Vasovagal reactions in whole blood donors at three REDS-II blood centers in Brazil

BACKGROUND: In Brazil little is known about adverse reactions during donation and the donor characteristics that may be associated with such events. Donors are offered snacks and fluids before donating and are required to consume a light meal after donation. For these reasons the frequency of reactions may be different than those observed in other countries. STUDY DESIGN AND METHODS: A cross-sectional study was conducted of eligible whole blood donors at three large blood centers located in Brazil between July 2007 and December 2009. Vasovagal reactions (VVRs) along with donor demographic and biometric data were collected. Reactions were defined as any presyncopal or syncopal event during the donation process. Multivariable logistic regression was performed to identify predictors of VVRs. RESULTS: Of 724,861 donor presentations, 16,129 (2.2%) VVRs were recorded. Rates varied substantially between the three centers: 53, 290, and 381 per 10,000 donations in Recife, Sao Paulo, and Belo Horizonte, respectively. Although the reaction rates varied, the donor characteristics associated with VVRs were similar (younger age [18-29 years], replacement donors, first-time donors, low estimated blood volume [EBV]). In multivariable analysis controlling for differences between the donor populations in each city younger age, first-time donor status, and lower EBV were the factors most associated with reactions. CONCLUSION: Factors associated with VVRs in other locations are also evident in Brazil. The difference in VVR rates between the three centers might be due to different procedures for identifying and reporting the reactions. Potential interventions to reduce the risk of reactions in Brazil should be considered

Highly Differentiated, Resting Gn-Specific Memory CD8+ T Cells Persist Years after Infection by Andes Hantavirus

In man, infection with South American Andes virus (ANDV) causes hantavirus cardiopulmonary syndrome (HCPS). HCPS due to ANDV is endemic in Southern Chile and much of Argentina and increasing numbers of cases are reported all over South America. A case-fatality rate of about 36% together with the absence of successful antiviral therapies urge the development of a vaccine. Although T-cell responses were shown to be critically involved in immunity to hantaviruses in mouse models, no data are available on the magnitude, specificity and longevity of ANDV-specific memory T-cell responses in patients. Using sets of overlapping peptides in IFN-γ ELISPOT assays, we herein show in 78 Chilean convalescent patients that Gn-derived epitopes were immunodominant as compared to those from the N- and Gc-proteins. Furthermore, while the relative contribution of the N-specific response significantly declined over time, Gn-specific responses remained readily detectable ex vivo up to 13 years after the acute infection. Tetramer analysis further showed that up to 16.8% of all circulating CD3+CD8+ T cells were specific for the single HLA-B*3501-restricted epitope Gn465–473 years after the acute infection. Remarkably, Gn465–473–specific cells readily secreted IFN-γ, granzyme B and TNF-α but not IL-2 upon stimulation and showed a ‘revertant’ CD45RA+CD27−CD28−CCR7−CD127− effector memory phenotype, thereby resembling a phenotype seen in other latent virus infections. Most intriguingly, titers of neutralizing antibodies increased over time in 10/17 individuals months to years after the acute infection and independently of whether they were residents of endemic areas or not. Thus, our data suggest intrinsic, latent antigenic stimulation of Gn-specific T-cells. However, it remains a major task for future studies to proof this hypothesis by determination of viral antigen in convalescent patients. Furthermore, it remains to be seen whether Gn-specific T cells are critical for viral control and protective immunity. If so, Gn-derived immunodominant epitopes could be of high value for future ANDV vaccines

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Minority and foreign-born representation among US blood donors: demographics and donation frequency for 2006.

BackgroundHistorically, minority populations have represented only a small proportion of US blood donors, but recent trends in immigration and potential blood shortages emphasize the need for recruitment strategies to increase minority donations.Study design and methodsDonation data from a network of six US blood centers for 2006 were analyzed. Race/ethnicity, country of birth, and educational attainment data were collected specifically for the study and assessed for their influence on donation behavior. Logistic regression was used to determine independent associations with repeat donors status and annual donation frequency.ResultsA total of 1,288,998 donations from 729,068 donors were studied; most donors had data on race/ethnicity (97.1%) and country of birth (93.1%). The proportion of minority donors differed by blood center, with African American donors (16%) most common at the Southeastern blood center and Asian (12%), Hispanic (13%), and foreign-born donors (13%) most common at the Northern California blood center. Minority donors and those born in Mexico or Latin America were younger than white donors. Minority and non-US-born donors were less likely than white and US-born donors to be repeat donors (odds ratio [OR], 0.60-0.78), and most were less likely to give two or more annual donations (OR, 0.82-1.11).ConclusionMinority and Mexico/Latin America-born donors represent a younger and often first-time donor population compared to white and US-born donors, but their annual donation frequency was only slightly lower than white and US-born donors. Increasing the retention and donation frequency of minorities will be important for supplementing the blood supply

Demographic profile of blood donors at three major Brazilian blood centers: results from the International REDS-II study, 2007 to 2008

BACKGROUND: The profile of blood donors changed dramatically in Brazil over the past 20 years, from remunerated to nonremunerated and then from replacement to community donors. Donor demographic data from three major blood centers establish current donation profiles in Brazil, serving as baseline for future analyses and tracking longitudinal changes in donor characteristics. STUDY DESIGN AND METHODS: Data were extracted from the blood center, compiled in a data warehouse, and analyzed. Population data were obtained from the Brazilian census. RESULTS: During 2007 to 2008, there were 615,379 blood donations from 410,423 donors. A total of 426,142 (69.2%) were from repeat (Rpt) donors and 189,237 (30.8%) were from first-time (FT) donors. Twenty percent of FT donors returned to donate in the period. FT donors were more likely to be younger, and Rpt donors were more likely to be community donors. All were predominantly male. Replacement donors still represent 50% of FT and 30% of Rpt donors. The mean percentage of the potentially general population who were donors was approximately 1.2% for the three centers (0.7, 1.5, and 3.1%). Adjusting for the catchment`s area, the first two were 2.1 and 1.6%. CONCLUSIONS: Donors in the three Brazilian centers tended to be younger with a higher proportion of males than in the general population. Donation rates were lower than desirable. There were substantial differences in sex, age, and community/replacement status by center. Studies on the safety, donation frequencies, and motivations of donors are in progress to orient efforts to enhance the availability of blood.NHLBI Retrovirus Epidemiology Donor Study-II: International Componen

Enhanced classification of Chagas serologic results and epidemiologic characteristics of seropositive donors at three large blood centers in Brazil

BACKGROUND: A major problem in Chagas disease donor screening is the high frequency of samples with inconclusive results. The objective of this study was to describe patterns of serologic results among donors to the three Brazilian REDS-II blood centers and correlate with epidemiologic characteristics. STUDY DESIGN AND METHODS: The centers screened donor samples with one Trypanosoma cruzi lysate enzyme immunoassay (EIA). EIA-reactive samples were tested with a second lysate EIA, a recombinant-antigen based EIA, and an immunfluorescence assay. Based on the serologic results, samples were classified as confirmed positive (CP), probable positive (PP), possible other parasitic infection (POPI), and false positive (FP). RESULTS: In 2007 to 2008, a total of 877 of 615,433 donations were discarded due to Chagas assay reactivity. The prevalences (95% confidence intervals [CIs]) among first-time donors for CP, PP, POPI, and FP patterns were 114 (99-129), 26 (19-34), 10 (5-14), and 96 (82-110) per 100,000 donations, respectively. CP and PP had similar patterns of prevalence when analyzed by age, sex, education, and location, suggesting that PP cases represent true T. cruzi infections; in contrast the demographics of donors with POPI were distinct and likely unrelated to Chagas disease. No CP cases were detected among 218,514 repeat donors followed for a total of 718,187 person-years. CONCLUSION: We have proposed a classification algorithm that may have practical importance for donor counseling and epidemiologic analyses of T. cruzi-seroreactive donors. The absence of incident T. cruzi infections is reassuring with respect to risk of window phase infections within Brazil and travel-related infections in nonendemic countries such as the United States.NHLBINHLBI[HHSN268200417175C

Hormonal exposures and the risk of intracranial meningioma in women: a population-based case-control study

Professor. Authors Phillips, Koepsell, and Van Belle are also UW professors/researchers.Background: The role of exogenous hormone exposures in the development of meningioma is unclear, but these exposures have been proposed as one hypothesis to explain the over-abundance of such tumors in women. Methods: The association between oral contraception (OC) or hormone replacement therapy (HRT) and intracranial meningioma in women was investigated using a population-based, matched case-control study. Exposures for 143 cases and 286 controls matched on age within five years were obtained by interview. Diagnoses were confirmed histopathologically and estrogen and progesterone receptor assays conducted. Results: Although risk of meningioma appeared modestly elevated in past OC users (OR = 1.5, 95% CI 0.8 - 2.7), and in current users (OR = 2.5, 95% CI 0.5 - 12.6), the confidence intervals were wide. No significant association between meningioma risk and duration of OC use was found. Likewise, risk of meningioma was only weakly associated with past use of HRT (OR = 0.7, 95% CI0.4 - 1.3), and not at all with current use of HRT (OR = 1.0, 95% CI 0.5 - 2.2). Of 142 available specimens, 2 (1%) expressed estrogen receptors, whereas 130 (92%) expressed progesterone receptors (PR). OC use was associated with increased risk of a meningioma expressing less rather than more PR (OR = 3.2, 95% CI 1.3 - 8.0). Overall, in post menopausal women, HRT use appeared to confer a non-significant protective effect, and was not associated with low or high PR expressing meningiomas. Conclusion: This study found little evidence of associations between meningioma and exogenous hormone exposures in women but did suggest that some hormonal exposures may influence tumor biology in those women who develop meningioma.This study was funded by a grant (CA 60710) from the National Cancer Institute, Bethesda, Maryland, USA

Clonal hematopoiesis in sickle cell disease.

BACKGROUNDCurative gene therapies for sickle cell disease (SCD) are currently undergoing clinical evaluation. The occurrence of myeloid malignancies in these trials has prompted safety concerns. Individuals with SCD are predisposed to myeloid malignancies, but the underlying causes remain undefined. Clonal hematopoiesis (CH) is a premalignant condition that also confers significant predisposition to myeloid cancers. While it has been speculated that CH may play a role in SCD-associated cancer predisposition, limited data addressing this issue have been reported.METHODSHere, we leveraged 74,190 whole-genome sequences to robustly study CH in SCD. Somatic mutation calling methods were used to assess CH in all samples and comparisons between individuals with and without SCD were performed.RESULTSWhile we had sufficient power to detect a greater than 2-fold increased rate of CH, we found no detectable variation in rate or clone properties between individuals affected by SCD and controls. The rate of CH in individuals with SCD was unaltered by hydroxyurea use.CONCLUSIONSWe did not observe an increased risk for acquiring detectable CH in SCD, at least as measured by whole-genome sequencing. These results should help guide ongoing efforts and further studies that seek to better define the risk factors underlying myeloid malignancy predisposition in SCD and help ensure that curative therapies can be more safely applied.FUNDINGNew York Stem Cell Foundation and the NIH