bluuebunny/crossref_metadata_2025_split huggingface dataset:
PB1970 AUOTOIMMUNE HEMOLITIC ANEMIA (AIHA) IN CHILDHOOD. IS PRIMARY IMMUNE DISORDERS MORE OFTEN THAN EXPECTED IN ETIOLOGY OF SECONDARY AIHA
Authors: Patiroglu T. , Alper O. , Cansever M. , Unal E. , Yilmaz E. , Karakukcu M. 
Published: June 2019

Background:Auotoimmune hemolitic anemia (AIHA) results from redcell destruction due to circulating antibodies against redcell membrane antigens. They are classified etiologically into primary and secondary such as primary immune disorders (PID), infectious disease and connective tissue disorders (CTD).Aims:Herein, we aimed to evaluation of etiology in cases with AIHA.Methods:62 cases diagnosed on positive direct antiglobulin test (DAT)at department of pediatric hematology in Erciyes University Hospital were included in the study and their records have been retrosectively examined.Results:Mean age of all cases was 61.9 ± 51.9 months (range of 1‐92 months). The cases showed a male predilection (M:F = 1.2). The results showed that 34 of 62 cases had primary 28 secondary AIHA (12 PID, 7 infections, 4 CTD, 3 Hodgkin disease, 2 endocrinopathies) respectively. Mean Hb value in cases with AIHA was 6.9 ± 2.5 g/dl and mean Hb value in cases with secondary AIHA was 6.8‐2.6 g/dl. All of them had mean low level of haptoglobulin (7.2 mg/dl in primary AIHA, 6.2 mg/dl in secondary AIHA) and they had mean high level of total bilurubin (4.9 mg/dl in primary AIHA and 1.4 mg/dl in secondary AIHA). There was no significant difference of mean Hb value in two groups (p = 0.783) but there was significant difference of mean bilurubin value in two groups (p = 0.001). One Case with secondary AIHA had IgM cold autoantibody and 61 cases had IgG warm autoantibody. The cases with primary AIHA had more strong positive IgG autoantibody than the cases with secondary AIHA and there was significant difference of IgG autoantibody positivity in two groups (p = 0.044).Summary/Conclusion:AIHA presented with severe anemia and laboratory evidence of marked hemolysis. Especially, PID is more often than expected in etiology of secondary AIHA.
PB1987 SELECTIVE ACTIVATION OF TOLEROGENIC CELL DEATH PATHWAYS IN MESENCHYMAL STROMAL CELLS
Authors: Savoldelli R. , cheung T. , Galleu A. , Dazzi F. 
Published: June 2019

Background:Mesenchymal stromal cells (MSCs) have been successfully employed for their tolerogenic and immunosuppressive capabilities in different conditions. We have demonstrated that, following infusion, MSCs undergo apoptosis and that this apoptosis results in an immunosuppressive activity. However, it is unclear how MSCs respond to different death inducing stimuli and whether MSCs from different sources respond similarly when following analogous patterns.Aims:To characterize the molecular response of MSCs, obtained from different sources, to distinct cell death stimuli.Methods:MSCs were isolated from human bone marrow (BM‐MSCs) or umbilical cord (UC‐MSCs) of healthy donors and exposed to recombinant human Tumor necrosis factor‐a(TNF‐a) and Interferon‐g(IFN‐g) in combination or individually, anti‐FAS (activator), TNF‐related apoptosis‐inducing ligand (TRAIL), phytohemagglutinin (PHA) activated Peripheral Blood Mononuclear Cells (PHA‐aPBMCs), hydrogen peroxide (H2O2) with or without the presence of the pan‐caspase inhibitor Z‐VAD. After 24 h, the cells were harvested and stained for annexin V/7‐AAD and analyzed by flow‐cytometry. The cancer cell line MCF‐7 was used as a positive control.Results:BM‐MSCs showed high sensitivity to apoptosis induction when treated with FAS activator (11% of AnnV+/7‐AAD‐ and 72% AnnV+/7‐AAD+) and PHA‐aPBMCs (7% of AnnV+/7‐AAD‐ and 78% AnnV+/7‐AAD). Conversely, UC‐MSCs were more resistant to apoptosis mediated by FAS, since the percentages of AnnV+/7‐AAD‐ and AnnV+/7‐AAD+ were 63% and 9%. Both BM‐MSCs or UC‐MSCs were only marginally sensitive to TRAIL (35% of apoptosis). In all cases, apoptosis induction was caspase dependent, as demonstrated by the significant reduction (p < 0.001) of the proportion of apoptotic cells in both BM‐MSCs and UC‐MSCs in the presence of the pan‐caspase inhibitor Z‐VAD. Conversely, neither BM‐MSCs or UC‐MSCs were induced to undergo apoptosis when treated with TNF‐aalso at very high concentrations or in combination with IFN‐g. The efficacy of the recombinant TNF‐ain inducing cell death was confirmed by using the cell line MCF‐7 as sensitive controls. Finally, all MSCs were sensitive to H2O2.Summary/Conclusion:MSCs exhibit varying susceptibility to different apoptotic stimuli. Interestingly, although this property seems to be maintained across different tissues of MSC origin, we could find variable degrees of sensitivity to specific stimuli, thus suggesting that different MSCs may play distinct roles according to the specific environment.
PB1988 CANCER‐ASSOCIATED MECHANISMS OF MESENCHYMAL STEM CELLS REVEALED BY SINGLE‐CELL TRANSCRIPTOME ANALYSIS
Authors: Stucky A. , Chen X. , Li C. , cai J. , Zhang X. , Zhong J. 
Published: June 2019

Background:The detrimental effects of mesenchymal stem cells (MSCs) in some reports eclipse their benefits in clinical application, despite the support and adoption in bone marrow transplantation (BMT). Tumorigenicity has been observed and reported in experimental MSC therapies without clear explanation.Aims:Here we report a subpopulation of MSCs, which are resisted to oste single‐cell transcriptome analysis of individual MSCs at various stages of osteocyte differentiation and gene expression profiles in three discrete stages of osteogenesis.Methods:We identified a subpopulation of osteogenesis‐resistant MSCs which have cancer stem cell chatcteristics. Further pathway analysis indicated that the YAP1, β‐Catenin and Cadherin4/6 pathway involved in osteogenesis‐resistance.. Clinical surveys using 51 clinical databases across 6,965 patients revealed a correlation between YAP1/ β‐Catenin/Cadherin4/6 overexpression and cancer progression.Results:This study suggested that a differentiation‐resistant population of MSC is repsoible for the tumorogenicity of MSC, and intervention of the YAP1, β‐Catenin and Cadherin4/6 pathway could potentially prevent tumorgenicity in MSC therapies. suggests that there is a pre‐exist subpopulation of MSCs with cancer stem cell characteristics.Summary/Conclusion:Those OR‐MSC associated with active YAP1‐Cadherin pathway. Biologically active molecules targeting YAP1/ β‐Catenin/Cadherin could improve MSC therapy for a defined subset of patients by minimize the tumorgenicity of MSCs.
PB1989 SHORT‐TERM APPLICATION OF CAFFEIC ACID SPECIFICALLY PROMOTES EXPANSION OF HEMATOPOIETIC STEM CELLS
Authors: Liu Y. , Wang R. , Liu Y. , Liu X. , Wang Y. , Hou M. 
Published: June 2019

Background:Caffeic acid (CFA) is a commonly used medicine in China for treatment of various causes of thrombocytopenia and leukocytopenia, but the mechanism is unclear.Aims:To investigate the effect of CFA on umbilical cord blood hematopoietic stem cells (UCB–HSCs) in vitro and explore the differentiated effect of CFA on cell expansion and differentiation in various tissues in vivo.Methods:CD34+ HSCs were isolated from cord blood and cultured for expansion. After 7 days’ culture with CFA, the total cell number and proportion of CD34+ cells were detected. Differentiation ability was analyzed by colony formation assay and megakaryocytes inducing assay before and after expansion. Additionally, CD‐1 mice were administered with CFA or vehicle for 14 days and BrdU injection started from day 7. Blood cell count was examined every 3 days. The proportion in bone marrow nucleated cells and BrdU insertion rate of HSCs were detected by flow cytometry. Besides, the percentage and BrdU insertion rate of Lgr5+ stem cells in intestinal mucosa, Sca‐1+ cells in lung and CK‐18+ epithelial cells in kidney were also analyzed.Results:In HSC expansion tests, the mean number (4.40∗10^5/well) and proportion (60%) of CD34+ cell in CFA groups were significantly higher than controls (4.00∗10^5/well; 48%). In HSC colony formation assay and megakaryocytes inducing assay, there were no significant difference between CFA groups and control. In vivo, the mean proportion (1.59%) and BrdU insertion rate (5.18%) of HSCs in CFA groups were higher than control (0.65% and 2.24%). No statistical differences were observed in other tissues.Summary/Conclusion:CFA can promote expansion of UCB–HSCs. Administration of CFA for 14 days specifically increased the proportion and DNA synthesis rate of bone marrow HSC in mice.image
PB1994 HEMATOPOIETIC STEM CELL EXPANSION IN THE PRESENCE OF NICOTINE AMIDE AND IN THE MICROFLUIDIC DEVISE AND THE DBM SCAFFOLD
Authors: Asgari M. , asgari M. 
Published: June 2019

Background:The low number of umbilical cord blood cells is an important barrier to successful bonemarrow transplantation. Therefore, the growth of these cells while maintaining theirfunctional characteristics is of great importanceAims:Using microfluidic technology as well asculturing cells on 3D scaffolds like DBM has greatly contributed to the simulation of themechanical and chemical micro‐environment of the bone marrow tissue. There are alsospecific compounds for proliferation without differentiation of cells, one of them isnicotinamideMethods:In this study, hematopoietic stem cells were cultured 7 days in two groups: 1.In DBM in the microfluidic device 2. In DBM in the static state (control), under the followingConditions:1.negative control with feeder2.cytokine+feeder3.nicotinamide+feeder4.nicotinamide+cytokine+feederAfter 7 days, cell count, real‐time PCR, their purity using flow cytometry, Colony forming unit assayand apoptosis was evaluated. The status of the cells on the scaffold was observed usingelectron microscopy.Results:Our results indicated that more cells were counted in static culturethan microfluidic culture (perfusion), while the ability of cell colonization in microfluidicculture was far higher. The purity of HSCs was higher in microfluidic culture, and fewer cellsentered the apoptotic phase.Summary/Conclusion:Nicotinamide by preventing epigenetic changes resulting from laboratory cell culture, andthe microfluidic device associated with DBM by simulating bone marrow niche is a verya suitable compound for the development of these cells.
PB2005 LONG TERM SURVIVORS HODGKIN'S LYMPHOMA: A SINGLE CENTER EXPERIENCE
Authors: Gaudio F. , Perrone T. , Curci P. , Russo Rossi A.V. , di Noi M. , Urbano M. , Piccolomo A. , Laddaga F.E. , Zucano S. , Arcuti E. , Specchia G. 
Published: June 2019

Background:Since the introduction of modern radiotherapy and combination chemotherapy, Hodgkin lymphoma (HL) has become a highly curable malignancy with 5‐year survival rates of more than 80%. However, the life expectancy and quality of life of HL survivors are reduced by the occurrence of late adverse treatment effects.Aims:This retrospective study was focused on 96 patients with newly diagnosed HL treated at the University Hospital of Bari (Italy) between 2005 and 2008.Methods:Median age at diagnosis was 35 years (range 15‐83), 33 pts (34%) presented advanced stage (III‐IV), 43 (45%) bulky disease, 45 (47%) presented B symptoms, 26 (27%) extranodal disease.First line chemotherapy was ABVD in all the patients. The median number of chemotherapy lines was 1 (1‐5), 49 patients (51%) had undergone radiotherapyResults:At the end of treatment, 75 patients (78%) were in CR, and 24 patients (25%) in PR; 18 patients (24%) relapsed after a median follow‐up of 54 months (range: 12 – 62 months); 20 (21%) underwent autologous hematopoietic stem cells transplantation, 3 (3%) allogeneic stem cell transplantation.After a median follow‐up of 12 years, 83 patients (86%) remain alive and 13 (14%) have died (4 of A second neoplasia, 1 of infection, 8 of the disease). The 10‐year Kaplan‐Meier survival estimates were 84%. Three women were pregnant and 3 healthy children were born. The most prevalent chronic conditions At last follow‐up were: overweight/obesity (65%), elevated fasting glucose (38%), high total cholesterol (34%), and hypertension (25%).Summary/Conclusion:Results of this study offer indications about how long after the initial treatment the excess deaths from causes other than Hodgkin's disease begin to occur. However, challenges remain in establishing the optimal time to begin screening for potential late complications and in developing better surveillance guidelines. Further work is also needed to identify risk factors that may predict specific late effects.
PB2007 PRELIMINARY RESULTS OF USING BRENTUXIMAB VEDOTIN IN RELAPSE/REFRACTORY HODGKIN'S LYMPHOMA.
Authors: Jazyltayeva A. , Gabbasova S. , Kemelbekov N. , Karakulov R. , Nassypov B. , Sagyndikov G. , Ishkinin E. , Akanov A. , Taktybayeva A. , Mirzayeva M. , Seidlazym M. 
Published: June 2019

Background:Hodgkin disease (HL) is curable disease in up to 80% of patients, but for the remaining relapse/refractory patients no standard salvage therapy exists. Brentuximab vedotin comprises an anti CD30 antibody conjugated by a protease‐cleavable linker to a microtubule‐disrupting agent.Aims:The aim of the study is to evaluate the outcome of patients with relapse/refractory form of HL, who received Brentuximab vedotin.Methods:In our Institute 21 patients with HL were treated, from 2015 till 2018 years. 17 (81%) patients had a primary‐resistant form, four (19%) patients had relapse of the disease.The average age was 34.5 years (from 20 to 69 years), the average number of courses of therapy is 5.38 (from 3 to 8 courses). The mean follow‐up period was 17.9 months (from 4.1 to 38.1 months).Results:We have analyzed the survival of patients who received treatment. 21 patients who entered the study at the time of collection of information, 15 (71.4%) patients were alive. Median survival was 33.2 months. The standard error (SE) is 3.3 months, with 95% CI (26.8 ‐ 39.6).Among patients with a primary resistant form, 13 (76.5%) patients were alive, with a median survival of 28.1 months, a SE of 2.3 months of 95% CI (23.6–32.6). Among patients with a non‐primary resistant form, two (50%) patients were alive, while the median survival was 9.1 months, SE 2.4 months 95% CI (4.5–13.7). Eleven patients had a partial response to treatment (52, 4%), ten of them (90.9%) were alive, while the median survival was 27.9 months, SE 2.3 months 95% CI (23.5 ‐ 32.4).In three (14.3%) patients, a complete response to treatment was noted, of which three (100%) patients were alive. Cancer progression was noted in seven (33.3%) patients, two of them (28.6%) were alive, while the median survival was 27.9 months, SE 2.3 months 95% CI (23.5 ‐ 32.4).In analyzing six (28.6%) patients had AutoSCT, and 15 (71.4%) patients did not, due to low stem cell growth. Among patients, which didn’t have AutoSCT 11 (73.3%) patients were alive, with a median survival of 30.4 months, a SE of 2.7 months of 95% CI (25.1 ‐ 35.7). When analyzing the causes of mortality, all patients indicated the cause of death from the progression of cancer.Summary/Conclusion:The analysis of the results using Brentuximab Vedotin showed good results in treatment of relapse and refractory forms of HL. In patients who failed to perform autologous stem cell transplantation, showed median survival of 30.4 months. This indicates the possibility of using the drug as an alternative to this procedure for the primary resistant form of the disease or further therapy options.
PB2023 SPORADIC CASES OF MALARIA IN NORTHERN GREECE, A MALARIA FREE COUNTRY
Authors: Tsioni K. , KARANTANI K. , PYRPASOPOULOU A. , TSAMIS E. , ISSA M. , VAGDATLI E. 
Published: June 2019

Background:Malaria is a disease caused by protozoa of the genus Plasmodium and the main hosts are arthropods. Human transmission is preceeded by female mosquito Anopheles bite. Human pathogens are Plasmodium vivax, falciparum and malariae, Less common are Plasmodium ovale and knowlesi. Since 1974, Greece is a Malaria free country. Nevertheless, sporadic cases are reported.Aims:We report five cases of malaria admitted in a tertiary care hospital of Thessaloniki.Methods:Five patients, 15‐34 years old were admitted consecutively, in three different departments of a tertiary care hospital in northern Greece from 2/10/2018 to 10/10/2018 due to fever, fatigue and night malodorous sweats. All five patients were relatives. Two sisters, living in the same house and their cousin with her two children, living in the same residential area. None of them had recently travelled in an epidemic county or had a blood transfusion. The diagnosis was based on a peripheral blood smear which was performed due to anemia, thrombocytopenia and neutropenia reported upon admission of the first patient. Characteristic ring forms, merozoites, trophozoites inside red blood cells and gametocytes were observed. Rapid malaria test revealed non‐falciparum infection and samples for molecular diagnostic testing were collected. Molecular analysis established Plasmodium vivax infection. All patients were treated with atovaquone 250 mg/ proguanile 100 mg per os, 4 pills once a day, for three days. Patients responded promptly and continued eradication therapy with primaquine for the next 14 days. Patients follow up included weekly visits at the hospital, blood testing with FBC, peripheral blood smears and rapid malaria testing, for three consecutive weeks in order to establish Plasmodium full elimination.Results:All patients were cured without complications. Due to the severity of the disease, the Greek Center of disease control was called to locate the source of the disease and take action concerning public health.Summary/Conclusion:Given the fact that malaria is not a common diagnosis, clinicians should have a close collaboration with the laboratory, even in malaria free countries. New sporadic cases can be found due to population migration. Increased rainfall, also affects malaria transmission because it increases relative humidity, modifies temperature and affects mosquito population and is a probable cause for those five cases in Thessaloniki. All cases must be reported as soon as possible and general population should be protected. Prompt diagnosis and treatment are in favor of the patient and general population.
PB2030 COMBINATION OF INVASIVE ASPERGILLOSIS AND INVASIVE CANDIDIASIS IN ONCOHEMATOLOGICAL PATIENTS
Authors: Shagdileeva E. , Shadrivova O. , Shneyder T. , Ermolova S. , Bogomolova T. , Ignatyeva S. , Klimko N. 
Published: June 2019

Background:Candida spp. and Aspergillus spp. are the most common fungal pathogen an oncohematological patients. Publications about combination of invasive aspergillosis (IA) and invasive candidiasis (IC) are limited.Aims:To investigate the frequency, risk factors, treatment outcome in patients with combination of IA and IC.Methods:Retrospective analysis of 800 adult patients with proven and probable IA in 1998 ‐ 2017 yy. For the IA and IC diagnosis criteria EORTS/MSG, 2008 were used.Results:IC was detected in 10 patients, 1.25% of all IA patients. The patients’ age was from 18 to 59 years (median ‐ 37), men ‐ 60%. Among the underlying conditions acute leukemia prevailed ‐ 60%, lymphoma ‐ 10%, aplastic anemia ‐ 10%, and hemolytic uremic syndrome – 10%.Main risk factors were prolonged neutropenia – 90% (median – 10 days), lymphocytopenia ‐ 70% (median – 19 days), ICU stay – 50%, and glucocorticosteroid therapy – 40%.The main clinical variant of IC was candidemia (100%) with liver (10%) or spleen (10%) involvement. The main sites of IA were lungs (100%) and sinuses (20%).Diagnosis of IC was confirmed with blood culture in all patients: C. krusei – 40%, C. parapsilosis – 30%, Candida spp. – 30%. Positive galactomannan test in bronchoalveolar lavage (BAL) was in 80% patients. Microscopy of BAL revealed septated mycelium in 20% patients, BAL culture was positive (A.flavus) in 20% cases.All patients received antifungal therapy (voriconazole ‐ 60%, amphotericin B deoxycholate ‐ 60%, fluconazole – 30%, lipid amphotericin B – 20%, posaconazole – 20%). In patients with IA and IC 30‐days overall survival rate was 60%, 12‐weeks overall survival rate – 40%.Summary/Conclusion:Invasive candidiasis was detected in 1,25 % of patients with invasive aspergillosis. Main risk factors were prolonged neutropenia and lymphocytopenia, ICU stay, and glucocorticosteroid therapy. The main agents of invasive candidiasis were C. krusei ‐ 40% and C. parapsilosis – 30%. The main clinical variant of invasive candidiasis was candidemia (100%) with liver (10%) or spleen (10%) involvement. In patients with invasive aspergillosis and invasive candidiasis 30‐days overall survival rate was 60%, 12‐weeks overall survival rate – 40%.
PB2034 INVASIVE ASPERGILLOSIS IN PEDIATRIC PATIENTS WITH MALIGNANCIES
Authors: Dinikina Y. , Shadrivova O. , Belogurova M. , Ignatyeva S. , Bogomolova T. , Boichenko E. , Klimko N. 
Published: June 2019

Background:Invasive aspergillosis (IA) is an important cause of infectious morbidity and mortality in immunocompromised pediatric patients. Early recognition and initiation of antifungal treatment are key to the infection control and possibility to continue anticancer treatment.Aims:To evaluate risk factors and treatment results of IA in children with malignancies.Methods:Retrospective analysis of the pediatric register of IA in malignancies from 1997 to January 2019. For the probable and proven IA diagnosis EORTC / MSG, 2008 criteria were used.Results:46 pediatric patients with malignancies were included, median age ‐ 8 years, males – 69,5%. IA was diagnosed after cytostatic chemotherapy in 42 patients (91,3%), in debut of cancer prior to chemotherapy – 4 (8,7%). Hematological malignancies were underlying diseases in 39 patients (84,7%), solid tumors – 7 (15,2%). Most frequent hematological diagnoses were myeloid leukemia (34,7%) and acute lymphoblastic leukemia (34,7%). Among solid malignancies – central nervous system tumors (42,8%). Risk factors of IA were prolonged ≥10 days neutropenia – 82,6%, steroid therapy – 50%, long‐term lymphocytopenia – 45,6%, severe bacterial infections (30,4%), and cytomegalovirus infection (8,8%). Main site of IA were lungs (89,1%), clinical signs were non‐specific. Typical imaging findings included the halo sign – 32,6% and air crescent sign – 4,3%. Galactomannan test in bronchoalveolar lavage fluid was positive in 83 %, in serum and cerebrospinal fluid – 37%. Mycological examination of specimen was attempted in 25% of patients. Among them septated hyphae by microscopy was diagnosed in 20%. Aspergillus spp. were isolated in culture in 28%. The etiology agents were A.fumigatus – 57%, A.niger – 29%, and A.ustus – 14%. Antifungal treatment received 100% of patients, with voriconazole only – 54,3%. 12‐week survival was 81%. In all cases of IA before chemotherapy after infection control anticancer therapy was continued. 63% of patients continued antifungal therapy concomitantly chemotherapy, voriconazole was canceled during vincristine use.Summary/Conclusion:Cases of IA in children with hematological malignancies were registered more frequently compared to solid tumors (84,7% vs 15,2%). The main risk factors of IA were prolonged neutropenia (82,6%), steroid therapy (50%), lymphocytopenia (45,6%). 12‐weeks overall survival was 81%. There were no contraindications for anticancer therapy to continue after infection control. In cases of continuation of antifungal treatment drug‐drug interactions should be considered.