bluuebunny/crossref_metadata_2025_split huggingface dataset:
Goals for chronic myeloid leukemia TK inhibitor treatment: how little disease is too much?
Authors: Mauro Michael J. 
Published: November 2014

Abstract
Tyrosine kinase inhibitors, now numbering 5 for the treatment of Philadelphia chromosome–positive leukemia, have proven ability to reduce clonal disease burden rapidly, dramatically, and durably, especially in chronic myeloid leukemia in the chronic phase. Deep molecular remissions are likely in most chronic phase patients and expectations on timing of response have been developed, validated as best as possible, and evolved over time. Increasing attention has been given to the initial decline of Bcr-Abl1 transcripts and the ultimate depth of molecular remission, overshadowing but not displacing the traditional role of cytogenetic response. This chapter reviews the evolution of response milestones for chronic phase chronic myeloid leukemia and tries to answer the question of how little disease is too much.
All transplantation-eligible patients with myeloma should receive ASCT in first response
Authors: Moreau Philippe , Attal Michel 
Published: November 2014

AbstractIn this last decade, one of the major advances in the management of multiple myeloma has been the introduction of the novel agents thalidomide, bortezomib, and lenalidomide as part of frontline treatment in young patients eligible for high-dose therapy (HDT) and autologous stem cell transplantation (ASCT). These drugs have markedly improved the rate of complete remission both before and after ASCT without substantially increasing toxicity. The implementation of an “optimal strategy” consisting of novel-agent-based induction, HDT, and the use of novel agents in consolidation and maintenance may result in a 5-year survival rate of 80% and cure might be considered in a subset of patients who present with good prognostic features at the time of diagnosis. Nevertheless, the high efficacy of the novel agents has led some groups to test these agents upfront without ASCT. At the end of 2014, preliminary randomized data favor early ASCT plus novel agents over novel agents alone. Therefore, the optimal approach to the treatment of multiple myeloma is still to propose the most effective treatment that should involve the use of frontline ASCT in young patients eligible for HDT.
New insights into treatment of venous thromboembolism
Authors: Moll Stephan 
Published: November 2014

Abstract
Several advances have occurred over the last 2 years in the clinical management of venous thromboembolism (VTE), as evidenced by several high-profile publications in top-tier medical journals. The translation of the knowledge gained into routine clinical practice is an important challenge so that VTE is managed optimally and established and new anticoagulants are used effectively and safely. This chapter reviews issues of VTE treatment from acute management to treatment of long-term complications, addressing new data gained in the last 2 years and putting them into a clinical context, with the goal of improved everyday VTE management.
Monitoring target-specific oral anticoagulants
Authors: Konkle Barbara A. 
Published: November 2014

Abstract
Target-specific oral anticoagulants are approved for use for the prevention of stroke in atrial fibrillation and for the prevention and treatment of venous thrombosis without the need for laboratory monitoring. However, there are clinical settings in which laboratory measurement of anticoagulant effect is needed. These may include patients with life-threatening bleeding or those requiring emergency surgery, in the setting of renal or hepatic failure, or patients with thrombosis on therapy. This chapter reviews the use of laboratory testing to assess the anticoagulant effect of these drugs. In addition, because these drugs can interfere with other laboratory testing, available data on these interactions are presented.
What is the effect of rivaroxaban on routine coagulation tests?
Authors: Siegal Deborah M. , Konkle Barbara A. 
Published: November 2014

Abstract
A 78-year-old female presents to the emergency department with a traumatic hip fracture. Her past medical history is significant for atrial fibrillation for which she receives rivaroxaban 20 mg daily. Her dose was last taken 12 hours ago. Routine bloodwork conducted in the emergency department shows prothrombin time, international normalized ratio, and activated partial thromboplastin time within the normal range, and estimated glomerular filtration rate of 50 mL/min/1.73 m2 (normal is >90 mL/min/1.73 m2) You are asked by the surgical team to confirm that it is safe to proceed with surgery at this time using neuraxial anesthesia.
Pharmacogenomics of antiplatelet drugs
Authors: Sabatine Marc S. , Mega Jessica L. 
Published: November 2014

Abstract
Clopidogrel, a platelet P2Y12 inhibitor, is one of the most widely prescribed drugs in cardiovascular medicine because it reduces ischemic and thrombotic complications. It is a prodrug requiring biotransformation into the active metabolite by the hepatic cytochrome 450 system, especially the CYP2C19 enzyme. Candidate gene studies and genome-wide association studies have identified loss-of-function CYP2C19 variants to be associated with a diminished pharmacologic response. Specifically, compared with noncarriers, carriers of at least one copy of a loss-of-function CYP2C19 allele have ∼30% lower levels of active clopidogrel metabolite and ∼25% relatively less platelet inhibition with clopidogrel. Moreover, in patients treated with clopidogrel predominantly for percutaneous coronary intervention, carriers of 1 or 2 CYP2C19 loss-of-function alleles are at increased risk for major adverse cardiovascular outcomes, with an ∼1.5-fold increase in the risk of cardiovascular death, myocardial infarction, or stroke as well as an ∼3-fold increase in risk for stent thrombosis. Tripling the dose of clopidogrel in carriers of a CYP2C19 loss-of-function allele can achieve on-treatment platelet reactivity comparable to that seen with the standard 75 mg dose in wild-type individuals, but the impact on clinical outcomes remains unknown. Alternatively, 2 third-generation P2Y12 inhibitors are available: prasugrel and ticagrelor. These drugs are superior to clopidogrel in reducing ischemic outcomes and are unaffected by CYP2C19 loss-of-function alleles.
Management of MPN beyond JAK2
Authors: Harrison Claire N. , Garcia Natalia Curto 
Published: November 2014

Abstract
Thrombocytosis has a large number of potential underlying causes, but the dominant group of hematological conditions for consideration in this setting are the myeloproliferative neoplasms (MPNs). In this chapter, we consider several key linked questions relating to the management of thrombocytosis in MPNs and discuss several issues. First, we discuss the differential diagnosis of thrombocytosis, which myeloid disorders to consider, and practical approaches to the discrimination of each individual MPN from other causes. Second, there have been several major advances in our understanding of the molecular biology of these conditions and we discuss how these findings are likely to be practically applied in the future. Third, we consider whether there is evidence that thrombocytosis contributes to the complications known to be associated with MPN: thrombosis, hemorrhage and transformation to leukemia and myelofibrosis. Last, we review current ideas for risk stratification and management of essential thrombocythemia and polycythemia vera as the 2 entities within the MPN family that are most frequently associated with thrombocytosis.
Anticoagulation and in vitro fertilization and ovarian stimulation
Authors: Bates Shannon M. 
Published: November 2014

AbstractAssisted reproductive technology is widely used to treat couples affected by infertility. Complications associated with assisted reproduction include venous thromboembolism, ovarian hyperstimulation syndrome, and recurrent implantation failure. It has also been proposed that thrombophilia may be associated with an increased likelihood of these events. Although data are limited, antithrombotic therapy is frequently used to enhance the likelihood of successful assisted reproduction. This chapter reviews the risks of venous and arterial thromboembolism associated with assisted reproduction, as well as available data regarding the impact of thrombophilia on the risks of thromboembolism and failure of implantation. The role of antithrombotic therapy in reducing the likelihood of these events, along with recommendations from various guidelines, are also discussed.
Replacing bad (F)actors: hemophilia
Authors: Doering Christopher B. , Spencer H. Trent 
Published: November 2014

AbstractHemophilia A and B are bleeding disorders that result from functional deficiencies in specific circulating blood clotting factors termed factor VIII (FVIII) and factor IX (FIX), respectively, and collectively display an incidence of 1 in 4000 male births. Stem cell transplantation therapies hold the promise of providing a cure for hemophilia, but currently available transplantable stem cell products do not confer endogenous FIX or FVIII biosynthesis. For this reason, stem cell–based approaches for hemophilia have focused primarily on genetic engineering of pluripotent or multipotent stem cells. While pluripotent stem cells have been branded with high expectation and promise, they remain poorly characterized in terms of clinical utility and safety. In contrast, adult-lineage-restricted stem cells are established agents in the clinical armamentarium. Of the clinically established stem cell types, hematopoietic stem cells (HSCs) are the most utilized and represent the standard of care for several genetic and acquired diseases. Furthermore, HSCs are ideal cellular vehicles for gene therapy applications because they self-renew, repopulate the entire blood lineage while concurrently amplifying the transgene copy number >106 fold, and also have direct access to the bloodstream. Current research on HSC transplantation gene therapy approaches for hemophilia A and B is focused on the following: (1) identification of safe and efficient methods of nucleic acid transfer, (2) optimization of transgene product expression, (3) minimization of conditioning-regimen-related toxicity while maintaining HSC engraftment, and (4) overcoming preexisting immunity. Based on the existing data and current rate of progress, clinical trials of HSC transplantation gene therapy for hemophilia are predicted to begin in the coming years.
Caring for the long-term survivor after allogeneic stem cell transplantation
Authors: Bhatia Smita 
Published: November 2014

Abstract
Survivors of allogeneic hematopoietic cell transplantation (HCT) are at risk of developing long-term complications such as subsequent malignancies and cardiopulmonary compromise. The prevalence of chronic health conditions approaches 75% among allogeneic HCT survivors and that for severe or life-threatening conditions exceeds 20%. This chapter describes the burden of morbidity carried by HCT survivors to help healthcare providers and policy makers understand the scope of the problem and the need for life-long follow-up and proactive care for this vulnerable population.
The target-specific oral anticoagulants: practical considerations
Authors: Garcia David A. 
Published: November 2014

Abstract
More than 4 years have passed since the first approval of a target-specific oral anticoagulant (TSOAC) in the United States, and the number of clinicians who have prescribed (or considered prescribing) one or more of these medications is increasing. Although these agents may, in properly selected patients, offer advantages over more traditional therapies, their lack of familiarity can be intimidating. Clinicians who are prescribing the TSOACs face a number of management questions not definitively answered by the registration trials. This chapter reviews some of these situations, including updated information on the periprocedural management of TSOACs and the latest evidence about how to best measure TSOAC effect. The lack of an antidote and other considerations that may be relevant when deciding between newer and more traditional anticoagulant medications are also discussed.
Reversing targeted oral anticoagulants
Authors: Hoffman Maureane , Monroe Dougald M. 
Published: November 2014

AbstractDabigatran, rivaroxaban, and apixaban are orally active anticoagulants that are approved in many countries. Dabigatran inhibits thrombin, whereas rivaroxaban and apixaban are factor Xa inhibitors. In clinical trials, these novel oral anticoagulants were at least as effective as warfarin for preventing stroke in patients with atrial fibrillation, but with a lower rate of serious bleeding. However, the lack of true antidotes for these agents has caused concern when patients suffer life-threatening bleeding or trauma or require emergent invasive procedures. True antidotes are under development for all of these agents. In the meantime, activated and nonactivated prothrombin complex concentrates have been used as reversal agents. Factor VIIa may also be effective for reversal of the factor Xa inhibitors. Reversal of novel oral anticoagulants by these hemostatic agents has not been studied in bleeding human patients, so their true efficacy and appropriate dosing are not known.
Bloodless medicine: what to do when you can't transfuse
Authors: Resar Linda M.S. , Frank Steven M. 
Published: November 2014

Abstract
A better understanding of risks associated with allogeneic blood transfusions (ABTs), along with a growing population of patients who do not accept transfusions, have led to the emergence of new treatment paradigms with “bloodless medicine.” In this chapter, we review prior studies describing management and outcomes in patients who refuse transfusion (referred to as “bloodless patients” herein) and summarize the approaches used at our institution. Bloodless management for surgical patients includes treatment of preoperative anemia, use of autologous blood salvage, and minimizing blood loss with procedures. Other adjuncts for both medical and surgical patients include minimizing blood loss from laboratory testing using pediatric phlebotomy tubes and conservative testing. Anemia can be treated with erythropoiesis-stimulating agents, as well as iron, folate, and B12 when indicated. Although there are limited retrospective studies and no prospective studies to guide management, prior reports suggest that outcomes for surgical patients managed without ABTs are comparable to historic controls. A recent risk-adjusted, propensity-matched, case-control study of outcomes of all hospitalized patients who refused ABT at a large academic health center showed that bloodless management was not an independent predictor of adverse outcomes. Surprisingly, there was a lower overall mortality in the bloodless group and discharge hemoglobin levels were similar for both bloodless and control groups. Further research is now needed to optimize therapy and identify novel interventions to manage bloodless patients. Lessons learned from bloodless patients are likely to benefit all patients given recent evidence suggesting that patients who avoid ABTs do as well, if not better, than those who accept transfusions.
Five hematologic tests and treatments to question
Authors: Hicks Lisa K. , Bering Harriet , Carson Kenneth R. , Haynes Adam E. , Kleinerman Judith , Kukreti Vishal , Ma Alice , Mueller Brigitta U. , O'Brien Sarah H. , Panepinto Julie A. , Pasquini Marcelo C. , Rajasekhar Anita , Sarode Ravi , Wood William A. 
Published: November 2014

AbstractChoosing Wisely® is a medical stewardship initiative led by the American Board of Internal Medicine Foundation in collaboration with professional medical societies in the United States. The American Society of Hematology (ASH) released its first Choosing Wisely® list in 2013. Using the same evidence-based methodology as in 2013, ASH has identified 5 additional tests and treatments that should be questioned by clinicians and patients under specific, indicated circumstances. The ASH 2014 Choosing Wisely® recommendations include: (1) do not anticoagulate for more than 3 months in patients experiencing a first venous thromboembolic event in the setting of major, transient risk factors for venous thromboembolism; (2) do not routinely transfuse for chronic anemia or uncomplicated pain crises in patients with sickle cell disease; (3) do not perform baseline or surveillance computed tomography scans in patients with asymptomatic, early-stage chronic lymphocytic leukemia; (4) do not test or treat for heparin-induced thrombocytopenia if the clinical pretest probability of heparin-induced thrombocytopenia is low; and (5) do not treat patients with immune thrombocytopenia unless they are bleeding or have very low platelet counts.
Timing of allogeneic stem cell transplantation for myelodysplastic syndromes and aplastic anemia
Authors: Cutler Corey 
Published: November 2014

Abstract
Allogeneic hematopoietic stem cell transplantation (HSCT) for myelodysplastic syndrome (MDS) is a potentially curative procedure, but is associated with a significant risk of morbidity and mortality. With the recent approval of disease-modifying agents, the appropriate timing of allogeneic HSCT needs to be addressed. Similarly, the optimal use of these disease-modifying agents before HSCT needs to be determined. In severe aplastic anemia, HSCT is a proven cure, but HLA-matched sibling donors are found in fewer than 25% of newly diagnosed patients. The use of early unrelated donor HSCT is an evolving concept that will become more accepted as improvements in HSCT outcomes continue.
Closure of small and medium size umbilical hernias with the Proceed Ventral Patch in obese patients: a single center experience
Authors: Wassenberg Dirk , Zarmpis Nikolaos , Seip Nora , Ambe Peter C 
Published: November 2014

Abstract
Obesity is a risk factor for the development of umbilical hernia. Open hernia closure could be challenging in obese patients leading to high rates of recurrence. The aim of this study was to investigate the effectiveness and safety of hernia patches in the management of obese patients with umbilical hernias. All the patients included in this study were managed in the department of surgery of a primary care hospital in Germany. The data of patients undergoing umbilical hernia repair within a two-year period was retrospectively reviewed. Patients managed with the PVP were included for analysis. 24 obese patients were analyzed. Small and medium size patches were used in 15 and 9 patients respectively. The median duration of surgery was 40 min and the median length of hospital stay was 4d. The mean length of follow-up was 12 ± 9 months (range: 6–30 months). The rate of recurrence was 4.1% and the rate of complication was 8.3%. Obese patients presenting with small and medium size umbilical hernias could be safely and effectively managed with prosthetic patches like the Proceed Ventral Patch. However, the limited overlap zone following hernia closure with such a patch can be an issue.
Transcriptional fingerprints of antigen-presenting cell subsets in the human vaginal mucosa and skin reflect tissue-specific immune microenvironments
Authors: Duluc Dorothée , Banchereau Romain , Gannevat Julien , Thompson-Snipes Luann , Blanck Jean-Philippe , Zurawski Sandra , Zurawski Gerard , Hong Seunghee , Rossello-Urgell Jose , Pascual Virginia , Baldwin Nicole , Stecher Jack , Carley Michael , Boreham Muriel , Oh SangKon 
Published: November 2014

Abstract
Background
Dendritic cells localize throughout the body, where they can sense and capture invading pathogens to induce protective immunity. Hence, harnessing the biology of tissue-resident dendritic cells is fundamental for the rational design of vaccines against pathogens.

Methods
Herein, we characterized the transcriptomes of four antigen-presenting cell subsets from the human vagina (Langerhans cells, CD14- and CD14+ dendritic cells, macrophages) by microarray, at both the transcript and network level, and compared them to those of three skin dendritic cell subsets and blood myeloid dendritic cells.

Results
We found that genomic fingerprints of antigen-presenting cells are significantly influenced by the tissue of origin as well as by individual subsets. Nonetheless, CD14+ populations from both vagina and skin are geared towards innate immunity and pro-inflammatory responses, whereas CD14- populations, particularly skin and vaginal Langerhans cells, and vaginal CD14- dendritic cells, display both Th2-inducing and regulatory phenotypes. We also identified new phenotypic and functional biomarkers of vaginal antigen-presenting cell subsets.

Conclusions
We provide a transcriptional database of 87 microarray samples spanning eight antigen-presenting cell populations in the human vagina, skin and blood. Altogether, these data provide molecular information that will further help characterize human tissue antigen-presenting cell lineages and their functions. Data from this study can guide the design of mucosal vaccines against sexually transmitted pathogens.
Prediction of microstructure evolution during multi-stand shape rolling of nickel-base superalloys
Authors: Subramanian Kannan , Cherukuri Harish P 
Published: November 2014

AbstractIn this paper, a comprehensive numerical approach to predict the microstructure of nickel-base superalloys during multi-stand shape rolling is presented. This approach takes into account the severe deformation that occurs during each pass and also the possible reheating between passes. In predicting the grain size at the end of the rolling process, microstructural events such as dynamic recrystallization (DRX), metadynamic recrystallization (MDRX), and static grain growth are captured at every deformation step for superalloys. Empirical relationships between the average grain size from various microstructural processes and the macroscopic variables such as temperature (T) and effective strain (

ε

̄

) and strain rate (

ε

̄

̇

) form the basis for the current work. These empirical relationships are based on Avrami equations. The macroscopic variables are calculated using a finite element analysis package wherein the material being rolled is modeled as a non-Newtonian fluid with viscosity that depends on the effective strain rate, strain, and temperature. A two-dimensional transient thermal analysis is carried out between passes that can capture the MDRX and/or static grain growth during the microstructural evolution. The presented microstructure prediction algorithm continuously updates two families of grains, namely, the recrystallized family and strained family at the start of deformation in any given pass. In addition, the algorithm calculates various subgroups within these two families at every deformation step within a pass. As the material undergoes deformation between the rolls, recrystallization equations are invoked depending on critical strain and strain rate conditions that are characteristics of superalloys. This approach predicts the microstructural evolution based on recrystallization kinetics and static grain growth only. The methodology was successfully applied to predict the microstructure evolution during the multi-pass rolling of nickel-base superalloys. The predicted results for Alloy 718 for a 4-stand rolling followed by air cooling and for a 16-stand rolling followed by a combination of air and water cooling are also compared with experimental observations.