Blood
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Transfusions of RBCs stored for longer durations are associated with adverse effects in hospitalized patients. We prospectively studied 14 healthy human volunteers who donated standard leuko-reduced, double RBC units. One unit was autologously transfused "fresh" (3-7 days of storage), and the other "older" unit was transfused after 40 to 42 days of storage. ⋯ In addition, only after the older transfusion, transferrin saturation increased progressively over 4 hours to a mean of 64%, and non-transferrin-bound iron appeared, reaching a mean of 3.2μM. The increased concentrations of non-transferrin-bound iron correlated with enhanced proliferation in vitro of a pathogenic strain of Escherichia coli (r = 0.94, P = .002). Therefore, circulating non-transferrin-bound iron derived from rapid clearance of transfused, older stored RBCs may enhance transfusion-related complications, such as infection.
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Idiopathic aplastic anemia (AA) is a common cause of acquired BM failure. Although autoimmunity to hematopoietic progenitors is thought to be responsible for its pathogenesis, little is known about the molecular basis of this autoimmunity. Here we show that a substantial proportion of AA patients harbor clonal hematopoiesis characterized by the presence of acquired copy number-neutral loss of heterozygosity (CNN-LOH) of the 6p arms (6pLOH). ⋯ A large-scale epidemiologic study on the HLA alleles of patients with various hematologic diseases revealed that the 4 HLA alleles were over-represented in the germline of AA patients. These findings indicate that the 6pLOH(+) hematopoiesis found in AA represents "escapes" hematopoiesis from the autoimmunity, which is mediated by cytotoxic T cells that target the relevant auto-antigens presented on hematopoietic progenitors through these class I HLAs. Our results provide a novel insight into the genetic basis of the pathogenesis of AA.
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Publication bias is the preferential publication of research with positive results, and is a threat to the validity of medical literature. Preliminary evidence suggests that research in blood and marrow transplantation (BMT) lacks publication bias. We evaluated publication bias at an international conference, the 2006 Center for International Blood and Marrow Transplant Research (CIBMTR)/American Society for Blood and Marrow Transplantation (ASBMT) "tandem" meeting. ⋯ Furthermore, positive studies were published in journals with a mean impact factor of 6.92, whereas journals in which negative/unstated studies were published had an impact factor of only 4.30 (P = .02). We conclude that publication bias exists in the BMT literature. Full publication of research, regardless of direction of results, should be encouraged and the BMT community should be aware of the existence of publication bias.
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We report results from a study exploring the combination of romidepsin, bortezomib, and dexamethasone for the treatment of patients with multiple myeloma (MM) previously treated with > 1 prior therapy. The primary objective was to determine the maximum tolerated dose (MTD) of the combination using a novel accelerated dose-escalation schedule in patients with relapsed or refractory MM. The secondary objective was to determine overall response (OR), time to progression (TTP), and overall survival (OS). ⋯ The median TTP was 7.2 (95% CI: 5.5-19.6) months, and the median OS was > 36 months. This regimen shows activity with manageable toxicity and warrants further evaluation. This trial was registered at www.clinicaltrials.gov as NCT00431990.
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Case Reports
Warfarin and acetaminophen interaction: a summary of the evidence and biologic plausibility.
Ms TS is a 66-year-old woman who receives warfarin for prevention of systemic embolization in the setting of hypertension, diabetes, and atrial fibrillation. She had a transient ischemic attack about 4 years ago when she was receiving aspirin. ⋯ She has had back pain over this same period and has been taking acetaminophen at doses at large as 650 mg four times daily, with her dose varying based on her symptoms. You recall a potential interaction and wonder if (1) her acetaminophen use is contributing to her loss of INR control, and (2) does this interaction place her at increased risk of warfarin-related complications?