bluuebunny/crossref_metadata_2025_split huggingface dataset:
Augmented Effects on Neovascularization by Mixing the Conditioned Medium from Early EPCs into Late EPCs Derived from Human Cord Blood.
Authors: Yoo Eun-Sun , Ahn Jee-Young , Bae Yun-Kyung , Kong Jee Hyun , Lee Sang Min , Mun Yeung-Chul , Lee Kyoung-Eun , Seong Chu-Myong 
Published: April 2020

Abstract
Recently, we have reported on two different types of EPCs from human umbilical cord blood(ASH 2005, Abstract #1706). These EPCs had different biologic properties in angiogenic capabilities during the HCB ex vivo expansion. In this present study, the aim is to examine the synergism by mixing the conditioned medium from the early EPCs into the late EPCs on neovascularization. The mononuclear cells from the HCB were cultures using an EGM-2 medium with VEGF, IGF-1 and FGF for 21 days. We found early spindle-shaped cells(early EPCs), which were grown in the first week of the culture and late cobblestone shaped cells(late EPCs) which peaked in their growth in the third week of the culture. First, we compared the two types of cells in terms of phenotypic expressions and migration ability. Next, we examined their proliferation capacity and tube formations in the Matrigel plate under the conditions that the early outgrowing cells-contained medium was added to the cobblestone shaped cells. The late-appearing cobblestone shaped cells were positive for VEGFR2, VE-cadherin, CD31, CD34 and CXCR-4 but not for CD14 and CD54. These late outgrowing cells expressed high levels of mRNA on the endothelial marker genes and effectively formed capillary tubes in the Matrigel plates. The early spindle cells excreted more angiogenic cytokines and had more migratory ability. When the early spindle-shaped cell-conditioned medium was added to the late cobblestone shaped outgrowing cells, significantly higher proliferation and tube formation measured by the area and length of tubes were found. These results suggested that the two types of cells raised with different biologic properties during the ex vivo HCB expansion and the angiogenic capacity of late EPCs were augmented by a mutual interaction via the excreted cytokines from early EPCs. These finding may have potential applications for a “cell therapy” in situations such as vascular injuries (ie, hindlimb ischemia/myocardial infarction). Murine models are being tested to see whether the injections of two different EPCs will result in synergic noevascularization in our Lab.
Marrow Contributes to Kidney Vasculogenesis in Humans.
Authors: Gurevitz Stacy A. , Jorgensen Marda L. , Scott Edward W. , Cogle Christopher R. 
Published: April 2020

Abstract
The hematopoietic stem cell (HSC) is capable of contributing to vasculogenesis in response to ischemic injury. We have previously demonstrated that adult hemangioblast activity also exists within the capabilities of human hematopoietic stem/progenitor cells (HSC/HPC). However, we question the clinical relevance of adult hemangioblast activity. Thus, to address this question, we sought to analyze the marrow contribution to blood vessels within damaged vascular beds. Given the nephrotoxic side effects of chemotherapy and hematopoietic cell transplantation regimens, we identified kidney tissues from women (n=4) who received hematopoietic cell transplantations from male donors. Kidney tissues were stained for CD31, CD45, and XY FISH. One hundred forty vascular fields were analyzed. Fields were divided into three zones based on physiologic functions: glomerular, arteriolar (afferent & efferent), and medullary. In ever zone we identified male/marrow-derived endothelial cells contributing to kidney vasculature. However, each zone differed as to the degree of male/marrow-derived vascular contribution. In the glomerular regions, 36% of glomeruli contained one or more marrow-derived endothelial cells, as determined by orientation at the lumen edge, CD31 surface expression, and Y chromosome staining. In contrast, only 4% of arterioles contained male/marrow-derived endothelial cells. In the medulla, 9% of blood vessels contained male/marrow-derived blood vessels. The median number of marrow-derived endothelial cells in all regions was 1 male cell per blood vessel in field. In conclusion, human marrow can contribute modestly to kidney vasculature, especially in glomeruli. These results expose a potential strategy of kidney vessel repair by illuminating marrow-derived vasculogenesis within the kidney.
The Variation of Platelet Function in Gestational Diabetes Mellitus.
Authors: Li Yiqing , Yin Songmei , Nie Danian , Wang Xiuju , Xie Shuangfeng , Ma Liping , Wu Yudan 
Published: April 2020

Abstract
Gestational diabetes mellitus (GDM) was as glucose intolerance of different severity that onset or first recognition during the current pregnancy. GDM was a special complication of pregency and the most common cause of fetal and maternal mortality and morbidity. The etiology of this disease is not clear. Increased platelet function was common in normal pregnancy or type 2 diabetes mellitus (DM) patients in the last decade. However, when pregnancy plus type 2 DM, that is, the GDM, was the platelet function still changed? In the current study, we tested blood platelet function including platelet counts (PC), mean platelet volume (MPV) and granule membrane protein-140 (GMP-140, also known as P-selectin, CD62P) in pregnant women with GDM. CD62P was a sensitive index to evaluate platelet activation. PC and MPV would alter when platelets had been destructed significantly, so they were sensitive indexes for platelet activation too. PC was (206.02±60.23)×109/L in GDM, (228.76±56.24)×109/L in normal pregnancy, (219.76±58.14)×109/L in type 2 DM without pregnancy. MPV was 9.53±1.64fl in GDM, 8.74±1.59fl in normal pregnancy, 9.16±1.23fl in type 2 DM without pregnancy. The PC and MPV had no significant difference among GDM, normal pregnancy and type 2 DM without pregnancy (P&gt;0.05). The expression of CD62P was higher than that of normal pregnancy or type 2 DM (41.82±12.95% vs. 26.21±7.09% or 24.18±8.79% P&lt;0.05). These results indicate that there were much more platelet activation in GDM compared with normal pregnancy or type 2 DM, but the platelet destruction was not increased. Inhibition of activated platelet may be a new therapeutic strategy for the treatment of GDM. However, whether there was special role affecting platelet activation directly in GDM was unknown. The concrete mechanism underlying GDM platelet dysfunction need more elucidated.
The Use of Recombinant Factor VIIa (NovoSeven®) in a Patient with Bernard Soulier Syndrome and Dental Extraction.
Authors: Gerhardt Andrea , Scharf Rudiger E. , Zotz Rainer B. 
Published: April 2020

Abstract
Background: Bernard Soulier syndrome is a rare autosomal recessive platelet function disorder that impairs platelet adhesion to von Willebrand factor, especially at high shear flow. The disorder results from partial to complete deficiency or dysfunction of the GP Ib-IX-V receptor. Bernard Soulier syndrome typically results in prolonged bleeding time, thrombocytopenia, and giant platelets. The main clinical symptoms, evident from early childhood, include frequent episodes of epistaxis and hemorrhage associated with mucocutaneous bleeding or trauma. Specific treatment of bleeding episodes or prophylaxis for the prevention of bleeding during surgical procedures are platelet transfusions. This treatment option is not devoid of complications.
Alloimmunization by HLA antigens and antibody formation to the GPIb-IX-V complex frequently occur and, thus limit future responses to platelet transfusions. Recent patient studies have suggested that recombinant factor VIIa (rVIIa, NovoSeven®) may be an effective therapy for treatment of bleeding in patients with congenital platelet function defects and other acquired platelet disorders, including thrombocytopenia.
Case Reports: We report on our experience with rFVIIa in a 21-year-old woman with Bernard Soulier syndrome and dental extraction (2 wisdom teeth). In 2000, after a first extraction of one wisdom tooth, that was covered by administration of DDAVP and platelet transfusion, a bleeding episode occurred, requiring resurgery. This time rFVIIa was used as first line therapy. An initial dose of rFVIIa (100 μg/kg/bw) was administered 15 min. prior to surgery, followed by two doses of 90 μg/kg/bw at 120 min intervals postoperatively. In the first three days after surgery, 90μg/kg/bw rFVIIa were administered every 12 hrs. Tranexamic acid (Cyklokapron® 3 x 1 g/d) was started postoperatively and continued for 10 days. There were no postoperative bleeding episodes and no platelet transfusion was required.
In conclusion, rFVIIa in combination with tranexamic acid appears to be an effective and safe therapeutic alternative for prophylaxis of bleeding episodes in dental extraction in patients with Bernard Soulier syndrome.
Anti-CD20 Monoclonal Antibody (Rituximab) as an Optional Treatment for Intractable Acquired Glanzmann’s Thrombasthenia.
Authors: Blickstein Dorit , Lahav Judith , Molad Yair , Inbal Aida 
Published: April 2020

Abstract
Glanzmann’s thrombasthenia is an autosomal recessive bleeding disorder characterized by severely reduced or absent platelet aggregation in response to physiologic agonists because of quantitative or qualitative abnormalities of platelet glycoprotein IIb/IIIa (GpIIb/IIIa). Acquired Glanzmann-like thrombasthenia may develop as a result of autoantibodies specific to platelets GpIIb/IIIa and has been described in association with autoimmune disorders. Patients with the acquired form experience variable degrees of mucocutaneous bleeding, and their platelets fail to aggregate with agonists such as ADP, thrombin, collagen, or epinephrine, whereas ristocetin-induced aggregation is normal. Treatment consists of a combination of one or more of the following: corticosteroids, chemotherapy, plasma exchange and high dose intravenous immunoglobulin (IVIG). We present a 75-year old woman with SLE who developed ITP at the age of 60 and underwent splenectomy with subsequent normalization of platelet counts. However, since that operation, the patient has been admitted several times due to variable degrees of mucocutaneous bleeding, including one episode of massive gastrointestinal hemorrhage. Platelet counts were 184 to 284 X 103/μL. Laboratory evaluation revealed a bleeding time of 15 minutes (normal 0.5 to 8 minutes) and no aggregation of platelets in response to ADP, epinephrin, collagen, and thrombinbut normal ristocetin-induced aggregation. Addition of 25% of patient’s platelet poor plasma to normal whole blood revealed reduced platelet deposition by 61% using cone and plate analyzer, thus, confirming the diagnosis of acquired Glanzmann’s thrombasthenia due to autoantibodies. Because of treatment failure with corticosteroids, immunosuppession and IVIG, anti-CD20 monoclonal antibody (Rituximab) 375 mg/kg/week for 4 weeks was administered resulting in normalization of platelets aggregation and complete clinical remission. Anti-CD20 therapy might be a therapeutic option for intractable antibody-mediated acquired thrombasthenia.
Incidence and Risk Factors for Severe Thrombocytopenia in Lymphoma Patients Receiving Chemotherapy.
Authors: Huen Auris , Zhou Xiao , Teegala Shyam , Ji Yuan , Fayad Luis , Romaguera Jorge Enrique , Hagemeister F.B. , Vadhan-Raj Saroj 
Published: April 2020

Abstract
Background: Severe thrombocytopenia (TCP) can be a serious complication of chemotherapy (CT) in lymphoma patients (pts), however the exact incidence with the current regimens and risk factors for TCP are not well known.
Methods: A retrospective cohort study was conducted to determine the incidence of TCP, and logistic regression analysis were performed to identify the clinical and laboratory features correlated with severe TCP in lymphoma. Medical records of 538 consecutive pts out of the 1050 lymphoma pts, who were newly referred to MDACC in 2003, were reviewed.
Results: 202 pts who received &gt; 1 cycle of treatment were included in the analysis. The total number of CT cycles (with PLT counts) for the 202 pts was 985 (median 6, range, 1–20). Grade (gr) 4 TCP (PLT nadir &lt; 25x103/μL) was observed in 39% (79/202) of pts and 20% (196/985) of cycles. The median cycle in which gr 4 TCP occurred was 2 (range, 1 to 11), and median PLT nadir count for gr 4 TCP was 12x103/μL (3 to 24x103/μL). The regimens most commonly associated with gr 4 TCP were Hyper-CVAD/ Ara-c/Mtx (31/35=89%), ESHAP (6/7=86%), ASHAP (3/4=75%), and ICE (5/7=71%) + rituxan, and the most common histological subtypes were MCL (15/19=79%), Burkitts lymphoma (7/9=78%), T cell lymphoma (10/17=58%), and LCL (31/64=48%). Thirty two of 79 (41%) gr 4 TCP pts had bleeding as compared to 8 of 123 (7%) pts with higher PLT counts (p=0.0001). Overall, the incidence of bleeding was 20% (40/202) by pts and 6% (60/985) by cycles; however, the most incidents [95% (57/60)] were minor. 80% (63/79) of Grade 4 TCP pts received PLT transfusions, as compared to only 2% (2/123) of the rest (p&lt;0.0001). Using multivariate logistic regression, histological gr, (highly aggressive or aggressive vs indolent: OR=10.402, 95% CI, 3.991 to 27.107, p&lt;0.0001), baseline PLT count (≤150 vs &gt;150x103/μL: OR=4.610, 95% CI, 1.366 to 15.560, p=0.0138), prior therapy (yes vs. no: OR=2.575, 95% CI, 1.337 to 4.961, p=0.0047), Beta2 Microglobulin (B2M) (≥2 vs &lt;2mg/L: OR=2.846, 95% CI, 1.401 to 5.783, p=0.0038), age (&gt;60 vs. ≤60 yrs: OR=0.479, 95% CI, 0.241 to 0.952, p=0.0356) were the most important risk factors for grade 3 or 4 TCP.
Conclusions: The incidence of severe TCP in this population is high. Baseline pt characteristics including histological gr, PLT counts, prior therapy, age and serum B2M were found to be significant risk factors predictive for chemotherapy-induced TCP (CIT). These findings could be useful to identify high risk pts for consideration of treatment approaches for prevention and treatment of CIT.
Outcome of Recombinant Factor VIIa Use for Alveolar Hemorrhage in Hematopoietic Stem Cell Transplant Recipients.
Authors: Gupta Sachin , Gupta Aditya , Jain Amit , Warneke Carla L. , Giralt Sergio , Eapen Georgie A. 
Published: April 2020

Abstract
Background: Hematopoietic Stem Cell Transplantation (HSCT) is being widely used as an adjunct to conventional chemoradiotherapy for many hematologic and solid malignancies and some non-malignant hematologic conditions. Alveolar Hemorrhage (AH), seen in 1 to 19% of HSCT recipients has a mortality of 70–100%. Case reports have suggested that administration of recombinant factor VIIa to patients with AH results in rapid clinical improvement and improved survival. Objectives: To study the impact of recombinant Factor VIIa administration in HSCT recipients with AH at M.D. Anderson Cancer Center.
Methods: A retrospective review of all adult patients who underwent bronchoscopy after HSCT between January 1, 2002 and December 31, 2004 for a presumptive diagnosis of AH. Outcome measures analyzed included requirement for positive pressure ventilation over the six months following bronchoscopy, the length of index hospitalization and survival. Pearson chi-squared tests, Fisher’s exact tests, and Wilcoxon rank sum tests were used for statistical analyses.
Results: Eighty seven patients were diagnosed with AH during the study period. Recombinant factor VIIa was administered to 24 patients with alveolar hemorrhage. All 24 patients received high dose steroids and intensive supportive care. Along with factor VIIa, 16 patients received platelet transfusions to keep platelet count above 50×109/L, 4 received desmopressin (DDAVP), and 3 received aminocaproic acid. Only 63% were alive at 30 days after bronchoscopy and 38% after 6 months. Overall, 17 of the 24 patients (71%) receiving factor VIIa died during the study period. Seventy five percent required positive pressure ventilation within 6 months of diagnosis. The median duration of hospitalization was 11 days (SD ± 10 days). No thrombotic complications were observed in any of these 24 patients. There were no statistically significant differences in median survival, 1 and 6-month survival, requirement for positive pressure ventilation, respiratory failure as the cause of death, or duration of hospital stay after bronchoscopy between patients with AH who received factor VIIa and those who did not (p=&gt;0.6 for all outcomes).
Conclusion: In our study of 24 patients with AH who received recombinant factor VIIa for AH, no significant improvement in survival or alteration in the hospital course was observed. Further prospective studies are needed to clarify the role of Factor VII for this indication.
Dose-Dense Induction Followed by Autologous Stem Cell Transplant (ASCT) as 1st Line Treatment in Peripheral T-Cell Lymphomas (PTCL) - A Phase II Study of the Nordic Lymphoma Group (NLG).
Authors: d’Amore Francesco , Relander Thomas , Lauritzsen Grete , Jantunen Esa , Hagberg Hans , Anderson Harald , Cavallin-Ståhl Eva , Holte Harald , Østerborg Anders , Merup Mats , Hansen Mads , Telhaug Ragnar , Erlanson Martin , Kuittinen Outi , Gadeberg Ole , Delabie Jan , Sundström Christer , Ralfkiær Elisabeth , Vornanen Martine , Jensen Charlotte B. 
Published: April 2020

Abstract
Systemic PTCL, with the exception of alk-positive anaplastic large cell lymphoma (ALCL), have a poor prognosis. ASCT has been shown to have a favourable impact on relapsed PTCL. Therefore, the NLG designed a prospective multicenter phase II study to evaluate the impact of a dose-intensified induction schedule (6 courses of two-weekly CHOEP) consolidated in 1st PR/CR with high-dose therapy (BEAM) followed by ASCT in previously untreated systemic PTCL. This is the largest prospective PTCL-specific trial published so far. Newly diagnosed non-primary cutaneous PTCL cases aged 18–67 yrs were eligible for enrollment. Cases of alk-positive ALCL were excluded. From Oct 2001 to Feb 2006, 99 histologically confirmed PTCL cases were included in the study: PTCL unspecified (n=41), alk-neg ALCL (n=24), AILT (n=15), enteropathy-type (n=12), panniculitis-like (n=3), T/NK nasal-type (n=2), hepatosplenic (n=2). The M/F ratio was 1.8 and the median age 55 yrs (range 20–67 yrs). Although almost 2/3 of the cases presented with advanced-stage disease (62%), B-symptoms (61%) and/or elevated s-LDH (63%), the majority of them (65%) had a good performance score (WHO 0–1) at diagnosis. Of the 77 patients, where information was available for all 6 induction courses, 68 (88%) were in CR (31) or PR (37) after the 3rd and 66 (86%) after the 6th course. A total of 58 patients (75%) went through ASCT indicating that at least a fourth of this younger patient cohort has a primary refractory disease and fails therapy before reaching the transplant. Treatment-related toxicity after both induction and high-dose treatment was manageable. Of the 58 transplanted patients, 50 (86%) were still in remission at re-evaluation short after transplant. In 39 patients follow-up data one year post-transplant were available: 30 are still in CR and 9 have relapsed, suggesting that post-transplant relapses probably account for another 25% of the original patient cohort. In conclusion, the present data indicate that a time- and dose-intensified schedule is feasible and effective in previously untreated systemic PTCL. Continuous remissions are not uncommon, but a longer follow-up is needed to further characterize long-term remission rates and evaluate their impact on time-to-treatment failure and overall survival.
Increased Tendency of Venous Thrombosis in Patients with Hematology Malignancies with Over-Expression of TF and Heparanase.
Authors: Corinaldesi Giorgio , Corinaldesi Christian 
Published: April 2020

Abstract
Patients with hematology malignancies have an increased risk of deep vein thrombosis and lower limb lymphedema which is often increased by an intensive chemioterapy or by a myeloablative regimen that often requires multiple platelet-transfusion. Hypercoagulability in cancer patients is associated to phlogosis (the mRNA levels for pro-inflammatory cytokines IL-1, IL-8, LIF, MIP2-alfa were also increased), dysprotidemia, age, bed rest, cancer cell prothrombotic properties (including activation of blood coagulation), impairment of fibrinolytic pathways, alterations of endothelium, increase of the clotting activation markers, and up-regulation of such genes as those coding for transcription factors (c.fos EGR-1, ETO101, c-Myc, Fry-1), over-expression of TF, over-expression of heparanase and formation of a fibrin coat.
Both the over-expression of TF and the formation of the TF/VIIa complex induce multiple cellular responses that include proteolytic activity, calcium fluxes, p44/p42 mitogen activated protein kinase phosphorylation, and generation of thrombin. The over-expression of heparanase increased angiogenesis, tumor growth, and metastasis.
To investigate the incidence of VTE (venous thromboembolism), and DVT (deep venous thrombosis) in patients with hematology malignancies we have studied 22 patients: 7 with a myeloproliferative disorder (5 with polycythemia rubra vera, 2 with essential thrombocyhemia), 4 with lymphoma, and 11 with leukemia. No patients had suffered from venous or arterial thrombosis before diagnosis of cancer, 14 patients had a first symptomatic thrombosis occurring five months after diagnosis, 4 after starting cytoreductive treatment, 5 patients had a recurrent thrombosis during remission of their disease, no significant differences were found in the cumulative incidence of thrombosis after stratification of the patients respectiely to sex, age, and transient factors (surgery, immobilization, cateteri). For the diagnosis of DVT: CUS (compression ultrasonografy) was performed in all patients combined with D-Dimer levels. Besides we have studied the levels of TF and Heparanase (anti-heparanase antibodies IgG 2BK: HP3/17). The incidence of VTE/DVT has been demonstrated to be associated with the highest levels of TF and Heparanase.