bluuebunny/crossref_metadata_2025_split huggingface dataset:
Barriers Pushed Aside: Insights on Career and Family Success from Women Leaders in Academic Otolaryngology
Authors: Meyer Tanya K. , Bergmark Regan , Zatz Marcy , Sardesai Maya G. , Litvack Jamie R. , Starks Acosta Anne 
Published: April 2019

ObjectiveAlthough the literature adequately identifies the current gender inequality that exists in academic otolaryngology and describes the barriers to advancement of women in academic medicine, there is little information regarding the daily details of how successful women in academic otolaryngology achieve work‐life balance. This study was designed to better understand how women in academic otolaryngology achieve work‐life balance while negotiating family and childrearing commitments, clinical workload, and scholarly activity, as well as to highlight coping strategies and behaviors that women have used to achieve these successes.Study DesignQualitative research design.MethodsThirteen successful women in academic otolaryngology with children were recruited using a networking/snowball sampling methodology to participate in a semistructured qualitative interview about the daily process of work‐life balance in an academic otolaryngology practice. A focus group of 7 additional participants was held to validate critical topics/themes.ResultsFour broad categories of findings emerged from the study: (1) participants’ strong commitment to academic medicine, (2) the fluid/elusive nature of work‐life balance, (3) specific approaches to successfully managing home life, and (4) insights related to achieving psychoemotional health.ConclusionsThe conflicting demands between home and professional life are one of the barriers to recruiting, promoting, and retaining women in academic otolaryngology. Fostering a better environment for work‐life balance is critical to promote the advancement of women in otolaryngology and otolaryngology leadership.
Monitoring blood biomarkers to predict nivolumab effectiveness in NSCLC patients
Authors: Passiglia Francesco , Galvano Antonio , Castiglia Marta , Incorvaia Lorena , Calò Valentina , Listì Angela , Mazzarisi Salvatore , Perez Alessandro , Gallina Giuseppe , Rizzo Sergio , Soto Parra Hector , Bazan Viviana , Russo Antonio 
Published: April 2019

Background: We investigated whether early dynamic changes of circulating free (cfDNA) levels as well as the neutrophil to lymphocyte ratio (NLR) could predict nivolumab effectiveness in pretreated patients with advanced non-small cell lung cancer (NSCLC). Methods: A total of 45 patients receiving nivolumab 3 mg/kg every 2 weeks were enrolled. Patients underwent a computed tomography scan and responses were evaluated by the response evaluation criteria in solid tumors. Peripheral blood samples were obtained from the patients and the cfDNA level as well as the NLR were assessed. Time to progression (TTP) and overall survival (OS) were determined. Results: Patients with increased cfDNA >20% at the sixth week reported significantly worse survival outcomes (median OS: 5.7 versus 14.2 months, p < 0.001; median TTP: 3.3 versus 10.2 months, p < 0.001), as well as patients with increased NLR >20% (median OS: 8.7 versus 14.6 months, p = 0.035; median TTP: 5.2 versus 10.3 months, p = 0.039). The combined increase of cfDNA and NLR >20% was associated with significantly worse survival outcomes as compared with the remained population (median OS: 5.8 versus 15.5 months, p = 0.012; median TTP: 3.2 versus 11.9 months, p = 0.028). Multivariable analysis identified three significant factors associated with worse OS: combined cfDNA/NLR increase >20% [hazard ratio (HR): 5.16; 95% confidence interval (CI), 1.09–24.29; p = 0.038], liver metastasis (HR: 0.44; 95% CI, 0.20–0.96; p = 0.038), and extra-thoracic disease (HR: 0.33; 95% CI, 0.12–0.89; p = 0.029). Conclusion: An early combined increase of both cfDNA and NLR over the course of the first 6 weeks of nivolumab therapy predicted worse survival in pretreated patients with advanced NSCLC, suggesting a potential role in the real-time monitoring of immunotherapy resistance.
Pancreas‐specific plasma amylase for assessment and diagnosis of chronic pancreatitis: New insights on an old topic
Authors: Olesen Søren Schou , Krarup Henrik , Poulsen Jakob Lykke , Christensen Jeppe Hagstrup , Sheel Andrea Rhiannon Glynne , Sutton Robert , Greenhalf William , Halloran Christopher , Drewes Asbjørn Mohr 
Published: April 2019

BackgroundPancreatic function testing and imaging are used to inform the diagnosis of chronic pancreatitis, but most of these methods are time‐ and cost‐consuming or lack diagnostic accuracy.ObjectiveWe investigated the utility of pancreas‐specific plasma amylase for assessment and diagnosis of chronic pancreatitis.DesignThis was a prospective study of 121 consecutive patients with chronic pancreatitis and a reference population of 94 healthy controls. Pancreas‐specific plasma amylase level was determined and analysed for its association with exocrine pancreatic insufficiency, diabetes and other clinical variables. Receiver operating characteristic curve analyses were performed to determine the diagnostic utility of plasma amylase for diagnosing chronic pancreatitis and to study associations with disease severity. The findings were validated in a further cohort of 57 patients with chronic pancreatitis.ResultsSignificant and independent associations between plasma amylase level and duration of chronic pancreatitis as well as the presence of exocrine pancreatic insufficiency and diabetes were observed (all p < 0.001). An amylase level below 17.3 U/l had a high specificity (94%) and moderate sensitivity (59%) for the diagnosis of chronic pancreatitis. Diagnostic performance was influenced by disease stage with the best performance observed for advanced disease. The findings were replicated in the validation cohort.ConclusionPancreas‐specific plasma amylase may provide a clinically useful mean for assessment and diagnosis of chronic pancreatitis.
Minimal residual disease in adult ALL: technical aspects and implications for correct clinical interpretation
Authors: Brüggemann Monika , Kotrova Michaela 
Published: April 2019

Abstract
Nowadays, minimal residual disease (MRD) is accepted as the strongest independent prognostic factor in acute lymphoblastic leukemia (ALL). It can be detected by molecular methods that use leukemia-specific or patient-specific molecular markers (fusion gene transcripts, or immunoglobulin/T-cell receptor [IG/TR] gene rearrangements), and by multi-parametric flow cytometry. The sensitivity and specificity of these methods can vary across treatment time points and therapeutic settings. Thus, knowledge of the principles and limitations of each technology is of the utmost importance for correct interpretation of MRD results. Time will tell whether new molecular and flow cytometric high-throughput technologies can overcome the limitations of current standard methods and eventually bring additional benefits. MRD during standard ALL chemotherapy is the strongest overall prognostic indicator and has therefore been used for refining initial treatment stratification. Moreover, MRD positivity after the maintenance phase of treatment may point to an impending relapse and thus enable salvage treatment to be initiated earlier, which could possibly improve treatment results. The prognostic relevance of pretransplantation MRD was shown by several studies, and MRD high-risk patients were shown to benefit from stem cell transplantation (SCT). Also, MRD positivity after SCT correlates with worse outcomes. In addition, MRD information is very instructive in current clinical trials that test novel agents to evaluate their treatment efficacy. Although conventional clinical risk factors lose their independent prognostic significance when combined with MRD information, recently identified genetic markers may further improve the treatment stratification in ALL.
Direct oral anticoagulants: now also for prevention and treatment of cancer-associated venous thromboembolism?
Authors: Pabinger Ingrid , Riedl Julia 
Published: April 2019

Abstract
Data on specific studies in cancer patients using direct oral anticoagulants (DOACs) for the prevention and treatment of venous thromboembolism (VTE) are still scarce. For preventing VTE with DOACs, current experience is still very limited, so definite conclusions cannot yet be drawn. However, DOACs have so far been compared with vitamin K antagonists (VKAs) in patients with acute VTE in 5 studies, and several hundreds of patients included in these studies had either active cancer, a history of cancer, or a new occurrence of cancer during the course of disease. Meta-analyses have revealed an at least similar efficacy and safety profile of DOACs compared with VKAs. A number of studies of cancer patients investigating primary prevention and treatment are underway, and some will be finalized soon. Nevertheless, we might need further trials, specifically on the prevention of VTE in patients who are at particularly high risk. This article also includes a personal opinion on the use of DOACs in cancer patients. In conclusion, the currently available data show that DOACs might be safe and efficacious in the treatment of VTE, however, this has yet to be proven in specifically designed trials in patients with cancer. With regard to prevention, thus far, even less data exist, and the outcomes of the ongoing studies have to be evaluated before DOACs may be used for primary prevention.
Fixed duration vs continuous therapy in multiple myeloma
Authors: Ludwig Heinz , Zojer Niklas 
Published: April 2019

Abstract
The introduction of new drugs with less severe toxicity profiles than those of conventional antimyeloma agents allowed the evaluation of continuous therapy compared with fixed duration therapy. In transplant-eligible patients, consolidation therapy with bortezomib or bortezomib-based regimens showed significant progression-free survival (PFS) benefit in cytogenetic standard-risk patients and to a lesser extent, high-risk patients. Continuous therapy with lenalidomide maintenance treatment after autologous stem cell transplantation resulted in a significant survival gain. In transplant noneligible patients, continuous lenalidomide-dexamethasone therapy improved survival over fixed duration melphalan-prednisone-thalidomide. The concept of prolonged treatment in elderly patients is supported by some other studies, but most of them revealed a gain in PFS only. Young patients with unfavorable prognosis show a greater willingness to accept long-term treatment, whereas the readiness to undergo such treatments and the benefits therefrom decline with increasing age and decreasing fitness, rendering fixed duration therapy a suitable option in elderly frail patients.
Controversies in venous thromboembolism: to treat or not to treat superficial vein thrombosis
Authors: Beyer-Westendorf Jan 
Published: April 2019

Abstract
The management of superficial vein thrombosis (SVT) is poorly defined and remains controversial overall. SVT has long been considered a benign, self-limited disease, but recent studies show that SVT carries a nonnegligible risk for recurrence, deep vein thrombosis, or pulmonary embolism. Current guidelines recommend the use of low-molecular-weight heparin or fondaparinux, but results of several surveys indicate that the majority of patients with SVT receive nonanticoagulant therapy only, which includes compression stockings or bandages, nonsteroidal anti-inflammatory drugs, topical application of heparin gel, or surgical interventions. However, several recent observational and interventional studies provide better insight into the optimal treatment of patients with SVT who are at different risks for thromboembolic complications. This educational review summarizes the available evidence and aims to provide practical guidance based on a clinical decision pathway.
Symptomatic subsegmental pulmonary embolism: to treat or not to treat?
Authors: Carrier Marc , Klok Fredrikus A. 
Published: April 2019

Abstract
The introduction of computed tomographic pulmonary angiography and its recent increasing availability has led to a significant rise in its use to help clinicians diagnose acute pulmonary embolism (PE). This has led to a significant increase in the incidence of PE diagnoses. Simultaneously, the case fatality rate of acute PE has been decreasing and no significant change in its mortality has been noted, suggesting that the additional PE diagnoses are less severe and these patients might not benefit from anticoagulation therapy. This also seems to be correlated with an increase in the diagnosis of PE localized in the subsegmental pulmonary arteries (subsegmental pulmonary embolism [SSPE]). The clinical importance of SSPE is unclear. Whereas some studies have shown that it might be reasonable to manage patients with SSPE without anticoagulation, others have not. Although the current medical literature is limited, it suggests that a subgroup of patients with SSPE might be safely managed without the use of anticoagulant therapy. Current clinical practice guidelines suggest that clinicians take an individualized approach after carefully assessing the risk/benefit ratio for patients with SSPE and negative leg limb ultrasonography results. Prospective studies are ongoing and results are eagerly awaited to help tailor the management of this patient population.
Primary mediastinal B-cell lymphoma: biology and evolving therapeutic strategies
Authors: Dunleavy Kieron 
Published: April 2019

Abstract
Primary mediastinal B-cell lymphoma (PMBCL) is recognized as a distinct clinicopathologic entity that predominantly affects adolescents and young adults and is more common in female subjects. Although PMBCL is considered to be a subtype of diffuse large B-cell lymphoma, its clinical, morphologic, and biological characteristics overlap significantly with those of nodular sclerosing Hodgkin lymphoma (NSHL). Over the past few years, the shared biology of these 2 entities has been highlighted in several studies, and mediastinal gray zone lymphoma, with features intermediate between PMBCL and NSHL, has been recognized as a unique molecular entity. Although there is a lack of consensus about the optimal therapeutic strategy for adolescent and young adult patients newly diagnosed with PMCBL, highly curative strategies that obviate the need for mediastinal radiation are favored by most. Progress in understanding the biology of PMBCL and its close relationship to NSHL have helped pave the way for the investigation of novel approaches such as immune checkpoint inhibition. Other strategies such as adoptive T-cell therapy and targeting CD30 are also being studied.
Rigorous and practical quality indicators in sickle cell disease care
Authors: Oyeku Suzette O. , Faro Elissa Z. 
Published: April 2019

AbstractIn recent years, several sickle cell–specific quality indicators have been developed using rigorous approaches. A review of the history and current status of the development of sickle cell–specific indicators highlights opportunities for future refinement. Despite efforts at alignment, lack of strong evidence hinders the adoption of current quality indicators across stakeholder groups. There are many directions in which to take the current existing quality indicators, including expanding to different age groups, aims of care such as safety and equity, and better understanding of contextual and environmental factors.
Chronic organ failure in adult sickle cell disease
Authors: Vichinsky Elliott 
Published: April 2019

Abstract
Sickle cell disease is now a chronic adult illness characterized by progressive multiorgan failure, particularly involving the brain and kidney. The etiology is multifactorial; it includes hemolysis and nitric oxide deficiency. As patients age, most experience neurologic insult. Twenty-five percent of older adults have had a clinical stroke and at least half of the population have had a silent infarct, cortical atrophy, and neurocognitive impairment. Periodic screening with neuroimaging and neurocognitive testing is recommended. Identification and correction of modifiable risk factors such as nocturnal hypoxemia, obstructive sleep apnea, and physical exercise programs should be implemented. Patients with neurocognitive impairment require cognitive remediation and educational accommodations. Chronic renal disease occurs in 25% of older adults and results in 50% of their deaths. Renal failure often develops insidiously. It can be prevented or minimized by early screening and treatment of modifiable risk factors including hypertension and microalbuminuria. There is an increasing number of therapeutic options, including inhibitors of the renin angiotensin system, angiotensin-II receptor blockers, endothelin-1 receptor antagonist, and haptoglobin therapy. Patients with sickle cell disease have increased mortality rates from renal failure compared with nonsickle cell patients, in part from a lack of access to early multidisciplinary care, including timely initiation of dialysis and renal transplantation.
How and when to decide between epigenetic therapy and chemotherapy in patients with AML
Authors: Dombret Hervé , Itzykson Raphael 
Published: April 2019

Abstract
Remission induction with chemotherapy has long been the frontline treatment of acute myeloid leukemia (AML). However, intensive therapy is limited in frail patients by its associated toxicity and higher rates of failure or relapse in patients with chemoresistant disease, such as secondary AML or poor-risk cytogenetics. Frailty and chemoresistance are more frequent in older adults with AML. In recent years, epigenetic therapies with the hypomethylating agents decitabine and azacitidine have been thoroughly explored in AML. The results of two pivotal studies carried out with these agents in older adults with newly diagnosed AML have challenged the role of intensive chemotherapy as the frontline treatment option in this high-risk population. Here, we review the results of treatment with intensive chemotherapy and hypomethylating agents in older patients with AML; discuss the patient- and disease-specific criteria to integrate into treatment decision making; and also, highlight the methodological limitations of cross-study comparison in this population.
Myeloproliferative neoplasms: from origins to outcomes
Authors: Nangalia Jyoti , Green Anthony R. 
Published: April 2019

Abstract
Substantial progress has been made in our understanding of the pathogenetic basis of myeloproliferative neoplasms. The discovery of mutations in JAK2 over a decade ago heralded a new age for patient care as a consequence of improved diagnosis and the development of therapeutic JAK inhibitors. The more recent identification of mutations in calreticulin brought with it a sense of completeness, with most patients with myeloproliferative neoplasm now having a biological basis for their excessive myeloproliferation. We are also beginning to understand the processes that lead to acquisition of somatic mutations and the factors that influence subsequent clonal expansion and emergence of disease. Extended genomic profiling has established a multitude of additional acquired mutations, particularly prevalent in myelofibrosis, where their presence carries prognostic implications. A major goal is to integrate genetic, clinical, and laboratory features to identify patients who share disease biology and clinical outcome, such that therapies, both existing and novel, can be better targeted.
Emerging options in multiple myeloma: targeted, immune, and epigenetic therapies
Authors: Kumar Shaji 
Published: April 2019

AbstractConsiderable progress has been made in the treatment of multiple myeloma in the past decade with median survival for the disease improving significantly. This has come through a combination of better understanding of the disease biology and coordinated research into new treatment approaches including better supportive care. However, patients eventually become refractory to available treatments and succumb to the disease, highlighting the need to develop new treatment approaches. The genetic heterogeneity in the disease and clonal evolution under treatment pressure underlie the development of resistance, underscoring the need to develop more effective therapies that can eradicate the disease at initial treatment as well as the need for new classes of drugs with varying mechanisms of action. To this end, there has been intense focus on exploring novel approaches to therapy including small-molecule inhibitors targeting specific abnormalities, immune therapies including monoclonal antibodies and adaptive T-cell therapy, as well as epigenetic approaches. Although many of these drugs are in the early stages of clinical development, the early data appear to be very promising. Many of these drugs can be safely and effectively combined with the current treatment classes such as proteasome inhibitors and immunomodulatory drugs, further enhancing the treatment options for myeloma.
Biology of CNS lymphoma and the potential of novel agents
Authors: Rubenstein James L. 
Published: April 2019

Abstract
Primary and secondary CNS lymphomas are aggressive brain tumors that pose an immense challenge to define in terms of molecular pathogenesis, as well as to effectively treat. During the past 10 years improvements in survival have been achieved with the implementation of anti-CD20 immunotherapy and optimization of dose-intensive consolidation strategies. The applications of whole-exome sequencing, comparative genomic hybridization, transcriptional profiling, and examination of the tumor microenvironment, particularly in the context of clinical investigation, provide insights that create a roadmap for the development and implementation of novel targeted agents for this disease. A body of genetic evidence strongly suggested that primary CNS lymphomas (PCNSLs) are likely largely dependent on NF-κB prosurvival signals, with enrichment of mutations involving the B-cell receptor pathway, in particular myeloid differentiation primary response 88 and cluster of differentiation 79B. The first set of early-phase investigations that target NF-κB in PCNSL have now been completed and support the NF-κB hypothesis but at the same time reveal that much work needs to be done to translate these results into meaningful advances in survival for a large fraction of patients. Insights into secondary prosurvival pathways that mediate drug resistance is a priority for investigation. Similarly, further evaluation of the immune-suppressive mechanisms in the CNS lymphoma tumor microenvironment is requisite for progress. Combinatorial interventions that promote the antitumor immune response have significant potential. With increasing availability of targeted agents, there is also a need to develop more sensitive imaging tools, not only to detect this highly invasive brain neoplasm but also potentially to define an evolving molecular phenotype to facilitate precision medicine.