Current opinion in hematology
-
Induced pluripotent stem cell (iPSC) technology, which uses defined transcription factors to reprogram somatic cells to become pluripotent cells, offers a significant technical simplicity and enables generation of patient-specific pluripotent stem cells with reduced ethical concerns. This review will focus on recent progresses in understanding of iPSCs and improved methods of generating iPSCs. ⋯ iPSC technology provides unprecedented opportunities in biomedical research and regenerative medicine. However, there remain a great deal to learn about iPSC safety, the reprogramming mechanisms, and better ways to direct a specific reprogramming process. The iPSC field will flourish on its mechanistic studies, iPSC-based disease modeling, and identification of new small molecules that modulate reprogramming.
-
The pathophysiology of Philadelphia-chromosome negative myeloproliferative disorders has significantly advanced with the discovery of JAK2V617F. The prevalence of JAK2V617F mutation has made it a much anticipated target for inhibition; this review will update and assess progress. ⋯ The prevalence of the JAK2V617F mutation in the classic Philadelphia-chromosome negative myeloproliferative disorders has made it a much anticipated target for inhibition. Present in greater than 90% of patients with polycythemia vera and approximately 50% of patients with essential thrombocythemia and primary myelofibrosis, it has been hoped that targeted inhibition of JAK2V617F would achieve similar disease control as imatinib mesylate has produced in chronic myeloid leukemia. However, JAK2V617F in the Philadelphia-chromosome negative myeloproliferative disorders, unlike bcr/abl tyrosine kinase in chronic myeloid leukemia, is not a causative but rather a secondary somatic mutation. As the JAK2 inhibitors move into phase III clinical trials, their efficacy and role in therapy is becoming clearer; however, there are still many questions needing answers.
-
Curr. Opin. Hematol. · Nov 2009
ReviewHemostatic strategies for minimizing mortality in surgery with major blood loss.
Continued hemorrhage remains a major contributor of mortality in massively transfused patients and controversy regarding their optimal management exists. This article reviews recent advances that impact the use and effectiveness of massive transfusion. ⋯ Implementation of more aggressive hemostatic resuscitation strategies in massively bleeding patients seems reasonable, and optimally, thrombelastography should be used to monitor coagulopathy and guide FFP and platelet transfusions.
-
Curr. Opin. Hematol. · May 2009
ReviewAcute pain in children and adults with sickle cell disease: management in the absence of evidence-based guidelines.
Acute, vaso-occlusive pain is the most characteristic complication of sickle cell disease (SCD). Although there has been rigorous work examining the pathogenesis of vaso-occlusion, fewer studies have focused on approaches to the clinical management of acute pain. In this review, we will examine the epidemiology and management strategies of acute pain events and we will identify limitations in the best available studies. ⋯ Unfortunately, most clinical practice guidelines for the management of acute pain are not based on randomized clinical trials. As a result, our practice of pain management is primarily limited to expert opinion and inferences from observational studies. Additional clinical trials in management of acute pain in children and adults with SCD are critical for the development of evidence-based guidelines.