Hematology
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New epidemiological findings recast pain in sickle-cell disease (SCD) as being more often a chronic manifestation than was previously thought, although acute pain is still the hallmark of the disease. SCD pain intensity, the number of painful locations, and the frequency of hospitalizations due to SCD pain may worsen with age. In adults and even in children, the quantity and severity of SCD pain may be vastly underestimated, because most of the "iceberg" of SCD pain is "submerged" at home, and only the tip of the iceberg is seen by health care providers when acute SCD care is rendered in emergency rooms and hospitals. ⋯ At first, increasingly worse nociceptive pain from vaso-occlusion and local lesions may evolve over the first two decades of life. Then, in the third and following decades, central neuropathic pain may also evolve due to past and continuing nociceptive stimuli. New findings confirm environmental contributors to SCD pain, including seasonal (colder) temperatures, barometric pressure, and wind speed.
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Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia intermedia, a less-severe form of thalassemia, are intermittently or rarely transfused. An allogeneically matched bone marrow transplant is curative, although it is restricted to those with matched donors. ⋯ Lentivirus vectors, on the other hand, have now been shown in several studies to correct mouse and animal models of thalassemia. The immediate challenges of the field as it moves toward clinical trials are to optimize gene transfer and engraftment of a high proportion of genetically modified HSCs and to minimize the adverse consequences that can result from random integration of vectors into the genome by improving current vector design or developing novel vectors. This article discusses the current state of the art in gene therapy for β-thalassemia and some of the challenges it faces in human trials.