1,720,973 research outputs found
Understanding and overcoming resistance to tyrosine kinase inhibitors (TKIs) in Chronic myeloid leukemia (CML)
No full textIntroduction: Chronic myeloid leukemia (CML) represents one of the first neoplasms whose molecular pathogenesis was successfully unraveled, with tyrosine kinase inhibitors (TKIs) representing one of the first-targeted therapies. TKIs have revolutionized long-term outcomes of CML patients and their life expectancy. Nonetheless, a minority of patients will develop TKI resistance due to a complex and multifactorial process that ultimately leads to the emergence of an unresponsive cancer clone. Overcoming TKI resistance is considered one of the major challenges in CML management. Areas covered: In this review, the main findings extrapolated from published research, guidelines, and clinical trials regarding TKI resistance (published before October 2024) are discussed. Data have been obtained through broad research on Medline, Embase, Pubmed, and archives from EHA and ASH congresses. Expert opinion: Nowadays, asciminib and ponatinib have expanded the therapeutic arsenal for resistant-CML management and allogenic transplant still represents an important alternative in the context of multiple TKI failures. Off-label use of TKIs combination therapies, although theoretically appealing, lacks robust clinical evidence and regulatory approval. Looking ahead, the introduction of novel technologies such as digital PCR (dPCR) and next generation sequencing (NGS) holds great potential to revolutionize the management of TKI-resistant CML cases
Validation of imatinib therapy failure score (IMTF) in chronic phase chronic myeloid leukemia in real life practice
No full textThe outcome of chronic myeloid leukemia (CML) patients improved in the last decade. Clinical prognostic scoring systems aim to provide information about survival in the long-term, without determining from baseline the subset of patients who require a strictly monitoring because at increased risk of failure. Imatinib, the first-generation tyrosine kinase inhibitor (TKI), is still widely used as frontline treatment: recently, the imatinib therapy failure (IMTF) score was proposed to identify the failure free survival. Aim of our study was to validate this index in a large cohort of patients treated with imatinib
Pharmacotherapeutic advances for chronic myelogenous leukemia: beyond tyrosine kinase inhibitors
No full textIntroductionDespite the notable success of tyrosine kinase inhibitors
(TKIs) in treating chronic myeloid leukemia (CML), a subset of patients
experiences resistance, or relapse after discontinuation. This challenge
is attributed to the Ph+ leukemia stem cells (LSCs) pool not fully
involved in the inhibition process due to the current therapeutic
approach.Areas coveredCurrent pharmacological advancements in CML
therapy focus on targeting LSCs, intervening in self-renewal pathways,
and exploiting biological vulnerabilities. Beyond BCR::ABL1 inhibition,
innovative approaches include immunotherapy, epigenetic modulation, and
interference with microenvironmental mechanisms.Expert opinionDiverse
therapeutic strategies beyond TKIs are under investigation.
Immunotherapy with interferon-alpha (IFN-alpha) shows some biological
effects, although further research is needed for optimal application in
enhancing discontinuation rates. Other compounds were able to mobilize
Ph+ LSCs from the bone marrow niche (DPP-IV inhibitor vildagliptin or
PAI-1 inhibitor TM5614) increasing the LSC clearance or target the CD26,
a Ph+ specific surface receptor. It is noteworthy that the majority of
these alternative strategies still incorporate TKIs. In conclusion,
novel therapeutic perspectives are emerging for CML, holding the
potential for substantial advancements in disease treatment
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Systemic mastocytosis: 2023 update on diagnosis and management in adults
No full textIntroductionSystemic mastocytosis (SM) is a complex and heterogeneous disease, characterized by the clonal accumulation of mast cells in one or more organs. In 2022 both the World Health Organization (WHO) and the International Consensus Classification (ICC) modified the diagnostic and classification criteria of SM. Moreover, the identification of new clinical and molecular variables has improved prognostic tools and led to increasingly individualized therapeutic strategies.Areas coveredThe aim of this review is to present the updates introduced by the International Consensus Classification in diagnostic criteria of SM. In addition, we report the latest data available from the most important clinical trials in patients both with non-advanced and advanced disease, including elenestinib and bezuclastinib.Expert opinionDiagnosis and classification of SM has evolved over years. The most recent WHO and ICC classification improved SM diagnostic work-up, providing clinicians with a clear and simplified diagnostic scheme. New approved targeted therapies such as midostaurin and avapritinib modified the treatment paradigm in patients in advanced stage, and next-generation inhibitors actually investigated in clinical trials are expected in the next future
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Case Report: Infectious prophylaxis in hematological malignancies
No full textPatients with hematological malignancies and past serological evidence of hepatitis B are at risk for HBV reactivation. In myeloproliferative neoplasms, continuous treatment with the JAK 1/2 inhibitor ruxolitinib confers a moderate risk of reactivation (1-10%); nevertheless, no prospective randomized data are available to strongly recommend HBV prophylaxis in these patients. Here, we report a case of primary myelofibrosis and past serological evidence of HBV infection, treated with ruxolitinib and concomitant lamivudine, developing HBV reactivation due to premature withdrawal of prophylaxis. This case underlines the potential need for persistent HBV prophylaxis in the setting of ruxolitinib treatment
Dispelling the Myths Behind First-author Citation Counts
Full text linkWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
- …
