Faculty Bibliography

Background/Case Studies: Wrong blood in tube (WBIT) continues to be one of the leading causes of serious adverse transfusion outcomes. WBIT occurs from misidentification of the intended recipient at the time of sample collection. In the USA WBIT is reported to occur in 1/1000 samples, and internationally it is 0.5/1000. My institution's rate of WBIT while meeting the USA standard has been a persistent concern and potential patient safety problem. I sought to assess whether my institution's rate of WBIT was in line with other local metropolitan hospitals that face similar financial, staffing, and patient population challenges. Study Design/Methods: The results of all of my institutions type and screen ABO/Rh confirmation samples from 1-1-09 to 3-31-11 were evaluated. The number of identified ABO discrepancies at my institution during this period was compared to the numbers reported by 10 other institutions (some reported for more than one year). Statistical analysis was performed. Results/Findings: My institution reported 109,942 ABO/Rh results and 68 WBIT discrepancies. The other 10 labs reported 372,014 ABO/Rh results and 83 WBIT events. My institution's mean rate of WBIT was statistically significantly higher (p < 0.05) at 0.069 +/?0.022 (0.67/1000) than the others at 0.022+/?0.023 (0.22/1000). The rate of WBIT was similar (0.069 versus 0.073) at the two largest public hospitals. However, some of the lowest WBIT rates were found at other public hospitals and large institutions. Conclusion: WBIT remains a challenge. Clinicians must understand the importance of and buy into the importance of proper patient identification to prevent WBIT. Unless everyone who draws blood bank specimens follows the protocol for patient identification, safety will not be improved. Human errors continue to lead to WBIT errors. Electronic barrier systems need to be considered. (Table presented)

Mendelian disorders are individually rare but collectively common, forming a 'long tail' of genetic disease. A single highly accurate assay for this long tail would allow the scaling up of the Jewish community's successful campaign of population screening for Tay-Sachs disease to the general population, thereby improving millions of lives, greatly benefiting minority health and saving billions of dollars. This need has been addressed by designing a universal carrier test: a non-invasive, saliva-based assay for more than 100 Mendelian diseases across all major population groups. The test has been exhaustively validated with a median of 147 positive and 525 negative samples per variant, demonstrating a multiplex assay whose performance compares favourably with the previous standard of care, namely blood-based single-gene carrier tests. Because the test represents a dramatic reduction in the cost and complexity of large-scale population screening, an end to many preventable genetic diseases is now in sight. Moreover, given that the assay is inexpensive and requires only a saliva sample, it is now increasingly feasible to make carrier testing a routine part of preconception care

Nonreplicating vectors are being considered in HIV-1 vaccine design. However, nonreplicating viruses are typically weak immunogens, leading to efforts to target the vaccine to mature dendritic cells (DCs). We have studied a single-cycle form of HIV-1, prepared by pseudotyping envelope-defective HIV-1 plasmids with the envelope from vesicular stomatitis virus (VSV) G protein (VSV-G), to which most humans lack preexisting immunity. The nonreplicating, VSV/HIV-1 efficiently infected the immature stage of DC development, in this case represented by monocytes cultured with GM-CSF and IL-4. A majority of the cells reverse transcribed the HIV-1 RNA, and a minority expressed gag protein. The infected populations were further matured with CD40 ligand, leading to strong stimulation of autologous T cells from HIV-1-infected individuals, but not controls. Enriched CD8(+) T cells from 12/12 donors released IFN-gamma (50-300 enzyme-linked immunospots/200,000 T cells) and proliferated. Macrophages were much less efficient in expanding HIV-1-responsive T cells, and bulk mononuclear cells responded weakly to VSV/HIV-1. CD4(+) T cells from at least half of the donors showed strong responses to VSV/HIV-1-infected DCs. Presentation to CD8(+) T cells, but not to CD4(+), was primarily through an endogenous pathway, because the responses were markedly reduced if envelope-defective virus particles or reverse transcriptase inhibitors were added. Therefore, nonreplicating vaccines can be targeted to immature DCs, which upon further maturation induce combined and robust CD4(+) and CD8(+) immunity.