bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal Frequency of Aspirin Resistance after Observed Aspirin Ingestion.
Authors: Schwartz Kenneth A. , Schwartz Dianne E. , Barber Kimberly , Reeves Mathew , DeFranco Anthony C. 
Published: April 2020

Abstract
Poor compliance is an important cause of aspirin resistance. Our goal was to investigate amount of aspirin induced inhibition of platelets independent of compliance. We investigated the net amount of aspirin induced inhibition of platelets by comparing Platelet Prostaglandin Agonist (PPA) stimulated platelet aggregations before, off aspirin, with the platelet inhibition that occurred 2 hours after observed aspirin ingestion. 217 post-myocardial infarction patients who had taken aspirin for at least 30 days were evaluated at two time points. The first time point was 7 days after they had signed informed consent to stop taking aspirin as well as nonsteroidal anti-inflammatory drugs (NSAIDs). The second time point was 2 hrs after they were observed to ingest 325mg of aspirin. Platelets were evaluated using 2 different agonists in a light aggregometer. Arachidonic acid (AA) was used as a qualitative check to see if the patients at the first time point had really refrained from taking aspirin and NSAIDs for 7 days and PPA which mainly activates platelets via the prostaglandin pathway and can detect degrees of aspirin induced platelet inhibition. The slope of the PPA stimulated aggregation curve was used to measure aspirin induced platelet inhibition. The net aspirin response was calculated by determining the paired difference between the PPA slopes at the two time points. Compliance with the directive of not taking aspirin or NSAIDs before the first time point was checked with AA stimulated aggregometry and 45 patients were judged to be noncompliant. We defined aspirin resistance as a minimal change in PPA slope of 15 or less. Of the patients who had complied with the directive not to take aspirin or NSAIDs for 7 days as determined by AA aggregometry only 7 (3.2%) were aspirin resistant. The net aspirin response was directly related to the PPA slope off aspirin (p&lt;0.001). When the 45 patients who were judged by AA aggregometry to be noncompliant with the directive to refrain from taking aspirin or NSAIDs were removed from the analysis, the direct relationship between the slope of the off aspirin PPA aggregation and the net aspirin response remained significant (p&lt;0.001). The amount of platelet inhibition in the compliant group 42±16 was significantly larger than the platelet inhibition in the noncompliant group 36±16 (p=0.02). We conclude that: 1. a small percent of patients, 3.2%, whose net amount of aspirin induced platelet inhibition was less than 15 may be resistant to aspirin because of mechanisms unrelated to compliance and 2. The net amount of aspirin induced inhibition of platelets is directly related to the slope of the “off” aspirin PPA stimulated aggregation curve.
Myeloablative Conditioning of Patients with Myelofibrosis with Myeloid Metaplasia Using i.v. Treosulfan and Autologous Peripheral Blood Progenitor Cell Transplantation (PBPCT) with High Doses of CD34+ Cells Results in Hematologic Responses - 32 Months Follow-Up of Three Patients and Short-Term Results of a New Study.
Authors: Fruehauf Stefan , Buss Eike C. , Toplay Julian , Kreipe Hans H. , Ho Anthony D. 
Published: April 2020

Abstract
Myelofibrosis with myeloid metaplasia (MMM) is a chronic myeloproliferative disorder. Myeloablation with high-dose treosulfan and autologous PBPCT provides a palliative approach. A minimum of 5 x 106 CD34+ cells/kg was collected in all patients after G-CSF-priming (16 μg/kg/d for 4 days). Myeloablation consisted of treosulfan (total dose 42 g/m2). To date we have transplanted 3 patients, all female on an individual basis. We observed a prolonged time to reconstitution of leucocytes &gt; 1/nl post transplantation of 28 days (#1, #2) and 38 days (#3). The observation period post transplantation is 32 months now. Patient #1, who required erythrocyte transfusions twice weekly pretransplant received her last erythrocyte transfusion on day 56; her last Hb-value is 9.5 g/dl. The second patient (#2) recovered to platelet counts higher than pre transplantation (58/nl) at 3 months (143/nl) and had 125/nl at last follow-up. Pat. #3 showed a marked reduction of max. spleen size and a rise in Hb from 9 g/dl to 12 g/dl after 12 months, the last Hb value at 26 months was 7.6 g/dl and she received about 3 erythrocyte transfusions per month again. She then underwent allogeneic transplantation from her sister and is currently alive and well. Three male patients were treated in a new one-armed, multicenter study applying the aforementioned protocol. In two patients we observed again a prolonged reconstitution period of 28 (S1) and 44 (S2) days. In one patient (S1) leukocytosis and thrombocytosis resolved while transfusion dependent anemia persisted. In the second patient (S2) transfusion dependent anemia persisted. He received a backup transplantation but still remains transfusion-dependent. Patient S3 had a critical thrombocytopenia of 16/nl before transplantation and proved to be refractory to thrombocyte transfusions post-transplantation. He developed cerebral hemorrhage and died. The conditioning regimen was well tolerated and despite the prolonged aplasia period neutropenic fever was rare (median 1 day, range 0–6 days). The overall response rate was 60%, the mortality rate was 17% which is both compatible with previous data of autologous transplantation in MMM patients undergoing busulfan conditioning. This multicenter study is continuing to recruit patients (http://leukaemie.krebsinfo.de/kn_home/Studien/studie_101.html).
Phenotypic Correction of von Willebrand Disease Type 3 Blood-Derived Endothelial Cells with Lentiviral Vectors Expressing von Willebrand Factor.
Authors: De Meyer Simon F. , Vanhoorelbeke Karen , Chuah Marinee K. , Pareyn Inge , Gillijns Veerle , Hebbel Robert P. , Deckmyn Hans , Vandendriessche Thierry 
Published: April 2020

Abstract
Von Willebrand disease (VWD) is the most common inherited bleeding disorder, caused by quantitative (type 1 and 3 VWD) or qualitative (type 2 VWD) defects in von Willebrand factor (VWF). Gene therapy is an appealing strategy for treatment of type 3 VWD since it is caused by a single gene defect and since VWF is secreted into the circulation, obviating the need for targeting specific organs or tissues. However, development of gene therapy for VWD has been hampered by the considerable length of the VWF cDNA (8.4 kb) and the inherent complexicity of the VWF protein which requires extensive post-translational processing. The objective of this study consisted of developing a gene-based approach for VWD using lentiviral transduction of blood-outgrowth endothelial cells (BOECs) to express functional VWF. A lentiviral vector encoding the complete human VWF protein was used to transduce BOECs isolated from type 3 VWD dogs resulting in high transduction efficiencies (95.6 ± 2.2 %). These BOECs are completely deficient in VWF due to a point mutation in the VWF gene responsible for impaired VWF synthesis. Transduced VWD BOECs efficiently expressed fully functional vector-encoded VWF (4.6 ± 0.4 U/24hr per 106 cells, figure 1), with normal binding to GPIbα and collagen and normal multimeric pattern resulting in phenotypic correction of these cells, which had not been shown previously. These results indicate that BOECs are attractive target cells for gene therapy of type 3 VWD.
Generation of CMV-Specific T-Lymphocytes for Adoptive Immunotherapy: A Comparison of Artificial Antigen-Presenting Cells and Autologous Dendritic Cells Pulsed with CMV-pp65 Protein-Spanning Pentadecapeptide Pools.
Authors: Kollen Wouter J.W. , Trivedi Deepa , Stephan Matthias , Sadelain Michel , O’Reilly Richard J. 
Published: April 2020

Abstract
Adoptive transfer of virus-specific T-cells constitutes a promising approach for the treatment and prevention of cytomegalovirus (CMV) infections complicating allogeneic HSC transplants. Current strategies employing peptide-pulsed donor-derived dendritic cells (DCs) for antigen presentation are effective, but limited by availability of adequate numbers of DCs and the time required for their generation. We established a series of immediately accessible, replenishable, artificial antigen-presenting cells (AAPCs), consisting of mouse 3T3 cells transduced to express human B7.1, LFA-3, ICAM-1, β2-microglobulin and one HLA class I allele (Papanicolaou et al., Blood 2003). We then compared yields of CMV-peptide-specific T-cells when T-cells from HLA A0201 seropositive donors were sensitized with autologous DCs or HLA A0201 AAPCs loaded with a known HLA A0201-binding immunogenic nonamer of CMV-pp65 (NLVPMVATV) or a pool of pentadecapeptides spanning CMV-pp65, which included the 15-mer No. 123 (AGILARNLVPMVATV) containing this epitope. Peptide loading was performed in the presence or absence of serum in order to distinguish peptide editing mediated by ectopeptidases in the serum or expressed by the different APCs. Results from repeated experiments employing three HLA A0201 CMV-seropositive donors demonstrated that the yields of epitope-specific T-cells following 14–28 day sensitization with AAPCs loaded with the NLVPMVATV nonamer consistently exceeded those generated in response to peptide-loaded autologous DCs, as assessed by enumerating peptide-HLA A0201 tetramer-binding and peptide-specific IFN-γ producing T cells. High and selective yields of NLV-specific T-cells were obtained when the T-cells were sensitized with AAPCs or DCs loaded with the CMV-pp65-spanning pool of 15-mers in the presence or absence of serum suggesting that ectopeptidases expressed on the DCs and AAPCs appropriately clip and edit the 15-mers after binding to HLA A0201. Even higher yields were achieved when the T-cells were sensitized with AAPCs transduced to express the full length CMV-pp65 protein, confirming the potential of the mouse-derived AAPCs to process this protein and load immunogenic epitopes on HLA A0201. T-cells generated in response to peptide-loaded or transduced AAPCs also specifically lysed nonamer-loaded HLA A0201 expressing targets. Taken together, these studies indicate that mouse-derived AAPCs can efficiently process endogenous protein and edit exogenous 15-mer peptides for binding and presentation by the single expressed HLA allele. Use of these AAPCs loaded with overlapping peptides or transduced to express an immunogenic protein may thus provide advantages in terms of immunogenicity, immediate accessibility and broad applicability for rapid production of antigen-specific T-cells for adoptive immunotherapy.
Usefulness of Peripheral Blood Smears in Identifying the Causes of Anemia in Adults.
Authors: McPhedran Peter , Hall Robert B. 
Published: April 2020

Abstract
Anemia is common in hospital patients, being found in about half of the automated complete blood counts (CBCs) done on adults aged 20+ at our hospital. Often the reason for the anemia is immediately apparent (post-operative state, end stage renal disease without erythropoietin treatment), but often it is not. Many tests are available for the differential diagnosis of the causes of the anemia. Morphologic evaluation of a Wright-stained blood smear by a skilled observer is labor intensive, but sometimes useful in the differential diagnosis of anemia. When unexplained anemia is identified in a patient on the Medical Service at our teaching hospital, the ward team may also send an intern or a medical student to check out the smear. The potential diagnostic yield of any of these evaluations (the skilled observer, the intern, the student) is unknown. We did a prospective evaluation of 202 consecutive adults with initially unexplained anemia (Hb &lt;12 in men, &lt;11 in women). Using accepted, pre-established criteria for etiologic diagnosis of the causes of anemia, and available data (plus additional smear evaluations by ourselves, ferritins, free erythrocyte protoporphryns, and a few other tests) we felt we were able to establish the causes of anemia in 86% of the patients. We also referred to standard morphologic criteria for diagnosing specific blood disorders in order to see how much could be learned from the blood smears of these patients, alone. Of 147 patients whose blood smears were of acceptable quality, 30 (21%) of the blood smears were diagnostic (or close to diagnostic), and an additional 46% were supportive of the correct diagnosis. For example, iron deficiency anemia was considered the morphologic diagnosis if the blood smear showed severe hypochromia, “pencil-form” elliptocytes, and thrombocytosis. Hypochromia alone would be considered supportive of the diagnosis of iron deficiency, but require more consideration of alternatives (thalassemia trait, chronic disease, etc). Thus, in evaluating anemia in adults, a good peripheral blood smear, carefully evaluated by a trained observer, is likely to be diagnostic, or very helpful, in 20% or more of the patients.
Risk Reduction of Chronic Graft Versus Host Disease by Anti-CD20 Treatment (Rituximab).
Authors: Van Hoef Marlies E.H.M. 
Published: April 2020

Abstract
Introduction:
Chronic graft versus host disease (cGVHD) occurs in 30–50% of adults transplanted by non-myeloablative (reduced intensity conditioning) allogeneic transplant, whereas it is rare in children. The syndrome complex manifests itselves as auto-immune disease. Dysregulation of B-cell function has also been reported in auto-immune diseases. This is a rationale for B-cell depletion.
We considered that B-cell depletion might have a therapeutic effect in cGVHD and reduce the risks associated with cGVHD. Based on these assumptions we applied risk reduction principles and defined a plan for cure of cGVHD.
Methods:
To identify the risks associated with B-cell depletion in cGVHD we performed a medline search on anti-CD20 or B-cell depletion or rituximab and cGVHD. The publications were analyzed and those applicable to the topic evaluated. Clinical research methods were applied to define a plan for risk reduction of cGVHD.
Results:
The medline search revealed that rituximab was used for B-cell depletion in cGVHD and in auto-immune diseases. In advanced cGVHD complete and partial remissions of a variety of manifestations of cGVHD were reported. Complete remissions could also be induced early during the disease course of single manifestations of cGVHD not responsive to immune suppressive treatment or as initial treatment. The dose of rituximab varied from 1 to 4 weekly courses of rituximab 375 mg/m2, with repetitions of this schedule in advanced disease to induce complete response. During reported follow-up responding manifestations did not recur. Rituximab treatment was well tolerated with appropriate anti-allergic prophylaxis. The results support the concept that anti-CD20 treatment might cure cGVHD manifestations at first diagnosis; it is too early to define whether it also serves as prophylactic for development of new manifestations. The observations were discussed with the company marketing rituximab and a study plan was designed. This study plan is being discussed with study centers for risk reduction of cGVHD by rituximab. The risk reduction plan will be presented
Canadian Variation in Blood Product Demand Is Influenced by Provincial Rates of Coronary Artery Bypass Graft Surgery.
Authors: Pendergrast Jacob M. 
Published: April 2020

Abstract
BACKGROUND: Despite similarities in demography and health care delivery, Canadian provinces exhibit significant variation in population adjusted-rates of blood product usage. A study was conducted to identify factors which underlie this variation.
METHODS: Potential drivers of blood product consumption were identified through literature review, and then mapped to parameters for which provincial data were available from analytic reports published by the Canadian Institute for Health Information. Blood product issues per province for the year 2001 were obtained from annual reports published by Canadian Blood Services and HémaQuébec. All data were controlled for provincial population using data from Statistics Canada. Linear regressions for each parameter were calculated separately for erythrocyte, plasma and platelet issues. Variables that were statistically significant by univariate regression analysis were subjected to multiple regression modeling.
RESULTS: Provincial variation in erythrocyte demand was statistically correlated with the following by univariate regression analysis: population density, coronary artery bypass graft (CABG) procedures and peptic ulcer diagnoses. By multivariate analysis, only CABG procedures continued to have a statistically significant correlation. For plasma issues, univariate analysis revealed average physician age, average specialist age, and CABG procedures as statistically significant drivers. However, by multivariate analysis only CABG procedures retained statistical significance. For platelet issues, average specialist age, cardiovascular procedures, CABG procedures, and number of full-time equivalent general surgeons were statistically significant drivers of provincial variation. However, none of these variables retained statistical significance by multiple regression modeling.
CONCLUSIONS: The population-adjusted rate of coronary artery bypass procedure graft surgery was a statistically significant driver of provincial variation in erythrocyte and plasma issues in the year 2001, a finding which may be of use in demand forecasting.
Characteristics and Survival of 29 Patients with Sezary Syndrome.
Authors: Sampogna Francesca , Frontani Marina , Baliva Giannandrea , Abeni Damiano , Lombardo Giuseppe A. , Monopoli Alessandro , Barbieri Claudio , Benucci Roberto , Marrazza Giuseppe , Alvetreti Gabriele , Didona Biagio , Scala Enrico , Russo Giandomenico 
Published: April 2020

Abstract
We created a relational database of patients with cutaneous T-cell lymphoma (CTCL) to collect in a standardised fashion, anagraphic variables, clinical history, clinical, histological, haematological, and immunological information on CTCL patients hospitalised at IDI-IRCCS, Rome, Italy. At present, there are data on 424 patients, hospitalised from 1983 to July 2005. Active follow-up is performed yearly to ensure a standardised ascertainment of survival time. For deceased patients, the actual date of death (for all causes) is recorded, while surviving patients are censored at the date of last contact.
The database includes 29 patients with Sezary syndrome (SS). Follow-up times ranged from 0 to 105 months. At first hospitalisation the median values of cells/mL were: white blood cells (WBC) 8750, neutrophils 4250, eosinophils 140, basophils 120, lymphocytes 2760, monocytes 500, CD3+ 2780, CD4+ 2431, CD8+ 192, CD19+ 96. Seventeen patients were deceased. We included in the Kaplan-Meier survival analysis only patients who were diagnosed before July 2004 (n=26). Median survival time from diagnosis was 52 months. No significant differences were observed in mortality for WBC (cutoff 9000 cells/uL), neutrophils (cutoff 4500 cells/uL), basophils (cutoff 200 cells/uL), lymphocytes (cutoff 3000 cells/uL), monocytes (cutoff 500 cells/uL), CD3+ (cutoff 2000 cells/uL), CD4+ (cutoff 2000 cells/uL), CD8+ (cutoff 200 cells/uL), CD19+ (cutoff 70 cells/uL). A lower survival was observed for patients with eosinophils &lt;200 cells/uL (p=.08).
Survival in patients with SS does not seem to be influenced by haemathologic parameters. However, patients with long-term survival (&gt;90 months) are observed, and their characteristics should be further investigated.
Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004. Survival analysis of 26 patients with Sézary syndrome, Rome, Italy, 1991–2004.
Economical Analysis of Implementation of External Quality Controls in a General Hospital Hematology Laboratory.
Authors: Recasens Valle , Rubio-Martinez Araceli , Giraldo Pilar , Lucia Jose F. , Dobon Manuela , Montanes Maria A. , Bustamante Eduardo , Garcia-Mata Juan R. , Portillo Juan R. , Giralt Manuel 
Published: April 2020

Abstract
Introduction: The Spanish rule UNE-EN ISO 15189 concerning to Clinical Laboratory establish the realization of external quality controls (EQC) in order to compare results between laboratories. In 2004, external quality controls programs were initiated in our laboratory provided by the AEHH and SEQC.
Aim: To analyze the increase of cost in each determination when we apply these quality measures.
Material and methods: Period of study January 2004– December 2004. Encoded information obtained from ModulabWin informatics system. Determinations provided by AEHH: general hematology (RBC, Hb, HTC, MCV, MHC, HMCC, WBC, reticulocytes, cellular morphology, platelets, protrombine time, partial tromboplastine time, fibrinogen) AT III, F VIII, Hb A2 and F, automated reticulocytes, activated protein C resistance, differential count of WBC: (neutrophiles, monocytes, lymphocytes, eosinophils, basophiles), erythrocyte sedimentation rate (ESR). Determinations provided by SEQC: total proteins, albumin, complement C3 and C4, IgA, IgG, IgM, transferrine, iron serum levels, haptoglobine, ferritine, reactive protein C, b 2-microglobuline. For each ECQ with only one specimen for a unique determination the increase of costs was calculated as follow: EQC cost / total number of determinations. For each EQC with more than one determination the increase of costs was calculated as follow: (EQC cost / total number of parameters)/ total number of determinations.
Results: In ECQ with only one specimen for a unique determination, the increase of cost for each determination was ESR: 0.0033€, AT III: 0,1051€, FVIII: 1.79€, automated reticulocytes: 0,0334€, differential count of WBC 0,0033€. In EQC with more than one determination the increase of cost: were: Albumin and total proteins 0,0030€; C3 and C4: 0,0473€; activated protein C resistance: 0,0059€; IgA, IgG, IgM and b-2 microblobuline: 0,0030€; iron serum levels, Transferrine and Ferritine: 0,0025€; Haptoglobine: 0,0057€; RBC, Hb, HTC MCV, MHC, HMCC, WBC, platelets: 0,0003€ and for protrombine time, partial tromboplastine time and fibrinogen: 0,0007€.
Conclusions: The EQC for F VIII has been the more expensive control related to the number of determinations, however it is justified because our laboratory is reference center for the area. The incorporation of EQC hardly has increase the global costs of different determinations in a General Hematology Laboratory, nevertheless the quality, reproducibility, validity and security of results obtained with this procedure justify the slight increase of costs. This work has been partially supported by a grant from Aragon Health Service.