bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economy Class Syndrome: A “Pilot” Study.
Authors: Kristinsson Sigurdur Y. , Vidarsson Brynjar , Love Thorvardur J. , Rafnsson Vilhjalmur , Hrafnkelsson Jon , Onundarson Pall T. 
Published: April 2020

Abstract
Introduction: Air travel associated venous thromboembolism (VTE) has been termed the economy class syndrome (ECS). Risk factors for ECS are divided into i) patient related; age, previous VTE, thrombophilia, malignancy and ii) cabin related; hypoxia, low humidity, dehydration and prolonged sitting. No study to date has looked at the incidence of VTE in healthy frequent flyers. The aim of this study was to see if professional pilots are at increased risk of VTE.
Materials and methods: A retrospective cohort of 206 pilots working for a single airline operating on medium duration (3–7 hour) international routes from 1991–2000 was studied. Landspitali University Hospital is the only hospital serving Reykjavik, Iceland and its neighboring communities, and it is the sole primary hospital for approximately 130.000 people age 18 and over. Databases of clinical and radiographic diagnoses made at Landspitali University Hospital were searched for codes consistent with deep vein thrombosis (DVT) and pulmonary embolism (PE) occurring from 1991 to 2000. A computerized database of pilot personal identification numbers was then record linked to this VTE cohort from Landspitali University Hospital to see if any of the pilots had been diagnosed with VTE. For comparison purposes, a subgroup of the hospital database cohort and the underlying Reykjavik population was defined to match the gender and age characteristics of the pilot group. Expected number of cases with VTE among pilots was then calculated by extrapolating the observed prevalence of VTE among this subgroup to the pilot cohort. Finally, the relative risk of VTE for the pilots was calculated with p-value and 95% confidence interval.
Results: Two hundred and six male pilots (median age 37 years, range 26–69) were included in the study. A total of 2263 patients were diagnosed with VTE at the Landspitali during the 10 year period, 931 with DVT and 1509 with PE, of whom 177 had both DVT and PE. There were 46,016 males aged 26 to 69 years living in the service area. Of these, 447 developed VTE. Extrapolating from the observed proportion of males age 26–69 diagnosed with VTE in the greater Reykjavik area, the expected number of VTE in the pilot cohort was found to be two. Of the 206 pilots, none was diagnosed with DVT or PE at Landspitali University Hospital during the study period. The relative risk of VTE in the pilot group was found to be 0, with no applicable lower limit to the 95% confidence interval, an upper limit of 1.83, and a p-value of 0.14.
Conclusion: Professional airline pilots flying medium range distances do not have an increased risk of VTE and therefore they seem not to develop the ECS. This study does not point to an increased risk of VTE in healthy travelers in association with medium range flights.
Factor VIII Levels Measured at the Time of Diagnosis of Acute Idiopathic Venous Thromboembolism Are Higher Then When Measured Six-Months Post Diagnosis.
Authors: Kovacs Michael J. , Keeney Michael , MacKinnon Karen 
Published: April 2020

Abstract
Background: Thrombophilia screens are performed frequently in persons with a history of acute venous thromboembolism especially in those for whom the etiology is unprovoked or idiopathic. The optimal timing of the thrombophilia screen is controversial. Elevation of Factor VIII levels are a more recently described thrombophilia that is felt to be hereditary, however, the exact mode of inheritance is not certain. Factor VIII is also known to be elevated as an acute phase reactant. The accuracy of assessing Factor VIII levels at the time of diagnosis of acute venous thromboembolism is not known. The purpose of this study was to determine if there is a difference in Factor VIII levels measured at the time of diagnosis of acute venous thromboembolism as compared to six months later while patients are on oral anticoagulation.
Methods: Consecutive patients with a first episode of idiopathic acute venous thromboembolism were eligible. Patients were excluded if they were &lt;18 years of age or had already been started on oral anticoagulants. Plasma was collected within 48 hours of diagnosis in.105 mmol sodium citrate, double spun at 1,500 G and frozen at −70 Celsius for batch testing. Factor VIII levels were assessed with a three point assay on an ACL 9000 (Beckman Coulter, Mississauga). A seven-point reference curve was used for all factor assays. Linear regression showed r2 values were always &gt; 0.99 on calibration lines. Controls at two levels, 1.00 U/mL normal pooled plasma and 0.32 U/mL were run with all assays. All patients were treated with dalteparin at 200u/kg sc daily for 5–7 days and simultaneously initiated on warfarin for six months. At the six-month point repeat Factor VIII assessments were performed while the patients were still receiving oral anticoagulation with warfarin.
Results: There were 61 patients (37 male) and the mean age was 50.4 years (18–85 years). Thirty patients had deep vein thrombosis, 23 pulmonary embolism and 8 patients had both diagnoses. The patients’ Factor VIII levels at baseline and six months were compared. At baseline the mean Factor VIII level was 1.77 units/ml and at six months it was 1.59 units/ml. The 95% confidence interval for difference in means was 0.04 – 0.32. These results were statistically significant, (paired t-test p=.01).
Conclusion: This study confirms that caution should be used in interpreting Factor VIII levels drawn as part of a thrombophilia screen at the time of diagnosis of acute idiopathic venous thromboembolism. Factor VIII levels will be lower six-months later when patients are stable on oral anticoagulation.
Antiplatelet Treatment with Aggressive Lipid Lowering Therapy and Reduction of Clinical Event after Ischemic Stroke.
Authors: Corinaldesi Giorgio , Corinaldesi Christian 
Published: April 2020

Abstract
The objective of the present study is to investigate the effects of anticoagulation and inhibition of platelet aggregation, which is strongly related with ischemic stroke, with aspirin 100 mg/once daily and clopidogrel 75 mg/once daily together with atorvastatin 80 mg/once daily then evaluating the event free survival in patients who had stroke with LDL-C &gt; 130 mg/dl. An hypolipidaemic diet was given to every patient. As known statins other than reducing LDL-C (silent killer), has many other effects characterized by a wider and wider checklist: reduction of plasmatic levels of C-reactive protein, of MCP-1, and the monocyte traffic, of IL-6, TNF-alfa, of S-VCAM-1, of COX-2 and MMP-9, and upregulate the TPA, and downregulate the PAI-1, statins also reduce the expression of CD40 on the endothelial surface, thus augmenting the EPC (endothelial progenitor cells) involved in neo-vascularization of ischemic tissue, with a final protective effects over the vascular endothelium, including the plaque stabilization.
We have studied 67 patients with a previous ischemic stroke aged between 58 and 72 years (25% smoker, 32% with hypertension, 14% with diabetes, 6% with obesity), with LDL-C higher than 130 mg/dl, evaluating in particular the lipidic profile (total cholesterol, HDL, LDL, TG, Lpa), fibrinogen and d-dimer for a total period of 36 months. We observed a clear reduction of lipidic parameters: Total-C &lt;42%, LDL-C &lt;46%, TG &lt;30%, ApoB &lt;35%, d-dimer &lt;10%, and we did not observe any increase in transaminases, CPK, or fibrinogen.
We observed 12 patients with relapsing clinical events requiring emergency hospitalization: 1 exitus for second stroke two months after the first event, 11 cases of RIND, with less than 4 transitory ischemic episodes, with the total length of events significantly reduced after the first 18 weeks of treatment. We have observed 22 adverse effects events: 4 cases of epistaxis, 2 case of tooth bleeding, 3 of abdominal pain, 9 of muscular pain, 2 of chest pain, 2 case of headache, however, these events did not influence the course of the pharmacological treatment; 55 patients did not refer any clinical problem, every patient has been followed on the basis of a three months period, and on demand.
The present study has demonstrated a secure efficacy of the aggressive combined treatment (antiplatelet + statin) in the management of patients with a previous stroke, showing a symptomatologic benefit (reduction of the total ischemic events and of the emergencies) with an overall improvement of the quality of life.
PARAMETER BEFORE AFTER TOTAL-C 320.0 mg/dl 180.0 mg/dl LDL-C 148.0 mg/dl 82.4 mg/dl HDL-C 38.6 mg/dl 44.2 mg/dl TG 180.0 mg/dl 108.2 mg/dl FIBRINOGEN 460.0 mg/dl 370.0 mg/dl FASTING GLUCOSE 110.0 mg/dl 96.0 mg/dl
Combined Use of Warfarin and Aspirin Decreases Mortality in Patients with Peripheral Arterial Disease.
Authors: Pasquale Donald , Jain Abhishek , Chikkappa G. 
Published: April 2020

Abstract
Anti-platelet therapy with aspirin (ASA) is standard therapy for patients with peripheral arterial disease (PAD). While ASA is not felt to impact the natural history of PAD, it decreases mortality from stroke, myocardial infarction, and other co-morbidities in the patients with PAD. Anticoagulation with warfarin (WAR) is indicated in arterial and venous thrombo-embolic conditions such as deep vein thrombosis and atrial fibrillation, but is generally considered not beneficial in patients with PAD. We retrospectively identified patients via ICD9 code who were diagnosed with PAD between January and December 2000, and assessed their course through July 2005. Of 530 individuals, 45 had a history of taking ASA and WAR concomitantly, 116 of taking WAR alone, 219 of taking ASA alone, and 150 received neither drug. Age, mortality, prevalence of hemorrhage and of co-morbid conditions (smoking, diabetes mellitus, atrial fibrillation, stroke, myocardial infarction, hypertension, coronary artery disease, hyperlipidemia, congestive heart failure, renal failure, and chronic obstructive pulmonary disease) that could affect mortality or hemorrhage were determined. Results are illustrated in the table.
Group WAR+ASA WAR ASA Neither n=45 n=116 n=219 n=150 ICH= Intracranial ST= Soft Tissue * Mean ± SD Mortality n (%) 12 (26.7) 51 (44.0) 91 (41.6) 71 (47.3) Hemorrhage N (%) 6 (13.3) 10 (8.6) 6 (2.7) 17 (11.3) Type of Hemorrhage 3-GI 8-GI 6-GI 13-GI 2-ICH 1-Nose 3-ICH 1-ST 1-ST 1-Hematuria Age* 73 ± 9 73 ± 9 73 ± 9 72 ± 11 Co-Morbid Conditions/Patient* 5.4 ± 1.7 4.1 ± 1.6 3.5 ± 1.6 2.9 ± 1.7 INR* 2.2 ± 0.7 2.2 ± 0.5
The higher number (not statistically significant) of co-morbid conditions in patients receiving WAR was because most of these individuals had atrial fibrillation. We observed a significant decrease in mortality in patients receiving WAR+ASA compared to patients on WAR alone (Chi-square, p=0.044) and neither drugs (p=0.014), and a trend for decreased mortality compared with patients on ASA alone (p=0.062). However, we observed an increased prevalence of hemorrhage in patients receiving WAR with or without ASA compared with individuals receiving ASA alone (WAR vs ASA p=0.016; WAR+ASA vs ASA p=0.002). We suspect that the frequent hemorrhagic events observed in individuals on neither drug may in part explain why these individuals were not on ASA and/or WAR. This retrospective data suggests combination therapy with WAR+ASA may be better than either agent alone or no therapy for reducing mortality in patients with PAD. Further, this data suggests that the pathogenesis of PAD may involve both platelet and non-platelet mediated hypercoagulable states.
Discordance between the 1st and 2nd Low Molecular Weight Heparin Standards. Implications for Dosing.
Authors: Jeske Walter P. , Cunanan Josephine , Hoppensteadt Debra , Walenga Jeanine M. , Iqbal Omer , Florian-Kujawski Michelle , Fareed Jawed 
Published: April 2020

Abstract
Soon after the introduction of low molecular weight heparins (LMWHs) as antithrombotic agents, a LMWH standard to cross-reference the potency of commercially available LMWHs was developed. For the past 15 years, this standard has been used by manufacturers to cross-reference their branded LMWHs. The 1st LMWH standard (85/600) was produced by nitrous acid digestion of porcine mucosal heparin. This standard had characteristics that were comparable to dalteparin. Because of the widespread use of the first standard, the supplies are now depleted necessitating the introduction of new standard material. The WHO has introduced a 2nd LMWH standard which is also produced by nitrous acid digestion and which mimics the commercially available LMWH reviparin. The molecular weight profile and the biologic activities, including SERPIN affinity, of these two standards are very distinct. When used to cross-reference commercially available LMWHs such as enoxaparin, the new standard consistently overestimates the anti-Xa potency by 5–10% in comparison to the first standard. Such an overestimation may lead to a reduction in dosage and have a significant impact on the clinical dosing of LMWH in various indications. As many generic versions of LMWHs are currently being introduced, a systematic study was carried out to cross-reference three commercially available generic products from India and South America against the first and second LMWH standards using amidolytic anti-Xa and anti-IIa assays. Differences were observed in the slopes of the concentration-response curves for these standards in both the anti-Xa and anti-IIa assays. The potencies of the generic LMWHs ranged from 141 to 152 U/mg in relation to the first standard and from 132 to 143 U/mg in relation to the second standard. On average, the anti-Xa potency was 6.5% lower when calculated with the 2nd standard. The differences in anti-IIa potency were further amplified and exhibited wider variation. On average, the anti-IIa potency was 18.9% lower when calculated with the 2nd standard. These studies clearly demonstrate that the limitations in the use of the first and second LMWH standards for cross-referencing commercially available LMWHs and their potential generic versions. If the 2nd standard is used, it should first be cross-referenced against the first standard in order to properly assign the anti-Xa and anti-IIa activities. This study also underscores the need for developing individual standards for each of the branded products. Such standards should be defined in terms of not only anti-Xa and anti-IIa activity, but also in terms of anticoagulant activity in global clotting assays such as the USP assay, activated clotting time (ACT), aPTT and Heptest. Such designations will be particularly useful in evaluating the potential equivalence of generic versions of branded LMWHs.
Use of Venipuncture Blood Sample for INR Testing on a Point of Care Machine.
Authors: Dhami Mandeep S. , Bulgaru Anca , Jagathambal K. , Kapur Dinesh , Norris Francine , Slater Dennis E. , Cavanaugh Jeri 
Published: April 2020

Abstract
Point of care (POC) testing of International Normalized Ratio (INR) for monitoring warfarin therapy is rapidly becoming procedure of choice for patients requiring long term oral anticoagulation. This method allows for fingerstick blood sample to be used for INR testing at the point of service with immediate dose modification as needed. Most patients prefer a fingerstick method for blood draw to venipuncture. It is not known if venipuncture blood sample can be used for testing on POC machines. A significant number of patients in an oncology practice need additional laboratory testing on the same day as INR testing. These patients therefore get a fingerstick for POC INR testing and a venipuncture for other tests. We compared results of INR from venipuncture sample run on a POC machine (CoaguChek monitor) using CoaguChek test strips (ISI-2.0) with the INR performed on MDA analyzer (ISI-2.0). Blood samples from 24 patients on warfarin therapy were drawn from antecubital vein by a clean stick in a 10 cc plastic syringe. A drop of blood was immediately placed on the CoaguCheck test strip. Next the same blood sample was used to fill a 3.2% sodium citrate tube for testing on MDA analyzer. Results were analyzed using regression analysis; the correlation coefficient (r), slope and intercept were determined and following graph of the regression analysis was generated (see figure 1).
Conclusions: These results show a good correlation (r-value&gt; 0.9) between the results of INR obtained on CoaguChek POC machine and the MDA analyzer using venipuncture blood sample. The preferred method to obtain blood sample for POC INR monitoring must remain fingerstick sample as per manufacturer’s recommendations. However, for those patients who need more than one blood sample done on the same day, a venipuncture sample as described above gives acceptable results when tested on CoaguCheck machine.
Figure Figure
Binding Properties of a Human Anti-Ib ScFv Antibody (HIb-1) to Native, Recombinant, and Transgenicially Expressed Human Platelet GP Ibα Antigen.
Authors: Kim Antony Y. , Bell George , Lovelock Joshua , Favre Elizabeth G. , Biswas Tapan K. , Yousef Mohammed , Miller Jonathan L. 
Published: April 2020

Abstract
HIb-1 is a single chain antibody (ScFv) originally obtained from the Griffin.1 library. ScFv from this library are derived from the in vitro recombination of germline human immunoglobulin VH and VL chain segments whose diversity has been greatly increased by mutagenesis directed at the CDR3 regions. HIb-1 was selected from the library by sequential biopanning first against CHO cells surface-expressing human GPIbα, and then against human platelets. Previous studies using Western blot analysis have shown that HIb-1 binds to an epitope within the 45 kDa amino-terminal portion of GPIbα (Lapan, Lyle, and Miller, 1999, Thromb. Haemost. 82S:393). HIb-1 displays inhibitory activity against both ristocetin-induced and shear-induced platelet aggregation. Biacore surface plasmon resonance analysis was used to establish dissociation constants between HIb-1and either the extracellular domain of GPIbα (i.e., “glycocalicin” or GC) derived from normal human platelets or the CHO-cell secreted GPIbα1–483 recombinant extracellular protein. With native GC immobilized on dextran sulfate, the KD for binding by analyte HIb-1 was ~600nM. With the wild-type recombinant GPIbα1–483 bound to dextran sulfate, the KD was only slightly higher at ~900 nM. We additionally studied a double mutant increase-of-function GPIbα1-483 containing the Gly233→Val233 and Met239→Val239 substitituions. The KD of HIb-1 binding to the double mutant was virtually identical to that of the wild-type, at ~900 nM. Binding of HIb-1 to native GC immobilized in an ELISA assay format was also performed. HIb-1 showed saturable binding, with a half-maximal binding concentration of approximately 170 nM. Flow cytometric analysis was also performed on platelets from murine GPIbα-null (i.e., “Bernard-Soulier”) mice that had been rescued with the human GPIbα transgene (Ware, Russell, and Ruggeri, 2000, PNAS, 97:2803), as well as upon normal mice. Murine platelets were gated using a rat anti-murine GPIIb/IIIa antibody. HIb-1 did not bind to normal murine platelets, but showed strong binding to platelets from the transgenic animals, comparable in intensity to that seen with the GPIbα mab SZ-2 (for which quantitative bead analysis indicated approximately 8,000 GPIbα receptors per platelet). It should be noted that the binding capabilities of HIb-1 to human GPIbα are those of a monovalent ScFv molecule of approximately 30 kDa, and may be sufficient for studies of in vivo GPIbα inhibition either in the case of acute injury model or of longer-term models involving repeated dosing. Model systems of more chronic inhibition, however, may require conversion of the ScFv into IgG molecules, in order to achieve greater avidity.
Transfusion Requirements in Nonmyeloablative Allogeneic Stem Cell Transplantation for Hematologic Malignancies.
Authors: Brown Jason W. , Triulzi Darrell J. 
Published: April 2020

Abstract
Nonmyeloablative allogeneic stem cell transplants (NM-ASCT) are increasingly being utilized to treat hematologic malignancies in settings where high dose, fully ablative regimens would not be tolerated. We identified 10 male and 13 female patients (n=23) ranging in age from 19 to 63 years old (mean=48) representing all patients whom had undergone NM-ASCT in the last five years. NM-ASCT were performed for acute myelogenous leukemia (n=7), non-Hodgkin’s lymphoma (n=6), Hodgkin’s disease (n=4), multiple myeloma (n=3), myelodysplastic syndrome (n=2), and acute lymphoblastic leukemia (n=1). The majority of patients had undergone at least one previous stem cell transplant (n=16). The mean number of stem cells infused per kilogram at time of transplant was 4.72 X 106 ±1.97 X 106 stem cells and mean time to engraftment was 15.8 ±5.15 days (3 consecutive days with ANC &gt;500). All of the subjects required both platelet and red cell transfusion during the period of analysis. Mean transfusion requirements in the 7 days prior to transplantation were 3.1 ±5.9 units of platelets and 1.2 ±1.5 units of packed red blood cells. Mean platelet transfusion requirements 90 days post transplant were 73.7 ±79.7 units and mean red cell requirements 11.6 ±8.3 units. Total mean transfusion requirements during the time period analyzed were 76.9 ±82.2 units of platelets and 12.8 ±8.9 units of packed red blood cells. There was no significant correlation between the number of stem cells infused per kilogram on day of transplant, the number of previous transplants, or the time to engraftment with red blood cell or platelet transfusion requirements. Our data illustrate a higher proportion of patients requiring platelet transfusions (100% vs. 23%) and red blood cell transfusions (100% vs. 63%) as well as a higher platelet transfusion requirement (median 48 vs. 0 units) and packed red blood cell transfusion requirement (median 11 vs. 2 units) than other authors have reported in a 60 day period in HLA-matched sibling NM-ASCT [Weissinger et al. Blood 98(13):3584-8, 2001]. As is illustrated by the percentage of patients undergoing previous fully ablative stem cell transplants, our patients represent a heavily pretreated population and this may account for the higher transfusion requirements seen in this analysis. Although patients undergoing NM-ASCT receive reduced intensity therapy, in our analysis their transfusion requirements remain substantial.