New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients\u27 quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

Programmed Cell Death Deregulation in BCR-ABL1-Negative Myeloproliferative Neoplasms

BCR-ABL1-negative myeloproliferative neoplasms are classically represented by primary myelofibrosis, polycythemia vera, and essential thrombocythemia. These entities are stem cell-derived clonal disorders characterized by hematopoietic progenitor autonomy or hypersensitivity to cytokines, most of them presenting mutations in Janus kinase 2 (JAK2), calreticulin (CALR), or myeloproliferative leukemia virus oncogene (MPL). Deregulation of pro- and antiapoptotic genes is also claimed as an important mechanism involved in cell resistance to cell death and accumulation of myeloid cells in myeloproliferative neoplasms. Apoptosis, as one of the best-characterized types of programmed cell death, has a clear role in hematopoiesis control. However, the exact pathways affected in BCR-ABL1-negative myeloproliferative neoplasms have not yet been fully clarified. This chapter will explore the modifications affecting programmed cell death pathways involved in myeloid proliferation and how these alterations might be exploited in single or combined targeted therapeutic strategies

New oral anticoagulants and their reversal agents

Atrial fibrillation is a commonly encountered pathology in medical practice, and its prevalence has shown a continuous rise over the past years. Atrial fibrillation has a significant impact on patients' quality of life, not only due to the standard anticoagulant treatment with vitamin K antagonists that require close monitoring and dose adjustment, but also due to the fragile equilibrium between hemorrhagic and thrombotic risks. The introduction of new oral anticoagulants (NOACs) in the treatment guidelines for atrial fibrillation has improved the quality of life, as NOACs do not require close monitoring or dose adjustments. However, even if the safety profile of the NOACs regarding the hemorrhagic risk is superior to vitamin K antagonists, the problem raised by an unexpected hemorrhage (e.g. severe hemorrhage after an accident) and the need for efficient hemostasis in a chronic anticoagulated patient has remained unsolved. To find a solution for this problem, reversal agents for NOACs have been developed and tested, and two of them, idarucizumab and andexanet-alpha, have already been approved by the FDA, thus making NOACs increasingly appealing as a choice of anticoagulation treatment

Exclusive and dissociative J/ψ photoproduction, and exclusive dimuon production, in p-Pb collisions at sNN\sqrt{s_{NN}} = 8.16 TeV

The ALICE Collaboration reports three measurements in ultraperipheral proton-lead collisions at forward rapidity. The exclusive two-photon process γγ→μ+μ- and the exclusive photoproduction of J/ψ are studied. J/ψ photoproduction with proton dissociation is measured for the first time at a hadron collider. The cross section for the two-photon process of dimuons in the invariant mass range from 1 to 2.5 GeV/c2 agrees with leading-order quantum electrodynamics calculations. The exclusive and dissociative cross sections for J/ψ photoproductions are measured for photon-proton center-of-mass energies from 27 to 57 GeV. They are in good agreement with HERA results

Measurements of Groomed-Jet Substructure of Charm Jets Tagged by D0 Mesons in Proton-Proton Collisions at s\sqrt{s} =13 TeV

Understanding the role of parton mass and Casimir color factors in the quantum chromodynamics parton shower represents an important step in characterizing the emission properties of heavy quarks. Recent experimental advances in jet substructure techniques have provided the opportunity to isolate and characterize gluon emissions from heavy quarks. In this Letter, the first direct experimental constraint on the charm-quark splitting function is presented, obtained via the measurement of the groomed shared momentum fraction of the first splitting in charm jets, tagged by a reconstructed D0 meson. The measurement is made in proton-proton collisions at s=13 TeV, in the low jet transverse-momentum interval of 15≤pTjet ch<30 GeV/c where the emission properties are sensitive to parton mass effects. In addition, the opening angle of the first perturbative emission of the charm quark, as well as the number of perturbative emissions it undergoes, is reported. Comparisons to measurements of an inclusive-jet sample show a steeper splitting function for charm quarks compared with gluons and light quarks. Charm quarks also undergo fewer perturbative emissions in the parton shower, with a reduced probability of large-angle emissions