American Donors Research Articles

Bridging the gap: Multi-omics profiling of brain tissue in Alzheimer's disease and older controls in multi-ethnic populations.

Multi-omics studies in Alzheimer's disease (AD) revealed many potential disease pathways and therapeutic targets. Despite their promise of precision medicine, these studies lacked Black Americans (BA) and Latin Americans (LA), who are disproportionately affected by AD. To bridge this gap, Accelerating Medicines Partnership in Alzheimer's Disease (AMP-AD) expanded brain multi-omics profiling to multi-ethnic donors. We generated multi-omics data and curated and harmonized phenotypic data from BA (n=306), LA (n=326), or BA and LA (n=4) brain donors plus non-Hispanic White (n=252) and other (n=20) ethnic groups, to establish a foundational dataset enriched for BA and LA participants. This study describes the data available to the research community, includingtranscriptome from three brain regions, whole genome sequence, and proteome measures. The inclusion of traditionally underrepresented groups in multi-omics studies is essential to discovering the full spectrum of precision medicine targets that will be pertinent to all populations affected with AD. Accelerating Medicines Partnership in Alzheimer's Disease Diversity Initiative led brain tissue profiling in multi-ethnic populations. Brain multi-omics data is generated from Black American, Latin American, and non-Hispanic White donors. RNA, whole genome sequencing and tandem mass tag proteomicsis completed and shared. Multiple brain regions including caudate, temporal and dorsolateral prefrontal cortex were profiled.

Blood donor questionnaires and infectious disease screening in Latin American countries.

Blood donor questionnaires are tools used to screen prospective blood donors to determine their eligibility. There are limited data regarding blood donor questionnaires and infectious disease screening of the blood supply in Latin American countries. This study aimed to survey donor centres in Latin American countries to learn more about blood donor screening and infection assessment. An international team of transfusion medicine professionals including medical directors and supervisors who work or collaborate with Latin American donor centres, called 'Comité de Investigación en Medicina Transfusional', designed a survey (16 questions) to characterize blood donor eligibility in Latin America. Eighty-two institutions from 14 Latin American countries responded to the survey. Most donor centres (66%; 54 of 82) had a donor deferral percentage between 5% and 25%, and the most common causes of deferrals were low haemoglobin and high-risk behaviour. Most donors in blood centres were directed family donors compared with voluntary donors. Infection evaluation included mostly serologic assessment (81%; 30 of 37) for human immunodeficiency virus (HIV), Hepatitis B, Hepatitis C, Treponema pallidum and Trypanosoma cruzi rather than nucleic acid tests (5%; 2 of 37). Heterogeneity exists in donor selection and infectious disease screening in Latin American countries. This survey provides valuable information to understand Latin American blood centre practices.

P-339 Identifying essential information for a valid informed consent (IC) of egg donors: An international Delphi study

Abstract Study question What information does an international group of professionals and egg donors consider relevant and morally necessary for prospective egg donors to provide valid IC? Summary answer In the first round, participants considered 56% of the information items relevant (e.g. all legal aspects) and 50% of the items as morally necessary information. What is known already Disclosure of relevant and adequate information is essential for IC in medical procedures like egg donation (ED). However, studies reveal inadequate risk awareness among donors. This raises questions about the adequacy of the provided information. The “Egg Donor Informed Consent Tool” aims to assess donors’ understanding of the ED process and its risks. However, Skillner et al. developed the tool exclusively with American endocrinologists and donors and do not touch upon all legal aspects or alternative hormone stimulation. No international study to date has determined what information professionals and egg donors consider relevant and morally necessary for prospective donors. Study design, size, duration This modified Delphi study used a survey in an iterative process of three rounds to reach a consensus on what information items are relevant and morally necessary for a valid informed consent of candidate egg donors. Invitations to participate were sent out in November 2023 and the first round lasted six weeks. Reminders and additional invitations were sent out every two weeks. Currently (January 2024), we are preparing the second round with 35 professional participants Participants/materials, setting, methods The 35 participants were experts in ED across diverse fields (social and medical sciences, bioethics, psychology, fertility medicine and law) from 14 countries. The egg donor part of round one is ongoing. The survey consisted of 13 categories and 118 information items, which participants score for relevance via a 4-point Likert scale and moral necessity on a dichotomous scale (yes/no). Content Validity Index (CVI) will be calculated for measuring relevance. A comment section was available. Main results and the role of chance Research shows that high content validity (“consensus”) is reached when there is an I-CVI (CVI per item) of .78 or higher. The same cut-off was selected to reach consensus for Moral Necessity. The following results are based on the first round, results from all three rounds will be presented at the congress. For 58 out of 131 information items, the I-CVI was lower than 0.78. The percentage of moral necessity was below 0.78 for 65 items. The relevancy for the total survey (S-CVI/Ave) for the first round was 0.80. Four information items reached a CVI of 1: all experts thought it was relevant for a candidate donor to know that 1) the need to undergo ovarian stimulation and 2) a pick-up procedure, as well as 3) her legal rights over the donated eggs after the pick-up procedure and 4) her legal right to withdraw consent. The latter is the only information item that scored a 100% of Moral Necessity. All 16 information items in the categories “issues concerning multiple donations”, “legal aspects” and “financial aspects” reached a consensus in relevance, but two of these items’ did not reach the cut-off of 0.78 for moral necessity. Limitations, reasons for caution There was a relatively low response rate of 24 percent, which can be attributed to the demographics of our population. These professionals typically have limited availability for participation and for some professionals the email addresses we found were outdated. Wider implications of the findings The final results can give professionals a standard of essential information to provide to make sure the women are adequately informed and know what to expect when they decide to donate. It also gives researchers a potential standard to evaluate the quality of the informed consent in fertility clinics. Trial registration number Not applicable

Can Happiness and Sadness Overcome Organ Donation Barriers Following Exposure to Radio Ads?

Concerns related to bodily integrity, medical mistrust, superstition, and disgust with respect to organ transplantation remain commonly cited barriers among African American, Caucasian, and Hispanic non-donors. The current study examined two narrative strategies for mitigating these barriers by eliciting feelings of happiness or sadness. African American, Caucasian, and Hispanic non-donors (N = 576) were randomly assigned to a radio ad that communicated either a recipient narrative or a waiting list narrative. As expected, the recipient narrative elicited greater feelings of happiness whereas the waiting list narrative aroused greater feelings of sadness. Moderated mediation analyses revealed models in which happiness, not sadness, was the mediator, such that the narrative frame was associated with ad persuasiveness. Additionally, only medical mistrust interacted with happiness to predict ad persuasiveness The results are discussed with an emphasis on message design strategies to employ among reluctant adult African American, Caucasian, and Hispanic potential donors.

Analysis of Variation in the Origin of the Obturator Artery in Midwestern American Donor Bodies.

The obturator artery (OA) is typically a branch of the anterior division of the internal iliac artery. However, an aberrant obturator artery origin may lead to clinical complications. Because of its locationin the pelvic cavity, the OA is at high risk of injury or laceration during a variety of pelvic surgeries. Regarding this, variations in the origins of the OA may result in bleeding that can often be overlooked, rendering treatment ineffective. Our study aimed to assess the origins and course of the OA in Midwestern American donor bodies. Sixty-two donor bodies were obtained from the Gift of Body Donation Program at A.T. Still University's Kirksville College of Osteopathic Medicine. The origin of each OA was documented and photographed. The OA was identified by observing the vessel's passage through the obturator foramen. Of 132 OAs studied, 72 (54.5%) had an aberrant OA. Further, 22 (16.7%) had an aberrant OA origin from the inferior epigastric artery, 20 (15.2%) had an aberrant OA origin from the posterior division of the internal iliac artery, 22 (16.7%) had an aberrant OA origin from dual origins of the anterior division of the internal iliac artery and the inferior epigastric artery, and eight (6.1%) had other aberrant OA origins. Overall, our results indicated anatomical variations are common in the origins and course of the OA. These data highlight the importance of considering variations in the OA and the prevalence of those variations during vascular and orthopedic procedures.

The Relationship between Time, Race, and Estrogen Receptor Alpha in Estradiol-Induced Dermal Fibrosis.

In the skin, estradiol (E2) promotes profibrotic and proinflammatory cytokines, contributing to extracellular matrix (ECM) deposition. However, the magnitude of the response differs. Using the human skin organ culture model, we evaluated donor characteristics and correlations that contribute to E2-induced interleukin-6 (IL-6), transforming growth factor beta 1 and 2 (TGFB1 and TGFB2), collagen IA2 (Col IA2), collagen IIIA1 (Col IIIA1), and fibronectin (FN) expressions. In vehicle- and E2-treated dermal skin tissue transcripts, we confirm differences in the magnitude; however, there were positive correlations between profibrotic mediators and ECM components 48 h after E2 treatment. Also, positive correlations exist between baseline and E2-induced TGFB1, IL-6, Col IIIA1, and FN transcripts. Since estrogen receptor alpha (ERA) can propagate E2's signal, we measured and detected differences in its baseline and fold change transcript levels, with a significant decline in baseline levels 48 h after incubation and an increase 48 h after E2 treatment. There was a trend to higher transcript levels in African American donors 24 h earlier. Finally, E2-induced ERA transcript levels negatively correlated with its own baseline levels and positively correlated with FN, TGFB1, and Col IA2 transcript levels. Therefore, our data suggest ERA, E2 exposure time, and race/ethnicity contribute to E2-induced dermal fibrosis.

Hi‐C analysis in frontal cortex using local ancestry identifies ancestry‐specific chromatin 3D interactions

AbstractBackgroundGenetic risk for Alzheimer Disease (AD) varies across populations with different ancestry. Three‐dimensional (3D) genome architecture regulates gene transcription. Genome‐wide Hi‐C analyses have revealed dynamic 3D genome changes during development and disease progression. The variation of 3D genome architecture on different ancestral background, however, has not been extensively studied, especially at high‐resolution level. Recently, we developed the DeepLoop pipeline enabling robust high‐resolution analysis. We applied DeepLoop to characterize 3D genome architecture in frontal cortex from African American (AA) and European (EU) donors while considering local ancestry (LA) in admixed samples.MethodsHi‐C libraries were constructed and ∼500 million of paired‐end reads were obtained in 8 samples (4 AA and 4EU) that were sex‐matched and homozygous for APOEε4. We partitioned Hi‐C data into compartment A (open and transcriptionally active chromatin) and compartment B (compacted and transcriptionally silenced chromatin). In total, 6206 compartment bins across the genome were compared at a 500kb resolution. DeepLoop was used to call chromatin loop (often represents promoter‐enhancer interaction) at a 5kb‐resolution. LA was calculated using RFMix with SNP‐array data and a reference panel from 1000 Genomes for EU, African (AF) and Amerindian (AI) ancestry.ResultsMost of the A and B compartments were consistent among individuals with only <5% of them switched between AA and EU individuals. The EU samples have slightly (107 bins) more transcriptionally active bins than the AA samples. While many of homozygous LA blocks displayed same chromatin loop pattern between and within ancestries, we did observe ancestry‐specific loop as well as differences between individuals of the same ancestry. Importantly, the presence of heterozygous LA (African/EU) at some loci displayed a composite loop pattern that was present in the same region of homozygous LA of African or EU ancestry.ConclusionThe 3D genome architecture can be variable between different ancestral backgrounds as well as between individuals of the same LA. We hypothesize that admixture of LA can create novel or demolish chromatin interactions observed in the homozygous LA. These data emphasize the importance of LA in identifying the causal loci contributing to AD in admixed population such as AF and Hispanic/Latino.

OA3‐AM23‐SN‐22 | “You Don't Know Where [the Blood] Goes”: Findings from Focus Group Discussions with Black/African American Donors and Non‐donors in Southeastern United States

OA3‐AM23‐SN‐22 | “You Don't Know Where [the Blood] Goes”: Findings from Focus Group Discussions with Black/African American Donors and Non‐donors in Southeastern United States

Influence of Race and High Laminar Shear Stress on TNFR1 Signaling in Endothelial Cells.

Tumor necrosis factor (TNF) binding to endothelial TNF receptor-I (TNFR-I) facilitates monocyte recruitment and chronic inflammation, leading to the development of atherosclerosis. In vitro data show a heightened inflammatory response and atherogenic potential in endothelial cells (ECs) from African American (AA) donors. High laminar shear stress (HSS) can mitigate some aspects of racial differences in endothelial function at the cellular level. We examined possible racial differences in TNF-induced monocyte adhesion and TNFR1 signaling complex expression/activity, along with the effects of HSS. Tohoku Hospital Pediatrics-1 (THP-1) monocytes were used in a co-culture system with human umbilical vein ECs (HUVECs) from Caucasian American (CA) and AA donors to examine racial differences in monocyte adhesion. An in vitro exercise mimetic model was applied to investigate the potential modulatory effect of HSS. THP-1 adherence to ECs and TNF-induced nuclear factor kappa B (NF-κB) DNA binding were elevated in AA ECs compared to CA ECs, but not significantly. We report no significant racial differences in the expression of the TNFR-I signaling complex. Application of HSS significantly increased the expression and shedding of TNFR-I and the expression of TRAF3, and decreased the expression of TRAF5 in both groups. Our data does not support TNF-induced NF-κB activation as a potential mediator of racial disparity in this model. Other pathways and associated factors activated by the TNFR1 signaling complex are recommended targets for future research.

Global transmission of broad-host-range plasmids derived from the human gut microbiome.

Broad-host-range (BHR) plasmids in human gut bacteria are of considerable interest for their ability to mediate horizontal gene transfer (HGT) across large phylogenetic distance. However, the human gut plasmids, especially the BHR plasmids, remain largely unknown. Here, we identified the plasmids in the draft genomes of gut bacterial isolates from Chinese and American donors, resulting in 5372 plasmid-like clusters (PLCs), of which, 820 PLCs (comPLCs) were estimated with>60% completeness genomes and only 155 (18.9%) were classified to known replicon types (n=37). We observed that 175 comPLCs had a broad host range across distinct bacterial genera, of which, 71 were detected in at least two human populations of Chinese, American, Spanish, and Danish, and 13 were highly prevalent (>10%) in at least one human population. Haplotype analyses of two widespread PLCs demonstrated their spreading and evolutionary trajectory, suggesting frequent and recent exchanges of the BHR plasmids in environments. In conclusion, we obtained a large collection of plasmid sequences in human gut bacteria and demonstrated that a subset of the BHR plasmids can be transmitted globally, thus facilitating extensive HGT (e.g. antibiotic resistance genes) events. This study highlights the potential implications of the plasmids for global human health.

IDENTIFYING HYPERTENSION IN TEENAGERS: DIFFERENCES BETWEEN EUROPEAN AND AMERICAN GUIDELINES

Objective: Since the measurement of blood pressure is an element in the qualification of volunteers presenting for blood donation, there is an opportunity to identify, in these ostensibly healthy individuals, those who might be at heightened risk of hypertensive heart disease. Since the classification of blood pressure differs when using the American College of Cardiology/American Heart Association and European Society of Cardiology/European Society of Hypertension guidelines, we took this opportunity to compare the prevalence of suspected hypertension in teenagers as differently identified by the two systems. Design and method: Participants in the study were American volunteer blood donors, age 16 to 19, who donated between the years 2015 and 2021 at an independent, community blood program serving some 200 hospitals. There were 87,051 females and 59,498 males. Systolic (SBP) and diastolic (DBP) blood pressures were measured using automated equipment (Welch Allyn, ProBP). The cut points chosen for hypertension were, by ACC/AHA criteria, > = 130 (SBP) or > = 80 mmHg (DBP). The ESC/ESH criteria for hypertension were > = 140 (SBP) and/or > = 90 mmHg (DBP). Results: The table shows percentages of male and female teenagers considered hypertensive by American and European guidelines. Conclusions: There are significant differences between the American and European guidelines in the diagnosis of hypertension in teenagers, with a higher prevalence by American guidelines. The risk for hypertension is higher in males than females by both guidelines.

Does flux through the hexosamine biosynthesis pathway differ between endothelial cells from African American and Caucasian donors?

People with Type 2 Diabetes (T2D) often exhibit endothelial dysfunction (EndoDys), which underlies the initiation of many diseases. African Americans (AA) have a greater prevalence of T2D and EndoDys than their Caucasian (CA) counterparts. To understand these differences, we examined glucose metabolism within the endothelium. Specifically, we sought to determine whether there are differences between AAs and CAs in the Hexosamine Biosynthesis Pathway (HBP), a route of glucose utilization that is upregulated in T2D. We hypothesized that endothelial cells (EC) from AA donors will show a greater flux through the HBP and express higher markers of EndoDys compared to CA donors. Human umbilical vein ECs (HUVECs), n=2-3/group, were incubated for 24hrs with high (HG, 30mM) or normal (5.5mM) glucose. Protein expression was measured via western blot for the: 1) HBP rate-limiting enzyme (Glutamine: fructose-6-phosphate amidotransferase, GFAT); 2) enzyme catalyzing the addition of HBP end-products to various proteins (O-GlcNAc transferase, OGT); and 3) attachment of O-linked N-acetylglucosamine moieties to various proteins (O-GlcNAcylation, O-GlcNAc), in addition to markers of EndoDys. Hyperglycemia did not differentially impact the expression of HBP markers GFAT or OGT between ECs from CA and AA donors (glycemic status [GS], p=0.6723; race, p=0.3807 and GS, p=0.8695; race, p=0.3536, respectively). Although total O-GlcNAc did not significantly increase with HG, there was a trend toward higher O-GlcNAcylation in AA ECs (p=0.0897). Upon further examination of O-GlcNAcylation, there were 3 prominent bands of highly O-GlcNAcylated proteins at >220kDa (band 1), ~150-200kDa (band 2), and ~85kDa (band 3). There was significantly higher O-GlcNAcylation of protein in band 2 for AA donors compared to CA donors (p=0.0362). The apoptotic marker, Caspase-3, did not change with HG (p=0.9219) nor differ in expression between races (p=0.2060). The inflammatory marker, VCAM, was significantly higher in cells from AA donors (p=0.002) but did not differ with GS (p=0.3468). There was no GS by race interaction found. EndoDys links T2D and other pathologies. We examined the HBP pathway of glucose utilization in ECs from CA and AA donors. There was a main effect of race related to inflammation and total O-GlcNAcylation, without differences in the expression of key proteins within the pathway. Our results suggest that the HBP may contribute to the racial differences in EndoDys, however, this relationship is not straightforward and does not seem to be exacerbated in the context of HG. Future research is needed to examine these unexpected discrepancies and interrogate the link between HBP flux within the endothelium, along with its connection to various pathologies This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Rethinking Donor and Recipient Risk Matching in Europe and North America: Using Heart Transplant Predictors of Donor and Recipient Risk.

In Europe, there is greater acceptance of hearts from higher-risk donors for transplantation, whereas in North America, the donor heart discard rate is significantly higher. A Donor Utilization Score (DUS) was used to compare European and North American donor characteristics for recipients included in the International Society for Heart and Lung Transplantation registry from 2000 to 2018. DUS was further evaluated as an independent predictor for 1-year freedom from graft failure, after adjusting for recipient risk. Lastly, we assessed donor-recipient risk matching with the outcome of 1-year graft failure. DUS was applied to the International Society for Heart and Lung Transplantation cohort using meta-modeling. Posttransplant freedom from graft failure was summarized by Kaplan-Meier survival. Multivariable Cox proportional hazard regression was applied to quantify the effects of DUS and Index for Mortality Prediction After Cardiac Transplantation score on the 1-year risk of graft failure. We present 4 donor/recipient risk groups using the Kaplan-Meier method. European centers accept significantly higher-risk donor hearts compared to North America. DUS 0.45 versus 0.54, P<0.005). DUS was an independent predictor for graft failure with an inverse linear relationship when adjusted for covariates (P<0.001). The Index for Mortality Prediction After Cardiac Transplantation score, a validated tool to assess recipient risk, was also independently associated with 1-year graft failure (P<0.001). In North America, 1-year graft failure was significantly associated with donor-recipient risk matching (log-rank P<0.001). One-year graft failure was highest with pairing of high-risk recipients and donors (13.1% [95% CI, 10.7%-13.9%]) and lowest among low-risk recipients and donors (7.4% [95% CI, 6.8%-8.0%]). Matching of low-risk recipients with high-risk donors was associated with significantly less graft failure (9.0% [95% CI, 8.3%-9.7%]) than high-risk recipients with low-risk donors (11.4% [95% CI, 10.7%-12.2%]) Conclusions: European heart transplantation centers are more likely to accept higher-risk donor hearts than North American centers. Acceptance of borderline-quality donor hearts for lower-risk recipients could improve donor heart utilization without compromising recipient survival.

Low risk of human T-lymphotropic virus infection in U.S. blood donors; Is it time to consider a one-time selective testing approach?

U.S. blood donors are tested at each donation for human T-lymphotropic virus (HTLV) antibodies. Depending on donor incidence and other mitigation/removal technologies, a strategy of one-time selective donor testing should be considered. Antibody seroprevalence was calculated for HTLV-confirmed-positive American Red Cross allogeneic blood donors from 2008 to 2021. Incidence was estimated for seven 2-year time periods using confirmed-positive repeat donors having seroconverted in 730 days. Leukoreduction failure rates were obtained from internal data from July 1, 2008-June 30, 2021. Residual risks were calculated using a 51-day window period. Between 2008 and 2021, >75 million donations (>18 million donors) yielded 1550 HTLV seropositives. HTLV seroprevalence was 2.05 antibody-positives per 100,000 donations (0.77 HTLV-1, 1.03 HTLV-2, 0.24 HTLV-1/2), and 10.32 per 100,000 among >13.9 million first-time donors. Seroprevalence differed significantly by virus type, sex, age, race/ethnicity, donor status, and U.S. census region. Over 14 years and 24.8 million person-years of observation, 57 incident donors were identified (25 HTLV-1, 23 HTLV-2, and 9 HTLV-1/2). Incidence decreased from 0.30 (13 cases) in 2008-2009 to 0.25 (7 cases) in 2020-2021. Female donors accounted for most incident cases (47 vs. 10 males). In the last 2-year reporting period, the residual risk was 1 per 2.8 million donations and 1 per 3.3 billion donations when coupled with successful leukoreduction (0.085% failure rate). HTLV donation seroprevalence for the years 2008-2021 varied by virus type and donor characteristics. Low HTLV residual risk and use of leukoreduction processes support the conclusion that a selective one-time donor testing strategy should be considered.

:Holy Digital Grail: A Medieval Book on the Internet

:<i>Holy Digital Grail: A Medieval Book on the Internet</i>

Increasing donor’s perceived value from charitable involvement: a multi-segment approach to the American donor market

Increasing donor’s perceived value from charitable involvement: a multi-segment approach to the American donor market

Abstract 27 Limitations of Current Human Cell, Tissue, and Cellular-based Product Donor Eligibility Guidance: Analyzing the Impact on a Large Public Cord Blood Bank

IntroductionCord blood (CB) is considered a human cell, tissue, and cellular-based product (HCT/P) by the U.S. Food and Drug Administration (FDA) and is licensed through a Biological Licensing Application (BLA). Cord blood units (CBUs) require less precise donor tissue matching than other stem cell sources, which increases their availability for racial/ethnic minorities. However, a small percentage of banked CBUs are used for transplants. Updating FDA donor eligibility guidance may expand licensed CBU supply and cord blood bank (CBB) sustainability.ObjectiveThe objectives of this study were to analyze the impact of Zika virus (ZIKV) donor screening recommendations on the licensing status of banked CBUs and to propose updated policy recommendations.MethodsA retrospective analysis of Carolinas Cord Blood Bank (CCBB) data (from January 2016 to May 2022) was performed to describe CBU eligibility and shipment status. Qualitative comparisons of FDA guidance to reduce the risk of relevant communicable diseases were completed for blood versus HCT/P.Results CCBB: 8,877 banked CBUs from 2016-2022 (85.3% licensed; 14.7% unlicensed) (Table 1). 4,361 (49.1%) of CBUs were from Caucasian donors and 1,349 (15.2%) were from African American donors. 689 (52.7%) CBUs were unlicensed due to ZIKV risk. The number of CBUs with ZIKV risk banked annually has decreased significantly since 2020, with 174 ZIKV-risk CBUs in 2020 versus 63 in 2021. 26 unlicensed CBUs collected in 2016 or later have been infused versus 210 licensed CBUs. 7 unlicensed, infused CBUs had identified ZIKV risk. No ZIKV transmission was reported from these transplants. FDA Guidance: HCT/P ZIKV recommendations have not been updated since 2018 despite FDA removal of ZIKV from the relevant transfusion-transmitted infections in 2021. Recommendations for minimizing transfusion-transmission risk of human immunodeficiency virus (HIV) and variant Creutzfeldt-Jakob disease (vCJD) were updated in 2020 and 2022, respectively, to increase blood supply. New vCJD guidance eliminated geographic risk-related donor restrictions.Table 1.Characteristics of CBUs banked at CCBB January 2016 to May 2022CBU StatusNumber of Units (%)Banked8,877 (100%) Banked, licensed7,569 (85.3%) Banked, unlicensed1,308 (14.7%) Banked with ZIKV risk (travel-related donor deferral)689 (7.8%) Banked with Hepatitis B core antibody positive82 (<1.0%)Infused236/8,877 (2.7%) Infused, licensed210 (89.0 %) Infused, unlicensed26 (11.0%) Infused, Caucasian donor134 (56.8%) Infused, African American donor28 (11.9%) Infused, unlicensed with ZIKV risk7/26 (26.9%) Infused, unlicensed with Hepatitis B core antibody positive3/26 (11.5%)DiscussionGuidance for reducing disease transmission for blood and blood components have recently been updated to increase blood supply. The FDA must consider new data to revise the HCT/P donor screening recommendations. Adopting these changes will increase the number of HCT/P donors, the quantity of licensed CBUs, and potentially improve access to cellular therapies for a more diverse patient population.

Analysis of 52 240 source plasma donors of convalescent COVID-19 plasma: Sex, ethnicity, and age association with initial antibody levels and rate of dissipation.

BackgroundCOVID‐19 convalescent plasma (CCP) was approved under emergency authorization to treat critically ill patients with COVID‐19 in the United States in 2020. We explored the demographics of donors contributing plasma for a hyperimmune, plasma‐derived therapy to evaluate factors that may be associated with anti‐SARS‐CoV‐2 antibody response variability and, subsequently, antibody titers.Study DesignAn electronic search of CCP donors was performed across 282 US plasma donation centers. Donations were screened for nucleocapsid protein‐binding‐IgG using the Abbott SARS‐CoV‐2 IgG assay.ResultsOverall, 52 240 donors donated 418 046 units of CCP. Donors were of various ethnicities: 43% Caucasian, 34% Hispanic, 17% African American, 2% Native American, 1% Asian, and 3% other. Females had higher initial mean anti‐SARS‐CoV‐2 antibody titers but an overall faster rate of decline (P < .0001). Initial antibody titers increased with age: individuals aged 55 to 66 years had elevated anti‐SARS‐CoV‐2 titers for longer periods compared with other ages (P = .0004). African American donors had the lowest initial antibody titers but a slower rate of decline (P < .0001), while Caucasian (P = .0088) and Hispanic (P = .0193) groups had the fastest rates of decline. Most donor antibody levels decreased below the inclusion criteria (≥1.50) within 30 to 100 days of first donation, but donation frequency did not appear to be associated with rate of decline.ConclusionSeveral factors may be associated with anti‐SARS‐CoV‐2 antibody response including donor age and sex. Evaluating these factors during development of future hyperimmune globulin products may help generation of therapies with optimal efficacy.

Disaster‐related giving accounts for large chunk of American's donations

Disaster‐related giving accounted for more than half of the total charitable donations made by more than a third of American donors over the last year or so, new research shows—largely the result of the chaos wrought by the COVID‐19 pandemic, the war in Ukraine and numerous wildfires, hurricanes, tornadoes and other natural disasters that have all spurred Americans to give.

253-LB: Ethnic Differences in Pancreatic Hormone Secretion in Health and T2D

Purpose: We tested the hypothesis that a critical biologic determinant of T2D disparities is based on ethnicity-related differences in pancreatic islet function. Methods: Utilizing donor tissues from the NIDDK-funded Human Pancreas Analysis Program (HPAP) , we examined both insulin and glucagon secretion from nondiabetic and diabetic Caucasian and African American donor islets. Initially, a physiological amino acid mixture was used to stimulate glucagon secretion, followed by low and high glucose to stimulate insulin secretion and suppress glucagon secretion. During the high glucose step, IBMX (0.1 mM) is added to potentiate secretion of both hormones. Insulin and glucagon concentration in perifusates and islet extracts was measured by radioimmunoassay or ELISA. Statistical comparisons were drawn by repeated measures ANOVA. Results: Comparing nondiabetic islets, we observed overlapping insulin secretion profiles between both ethnicities; however, glucagon secretion was distinctly greater in both nondiabetic African American (+111%) islets compared to nondiabetic Caucasian islets, under all interventions. In T2D, the reduction in insulin secretion was significantly greater in African American T2D donors (high glucose -76%; IBMX -76%) compared to Caucasian T2D donors (high glucose -47%; IBMX -50%) . More strikingly, glucagon secretion in T2D donors was markedly different based on ethnicity. Whereas Caucasian T2D islets exhibited a similar baseline of glucagon secretion compared to Caucasian controls, there was a marked reduction of glucagon secretion overall in African American T2D donors (-70%) compared to their corresponding controls. The largest detected difference was in IBMX-potentiation of glucagon secretion, which is higher in Caucasian T2D donors (+103%) but significantly decreased in African American T2D donors (-76%) . Preliminary analysis of hormone content in a subset of the donor islet preparations revealed no differences according to ethnicity. Conclusions: We propose that ethnicity-related differences in nondiabetic islet function may contribute to the enhanced risk of T2D. Disclosure N. M. Doliba: None. M. Brissova: None. K. H. Kaestner: None. D. A. Stoffers: Other Relationship; Biomarin, Correlagen. J. Roman: None. A. V. Rozo: None. W. Qin: None. C. Liu: None. A. Naji: None. M. R. Rickels: Advisory Panel; Sernova, Corp., Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S, Consultant; L-Nutra Inc. M. A. Atkinson: None. A. C. Powers: None. Funding This work is supported by 3UC4-112217-01S1 and U01-DK123594-02, UC4-DK-112217, UC4-DK-112232, and U01-DK-123716.