism or visceral thrombosis. Most had recurrent events. Our experience highlights the serious thrombotic risks associated with homozygous and compound heterozygous F VL and F II A20210G status but also indicates that some patients remain thrombosis free despite exposure to additional prothrombotic conditions. However, because of referral bias this series of patients may not truly reflect the overall occurrence of VTE in patients with homozygous or compound heterozygous inherited thrombophilia.

Disclosures:
No relevant conflicts of interest to declare.
Venous Thromboembolism in Cancer Patients Following Major Surgery
Authors: Toledano Tierry Haim , Kondal Dimple , Kahn Susan R. , Tagalakis Vicky 
Published: October 2019

Abstract
Abstract 5253

Background:
Venous thromboembolism (VTE), encompassing deep vein thrombosis (DVT) and pulmonary embolism (PE), is common in cancer patients and surgery is an important risk factor. The timing of post-operative VTE in cancer patients is uncertain.

Objectives:
We used the administrative health claims (RAMQ) and hospital discharge (MED ECHO) databases of Quebec, Canada to describe the occurrence of post-operative VTE in cancer patients and to explore anticoagulant use following hospital discharge.

Methods:
Using a previously defined cohort of individuals with a discharge diagnosis of VTE between January 1, 1994 and December 31, 2004 in MED ECHO which systematically records information on all hospital admissions in the province of Quebec, we identified patients with a cancer diagnosis in the 12 months preceding the VTE and who had major surgery in the 3 months prior to the VTE. Discharge diagnoses were defined according to the 9th edition International Classification of Diseases codes and surgical procedures according to the Canadian classification of diagnostic, therapeutic, and surgical procedures.

Results:
In all, 2706 patients with VTE had a cancer diagnosis and underwent major surgery in the 3 months preceding the VTE. The mean age was 65.9 years (SD=12.6) and 54% were female. The most common cancer was gastrointestinal (38%), and general surgery was the most frequent procedure (48%). The mean hospital stay was 29.8 days (SD=35.3). The mean time to VTE was 34.8 days (SD=68.3). In all, 34% of VTE events occurred after discharge. Among patients with post-discharge VTE (n=917), 4% had an out-patient anticoagulant prescription at discharge.

Conclusions:
Post-operative VTE in cancer patients often occurs after hospital discharge. This suggests that the risk of VTE extends beyond the immediate postoperative period. Prospective studies are needed to determine the effectiveness and safety of thromboprophylaxis beyond discharge in cancer patients undergoing surgery.

Disclosures:
Tagalakis: Sanofi Aventis: Research Funding; Pfizer: Research Funding.
Infantile SVT in Consequence of a Congenital Antithrombin Deficiency
Authors: Halimeh Susan , Dreher Stephan , Rosenbaum Thorsten , Rekus Martin , Rott Hannelore , Nowak-Gottl Ulrike , Faeser Britta 
Published: October 2019

Abstract
Abstract 5260
The liver-made antithrombin is a natural coagulation inhibitor in human blood. Exceptionally it takes effect in inhibiting the coagulation-supporting factors IIa (thrombin) and Xa. A congenital antithrombin deficiency leads to thrombosis and has to be heterozygous, because homozygous ATIII deficiencies are incompatible with life. Unfortunately it's dominant inherited.
In 1965 a congenital ATIII deficiency was first detected as a hereditary disease. There are two different types, type I describes a less produced ATIII deficiency, type II is a function loss of ATIII. Special testing can define more subclasses.
In cases of congenital ATIII deficiency, vascular blockage (thrombosis) appears, especially in leg veins. Released clots can cause pulmonal embolism, rarely are other arteries affected.
Although this disease is hereditary, it appears mostly between ages of 15 'til 30. Clinical trials showed that 80% of affected patient have a thrombosis or embolism until the age of 40. Has there be no kind of illness appeared until there, it's very improbable to get one becaus eof ATIII deficiency.
Every hundredth below the age of 70, who comes to a health care center has a ATIII deficiency. In total population it's a freqzuency of 1:2000 until 1:5000. Mostly there's a deficiency nown in familary history why they are investigated. The residual activity is between 40 – 60%.

Conclusion:
Most cases of thrombosis are treated with heparine. Heparin binds to ATIII, so ATIII can be much more effective and inhibits thrombin and Xa much more intense. For the future we have to make sure that antithrombin deficiencies especially in childhood have to be treated with phenprocumone.

Disclosures:
No relevant conflicts of interest to declare.
Inhibition of TLR-4 Prevents From Sepsis-Related eNOS/NO Disturbance in Human Platelets
Authors: Ma Liping , Yang Qiuhong , Chang Jianxing , Li Yiqing , Zhang Liping , Luo Xianming 
Published: October 2019

Abstract
Abstract 5264

Objective
Toll-like receptor 4 (TLR-4) has the ability to activate platelet and involve in intravascular coagulation, inflammatory cytokine and oxidative stressors release in sepsis. Nitric oxide (NO) synthesis in platelets is adjusted by iNOS and/or eNOS and contributes to platelet aggregation and adhesion. Our previous study has found that increased platelet aggregation in patients with sepsis was associated with the expression of TLR4 on platelets and NO synthesis in platelets. This study was to investigate whether inhibition of TLR-4 activation on platelets decreases eNOS(endothelial NO synthase)/NO disturbance-related platelet aggregation.

Methods
Blood samples were collected from 10 patients with severe sepsis and 10 healthy volunteers as controls. PRP(platelet-rich plasma) and PPP (platelet-poor plasma) were prepared for platelet aggregation, and platelet suspension (at a concentration of 2×108/mL platelets) for next experimemts. After the platelet suspension from healthy volunteers was incubated with L-Arginine (LA, 10 mM) alone, and LA and L-NAME (NΩ-Nitro-L-arginine methyl ester hydrochloride, 25mg/mL, a nonselective NOS inhibitor) for 1 hour, LPS(10.0μg/ml) was respectively added them. In separate experiments, the platelet suspension was preincubated with anti-TLR-4 Abs (10μg/mL) and then repeat above experiments. The levels of serine phosphorylation in eNOS (p-eNOS) and NO production, and platelet aggregation were determined with Western blotting, nitrate concentration analysis and platelet aggregometer, respectively.

Results
The protein levels of p-eNOS and NO production had 2.2-fold and 1.8-fold of increases in platelets from septic patients, and in vitro had 1.8-fold and 1.7-fold of increases in LA-incubated platelets stimulated with LPS as compared to controls. The p-eNOS expression and NO production were inhibited in the presence of L-NAME. Furthermore, thrombin-induced platelet aggregation was markedly promoted by LPS and L-NAME [(61 □ ‘98) %, (80□ ‘100)% versus (40□ ‘72)% of control) ], and the effect of LPS was abolished by LA pretreatment [(54□ ‘76)% ]. Blockade of TLR-4 didn't alter the elevated levels of p-eNOS and NO under LPS challenge, but the inhibition of L-NAME on p-eNOS and NO was significantly decreased. Importantly, blockade of TLR-4 significantly decreased platelet aggregation induced by LPS, and both LPS and L-NAME, but had no effects on LA pretreatment.

Conclusion
These data suggest that inhibition of TLR-4 may play a role in prevention from sepsis-induced platelet aggregation and maintaining platelet eNOS activity in sepsis.

Disclosures:
No relevant conflicts of interest to declare.
Leukopenia in Patients with Iron Deficiency Anemia
Authors: Lim Yoojoo , Lee Eun Young , Choi In Sil , Kim Tae-Yong , Yoon Sung-Soo , Kim Ki Hwan 
Published: October 2019

Abstract
Abstract 5279

Background:
There is a lack of clinical research regarding the effect of iron deficiency anemia on white blood cells (WBC).This study presents the incidence of leukopenia in patients with iron deficiency anemia and the relationship between the white blood cell count and the level of hemoglobin(Hb).

Patients and Method:
Medical records of patients over 12 years of age with iron deficiency anemia were reviewed. Patients with concomitant disease that may alter the WBC count such as hematologic malignancy, solid tumor, history of gastrectomy, vitamin B12 or folate deficiencies and active inflammation were excluded.

Results:
From January 2006 to December 2010, a total of 516 eligible patients were included. Median age was 47 years with female predominance (80.6%). Leukopenia was found in 91 patients (17.6%). The incidence of leukopenia was significantly higher in patients with hemoglobin level of less than 8 g/dL than those with higher level of hemoglobin (44/183, 24.0% vs. 47/333, 14.1%, P=0.005, Table 1).
The levels of WBC count were found to decrease in accordance with the decrease in hemoglobin level (Pearson's coefficient: 0.178, P<0.001, Figure 1). The decrease in WBC count was seen more often in younger patients. (R=0.104, P=0.018) Also, lymphocytes were found to decrease in both total number(R=0.282, P<0.001) and percentage (R=0.122, P=0.006) within total WBCs in proportion to the decrease in Hb level.

Conclusion:
This study shows the high incidence of leukopenia in patients with iron deficiency anemia. The severity of leukopenia correlates with the decrease of hemoglobin in dose-dependent manner. Among the WBC subsets, lymphocyte count was significantly affected.

Disclosures:
No relevant conflicts of interest to declare.