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Article ; Online: Estimating the incidence of HIV infection in repeat blood donors with low average donation frequency.

Brambilla, Donald J / Busch, Michael P / Glynn, Simone A / Kleinman, Steven H

2020 Volume 61, Issue 2, Page(s) 494–502

Abstract: Background: The standard approach to estimating HIV incidence in repeat blood donors includes only donors who made two or more donations in an estimation interval. In China and some other countries, large proportions of repeat donors donate only once in ...

Abstract	Background: The standard approach to estimating HIV incidence in repeat blood donors includes only donors who made two or more donations in an estimation interval. In China and some other countries, large proportions of repeat donors donate only once in a 1- or 2-year interval. The standard approach may not represent risk among all repeat donors in these areas. Two approaches to including all repeat donors in the incidence estimate were evaluated in a simulation study. Study design and methods: Under one approach, a donor infected at the first donation contributes a partial case to incidence that equals the proportion of time since the preceding donation that is in the estimation interval. Under the other, that donor contributes a full case if at least half the time since the previous donation is in the estimation interval and nothing otherwise. Infections identified at the second or subsequent donations in the interval contribute full cases as usual. The simulations involved proportions with single donations of 11% to 65% combined with a variety of patterns of rising, falling, or constant incidence. Results: The partial-case approach was unbiased under more test conditions than the whole-case approach and exhibited smaller bias when both were biased. Under both approaches, bias >10% occurred only when rates of single donations >50% were combined with large changes in incidence over time. Conclusion: The partial-case approach performed better than the whole-case approach. The conditions producing bias >10% are so extreme that they are unlikely to be encountered in the field.
MeSH term(s)	Bias ; Blood Donors/statistics & numerical data ; Blood Safety/methods ; China/epidemiology ; Cohort Studies ; Computer Simulation ; Follow-Up Studies ; HIV Infections/epidemiology ; Humans ; Incidence ; Models, Theoretical
Language	English
Publishing date	2020-10-24
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16144
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Article ; Online: Proposed revised nomenclature for transfusion-related acute lung injury.

Toy, Pearl / Kleinman, Steven H / Looney, Mark R

Transfusion

2017 Volume 57, Issue 3, Page(s) 709–713

Abstract: A decade ago, definitions of "transfusionߚrelated acute lung injury (TRALI)" and "possible TRALI" were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell ... ...

Abstract	A decade ago, definitions of "transfusionߚrelated acute lung injury (TRALI)" and "possible TRALI" were standardized for research and clinical diagnosis. Since then, evidence has confirmed that TRALI is often due to transfusion of white blood cell antibodies to at-risk patients, and the term "TRALI, antibody mediated" is appropriate for such cases. Other TRALI cases are non-antibody mediated. Because specific, nonantibody transfusion factors have not yet been confirmed to cause TRALI in humans, the general term "TRALI, non-antibody mediated" is appropriate for such cases. In contrast, evidence is against possible TRALI being due to transfusion with the more likely cause of the acute respiratory distress syndrome (ARDS) being the alternative ARDS risk factor present in these patients. We propose to drop the misleading term "possible TRALI" and to rename this category of cases as "transfused ARDS." These nomenclature updates will more accurately categorize ARDS cases that develop after transfusion.
MeSH term(s)	Acute Lung Injury/blood ; Acute Lung Injury/classification ; Humans ; Respiratory Distress Syndrome, Adult/blood ; Respiratory Distress Syndrome, Adult/classification ; Risk Factors ; Transfusion Reaction/blood ; Transfusion Reaction/classification
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.13944
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Article ; Online: Reply to concerns regarding dropping the term "possible TRALI".

Toy, Pearl / Kleinman, Steven H / Looney, Mark R

Transfusion

2016 Volume 56, Issue 9, Page(s) 2394–2395

Language	English
Publishing date	2016-09
Publishing country	United States
Document type	Letter
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.13734
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Article ; Online: Genetic regulation of carnitine metabolism controls lipid damage repair and aging RBC hemolysis in vivo and in vitro.

Nemkov, Travis / Key, Alicia / Stephenson, Daniel / Earley, Eric J / Keele, Gregory R / Hay, Ariel M / Amireault, Pascal / Casimir, Madeleine / Dussiot, Michaël / Dzieciatkowska, Monika / Reisz, Julie A / Deng, Xutao / Stone, Mars / Kleinman, Steven H / Spitalnik, Steven L / Hansen, Kirk C / Norris, Philip J / Churchill, Gary A / Busch, Michael P /

Roubinian, Nareg H / Page, Grier P / Zimring, James C / Arduini, Arduino / D'Alessandro, Angelo

Blood

2024

Abstract: Recent large-scale multi-omics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red ... ...

Abstract	Recent large-scale multi-omics studies suggest that genetic factors influence the chemical individuality of donated blood. To examine this concept, we performed metabolomics analyses of 643 blood units from volunteers who donated units of packed red blood cells (RBCs) on two separate occasions. These analyses identified carnitine metabolism as the most reproducible pathway across multiple donations from the same donor. We also measured L-carnitine and acyl-carnitines in 13,091 packed RBC units from donors in the Recipient Epidemiology and Donor Evaluation (REDS) study. Genome wide association studies against 879,000 polymorphisms identified critical genetic factors contributing to inter-donor heterogeneity in end-of-storage carnitine levels, including common non-synonymous polymorphisms in genes encoding carnitine transporters (SLC22A16, SLC22A5, SLC16A9); carnitine synthesis (FLVCR1, MTDH) and metabolism (CPT1A, CPT2, CRAT, ACSS2), and carnitine-dependent repair of lipids oxidized by ALOX5. Significant associations between genetic polymorphisms on SLC22 transporters and carnitine pools in stored RBCs were validated in 525 Diversity Outbred mice. Donors carrying two alleles of the rs12210538 SLC22A16 Single Nucleotide Polymorphism exhibited the lowest L-carnitine levels, significant elevations of in vitro hemolysis, and the highest degree of vesiculation, accompanied by increases in lipid peroxidation markers. Separation of RBCs by age, via in vivo biotinylation in mice and Percoll density gradients of human RBCs, showed age-dependent depletions of L-carnitine and acyl-carnitine pools, accompanied by progressive failure of the reacylation process following chemically induced membrane lipid damage. Supplementation of stored murine RBCs with L-carnitine boosted post-transfusion recovery, suggesting this could represent a viable strategy to improve RBC storage quality.
Language	English
Publishing date	2024-03-21
Publishing country	United States
Document type	Journal Article
ZDB-ID	80069-7
ISSN	1528-0020 ; 0006-4971
ISSN (online)	1528-0020
ISSN	0006-4971
DOI	10.1182/blood.2024023983
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Article: Prevalence of SARS-CoV-2 Viremia in Presymptomatic Blood Donors in the Delta and Omicron Variant Eras.

Saá, Paula / Fink, Rebecca V / Dawar, Hina / Di Germanio, Clara / Montalvo, Leilani / Wright, David J / Krysztof, David E / Kleinman, Steven H / Nester, Theresa / Kessler, Debra A / Townsend, Rebecca L / Spencer, Bryan R / Kamel, Hany / Vannoy, Jackie / Busch, Michael P / Stramer, Susan L / Stone, Mars / Norris, Philip J

Open forum infectious diseases

2023 Volume 10, Issue 5, Page(s) ofad253

Abstract: Presymptomatic plasma samples from 1596 donors reporting coronavirus disease 2019 infection or symptoms after blood donation were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and anti-S and anti-N antibodies. Prior ... ...

Abstract	Presymptomatic plasma samples from 1596 donors reporting coronavirus disease 2019 infection or symptoms after blood donation were tested for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA and anti-S and anti-N antibodies. Prior infection and vaccination both protected from developing SARS-CoV-2 RNAemia and from symptomatic infection. RNAemia rates did not differ in the Delta and Omicron variant eras.
Language	English
Publishing date	2023-05-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2757767-3
ISSN	2328-8957
ISSN	2328-8957
DOI	10.1093/ofid/ofad253
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Article ; Online: A comparison of methods for estimating the incidence of human immunodeficiency virus infection in repeat blood donors.

Brambilla, Donald J / Busch, Michael P / Dodd, Roger Y / Glynn, Simone A / Kleinman, Steven H

Transfusion

2017 Volume 57, Issue 3pt2, Page(s) 823–831

Abstract: Background: The incidence of human immunodeficiency virus (HIV) in repeat blood donors has been estimated using seven methods. Although incidence is always calculated as cases per person-time, approaches to selecting cases and calculating person-time ... ...

Abstract	Background: The incidence of human immunodeficiency virus (HIV) in repeat blood donors has been estimated using seven methods. Although incidence is always calculated as cases per person-time, approaches to selecting cases and calculating person-time vary. Incidence estimates have not been compared among methods. Study design and methods: The seven methods were compared in a simulation study. Because three methods used information from donations made before an estimation interval, 8 years of donation and infection history were simulated, and Years 7 and 8 were treated as the estimation interval for all methods. An exponential random variate was assigned to each donor to simulate the time to infection. Infection risk was constant over 8 years in one scenario but increased at various rates in seven other scenarios. The infection risk scenarios were combined with four mixes of donation frequency to generate 32 test conditions. Results: Three methods produced biased estimates under all conditions. Three other methods were biased under most conditions. Bias from most methods increased as donation frequency declined. The single method that consistently produced unbiased estimates was the only method that involved the standard epidemiological approach of tabulating all interdonation intervals (IDIs) within the estimation interval. Bias was eliminated from one of the consistently biased methods by a simple modification that involved the average IDI in a sample of donors. Conclusion: The standard epidemiological approach is recommended if required data are available. Otherwise, the modified method involving the estimated average IDI should be considered. Investigators should use caution when comparing incidence estimates among studies that use different estimation methods or donation frequencies.
MeSH term(s)	Blood Donors ; Female ; HIV Infections/epidemiology ; HIV-1 ; Humans ; Incidence ; Male ; Models, Biological
Language	English
Publishing date	2017-03
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Randomized Controlled Trial
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.13939
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Article ; Online: Associations between ABO non-identical platelet transfusions and patient outcomes-A multicenter retrospective analysis.

Transfusion

2023 Volume 63, Issue 5, Page(s) 960–972

Abstract: Background: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains ... ...

Abstract	Background: Due to platelet availability limitations, platelet units ABO mismatched to recipients are often transfused. However, since platelets express ABO antigens and are collected in plasma which may contain ABO isohemagglutinins, it remains controversial as to whether ABO non-identical platelet transfusions could potentially pose harm and/or have reduced efficacy. Study design and methods: The large 4-year publicly available Recipient Epidemiology and Donor Evaluation Study-III (REDS-III) database was used to investigate patient outcomes associated with ABO non-identical platelet transfusions. Outcomes included mortality, sepsis, and subsequent platelet transfusion requirements. Results: Following adjustment for possible confounding factors, no statistically significant association between ABO non-identical platelet transfusion and increased risk of mortality was observed in the overall cohort of 21,176 recipients. However, when analyzed by diagnostic category and recipient ABO group, associations with increased mortality for major mismatched transfusions were noted in two of eight subpopulations. Hematology/Oncology blood group A and B recipients (but not group O) showed a Hazard Ratio (HR) of 1.29 (95%CI: 1.03-1.62) and intracerebral hemorrhage group O recipients (but not groups A and B) showed a HR of 1.75 (95%CI: 1.10-2.80). Major mismatched transfusions were associated with increased odds of receiving additional platelet transfusion each post-transfusion day (through day 5) regardless of the recipient blood group. Discussion: We suggest that prospective studies are needed to determine if specific patient populations would benefit from receiving ABO identical platelet units. Our findings indicate that ABO-identical platelet products minimize patient exposure to additional platelet doses.
MeSH term(s)	Humans ; Platelet Transfusion/adverse effects ; Blood Platelets ; Retrospective Studies ; ABO Blood-Group System ; Blood Group Incompatibility/epidemiology ; Transfusion Reaction/etiology
Chemical Substances	ABO Blood-Group System
Language	English
Publishing date	2023-03-30
Publishing country	United States
Document type	Multicenter Study ; Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.17319
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Article ; Online: Association of proton pump inhibitor and histamine H2-receptor antagonists with restless legs syndrome.

Earley, Eric J / Didriksen, Maria / Spencer, Bryan R / Kiss, Joseph E / Erikstrup, Christian / Pedersen, Ole B / Sørensen, Erik / Burgdorf, Kristoffer S / Kleinman, Steven H / Mast, Alan E / Busch, Michael P / Ullum, Henrik / Page, Grier P

Sleep

2020 Volume 44, Issue 4

Abstract: Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly ... ...

Abstract	Restless legs syndrome (RLS) is a common sensorimotor disorder, which can disrupt sleep and is thought to be caused in part by low cellular iron stores. Proton pump inhibitors (PPI) and histamine H2-receptor antagonists (H2A) are among the most commonly used drugs worldwide and show evidence of causing iron deficiency. We conducted a case/non-case observational study of blood donors in the United States (N = 13,403; REDS-III) and Denmark (N = 50,323; Danish Blood Donor Study, DBDS), both of which had complete blood count measures and a completed RLS assessment via the Cambridge-Hopkins RLS questionnaire. After adjusting for age, sex, race, BMI, blood donation frequency, smoking, hormone use, and iron supplement use, PPI/H2A use was associated with RLS (odds ratio [OR] = 1.41; 95% confidence interval [CI], 1.13-1.76; p = 0.002) in REDS-III for both PPI (OR = 1.43; CI, 1.03-1.95; p = 0.03) and H2A (OR = 1.56; CI, 1.10-2.16; p = 0.01). DBDS exhibited a similar association with PPIs/H2As (OR = 1.29; CI, 1.20-1.40; p < 0.001), and for PPIs alone (OR = 1.27; CI, 1.17-1.38; p < 0.001), but not H2As alone (OR = 1.18; CI, 0.92-1.53; p = 0.2). We found no evidence of blood iron stores mediating this association. The association of PPI, and possibly H2A, consumption with RLS independent of blood iron status and other factors which contribute to RLS risk suggest the need to re-evaluate use of PPI/H2A in populations at particular risk for RLS.
MeSH term(s)	Histamine ; Histamine H2 Antagonists/adverse effects ; Humans ; Iron ; Proton Pump Inhibitors/adverse effects ; Restless Legs Syndrome/drug therapy ; Restless Legs Syndrome/epidemiology
Chemical Substances	Histamine H2 Antagonists ; Proton Pump Inhibitors ; Histamine (820484N8I3) ; Iron (E1UOL152H7)
Language	English
Publishing date	2020-10-27
Publishing country	United States
Document type	Journal Article ; Observational Study ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	424441-2
ISSN	1550-9109 ; 0161-8105
ISSN (online)	1550-9109
ISSN	0161-8105
DOI	10.1093/sleep/zsaa220
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Article ; Online: NT-proBNP levels in the identification and classification of pulmonary transfusion reactions.

Roubinian, Nareg H / Chowdhury, Dhuly / Hendrickson, Jeanne E / Triulzi, Darrell J / Gottschall, Jerome L / Looney, Mark R / Matthay, Michael A / Kor, Daryl J / Brambilla, Donald / Kleinman, Steven H / Murphy, Edward L

Transfusion

2020 Volume 60, Issue 11, Page(s) 2548–2556

Abstract: Background: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized ...

Abstract	Background: Consensus definitions for transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) have recently been revised; however, pulmonary transfusion reactions remain difficult to diagnose. We hypothesized that N-terminal pro-brain natriuretic peptide (NT-proBNP) levels could have utility in the identification and classification of pulmonary transfusion reactions. Study design and methods: We performed a secondary analysis of a case-control study of pulmonary transfusion reactions at four academic hospitals. We evaluated clinical data and measured NT-proBNP levels prior to and following transfusion in patients with TACO (n = 160), transfused acute respiratory distress syndrome (ARDS) [n = 51], TRALI [n = 12], TACO/TRALI [n = 7], and controls [n = 335]. We used Wilcoxon Rank-Sum tests to compare NT-proBNP levels, and classification and regression tree (CART) algorithms to produce a ranking of covariates in order of relative importance for differentiating TACO from transfused controls. Results: Pre-transfusion NT-proBNP levels were elevated in cases of transfused ARDS and TACO (both P < .001) but not TRALI (P = .31) or TACO/TRALI (P = .23) compared to transfused controls. Pre-transfusion NT-proBNP levels were higher in cases of transfused ARDS or TRALI with a diagnosis of sepsis compared to those without (P < .05 for both). CART analyses resulted in similar differentiation of patients with TACO from transfused controls for models utilizing either NT-proBNP levels (AUC 0.83) or echocardiogram results (AUC 0.80). Conclusions: NT-proBNP levels may have utility in the classification of pulmonary transfusion reactions. Prospective studies are needed to test the predictive utility of pre-transfusion NT-proBNP in conjunction with other clinical factors in identifying patients at risk of pulmonary transfusion reactions.
MeSH term(s)	Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Natriuretic Peptide, Brain/blood ; Peptide Fragments/blood ; Prospective Studies ; Respiratory Distress Syndrome/blood ; Respiratory Distress Syndrome/classification ; Transfusion-Related Acute Lung Injury/blood ; Transfusion-Related Acute Lung Injury/classification
Chemical Substances	Peptide Fragments ; pro-brain natriuretic peptide (1-76) ; Natriuretic Peptide, Brain (114471-18-0)
Language	English
Publishing date	2020-09-09
Publishing country	United States
Document type	Clinical Trial ; Journal Article ; Multicenter Study ; Research Support, N.I.H., Extramural
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/trf.16059
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Article ; Online: Infectivity of human immunodeficiency virus-1, hepatitis C virus, and hepatitis B virus and risk of transmission by transfusion.

Kleinman, Steven H / Lelie, Nico / Busch, Michael P

Transfusion

2009 Volume 49, Issue 11, Page(s) 2454–2489

MeSH term(s)	HIV Infections/transmission ; HIV-1/pathogenicity ; Hepacivirus/pathogenicity ; Hepatitis B/transmission ; Hepatitis B virus/pathogenicity ; Hepatitis C/transmission ; Humans ; Models, Biological ; Transfusion Reaction
Language	English
Publishing date	2009-11
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	208417-x
ISSN	1537-2995 ; 0041-1132
ISSN (online)	1537-2995
ISSN	0041-1132
DOI	10.1111/j.1537-2995.2009.02322.x
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