bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biomimetic Membrane Vesicles: Evaluation of Inflammatory Response In Vivo
Authors: Vasileva Olga , Garanina Ekaterina E , Rizvanov Albert A , Gomzikova Marina 
Published: November 2020

Introduction: Biomimetic membrane vesicles are produced from live cells using cytochalasin B which disrupts the structure of the cytoskeleton and facilitate generation of membrane vesicles under subsequent vortexing. Membrane vesicles are pinched off from the cell surface, surrounded by a cytoplasmic membrane and contain the cytoplasm of parental cell. It is known that mesenchymal stem cells (MSCs) are immunoprivileged. The aim of our study was to determine whether Cytochalasin B-induced membrane vesicles (CIMVs) derived from mesenchymal stem cells retain the immunoprivileged properties of parental cells.
Method: All experiments were carried out in compliance with the procedure protocols approved by Kazan Federal University and local ethics committee (protocol #5, date 27.05.2014). To analyze the immunogenicity, murine MSCs (7.5x104 cells) either CIMVs-MSCs (15µg) were injected i.v. in 8 week old mice (Mus musculus, C57Bl/6). CIMVs were used at a concentration equivalent to 7.5×104 MSCs based on total protein concentration. Serum isolation was performed after 2 hours post-administration. Secretion of inflammatory cytokines was evaluated using multiplex analysis BioPlex Pro Mouse 23 Plex kit. (BioRad, USA).
Results: We detected all investigated cytokines in serum of control and experimental mice: Eotaxin, G-CSF, GM-CSF, IFN-g, IL-10, IL-13, IL-17A, IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-5, IL-6, IL-9, IL12p40, KC, MCP-1, MIP-1a, MIP-1b, RANTES, TNFa. Allogenic MSCs but not CIMVs increased concentration of Eotaxin, G-CSF, IL-17A and IL-9. The level of GM-CSF, IFN-g, IL-10, IL-1a, IL-1b, IL-2, IL-3, IL-4, IL-5, IL-6, IL12p40, KC, MCP-1, MIP-1a, MIP-1b, RANTES, TNFa in mice serum were not affected by murine MSCs injection. Injection of CIMVs did not induce any statistically significant changes in cytokines level.
Conclusion: Elevated levels of Eotaxin, G-CSF, IL-17A and IL-9 cytokines after the i.v.injection of murine MSCs suggest that moderate allergy inflammation was developed after the MSCs allotransplantation. CIMVs injection did not induced increase of cytokines level in mice serum indicating absence of immunogenicity. Taken together our results demonstrate that CIMVs show less/no immunogenicity compared to parental MSCs. We believe that small diameter, better biodistribution and fusion with host cells lead to the non-immunogenicity of CIMVs. Thus, CIMVs are confirmed to be a perspective, new biomimetic vector system. This study was funded by the grant of the President of the Russian Federation for state support of the leading scientific schools of the Russian Federation НШ-2603.2020.4. Kazan Federal University was supported by the Russian Government Program of Competitive Growth.

Disclosures
No relevant conflicts of interest to declare.
Epidemiology and Clinicopathology of Hepatosplenic T-Cell Lymphoma (HSTCL): Analysis of a Pooled Database
Authors: Haddad Philip A , Hammoud Dalia , Gallagher Kevin M. 
Published: November 2020

Introduction:
HSTCL is a rare and rapidly progressive extranodal T-cell lymphoma. It accounts to for 1-2% of all T/NK cell lymphomas. Afflicting adolescents and younger adults, HSTCL commonly presents with constitutional symptoms, cytopenias, and hepatosplenomegaly. Up to a third of all the reported cases arise within a clinical context of immunosuppression. This analysis was conducted to update and expand our existing knowledge of this rare disease.
Methods:
In order to study the demographic characteristics, cytogenetic and molecular signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 360 cases. Kaplan-Meier survival curves were constructed. Cox proportional-hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathology factors on overall survival (OS).
Results:
A total of 360 patients with confirmed HSTCL were identified. The median age was 30 (0.8-86) years with a peak incidence between ages 13 and 26. There is male predominance with M:F ratio of 2.6 in the whole group, 6 in the immunosuppressed, 2.2 in γδ, and 1.2 αβ. HSTCL with TCRαβ tended to be more CD5+, CD8+, and CD57+. More than 90% presented with constitutional symptoms and had bone marrow involvement. Median overall survival of the whole group was 12 months. The median duration of symptoms to diagnosis is 2 months. The median time from immunosuppression to diagnosis is 5.3 years. Sex, age, jaundice, autoimmune hemolytic anemia, hemophagocytosis, and bone marrow involvement did not affect OS. Furthermore, i7 and/or +8 and TCR type did not impact OS. Compared to no treatment, combination chemotherapy and auto and allo stem cell transplant (SCT) were statistically superior with a median OS of 1, 9, 34, and 30 months respectively. While OS of combination chemotherapy was inferior to that of SCT, there was no significant difference between auto and allo SCT. Immunosuppression adversely impacted OS in the whole group (HR:0.40, p&lt;0.0001) and among the SCT subgroup (HR:0.38, p=0.06). There was no difference between immunosuppression with and without TNFα inhibitors. The quality of response prior to transplant also seemed to impact outcome though it did not reach statistical significance (p=0.07) with OS of 15, 30, and 44 months for none/transient, response less than CR, and CR respectively. Splenectomy improved survival in the whole group (HR:0.66; 95%CI 0.47-0.93). Further analysis revealed that splenectomy impacted survival in the context of combination chemotherapy but not SCT.
Conclusions:
This study presents an updated epidemiologic and clinicopathologic data from a pooled cohort of patients with HSTCL. It identifies the impact of immunosuppression, quality of response, treatment modalities as well as splenectomy on OS.

Disclosures
No relevant conflicts of interest to declare.
Correlation of Iron Levels with Asthma and Lung Function in Pediatric Patients with Sickle Cell Anemia
Authors: Shaikh Yusra D , Apollonsky Nataly , Bernstein Bruce 
Published: November 2020

Introduction:Significant morbidity and mortality in patients with sickle cell disease (SCD) is attributed to the pulmonary sequalae of the disease. Patients with SCD often suffer airway hyper-reactivity, acute chest syndrome (ACS), chronic lung disease, pulmonary hypertension (PHTN), and obstructive sleep apnea (OSA). Recent literature has provided evidence supporting the strong association between asthma and airway hyper-reactivity in SCD. One of the factors linked to chronic inflammation and asthma is iron status. The present study examined whether iron levels are associated with pulmonary complications in pediatric patients with SCD.
Method:Through retrospective review of electronic medical records (EMR) we evaluated patients with diagnosis of asthma and SCD. All patients with available PFT (3/21/2013-3/11/2020) and iron studies were included in the analysis. Chi square and ANOVA tests were used to explore relationships of respiratory conditions with lab data and relevant medical history.
Results:The analysis reviewed information of 100 patients with SCD -- 56 males and 44 females The sample population had the following genotypes: 63% Hemoglobin (Hb) SS, 23% Hb SC, 2% Hb S Beta Zero Thalassemia, and 12% Hb S Beta Thalassemia. 38% of these patients were receiving treatment via hydroxyurea. The results generated found that patients with a large airway obstruction (LAO) had a marginally statistically significantly higher serum iron level than those with no LAO (p=0.067.) Patients with homozygous Hb S disease were four times as likely to have a history of ACS (p=0.004) than those without and were marginally significantly more likely to be SS and SB0Thal (p=0.052). Patients with history of ACS had a significantly higher mean iron saturation and lower total iron binding capacity (TIBC.) Patients with PHTN had significantly higher serum iron levels (p=0.029).
Conclusion:Our findings reveal that while iron might play a more significant role in the development of PHTN and ACS in patients with SCD, the role in asthma is borderline in our sample. These findings, although of borderline statistical significance p=0.067, are clinically noteworthy. These results may open a new window for therapy targeted at maintaining iron in normal physiologic ranges to decrease pulmonary complications in patients with sickle cell anemia. Further studies with larger samples are necessary to clarify the meaning of our marginally significant findings.

Disclosures
No relevant conflicts of interest to declare.
Preparation of Targeted Platelet Carrier and Its Antitumor Effect
Authors: Du Ying , Chen Baoan 
Published: November 2020

Objective:Tumor targeting proteins were modified on the surface of platelets and chemotherapeutic drugs were encapsulated in platelets. Based on the fact that platelets can enter the tumor environment and interact with tumor cells, the functionalized platelets carrier has dual targeting effect to kill tumor cells.Methods:Aspirin was used to inhibit platelets aggregation and deformation in vitro to obtain complete platelets. Exogenous Tf (transferrin) was modified on platelets surface to target specific tumor cells (human multiple myeloma cell line RPMI8226). DOX (doxorubicin) was loaded into platelets. To verify the inhibitory effect of functional platelets vector on cell. To observe the distribution of targeted functional platelets vector and treatment effect on implant tumor in mice.Results:Aspirin can inhibit platelets aggregation and deformation during the preparation process effectively. Stable platelets can be modified by Tf and encapsulate DOX effectively. At the same time, the functional platelet vector can specifically aggregate in the implant tumor site in vivo and achieve effective anti-tumor effect.Conclusion:Platelets aggregation and deformation can be inhibited by aspirin effectively, which makes it a stable natural drug carrier. The antitumor effect can be achieved by the functional platelets.
Keywords:platelets, encapsulation, doxorubicin, tumor

Disclosures
No relevant conflicts of interest to declare.
Ruxolitinib for the Treatment of Polycythemia Vera: Response on Alternative Dose Versus Standard Dose
Authors: Cacciola Emma , Vecchio Veronica , Gentilini Cacciola Elio , Cacciola Rossella Rosaria 
Published: November 2020

The polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by increased hematocrit (HCT), elevated white-cell and platelet counts and splenomegaly. The most commonly used first line cytoreductive agent is hydroxyurea (HU). However, some patients have an inadequate response or have inacceptable side effects from HU. Ruxolitinib, a Janus kinase (JAK) 1 and 2 inhibitor, was shown to have a clinical benefit in patients with PV. A phase 3 study (RESPONSE) have shown that PV patients on Ruxolitinib at dose of 10 mg twice daily at week 32 had a complete hematologic remission. In this study were enrolled 40 patients with PV (30 men, 10 women; mean age 54 years, range 51-57) according to WHO criteria, assigned to Ruxolitinib at dose of 5 mg twice daily for clinical evidence of liver dysfunction. All patients were evaluated for JAK2V617F allele burden, HCT, white cells and platelets, splenomegaly and symptom burden, including pruritus, fatigue and night sweats. The mean duration of disease was 9 years. All patients received low-dose aspirin and underwent phlebotomy. Before Ruxolitinib, all patients had JAK2V617F allele burden &gt; 50%, HCT control on phlebotomy, high white cells (12x109/L) and elevated platelets (600x109/L) and spleen volume of 450 cm3 or more as measured by magnetic resonance imaging (MRI) or computed tomography (CT). After Ruxolitinib we observed a shortened response time at week 6 marked by JAK2V617F allele burden &lt; 50%, HCT &lt; 45% in the absence of phlebotomy, normal white cells and platelets (6x109/L and 320x109/L, respectively) and reduced spleen size as assessed by palpation and absence of symptoms. These data suggest that the Ruxolitinib treatment at the alternative dose of 5 mg twice daily can be effective in achieving a rapid and complete hematologic remission that is still present in these patients receiving this dose of Ruxolitinib at the time of this analysis.

Disclosures
No relevant conflicts of interest to declare.
Somatic Mutations Predict Poor Prognosis in Myelodysplastic Syndrome Patients with Normal Karyotypes
Authors: Zeng Xiangzong , Dai Min , Zhang Yu , Zhou Lingling , Zhou Ya , Liu Qifa 
Published: November 2020

Purpose: Somatic mutations are common in myelodysplastic syndrome (MDS), but its risk stratification is mainly based on cytogenetics. This study was to explore the prognostic significance of somatic mutations in MDS patients with normal karyotypes.
Patients and Methods: Three hundred and four patients with MDS were enrolled in this retrospective study. A genomic panel of 127 gene targets were detected by next-generation sequencing.
Results: Two hundred and Eighty-one (92.4%) patients carried at least one somatic mutation, while cytogenetics identified abnormalities in 140 (46.1%) patients. The 5 most frequently mutated genes were TET2, ASXL1, EZH2, TET1, FAT1, and TET2, TP53, TET1, EP300, SF3B1 in the patients with normal karyotypes and aberrant karyotypes, respectively. When mutations detected in &gt;5% of the whole cohort, they were included in analysis and the results showed that the frequency of TET2, TP53, ASXL1, CD101, KDM6A, SH2B3 and IL-3RA mutations was different between two groups(all P&lt;0.05). ASXL1, CD101, KDM6A, SH2B3, IL-3RA mutations were more common in normal karyotype group, while TET2 and TP53 were more common in aberrant karyotype group. Multivariable analysis showed that age (HR 1.02; P=0.027), IPSS-R(HR 1.80; P&lt;0.0001), TP53(HR 2.36; P&lt;0.0001) and DNMT3A (HR 1.83, P=0.044) were the risk factors while allo-HSCT(HR 0.50; P=0.001) was a protect factor for OS in the whole cohort. For sub-group analysis, IPSS-R(HR 1.54; P=0.005; HR 1.80; P&lt;0.0001, respectively), TP53 mutation(HR 2.49; P=0.030; HR 2.13; P=0.005, respectively) and allo-HSCT(HR 0.52; P=0.040; HR 0.37; P&lt;0.0001, respectively) retained the prognostic significance in both the normal karyotype and aberrant karyotype group. FAT1(HR 2.32; P=0.019), DNMT3A(HR 3.32; P=0.006) and IL-7R(HR 4.35; P=0.002) mutations were unfavorable factors for OS only in the normal karyotype group.
Conclusion: FAT1, IL-7R and DNMT3A mutations pretict poor prognosis in MDS patients with normal karyotypes.
Key words: Somatic mutation, Next-generation sequencing, Prognosis, Myelodysplastic syndrome

Disclosures
No relevant conflicts of interest to declare.
Diarrheal Morbidity in Patients Undergoing Hematopoietic Cell Transplantation - the Diagnostic Yield of Stool Cultures
Authors: Berger Tamar , Giladi Odil , Yahav Dafna , Ben-Zvi Haim , Pasvolsky Oren , Shargian-Alon Liat , Wolach Ofir , Rozovski Uri , Raanani Pia , Yeshurun Moshe 
Published: November 2020

Diarrhea affects a significant proportion of patients undergoing hematopoietic cell transplantation (HCT). In this single center retrospective study, we explored the diagnostic yield of stool cultures for enteric pathogens among patients undergoing HCT. Between May 2007 and April 2020, a total of 1072 individuals underwent autologous (n=603) and allogeneic (n=469) HCT. Overall, 947 stool culture samples were obtained from 561 (52%) patients with diarrheal illness during hospitalization for HCT. Most (99%) samples were obtained beyond 3 days of admission and mainly (77%) during neutropenia. Overall, only four (autologous HCT, n=3; allogeneic HCT, n=1) patients were diagnosed with positive stool culture (0.42%) and in all cases, Campylobacter spp. was the pathogen identified. All isolates grew from the first stool culture obtained. The number of stool cultures needed-to-test to diagnose one case of bacterial infection was 237. The cost of diagnosing one case of bacterial infectious diarrhea was 8,770 US dollars. The median time from admission to positive stool culture sample was 12 (range, 7 to 13) days. Patients with a positive stool culture did not have discerning clinical or laboratory characteristics. In conclusion, according to our experience, the yield of stool cultures for enteropathogens in patients undergoing HCT is extremely low and thus should be avoided in most cases.

Disclosures
Wolach: Amgen: Other: Fees for lectures and Consultancy; Janssen: Other: Fees for lectures and Consultancy; Pfizer: Consultancy, Honoraria; Novartis: Consultancy, Honoraria, Other: Fees for lectures and Consultancy; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Fees for lectures and Consultancy, Research Funding; Astellas: Consultancy, Honoraria, Other: Fees for lectures and Consultancy.
Combination of Homoharringtonine with Venetoclax and Azacitidine Excerts Better Treatment Response in Relapsed /Refractory Acute Myeloid Leukemia
Authors: Yu Guopan , Xu Na , Huang Fen , Fan Zhiping , Liu Hui , Shi Pengcheng , Zhou Hongsheng , Wang Zhixiang , Zhang Yu , Liu Qifa 
Published: November 2020

Overexpression of Bcl-2 is known to be an important factor for drug resistance in relapsed /refractory acute myeloid leukemia (R/R-AML). Combination of Bcl-2 inhibitor venetoclax with hypomethylating agents (HMA) has shown promising killing effect in elder patients with newly diagnosed AML, also worked in R/R-AML but with low rate of complete response (CR). High expression of Bcl-XL and/or Mcl-1 is the main reason for resistance to venetoclax. As an inhibitor of both Bcl-XL and Mcl-1, homoharringtonine (HHT) has presented a synegetic effect with venetoclax in inhibition of Mcl-1 and killing of lymphama. In this study, we analyzed the treatment response and safety of combination of HHT (1mg/m2 d1-7) with venetoclax (400mg d1-14) and azacitidine (75mg/m2 d1-7) (HVA) in R/R-AML. From 6, 2019 to 5, 2020, in Nanfang Hopsital, 22 patients with RR-AML were treated with HVA (HVA group), with a median age of 39(16-62) years, previous chemotherapy of 3(1-7) cycles. 15 (68.2%) relapsed within one year after allogenetic hematopoietic stem cell transplantation (allo-HSCT) and 12 (54.5%) previously exposed to HMA treatment. Meanwhile, 7 patients with RR-AML were treated with venetoclax combined with HMA (control group), with a median of 42(31-74) years, previous chemotherapy of 3(1-6) cycles. 2 (28.6%) relapsed after allo-HSCT and 5 (71.4%) had HMA exposure. In HVA group, totally 11/17(64.7%) patients acquired treatment response, and 7/15(46.7%) obtained CR/CRi, of whom 6 presented minimal residual disease (MRD) negative. While in control group, only 2/7(28.6%) acquired treatment response and 1 obtained CR. Subgroup analysis in HVA group showed allover response rate (ORR) was 9/13(69.2%) and CR rate was 6/11(54.5%) (all with MRD negative) in the patients with allo-HSCT. And in the patients without allo-HSCT ORR was 2/4(50.0%) and CR rate was 1/4. With a median follow-up of 6(1-7) months, one patient was bridged to allo-HSCT, 2 out of 7 patients with CR relapsed. All patients were well tolorated to both treatment regimens, showing as a median neutropenia of 9.5(5-14) days, 5 patients with Febrile neutropenia and 4 with pulmonary infection. In conclusion, combination of HHT with venetoclax and azacitidine (HVA) excerts better treatment response in R/R-AML, especially in those with allo-HSCT, and shows well tolorated. A multi-center prospective clinical trial (NCT04424147) has been initiated.
Key words: HVA regimen, relapsed /refractory acute myeloid leukemia, treatment response, safety

Disclosures
No relevant conflicts of interest to declare.
Hemorrhage Is a Major Cause of Blood Transfusion in COVID-19 Patients
Authors: Sanz Cristina , Faundez Anabel , García Carulla Anna , Rodriguez Aliberas Marta , Coromoto Anny , Pereira Arturo 
Published: November 2020

INTRODUCTION
Reports from China and other countries have allowed to quickly understand the clinical and biological features of COVID-19. In contrast, little has been published on the transfusion requirements of COVID-19 patients and the clinical characteristics of transfused patients.
PATIENTS AND METHODS
For this cross-sectional study, we reviewed the blood bank and clinic records of 80 consecutive patients diagnosed with COVID 19, who required red blood cells (RBC) transfusion at the Hospital Clinic of Barcelona over a period of 60 days, from mid-March to mid-May 2020. COVID-13 was confirmed by at least two PCR test in nasopharyngeal swaps. Categorical data were described as frequencies and percentage and continuous variables were summarized as median and interquartile range (IQR)
RESULTS
Median age was 71 years (IQR: 62-76) and 59 (74 %) patients were males. The patients' main clinical characteristics and the indications for transfusion are summarized in the table. In total, the 80 patients received 2,081 RBC units in 261 independent transfusion episodes. Number of days on transfusion support ranged from 1 to 44 (median: 5).
Bleeding was the indication for transfusion in 55 patients (69%), and included either large hematomas in 22 and external hemorrhage in 31. Anemia of critical illness was the reason for transfusion in 22 (27%) patients. Most patients were on anticoagulants at the time of transfusion or the two days before (table). In total, 138 of the 261 transfusion episodes (59%) were related to spontaneous (94) or procedure-related (44) bleeding. Spontaneous bleeding was more frequent in the retroperitoneal space and the gastrointestinal apparatus. Tracheostomy with endotracheal intubation, surgical interventions, and cannulation of femoral vessels were the main procedures behind non-spontaneous bleeding.
Hemorrhage was protracted and difficult to control and patients often required transfusion support for several days. Not rarely, hemorrhage recurred when the patient was restarted on anticoagulants. It was not unusual for bleeding from an anatomical location to be followed by, and overlapped with bleeding from a different location.
Seventeen patients died during the period on study. None of the deaths was ascribed to hemorrhage or the blood transfusion.
DISCUSSION
Bleeding, mostly related to the use of anticoagulants, was the main indication for RBC transfusion in patients with COVID-19.
Figure 1

Disclosures
No relevant conflicts of interest to declare.