bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy of Recombinant Activated Factor VII (rFVIIa) vs. Activated Prothrombin Complex Concentrate (APCC) in Patients with Hemophilia with Inhibitors: A Bayesian Meta-Analysis.
Authors: Treur Maarten Jacob , McCracken Fay , Heeg Bart , Joshi Ashish V. , Thurston Stephanie , Verheggen Bram , Marc Botteman , de Charro Frank , van Hout Ben 
Published: October 2019

Abstract
INTRODUCTION: The recent FENOC comparative trial (Astermark et al. 2007) reported comparable efficacy for rFVIIa and APCC in the treatment of joint bleeds in patients with hemophilia complicated by inhibitors. A systematic review was combined with a Bayesian meta-regression analysis to place the FENOC results within the context of earlier non-comparative studies and to identify key variables influencing treatment efficacy.
METHODS: A systematic literature search was performed using electronic databases, web based trial registers, and grey literature. Clinical studies and/or trials in hemophilia patients with inhibitors receiving on-demand treatment with rFVIIa or APCC were included. Outcome of interest was the time of successfully stopping joint bleeds taking explicit account of repeated dosing. To model the latter, the regression model included a repeating Gompertz hazard function to compare the efficacy of standard rFVIIa treatment (one 90 μg/kg rFVIIa infusion every 3 hrs) with standard APCC treatment (one 75 IU/kg APCC infusion every 12 hrs). The hazard function (the conditional probability of ending the bleeding) was characterized by a repeated pattern of fixed increases after each infusion and by subsequent decreases thereafter. It was assumed that each sequential infusion had the same effect on the hazard resulting in a shark tooth like function. Covariates included were medication type, medication type combined with dosage (measured in μg/kg for rFVIIa and IU/kg for APCC), efficacy rating scale method, and efficacy rater.
RESULTS: Of the 17 studies included in the systematic review, 14 provided adequate data to be included in the Bayesian model, reporting on almost 2,000 joint bleeds combined (of which 96 were from the FENOC itself). The analysis demonstrated that medication type combined with dosage appears to have a statistically significant effect on efficacy of treatment. For rFVIIa the model estimated that 75%, 94%, and 98% of bleeds would be treated effectively after 12, 24, and 36 hours respectively. In contrast, for APCC the model estimated that 39%, 63%, and 78% of bleeds would be treated effectively after 12, 24 and 36 hours respectively.
CONCLUSIONS: The FENOC study demonstrated similar efficacy levels for treatment with rFVIIa and APCC. In contrast, the present meta-analysis including 14 studies and almost 2,000 joint bleeds estimated that standard treatment with rFVIIa is likely to result in higher efficacy levels at the 12, 24 and 36 hour time points than treatment with APCC. This implies that treatment with rFVIIa may be associated with a faster time to joint bleed resolution than APCC.
Successful Treatment of Factor IX Inhibitor Complicated by Nephrotic Syndrome with Rituxan.
Authors: Bernstein Jonathan , Gupta Neepa , Berkowitz Rebecca 
Published: October 2019

Abstract
Nephrotic syndrome is a well known complication of the development of inhibitors in factor IX patients. Nephrotic syndrome has been treated with Rituxan as have factor IX inhibitors. We present a 4 year old male diagnosed with severe factor IX deficiency at 5 months of age after severe bruising.
History: Between 11/05 and 5/06 we treated a 3 yo male with history of factor IX deficiency and inhibitor as well as nephrotic syndrome with Rituxan. The child received 4 weekly doses of Rituxan at 375 mg/M2, followed by monthly doses at 375 mg/M2, for six months. He received monthly doses of IVIG at 1 gram/M2. In the last 2 months of the course, he was reexposed to factor IX (Alphanine).
Results: He has had no signs of an inhibitor and is on 3x per week dosing. He did redevelop nephrotic syndrome 17 months later but has since been placed in remission on a repeat course of Rituxan.
Conclusions: This is the first report of the successful treatment of both a Factor IX inhibitor and Nephrotic syndrome with Rituxan therapy.
Venous Thromboembolism and Non-Small Cell Lung Cancer: A Pooled Analysis of National Cancer Institute of Canada Clinical Trials Group (NCIC CTG) Trials.
Authors: Hicks Lisa , Cheung Matthew , Hasan Baktiar , Ding Keyue , Seymour Lesley , Leighl Natasha B. , Winton Timothy L. , Shepherd Frances A. 
Published: October 2019

Abstract
Purpose: To determine the incidence of venous thromboembolism (VTE) in patients with early and advanced non-small cell lung cancer (NSCLC); to explore predictive factors for VTE occurrence during trials in these populations, and to investigate the effect of VTE on overall survival in patients with NSCLC.
Patients and Methods: Data from three National Cancer Institute of Canada Clinical Trials Group trials were included in the analyses (n=1987). JBR.10 was a randomized study of post-resection adjuvant vinorelbine/cisplatin versus observation in stage IB/II NSCLC. BR.18 was a randomized study of paclitaxel/carboplatin ± the metalloproteinase inhibitor BMS-275291 in advanced NSCLC (1st line). BR.21 was a randomized study of erlotinib versus placebo in previously treated (2nd or 3rd line) NSCLC. The relationship between VTE, cancer treatment, concomitant medications, and baseline patient characteristics was explored with univariate and multivariate analysis. Cox regression analysis was performed to determine whether VTE was independently associated with survival. Each trial was analyzed separately; in addition a pooled analysis was performed with the advanced disease trials (BR.18 and BR.21).
Results: The incidence of VTE was 0% in the observation arm of JBR.10 and ranged from 3% in the adjuvant chemotherapy arm of JBR.10 to 8% in BR.18. In JBR.10, VTE was independently associated with the administration of adjuvant chemotherapy (p=0.015), baseline obesity (p=.001), and low platelet count (p=.007). For patients with advanced NSCLC, VTE was significantly more common in patients receiving chemotherapy (BR.18) compared to patients receiving erlotinib or placebo (BR.21) (8% vs 2%, p< 0.0001). In BR.18, but not BR.21, VTE was associated with a prior history of VTE (p=0.001). When BR.18 and BR.21 were pooled, prior VTE remained significant. In BR.18 and BR.21, VTE was associated with shorter survival in multivariate analysis (HR=1.69, 95%CI 1.32–2.17, p<.0001); further analyses, including JBR.10, are planned to explore this finding.
Conclusion: VTE is a frequent event in patients with advanced NSCLC and is associated with the administration of chemotherapy. Treatment with metalloproteinase or epidermal growth factor inhibitors does not appear to increase the risk of VTE. In early NSCLC, adjuvant chemotherapy, morbid obesity and a prior history of VTE are associated with increased risk. VTE is associated with shortened survival in patients with advanced NSCLC. Funding for this study was provided by the Canadian Cancer Society.
New Pulmonary Embolism Diagnostic Algorythm and the Thromboprophylaxis in a Hungarian Teaching Hospital.
Authors: Egyed Miklos , Zadori Peter , Rajnics Peter , Varga Csaba , Horvath Anita , Horvath Gyula 
Published: October 2019

Abstract
The aims of our study were to evaluate a new pulmonary embolism (PE) diagnostic algorythm and applied VTE prophylaxis. Therefore we reviewed and analysed the medical records of 507 patients with suspected PE. The patients were classified as having preventable or nonpreventable PE according to the risk and adequacy of the administered prophylaxis, or noncompliance if the indicated prophylaxis had been refused. 507 multislice computer tomograph angiography (MuCTA) were done (27 unsuccesful) with a susppected diagnosis of PE between oct.2004 and oct. 2006. From the 140 positive patients 106 were regularly controlled by physicians in different hospitals and 87 had to receive prophylaxis according to the recommendation of the ACCP 2004 guidelines. 7% of them refused it (noncompliance). 70% received inadequate prophylaxis, 23% of the patients (nonpreventable) received prophylaxis in accordance with the ACCP 2004 guidelines. Both Medical and surgical patients were in the preventable group. From the 61 preventable cases, the reason for the inadequacyof prophylaxiswas the omission of prophylaxis in 41, inadequate dose of prophylaxis in 9, inadequate lenght in 5, inadequate anticoagulant in 5 cases. MuCTA is a very useful method to diagnose PE. From the 480 evaluable suspected cases 140 patients found be positive (29%). Adherence to the prophylaxis guidelines is frightful, 70% of patients with PE for whom prophylaxis had been indicated, could have been prevented. The incidence of PE is still high despite adequate prophylaxis, which indicates that the guidelinesmay be needed to reevaluate. Quantitative d-dimer and CRP have very good negative predictive value for excluding PE.
Establishment of Cell Lines Stably Expressing HNA-1A, -1B, -2A, -4A, -4B, -5A and -5B Antigen with Low Background Reactivity in Flow Cytometric Analysis.
Authors: Yasui Kazuta , Miyazaki Toru , Watanabe Yoshihisa , Odagiri Miki , Matsuyama Nobuki , Furuta Rika A. , Kimura Takafumi , Ikeda Hisami , Hirayama Fumiya , Tani Yoshihiko , Shibata Hirotoshi 
Published: October 2019

Abstract
Antibodies to neutrophil antigens have been implicated in neonatal alloimmune neutropenia, autoimmune neutropenia, and transfusion-related acute lung injury. Although FCM analysis with a typed panel of neutrophils has been used to detect such antibodies, this procedure has two major limitations. First, only freshly isolated neutrophils can be used for the assay. Second, the assay cannot identify an HNA antibody in the presence of anti-HLA class I antibodies that react to panel neutrophils. To overcome these limitations, we established a panel of cell lines in which the HNA-1a (−1b; polymorphisms of HNA-1), HNA-2a, HNA-4a (−4b), or HNA-5a (−5b) gene was transduced using a retrovirus vector to confer stable transgene expression in K562 cells that dose not express HLA or HNA and not exhibit background reactivity to normal human serum samples. We confirmed the specificity of the one of each HNA expression on the K562 panel cells by using mAbs. We further showed that several well-characterized human sera containing antibodies against several HNAs were unambiguously identified by our panel cell lines. We also observed a lower background reactivity of the K562 panel cell lines compared with isolated neutrophils, which have been used for the panel to identify antibodies against HNA in human sera. These results indicate that the K562 panel cell lines provide a good panel for detecting HNA-reactive neutrophil antibodies in human sera.
Fatal Complication of Transfusion of No Irradiated Blood Product in an Immunocompetent Recipient.
Authors: Campos-Cabrera Gregorio , Campos-Cabrera Virginia , Campos-Cabrera Salvador , Campos-Villagomez Jose Luis 
Published: October 2019

Abstract
Transfusion-associated graft versus host disease (TA-GVHD) is a rare, but almost always a fatal complication. It has a mortality rate above 90%. For the development of TA-GVHD is need
immunocompetent cells in the blood product, incompatibility in HLA alloantigen, immune failure of the recipient against the donor cells.
The exact incidence is unknown, but more than 200 cases have been reported in the world literature and the molecular test for diagnostic where performed only in a very few of them. Thirty-five years old woman with multiple fractures in right leg from a car accident was treated in her rural town, she received a fresh whole blood transfusion from her sister and then went for surgery, antibiotics and analgesia where given; six days after she developed erytroderma in the upper chest, two days later generalized bone pain and weakness were aggregated, the next day erithroderma generalize and started with diarrhea and jaundice; her evolution was torpid with fever, more weakness and jaundice, pallor, purpura and oropharyngeal pain. She was sent for hematological evaluation to our tertiary care institution, and a TA-GVHD was considerate; a work up on that was performed and the CBC showed pancytopenia, LFT with elevation of bilirubins, transaminases and alkaline phosphatase; the bone marrow aspiration and biopsy with aplasia, the skin biopsy with lymphoid infiltration, junction of epidermis with dermis was intact and no leukocytoclastic vasculitis. She received methylprednisolone, cyclosporine, filgrastim, wide range antibiotics and amphotericin B, leukoreduced and irradiated blood products. Her evolution was torpid with deterioration of her conditions and 48 hour later she died of septic shock. There is no effective treatment for TA-GVHD and no difference between early o delayed diagnostic, the evolution is almost always fatal, that is why the prevention is needed with the leukoreduction and irradiation of blood products, specially in recipients with clear risk for development of TA-GVHD: congenital immunodeficiencies, fetuses y newborns, hematological cancers, solid tumors in chemotherapy, hemopoiectic and solid organ transplanted, and first and second degree relatives. Better policies, technology, education for the primary care physician and access to blood products with high quality is needed to prevent this type of complications, specially in rural areas where transfusions with whole fresh blood from relatives are performed commonly.
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A Pilot Trial To Assess College Student’s Willingness To Donate Blood.
Authors: Demmons Derrick G. , Crittenden Colleen P. , Lee Mark , Shaz Beth H. , Burnett Miriam , Hillyer Christopher D. 
Published: October 2019

Abstract
Background: Nationally, African Americans are significantly underrepresented in community blood donation programs. The need to understand the willingness to donate blood among African Americans is essential. In this study, we explore factors that serve as motivators and barriers to blood donation identified by college students at two Historical Black Colleges/Universities (HBCUs).
Methods: HBCU students at least 18 years of age were given the opportunity to complete a paper-based or on-line 41-item questionnaire to assess the participant’s demographic background, donation frequency, motivators and barriers toward donation, knowledge and beliefs regarding blood donation, and specific behavioral practices. No personal identifiers were used. Univariate and bivariate analyses were conducted to describe the sample.
Results: 409 individuals completed the survey. 95% self-identified as African-American and 45% of college students reported previously donating blood. Student’s felt that incentives, personal requests to donate from blood centers, blood drives sponsored by campus organizations, and the university involvement in promoting blood drives were significant motivating factors for donating blood (p<.05). Significant barriers against blood donation included believing donation was too painful, fear of feeling faint, dizzy, or nauseated, losing valuable time from school or work, too time consuming, and fear of deferral (p<.05).
Conclusions: College students are willing to donate blood based on convenience, accessibility, and support from their university. Campus-based recruitment methods geared towards students, specifically those of African American descent, may prove beneficial for increasing the general pool of African American blood donors.
Significant relationships between barriers, motivators, and donor status Χ2 Sig. *p<.05 Barriers against blood donation Too painful 60.20 .000 Would feel faint, dizzy, or nauseated 42.15 .000 Will lose valuable time from school/work 16.82 .002 Previously been told not to donate 8.49 .004 Takes too long 37.41 .000 Motivators toward blood donation Incentive for donating 14.56 .006 Personal request to donate from blood center 10.15 .038 Blood drive sponsored by campus organization 26.29 .000 University involvement in promoting blood drives 5.36 .021
Muc1 Expression Identifies Human Self-Renewing Stem/Progenitor Populations and Is Elevated in AML CD34+ Cells.
Authors: Fatrai Szabolcs , Daenen Simon M.G.J. , Vellenga Edo , Schuringa Jan J. 
Published: October 2019

Abstract
Mucin1 (Muc1) is a membrane glycoprotein which is expressed on most of the normal secretory epithelial cells as well as on hematopoietic cells. It is involved in migration, adhesion and intracellular signalling. Muc1 can be cleaved close to the membrane-proximal region, resulting in an intracellular Muc1 that can associate with or activate various signalling pathway components such as b-catenin, p53 and HIF1a. Based on these properties, Muc1 expression was analysed in human hematopoietic stem/progenitor cells. Muc1 mRNA expression was highest in the immature CD34+/CD38− cells and was reduced upon maturation towards the progenitor stage. Cord blood (CB) CD34+ cells were sorted into Muc1+ and Muc1− populations followed by CFC and LTC-IC assays and these experiments revealed that the stem and progenitor cells reside predominantly in the CD34+/Muc1+ fraction. Importantly, we observed strongly increased Muc1 expression in the CD34+ subfraction of AML mononuclear cells. These results tempted us to further study the role of Muc1 overexpression in human CD34+ stem/progenitor cells. Full-length Muc1 (Muc1F) and a Muc1 isoform with a deleted extracellular domain (DTR) were stably expressed in CB CD34+ cells using a retroviral approach. Upon coculture with MS5 bone marrow stromal cells, a two-fold increase in expansion of suspension cells was observed in both Muc1F and DTR cultures. In line with these results, we observed an increase in progenitor counts in the Muc1F and DTR group as determined by CFC assays in methylcellulose. Upon replating of CFC cultures, Muc1F and DTR were giving rise to secondary colonies in contrast to empty vector control groups, indicating that self-renewal was imposed on progenitors by expression of Muc1. A 3-fold and 2-fold increase in stem cell frequencies was observed in the DTR and Muc1F groups, respectively, as determined by LTC-IC assays. To determine whether the above mentioned phenotypes in MS5 co-cultures were stroma-dependent, we expanded Muc1F and DTR-transduced cells in cytokine-driven liquid cultures. However, no proliferative advantage or increase in CFC frequencies was observed suggesting that Muc1 requires bone marrow stromal cells. In conclusion, our data indicate that HSCs as well as AML cells are enriched for Muc1 expression, and that overexpression of Muc1 in CB cells is sufficient to increase both progenitor and stem cell frequencies.
Cleaved High Molecular Weight Kininogen (HKa) and Kininostatin (D5) Induce Apoptosis and Inhibit Migration and Invasion of Human Prostate Cancer Cells by Preventing AKT Phosphorylation and Cyclin D1 Synthesis and Disrupting the Interaction of UPAR and EGFR.
Authors: Liu Yuchuan , Pixley Robin , Fusaro Mario , Colman Robert W. 
Published: October 2019

Abstract
Tumor metastasis is a major factor in the mortality rate in human prostate cancer. Upregulation and activation of EGFR and/or uPAR in a variety of cancers have been shown to be associated with poor prognosis. HK, a component of the plasma kallikrein-kinin system, can be hydrolyzed by plasma kallikrein to bradykinin and HKa. HKa and D5 both have been demonstrated to have potent anti-angiogenic activity in vitro and in vivo. We previously published that D5 directly inhibits human colon carcinoma cell (HCT-116) proliferation in vitro by blocking the G1/S transition in the cell cycle. We now show that HKa [100 nM] inhibits the migration of human prostate tumor cell (DU145) about 50%. Cyclin D1 can activate p21 and p27 with concomitant cell migration. DU145 cells rapidly increase cyclin D1 synthesis in response to bFGF [1.2 nM]. HKa suppresses cyclin D1 expression as shown by Western blotting as well as cell immunoflourescence. Stimulation by bFGF or VEGF results in clustering of uPAR and EGFR on the surface of DU145 cells. Immunoflourescence shows that the addition of HKa disrupts the co-localization of uPAR and EGFR. HKa or a monoclonal antibody against uPAR decreases the phosphorylation of EGFR at Tyr 1173. The phosphorylation of ERK and AKT, which are downstream effectors of EGFR, is also inhibited by HKa. Kininostatin [300nM] induced apoptosis of human prostate cancer cells challenged with uPA [50 nM] or EGF [6.7 nM]. Matrigel invasion assay reveals that HKa [100 nM] decreases the invading cell number by 90%. These novel data indicate that HKa and kininostatin induce apoptosis and inhibit migration and invasion of human prostate cancer cells, indicating the therapeutic potential of kininostatin in metastasis human prostate cancer.
Hematopoietic Stem Cell Transplantation in Acute Lymphocytic Leukemia Patients: Umbilical Cord Blood Versus Bone Marrow Transplant.
Authors: Sun Zimin , Liu Huilan , Geng Liangquan , Liu Xin , Yang Huizhi , Zhu Weibo , Ding Kaiyang , Yao Wen , Yuan Xiao 
Published: October 2019

Abstract
Acute lymphocytic leukemia (ALL) is a life threatening disease with high rate of relapse. To date, there is no ideal treatment for ALL. Recently, stem cell transplantation has been used as a potential therapy. However, it is unclear what the best source of donor stem cells is and whether it is safe or effective to use these regimens in human patients. In this study, we evaluated the safety and outcomes of 22 patients with ALL after umbilical cord blood transplantation (UCBT) or bone-marrow from related donors (RD). Eleven patients received stem cells from HLA 0–2 (A,B,DRB1) mismatched UCBT (median infused dose, 3.77×107 nucleated cell NC/kg; range, 3.40– 7.49 ×107 NC/kg). The other 11 patients received stem cells from bone marrow from RD (median infused dose, 4.08×108 NC/kg; range, 1.86–9.82×107 NC/kg). All patients in both groups were comparable, as shown in Table 1. All patients received myeloablative conditioning (busulfanum/cyclophosphamide was used for the RD transplantation and anti-thymus globulin 7.5 mg/kg was used for the UCB transplantation) followed by infusion of allogenetic hematopoietc stem cells from either bone marrow or cord blood. Cyclosporine A (CsA) and mycophenolate mofetil (MMF) were administered for the prophylaxis of graft-versus-host disease (GVHD). Overall survival (OS), leukemia-free survival (LFS), transplantation-related mortality (TRM) and relapse rate between RD and UCB were shown in Table 2. The results demonstrated that despite the higher HLA mismatch rate and lower number of infused hematopietic stem cells, OS, LFS, TRM and relapse rate in UCB group were 81.8%, 81.8%, 0% and 18.2% which were significantly better than in the RD group. These data strongly suggest that UCBT could be a safe and effective therapy for patients with ALL.
Table 1 The Profiles of Patients RD UCBT High Risk ALL 7/11 7/11 HLA 0/6 Mismatched (%) 72.7 9.1 HLA 1/6 Mismatched (%) 27.3 81.8 HLA 2/6 Mismatched (%) 0 9.1 Median Age (years, range) 30 (8–63) 25 (3–38) Median Body Weight (kg, range) 51 (26–70) 40 (13–84) Table 2 Outcomes of ALL patients after UCB transplantation RD UCB P value Number of patients 11 11 Median follow up (years) 2.0 2.0 OS 2 yr % (95% CI) 36.4 81.8 <0.05 LFS 2 yr % (95% CI) 27.3 81.8 <0.05 Relapse 1yr % (95% CI) 27.3 0 <0.05 TRM 1 yr % (95% CI) 63.6 18.2 <0.05