Blood reviews
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Palliative medicine provides active evaluation and treatment of the physical, psychosocial and spiritual needs of patients and families with serious illnesses, regardless of curability or stage of illness. The hematologic malignancies comprise diverse clinical presentations, evolutions, treatment strategies and clinical and quality of life outcomes with dual potential for rapid clinical decline and ultimate improvement. While recent medical advances have led to cure, remission or long-term disease control for patients with hematologic malignancy, many still portend poor prognoses and all are associated with significant symptom and quality of life burden for patients and families. ⋯ Palliative care teams provide an additional layer of support to patients, family caregivers, and the primary medical team through close attention to symptoms and emotional, practical, and spiritual needs. Barriers to routine palliative care co-management in hematologic malignancies include persistent health professional confusion about the role of palliative care and its distinction from hospice; inadequate availability of palliative care provider capacity; and widespread lack of physician training in communicating about achievable goals of care with patients, family caregivers, and colleagues. We herein review the evidence of need for palliative care services in hematologic malignancy patients in the context of a growing body of evidence demonstrating the beneficial outcomes of such care when provided simultaneously with curative or life-prolonging treatment.
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The innate immune system orchestrated by leukocytes primarily neutrophils, serves to remove dead and dying host cells and to provide protection against invasion by pathogens. Failure of this system results in the onset of sepsis leading to grave consequences for the host. Together with mechanical methods to physically isolate and remove the pathogen, neutrophils also release an important set of proinflammatory biological modulators that mediate recruitment of additional cells to a site of infection and amplify the innate protective response. ⋯ NETs also contain the neutrophil secretary granule-derived serine proteases, neutrophil elastase and cathepsin G, known to regulate the reactivity of both neutrophils and platelets. Since the characterization of NETs in 2004, new studies of their functional effect in vivo continue to expand upon unexpected extracellular roles for DNA, and in doing so renew attention to the haemostatic role of the leukocyte. This review will provide a basic description of NETs and examine current knowledge of this important system of defense, including recent work illustrating a role for NETs in activation of thrombosis.
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Uncontrolled bleeding is the most common preventable cause of death for patients with severe injury. Coagulopathy inevitably accompanies severe bleeding, exacerbated by the ongoing blood loss and the treatments administered. ⋯ It then reports on the contemporary management of coagulopathic bleeding using new transfusion strategies. Finally this review presents some practical points to the delivery of transfusion for major blood loss in the modern hospital setting.
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Acute myeloid leukemia (AML) carrying nucleophosmin (NPM1) mutations displays distinct molecular and clinical-pathological features that led to its inclusion as provisional entity in 2008 WHO classification of myeloid neoplasms. Since NPM1 mutations behave as a founder genetic lesion in AML, they could be an attractive target for therapeutic intervention. Here, we discuss the potential for developing targeted therapies for NPM1-mutated AML with focus on: (i) interfering with the abnormal traffic of the NPM1 leukemic mutant, i.e., its cytoplasmic dislocation; (ii) disrupting the nucleolar structure/function by interfering with residual wild-type nucleophosmin and other nucleolar components acting as hub proteins; and (iii) evaluating the activity of epigenetic drugs (e.g., 5-azacytidine) or agents acting on differentiation and apoptosis. As quantitative assessment of NPM1 mutated transcript copies now provides the means to measure minimal residual disease, we also discuss the potential for intervening in NPM1-mutated AML before overt hematological relapse occurs (so-called pre-emptive therapy).
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Platelet transfusions are mainly used for patients with thrombocytopenia due to bone marrow failure, especially cancer patients developing severe chemotherapy-induced thrombocytopenia (e.g. patients with acute leukemia or other hematologic malignancies). A prophylactic transfusion strategy is now generally accepted in developed countries. Some clinical data, however, support the use of a therapeutic transfusion strategy at least for certain subsets of these patients. ⋯ Only evaluation of metabolism is included in international guidelines, but high-throughput methods for evaluation of activation and senescence/apoptosis are available and should be incorporated into routine clinical practice if future studies demonstrate that they reflect clinically relevant platelet characteristics. Finally, platelet transfusions have additional biological effects that may cause immunomodulation or altered angioregulation; at present it is not known whether these effects will influence the long-time prognosis of cancer patients. Thus, several questions with regard to the optimal use of platelet transfusions in cancer patients still need to be answered.