bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cure at what (systemic) financial cost? Integrating novel therapies into first-line Hodgkin lymphoma treatment
Authors: Huntington Scott F. 
Published: December 2019

Abstract
Classic Hodgkin lymphoma (cHL) stands out as success story in the field of medical oncology, with multiagent chemotherapy with or without radiation leading to durable remission for most patients. Large-scale clinical trials during the past 40 years have sought to minimize toxicities while maintaining strong efficacy, including efforts to reduce the size of radiation fields, minimize alkylator chemotherapy, reduce the number of chemotherapy cycles, and omit radiation in select populations. The last decade has also ushered in novel therapies, including brentuximab vedotin (BV), that have improved clinical outcomes for patients with cHL resistant to standard cytotoxic therapies. More recently, a large randomized trial compared BV plus chemotherapy with chemotherapy alone for first-line treatment of advanced stage cHL. With ∼24 months of available follow-up, the BV containing regimen was found to be associated with a reduction in the risk of progression, death, or incomplete response to first-line treatment (modified progression-free survival). Whether this early signal of improved efficacy is worth the additional acute toxicities and added drug-related expenses associated with incorporating BV into first-line treatment remains controversial. This chapter provides historical background; reviews the cost-effectiveness of available cHL therapies; and summarizes potential ways to balance innovation, affordability, and patient access to novel therapeutics.
Iron overload in transfusion-dependent patients
Authors: Coates Thomas D. 
Published: December 2019

AbstractBefore the advent of effective iron chelation, death from iron-induced cardiomyopathy occurred in the second decade in patients with transfusion-dependent chronic anemias. The advances in our understanding of iron metabolism; the ability to monitor iron loading in the liver, heart, pancreas and pituitary; and the availability of several effective iron chelators have dramatically improved survival and reduced morbidity from transfusion-related iron overload. Nevertheless, significantly increased survival brings about new complications such as malignant transformation resulting from prolonged exposure to iron, which need to be considered when developing long-term therapeutic strategies. This review discusses the current biology of iron homeostasis and its close relation to marrow activity in patients with transfusion-dependent anemias, and how biology informs clinical approach to treatment.
Sickle cell disease: a comprehensive program of care from birth
Authors: de Montalembert Mariane , Tshilolo Léon , Allali Slimane 
Published: December 2019

Abstract
As more children are appropriately being diagnosed, the burden of sickle cell disease is increasing greatly in Africa and in high-resource countries such as the United States and Europe. Early management is mandatory, but newborn screening is not implemented everywhere. Point-of-care testing devices are increasingly being used in low-resource countries, showing good sensitivity and specificity. Because the diagnosis is often traumatic for the families, the announcement should be made by an experienced person. The development of care networks is urgently required to facilitate daily life by defining the respective functions of nearby and highly specialized health care professionals, who should work in close collaboration. Comprehensive programs targeting the prevention of pneumococcal infections, malaria in infested zones, and stroke may substantially improve patient care. Hydroxyurea is increasingly being used, but whether it should be systematically prescribed in all children is debated, and its access is still limited in many African countries. Yearly checkups should be organized early in life in order to screen and then treat any organ impairment. Enhancing parents’ and patients’ knowledge and skills is mandatory.
Optimal disease management and health monitoring in adults with sickle cell disease
Authors: Howard Jo , Thein Swee Lay 
Published: December 2019

AbstractIn countries with access to organized health care, survival of children with sickle cell disease (SCD) has greatly improved, resulting in a growing population of adults with SCD. Transition from pediatric to adult care presents many challenges for the patient, who now faces the reality of emerging complications in many organs that are cumulative, adding to other age-related nonsickle conditions that interact and add to the disease morbidity. We recommend regular comprehensive annual assessments, monitoring for early signs of organ damage and joint clinics with relevant specialists, if applicable. While maintaining a low threshold for intervention with disease-modifying therapies, we should always keep in mind that there is no single complication that is pathognomonic of SCD, and nonsickle comorbidities should always be excluded and treated if present. We need to reevaluate our approach to managing adults with SCD by putting a greater emphasis on multidisciplinary care while proactively considering curative options (hematopoietic stem cell transplant and gene therapy) and experimental pharmacological agents for adults with SCD of all ages before complications render the patients ineligible for these treatments.
MRD evaluation of AML in clinical practice: are we there yet?
Authors: Freeman Sylvie D. , Hourigan Christopher S. 
Published: December 2019

Abstract
MRD technologies increase our ability to measure response in acute myeloid leukemia (AML) beyond the limitations of morphology. When applied in clinical trials, molecular and immunophenotypic MRD assays have improved prognostic precision, providing a strong rationale for their use to guide treatment, as well as to measure its effectiveness. Initiatives such as those from the European Leukemia Network now provide a collaborative knowledge-based framework for selection and implementation of MRD assays most appropriate for defined genetic subgroups. For patients with mutated-NPM1 AML, quantitative polymerase chain reaction (qPCR) monitoring of mutated-NPM1 transcripts postinduction and sequentially after treatment has emerged as a highly sensitive and specific tool to predict relapse and potential benefit from allogeneic transplant. Flow cytometric MRD after induction is prognostic across genetic risk groups and can identify those patients in the wild-type NPM1 intermediate AML subgroup with a very high risk for relapse. In parallel with these data, advances in genetic profiling have extended understanding of the etiology and the complex dynamic clonal nature of AML, as well as created the opportunity for MRD monitoring using next-generation sequencing (NGS). NGS AML MRD detection can stratify outcomes and has potential utility in the peri-allogeneic transplant setting. However, there remain challenges inherent in the NGS approach of multiplex quantification of mutations to track AML MRD. Although further development of this methodology, together with orthogonal testing, will clarify its relevance for routine clinical use, particularly for patients lacking a qPCR genetic target, established validated MRD assays can already provide information to direct clinical practice.
New advances in the diagnosis of von Willebrand disease
Authors: Sharma Ruchika , Haberichter Sandra L. 
Published: December 2019

Abstract
von Willebrand disease (VWD) is the most common autosomal inherited bleeding disorder, with an estimated prevalence of 1 in 1000 individuals. VWD is classified into quantitative and qualitative forms. Diagnosis of VWD is complex and requires (1) a personal history of bleeding symptoms, (2) family history of bleeding or VWD, and (3) confirmatory laboratory testing. There are certain bleeding assessment tools to objectively measure bleeding symptoms in patients that have been shown to correlate with the diagnosis as well as the severity of VWD. Laboratory diagnosis requires at least initially a measurement of von Willebrand factor (VWF) antigen levels, VWF platelet binding activity (VWF:RCo, VWF:GPIbM, and VWF:GPIbR), and factor VIII (FVIII) activity. Additional testing to confirm the specific subtype may include VWF collagen binding activity, low-dose ristocetin VWF-platelet binding, FVIII-VWF binding, VWF multimer analysis, and VWF propeptide antigen. Recent advances have been made regarding some of these assays. Molecular testing in VWD is not found to be useful in “low VWF” or most type 1 VWD cases but may be informative in patients with severe type 1 VWD, type 1C VWD, type 2 VWD, or type 3 VWD for accurate diagnosis, genetic counseling, and appropriate treatment. The diagnostic algorithm for VWD is complex, but advances continue to be made in improving VWF functional assays and diagnostic pathways.
Bleeding in critical care associated with left ventricular assist devices: pathophysiology, symptoms, and management
Authors: Leebeek F. W. G. , Muslem R. 
Published: December 2019

Abstract
Chronic heart failure (HF) is a growing health problem, and it is associated with high morbidity and mortality. Left ventricular assist devices (LVADs) are nowadays an important treatment option for patients with end-stage HF not only as a bridging tool to heart transplantation but also, as a permanent therapy for end-stage HF (destination therapy). The use of LVAD is associated with a high risk for bleeding complications and thromboembolic events, including pump thrombosis and ischemic stroke. Bleeding is the most frequent complication, occurring in 30% to 60% of patients, both early and late after LVAD implantation. Although the design of LVADs has improved over time, bleeding complications are still the most common complication and occur very frequently. The introduction of an LVAD results in an altered hemostatic balance as a consequence of blood-pump interactions, changes in hemodynamics, acquired coagulation abnormalities, and the strict need for long-term anticoagulant treatment with oral anticoagulants and antiplatelet therapy. LVAD patients may experience an acquired coagulopathy, including platelet dysfunction and impaired von Willebrand factor activity, resulting in acquired von Willebrand syndrome. In this educational manuscript, the epidemiology, etiology, and pathophysiology of bleeding in patients with LVAD will be discussed. Because hematologist are frequently consulted in cases of bleeding problems in these individuals in a critical care setting, the observed type of bleeding complications and management strategies to treat bleeding are also reviewed.
What we have learned about direct oral anticoagulant reversal
Authors: Siegal Deborah M. 
Published: December 2019

Abstract
Bleeding is the main complication of oral anticoagulant (OAC) therapy, with major bleeds occurring in about 2% to 4% of OAC-treated patients per year. Although direct oral anticoagulants (DOACs) reduce the risk of major, fatal, and intracranial hemorrhage, major DOAC-related bleeding is associated with substantial morbidity and mortality, with case-fatality rates of 8% to 15% reported. Specific reversal agents for dabigatran (idarucizumab) and factor Xa inhibitors (andexanet) correct laboratory indices of anticoagulant effect. Clinical studies suggest that the majority of patients receiving these agents for DOAC-associated major bleeds experience clinical hemostasis. However, uncertainty remains regarding the incremental benefit of these agents and prothrombin complex concentrates over supportive measures alone, based on cohort studies that lacked control groups. Similar methodologic limitations preclude firm conclusions regarding the harms associated with use of these agents. Importantly, patients with DOAC-related major bleeding have substantial short-term risks of thrombosis and mortality, emphasizing the need for individualized patient assessment and protocolized bleed management strategies that include assessment of candidacy for safe resumption of OACs. With expanding indications and increasing prevalence of DOAC-eligible patients, bleeding complications and their management represent an ever-greater major health problem.
Microbiota modification in hematology: still at the bench or ready for the bedside?
Authors: Severyn Christopher J. , Brewster Ryan , Andermann Tessa M. 
Published: December 2019

AbstractGrowing evidence suggests that human microbiota likely influence diverse processes including hematopoiesis, chemotherapy metabolism, and efficacy, as well as overall survival in patients with hematologic malignancies and other cancers. Both host genetic susceptibility and host-microbiota interactions may impact cancer risk and response to treatment; however, microbiota have the potential to be uniquely modifiable and accessible targets for treatment. Here, we focus on strategies to modify microbiota composition and function in patients with cancer. First, we evaluate the use of fecal microbiota transplant to restore microbial equilibrium following perturbation by antibiotics and chemotherapy, and as a treatment of complications of hematopoietic stem cell transplantation (HSCT), such as graft-versus-host disease and colonization with multidrug-resistant organisms. We then address the potential use of both probiotics and dietary prebiotic compounds in targeted modulation of the microbiota intended to improve outcomes in hematologic diseases. With each type of therapy, we highlight the role that abnormal, or dysbiotic, microbiota play in disease, treatment efficacy, and toxicity and evaluate their potential promise as emerging strategies for microbiota manipulation in patients with hematologic malignancies and in those undergoing HSCT.
From Budd-Chiari syndrome to acquired von Willebrand syndrome: thrombosis and bleeding complications in the myeloproliferative neoplasms
Authors: Stein Brady L. , Martin Karlyn 
Published: December 2019

AbstractThrombotic and hemorrhagic complications are prevalent in patients with essential thrombocythemia, polycythemia vera, and myelofibrosis. Given the impact on morbidity and mortality, reducing the risk of thrombosis and/or hemorrhage is a major therapeutic goal. Historically, patients have been risk stratified on the basis of traditional factors, such as advanced age and thrombosis history. However, multiple factors contribute to the thrombotic tendency, including gender, mutational profile, inflammatory stress, and abnormal cell adhesion. Management includes cardiovascular risk reduction and use of antiplatelet therapy, depending on myeloproliferative neoplasm subtype and mutational status. Anticoagulation is a mainstay of therapy for those with venous thrombosis, but practice patterns remain heterogeneous. Cytoreduction is indicated for higher-risk patients, but efficacy may depend on the involved vascular bed. Management of special situations, such as unusual site thrombosis, bleeding, the perioperative period, and pregnancy, are especially challenging. In this article, risk factors and treatment strategies for myeloproliferative neoplasm thrombosis and bleeding, including special situations, are reviewed. Insights gained from recent studies may lead to the development of a more precise risk classification and tailored therapy.
Common variable immune deficiency: case studies
Authors: Cunningham-Rundles Charlotte 
Published: December 2019

Abstract
Common variable immune deficiency (CVID) is one of the most common congenital immune defects encountered in clinical practice. The condition occurs equally in males and females, and most commonly in the 20- to 40-year-old age group. The diagnosis is made by documenting reduced serum concentrations of immunoglobulin G (IgG), IgA, and usually IgM, together with loss of protective antibodies. The genetics of this syndrome are complex and are still being unraveled, but the hallmarks for most patients, as with other immune defects, include acute and chronic infections of the sinopulmonary tract. However, other noninfectious autoimmune or inflammatory conditions may also occur in CVID, and indeed these may be the first and only sign that a significant immune defect is present. These manifestations include episodes of immune thrombocytopenia, autoimmune hemolytic anemia, or neutropenia, in addition to splenomegaly, generalized or worrisome lymphadenopathy, and malignancy, especially lymphoma. These issues commonly bring the patient to the attention of hematologists for both evaluation and treatment. This article discusses 3 cases in which patients with CVID had some of these presenting issues and what hematology input was required.
Rocuronium-induced anaphylaxis: a case report
Authors: Takahashi Kanako , Tanaka Satoru , Watanabe Masanori , Yamakage Michiaki 
Published: December 2019

Abstract
Background
Neuromuscular blocking agents are frequently a cause of anaphylaxis that occurs in the perioperative period, and a skin prick test is an examination for definite diagnosis.

Case presentation
We report our experience of a patient with rocuronium-induced anaphylaxis who was scheduled to undergo open-heart surgery. After induction of anesthesia, anaphylaxis was suspected because the patient’s blood pressure decreased, airway pressure increased, and skin flushing and edema were observed on her neck and arms. With rapid treatment, good progress was seen without complications. About 5 weeks later, skin prick tests were performed for rocuronium and vecuronium. She was positive for rocuronium and negative for vecuronium. Seven weeks after anaphylaxis, vecuronium was used for the surgery and she had no symptoms that indicated anaphylaxis. The operation was completed uneventfully.

Conclusion
We experienced a case of anaphylaxis caused by rocuronium. After a definite diagnosis had been made by a skin prick test, safe anesthesia management was possible using vecuronium during the reoperation.
Modified percutaneous radiologic gastrostomy technique without endoscopic or nasogastric access
Authors: Tabashy Reda , Darwish Amira , Ibrahim Ashraf , Gad El-Mola Mohamed 
Published: December 2019

Abstract
Background
The aim of this study is to evaluate the efficacy and safety of a modified percutaneous radiologic gastrostomy (MPRG) technique under ultrasound and fluoroscopic guidance without endoscopic or nasogastric access.

Results
The study included 24 patients: 10 males and 14 females whose ages ranged from 44 to 80 years old. Ten patients had esophageal cancer and 14 patients had neck cancer. Technical success was achieved in 23 out of the 25 procedures (92%). Two procedures failed (8%) and were converted to the conventional technique by using the nasogastric tube. No major complications were reported. Minor complications were observed in 5 patients (20%): intraperitoneal air and contrast leakage in 4 patients and focal mucosal dissection by the contrast in 1 patient.

Conclusion
The MPRG has high technical success rate, is safe with no major complications, and is most feasible when endoscopic or nasogastric access cannot be performed.
Public Preferences for New Information on Opioids
Authors: Testa Paul F. , Moffitt Susan L. , Schenk Marie 
Published: December 2019

Abstract
Context: Educating the public through information campaigns is a commonly used policy approach to public health problems. Yet, experimental methods that assess the impact of information campaigns may misestimate their effects by failing to account for respondents' willingness to receive new information.
Methods: This article uses a doubly randomized survey experiment conducted on a nationally representative sample, where some subjects are randomly assigned to an informational treatment about opioids while other subjects are given the choice of whether to receive treatment or not, to examine how public willingness to seek new information shapes the way they update their preferences about policies related to the opioid epidemic.
Findings: Among those likely to receive information, treatment has a large positive effect on increasing support for policies that address the opioid epidemic by about one half of a standard deviation. Among those who would avoid this information, preferences appear to be unmoved by treatment. These effects would be missed by standard experimental designs.
Conclusion: While redressing information asymmetries is only one part of a public health strategy for addressing the opioid epidemic, our findings highlight the importance of access to and receptiveness toward new information.
Tramadol Does Not Improve Performance or Impair Motor Function in Trained Cyclists
Authors: BEJDER JACOB , BREENFELDT ANDERSEN ANDREAS , BONNE THOMAS CHRISTIAN , PIIL JACOB FEDER , HAGEN LINN CAMILLA HAUAN , DEHNES YVETTE , EIBYE KASPER HVID , NYBO LARS , NORDSBORG NIKOLAI BAASTRUP 
Published: December 2019

ABSTRACT

Purpose
To investigate the hypothesis that a therapeutic oral dose of Tramadol improves cycling time trial performance and compromises motor-cognitive performance in highly trained cyclists.

Methods
Following two familiarization trials, 16 highly trained cyclists completed a preloaded time trial (1 h at 60% of peak power followed by a 15-km time trial) after ingestion of 100 mg Tramadol or placebo in a double-blind placebo-controlled counterbalanced crossover design separated by at least 4 d washout. Visuomotor tracking and math tasks were completed during the preload (n = 10) to evaluate effects on cognition and fine motor performance.

Results
Time trial mean power output (298 ± 42 W vs 294 ± 44 W) and performance (1474 ± 77 s vs 1483 ± 85 s) were similar with Tramadol and placebo treatment, respectively. In addition, there were no differences in perceived exertion, reported pain, blood pH, lactate, or bicarbonate concentrations across trials. Heart rate was higher (P < 0.001) during the Tramadol time trial (171 ± 8 bpm) compared with placebo (167 ± 9 bpm). None of the combined motor-cognitive tasks were impaired by Tramadol ingestion, in fact fine motor performance was slightly improved (P < 0.05) in the Tramadol trial compared with placebo.

Conclusions
In highly trained cyclists, ingestion of 100 mg Tramadol does not improve performance in a 15-km cycling time trial that was completed after a 1-h preload at 60% peak power. Additionally, a therapeutic dose of Tramadol does not compromise complex motor-cognitive or simple fine motor performances.