Oklahoma Blood Institute

Objectives Screening blood units for compatibility constitutes a Bernoulli series. Estimating the number of units needed to be screened represents a classic waiting time problem that may be resolved using the Negative Binomial Distribution. The currently recommended method for estimating the number of units screened, n , to find a required number of compatible units, r , with a given probability, p , is n = r/p . This coincides with the mean of the Negative Binomial Distribution so that the actual number of units screened will often be underestimated by the current method. Methods The cumulative distribution function of the Negative Binomial Distribution provides the probability of success (compatibility), F( n ; r , p ), as a function of the number of trials performed (attempted crossmatches), n , the probability of success on each trial, p , and the number of successes (compatible units) required, r . Choosing a threshold cumulative probability sufficiently high, such as F ~ 0.9, for example, will provide confidence that the projected number of units screened will be underestimated less often (~10% of the time). Results With F ≥ 0.9, the estimated number of attempted crossmatches ranges from 1.3 to 2.3 times as many as the number calculated by the current method. As a rule of thumb approximately 1.6 times the current estimated number provides a similar estimate ( n ~ 1.6∙ r / p ). Conclusions Waiting time underestimation will be reduced significantly by using the Negative Binomial Distribution solution and should be accompanied by improved customer satisfaction.

Background Previous systematic reviews have revealed an inconsistency of outcome definitions as a major barrier in providing evidence‐based guidance for the use of plasma transfusion to prevent or treat bleeding. We reviewed and analyzed outcomes in randomized controlled trials (RCTs) to provide a methodology for describing and classifying outcomes. Study Design and Methods RCTs involving transfusion of plasma published after 2000 were identified from a prior review (Yang 2012) and combined with an updated systematic literature search of multiple databases (July 1, 2011 to January 17, 2023). Inclusion of publications, data extraction, and risk of bias assessments were performed in duplicate. (PROSPERO registration number is: CRD42020158581). Results In total, 5579 citations were identified in the new systematic search and 22 were included. Six additional trials were identified from the previous review, resulting in a total of 28 trials: 23 therapeutic and five prophylactic studies. An increasing number of studies in the setting of major bleeding such as in cardiovascular surgery and trauma were identified. Eighty‐seven outcomes were reported with a mean of 11 (min–max. 4–32) per study. There was substantial variation in outcomes used with a preponderance of surrogate measures for clinical effect such as laboratory parameters and blood usage. Conclusion There is an expanding literature on plasma transfusion to inform guidelines. However, considerable heterogeneity of reported outcomes constrains comparisons. A core outcome set should be developed for plasma transfusion studies. Standardization of outcomes will motivate better study design, facilitate comparison, and improve clinical relevance for future trials of plasma transfusion.

Prior research identifies trust as critical to increase vaccine acceptance and uptake. However, few intervention studies have sought to develop or test strategies for bolstering vaccine-related trust. To address this gap, this exploratory study identifies features of COVID-19 vaccine hesitancy interventions that can promote or undermine trust across three interconnected domains: institutional, interpersonal, and product (the vaccine itself). We draw on focus groups (N = 27 participants) with community and university partners involved with hosting COVID-19 testing and vaccine events in underserved Oklahoma communities. Focus groups explored participants’ experiences serving community health needs and elicited feedback on proposed vaccine hesitancy interventions. Proposed interventions included two technology-based strategies (text message reminders and tablet-based testimonials and education) and one dialogue-based strategy (anti-body test interpretation). We find that community partners perceived local universities as trustworthy institutions because of their association with popular sports programs, academic credentials, and proximity, creating opportunities to address vaccine-related distrust through community-university partnerships. The most promising intervention strategies for building interpersonal trust included engaging in one-on-one dialogue and using autonomy enhancing approaches. Finally, interventions that successfully encouraged vaccine trust did so by incorporating personalized health information about individuals’ potential level of protection and susceptibility to the COVID-19 virus. These findings can inform future public health efforts to create trustworthy vaccine hesitancy interventions.

Using a training set consisting of twenty-two well-known semiconducting organic polymers, we studied the ability of a simple linear regression supervised machine learning algorithm to accurately predict the bandgap (BG) and ionization potential (IP) of new polymers. We show that using the PBE or PW91 exchange–correlation functionals and this simple linear regression, calculated BGs and IPs can be obtained with average percent errors of less than 3 and 4%, respectively. We then apply this method to predict the BG and IP of a group of new polymers composed of monomers used in the training set and their derivatives in AABB and ABAB orientations.

Background Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. Methods ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. Discussion RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Hypertension is a major risk factor for disease burden and mortality. A decrease in the kidney’sability to excrete sodium can lead to hypertension. Specifically, the proximal tubule (PT) and thickascending limb (TAL) of the nephron play crucial roles in the reabsorption of filtered sodium toregulate blood pressure (BP). Understanding the genetic and epigenetic factors that influence PTand TAL functions is essential for unraveling the molecular mechanisms underlying hypertension.GWAS identified over 1,000 BP-associated genomic loci comprising > 26,000 SNPs. Most (~90%)are in intronic and intergenic regions and may influence BP-relevant gene expression by yetunexplored epigenetic mechanisms. Better understanding of how non-coding genomic regionsregulate BP is critical to defining the genetic underpinnings of hypertension. To address this, weestablished chromatin state (open and closed chromatin) maps for PT and TAL from humans andinbred salt-sensitive rats (SS/JrHsdMcwi) using the Assay for Transposase-Accessible Chromatinwith Sequencing (ATAC-Seq). Linear dimensional reduction revealed that in both species, PT andTAL segments clearly separated, indicating their chromatin states were distinct. ATAC-seq “peaks”represent regions of open chromatin, and therefore likely to be within regulatory elements. Ahigher number of differential peaks was identified between human PT and TAL (65,823) comparedto rat (1,063). The number of PT and TAL enriched peaks also differs between species. Genomicdistribution of these differential peaks indicates the bulk fall within distal intergenic and intronicregions (human: 71.64%, rat: 88.81%) rather than the gene promoters or exonic regions for bothspecies. This indicates that the chromatin accessibility of regulatory regions is significantlydifferent between these two segments for both species. Our next steps are to identify upstreamregulators that differ between the kidney segments and species and integrate ATAC-Seq data withexpression data to define the association of non-coding regions with transcript levels. Our workhas generated chromatin state maps that may improve the understanding of the role of noncodinggenomic regions in the transcriptional regulation in PT and TAL in human and rat.

Francis S. Morrison MD was among the early developers and promoters of the American Society for Apheresis (ASFA). His work was pivotal in creating a lasting institutional structure from which American apheresis medical practice would develop decades after his death. Francis Morrison is honored each year at the ASFA annual meeting as ASFA awards the Francis S. Morrison MD Memorial Award Lecture to an individual who stands out as among its most accomplished members. This tribute seeks to describe the person and the key accomplishments of Francis S. Morrison in the historical context of a time when the future of apheresis medicine was uncertain.

Aberrant overexpression of Interleukin-8 (IL8) has been reported in Myelodysplastic Syndromes (MDS), Acute Myeloid Leukemia (AML), Myeloproliferative Neoplasms (MPNs) and other myeloid malignancies. IL8 (CXCL8) is a CXC chemokine that is secreted by aberrant hematopoietic stem and progenitors as well as other cells in the tumor microenvironment. IL8 can bind to CXCR1/CXCR2 receptors and activate oncogenic signaling pathways, and also increase the recruitment of myeloid derived suppressor cells to the tumor microenvironment. IL8/CXCR1/2 overexpression has been associated with poorer prognosis in MDS and AML and increased bone marrow fibrosis in Myelofibrosis. Preclinical studies have demonstrated benefit of inhibiting the IL8/CXCR1/2 pathways via restricting the growth of leukemic stem cells as well as normalizing the immunosuppressive microenvironment in tumors. Targeting the IL8-CXCR1/2 pathway is a potential therapeutic strategy in myeloid neoplasms and is being evaluated with small molecule inhibitors as well as monoclonal antibodies in ongoing clinical trials. We review the role of IL8 signaling pathway in myeloid cancers and discuss future directions on therapeutic targeting of IL8 in these diseases.

Background Oklahoma’s cumulative COVID-19 incidence is higher in rural than urban counties and higher than the overall US incidence. Furthermore, fewer Oklahomans have received at least one COVID-19 vaccine compared to the US average. Our goal is to conduct a randomized controlled trial using the multiphase optimization strategy (MOST) to test multiple educational interventions to improve uptake of COVID-19 vaccination among underserved populations in Oklahoma. Methods Our study uses the preparation and optimization phases of the MOST framework. We conduct focus groups among community partners and community members previously involved in hosting COVID-19 testing events to inform intervention design (preparation). In a randomized clinical trial, we test three interventions to improve vaccination uptake: (1) process improvement (text messages); (2) barrier elicitation and reduction (electronic survey with tailored questions/prompts); and (2) teachable moment messaging (motivational interviewing) in a three-factor fully crossed factorial design (optimization). Discussion Because of Oklahoma’s higher COVID-19 impact and lower vaccine uptake, identifying community-driven interventions is critical to address vaccine hesitancy. The MOST framework provides an innovative and timely opportunity to efficiently evaluate multiple educational interventions in a single study. Trial Registration ClinicalTrials.gov: NCT05236270, First Posted: February 11, 2022, Last Update Posted: August 31, 2022.

Background and objectives: Research in low-resource settings is inherently challenging. We sought to assess the factors that have impeded or facilitated transfusion medicine (TM) research in various African settings. Materials and methods: A qualitative case study was conducted of selected investigators in Africa; selection was based on productivity-spanning publication, leadership and research in TM. We designed a questionnaire to explore the factors impeding or facilitating TM research to understand the impact on the investigators' careers. Written responses were independently coded and double-checked for precision. Qualitative analysis was conducted, whereby responses were grouped thematically and clustered by relationship. The initial findings were discussed with respondents to validate and refine the interpretations. The recorded transcript was analysed and incorporated into the final analysis. Results: Six investigators participated in the study. Their responses yielded 471 coded comments: 389 from the questionnaires and 82 from the ensuing discussion. The most frequently cited factors described included knowledge and intellectual abilities (n = 104), personal effectiveness (n = 99), research and governance structure (n = 97), and engagement, influence and impact (n = 75). Four relationship clusters emerged from the facilitators (n = 42), barriers (n = 28), and common approaches (n = 26) to research, informing summary themes of adaptation, collaboration, perseverance, and resiliency. Conclusion: Individual attributes were found to be central to a successful TM research career in African settings. However, given other public health priorities and constraints, interpersonal relationships, organizational structures and the broader research context were important to TM researchers. Overcoming complexities demands adaptation, collaboration, perseverance and resiliency.

Background and aims: Elevated small dense low-density lipoprotein-cholesterol (sdLDL-C) has been reported to be associated with increased atherosclerotic cardiovascular disease (ASCVD) risk. Our aims were to determine whether direct and calculated sdLDL-C were significant independent ASCVD risk factors in sex and race subgroups. Methods: In a total of 15,933 participants free of ASCVD at baseline (median age 62 years, 56.7% female, 19.7% African American) fasting plasma lipids and sdLDL-C were measured by standardized automated methods. All subjects were followed for 10 years for incident ASCVD, which developed in 9.7% of subjects. SdLDL-C values were also calculated. Univariate and multivariate analyses were carried out to assess for independent associations with incident ASCVD after adjustment for all standard risk factors. Results: All standard risk factors were significantly associated with incident ASCVD on univariate analysis, as were direct and calculated sdLDL-C. These latter parameters were also significant when added to the pooled cohort risk equation. However, associations were significantly stronger for direct sdLDL-C and were not significant for calculated values once direct values were in the model. In contrast to calculated values, top quartile direct sdLDL-C was significantly independently associated with incident ASCVD versus bottom quartile values in all subjects and subgroups, except African Americans (hazard ratios ≥1.50, p < 0.01). Subjects with direct values ≥ 50 mg/dL versus <25 mg/dL had significantly higher independent ASCVD risk in all groups (hazard ratios >1.49, all p < 0.01). Conclusions: Having a direct small dense low-density lipoprotein cholesterol value ≥ 50 mg/dL is a significant independent ASCVD risk-enhancer.

Food allergy is a global health problem affecting up to 10% of the world population. Accurate diagnosis of food allergies, however, is still a major challenge in medical offices and for patients seeking alternative avenues of diagnosis. A flawless test to confirm or rule out a food allergy does not exist. The lack of optimum testing methods to establish precise clinical correlations remains a major obstacle to effective treatment. Certain IgE measurement methods, including component testing, have received FDA clearance, but they have been used primarily as an analytical tool and not to establish clinical correlations. Most allergy tests are still carried out within the laboratory, and skin tests outside a laboratory setting that are used for food allergy diagnosis rely on non-standardized allergens, according to the FDA definition. Epitope mapping and basophil activation test (BAT) have recently been proposed as a means of establishing better clinical correlations. Yet neither have received FDA clearance for widespread distribution. Of the two methods, the BAT has the advantage of being a functional assay. Over the past few years, several large private practice groups in the United States, have developed BAT as a clinical assay and have started using it in patient care. Given this clinical experience, the vast number of papers published on BAT (more than 1,400 as of 2022) and the trend toward increasing FDA regulation, it is essential to understand the roadmap for regulatory clearance of this assay.

The myelodysplastic syndromes (MDS) are a heterogeneous group of malignant hematopoietic stem cell disorders characterized by ineffective growth and differentiation of hematopoietic progenitors leading to peripheral blood cytopenias, dysplasia, and a variable risk of transformation to acute myelogenous leukemia. As most patients present with lower-risk disease, understanding the pathogenesis of ineffective hematopoiesis is important for developing therapies that will increase blood counts in patients with MDS. Various inflammatory cytokines are elevated in MDS and contribute to dysplastic differentiation. Inflammatory pathways mediated by interleukin (IL) 1b, IL-6, IL-1RAP, IL-8, and others lead to growth of aberrant MDS stem and progenitors while inhibiting healthy hematopoiesis. Spliceosome mutations can lead to missplicing of genes such as IRAK4, CASP8, and MAP3K, which lead to activation of proinflammatory nuclear factor κB-driven pathways. Therapeutically, targeting of ligands of the transforming growth factor β (TGF-β) pathway has led to approval of luspatercept in transfusion-dependent patients with MDS. Presently, various clinical trials are evaluating inhibitors of cytokines and their receptors in low-risk MDS. Taken together, an inflammatory microenvironment can support the pathogenesis of clonal hematopoiesis and low-risk MDS, and clinical trials are evaluating anti-inflammatory strategies in these diseases.

Background Previous studies have demonstrated low first-time donor return rates (DRR) following catastrophic events. Little is known, however, about the influence of demographic factors on the DRR of first-time donors during the COVID-19 pandemic, including the unique motivation of COVID-19 convalescent plasma (CCP) donors as compared to non-CCP donors. Study Design and Methods Thirteen blood collection organizations (BCOs) submitted deidentified data from first-time CCP and non-CCP donors returning for regular (non-CCP) donation during the pandemic. DRR was calculated as frequencies. Demographic factors associated with returning donors: race/ethnicity, gender, and generation (Gen Z: 19-24, Millennial: 25-40, Gen X: 41-56, and Boomer: >57 years old), within the CCP and non-CCP first-time cohorts were compared using chi-square test at p <0.05 statistical significance. Results From March 2020 through December 2021, there were a total of 44,274 first-time CCP and 980,201 first-time non-CCP donors. DRR were 14.6% (range 11.9-43.3%) and 46.6% (range 10.0-76.9%) for CCP and non-CCP cohorts, respectively. Age over 40 years (Gen X and Boomers), female gender, and White race were each associated with higher return in both donor cohorts (p<0.001). For the non-CCP return donor cohort, the Millennial and Boomers were comparable. Conclusion The findings demonstrate differences in returning donor trends between the two donor cohorts. The motivation of a first-time CCP donor may be different than a non-CCP donor. Further study to improve first-time donor engagement would be worthwhile to expand the donor base with focus on blood donor diversity emphasizing engagement of underrepresented minority and younger donors.

Despite great successes in oncology, patient outcomes are often still discouraging, and hence the diagnostic imaging paradigm is increasingly shifting toward functional imaging of the pathology to better understand individual disease biology and to personalize therapies. The dissolution Dynamic Nuclear Polarization (d-DNP) hyperpolarization method has enabled unprecedented real-time MRI sensing of metabolism and tissue pH using hyperpolarized [1-13C]pyruvate as a biosensor with great potential for diagnosis and monitoring of cancer patients. However, current d-DNP is expensive and suffers from long hyperpolarization times, posing a substantial translational roadblock. Here, we report the development of Re-Dissolution Signal Amplification By Reversible Exchange (Re-D SABRE), which relies on fast and low-cost hyperpolarization of [1-13C]pyruvate by chemical exchange with parahydrogen at microtesla magnetic fields. [1-13C]pyruvate is precipitated from catalyst-containing methanol using ethyl acetate and rapidly reconstituted in aqueous media. 13C polarization of 9 ± 1% is demonstrated after redissolution in water with residual iridium mass fraction of 8.5 ± 1.5 ppm; further improvement is anticipated via process automation. Re-D SABRE makes hyperpolarized [1-13C]pyruvate biosensor available at a fraction of the cost (<$10,000) and production time (≈1 min) of currently used techniques and makes aqueous hyperpolarized [1-13C]pyruvate "ready" for in vivo applications.

Purpose: Thrombocytopenia is a serious complication of MDS associated with an increased bleeding risk and worse prognosis. Eltrombopag (ELT), a thrombopoietin receptor agonist, can increase platelet counts and reverse anti-megakaryopoietic effects of lenalidomide (LEN) in preclinical studies. We hypothesized ELT would reduce the incidence of thrombocytopenia in MDS. Experimental design: We conducted a phase 2 multicenter trial of ELT and LEN in adult patients with low or intermediate-1-risk MDS with symptomatic or transfusion-dependent anemia or thrombocytopenia (NCT01772420). Thrombocytopenic patients were started on ELT and subsequently treated with LEN after platelets were increased. Patients without thrombocytopenia were started on LEN monotherapy and treated with ELT if they became thrombocytopenic. Results: 52 patients were enrolled; mean age was 71 years (range 34-93). ORR in the ITT population was 35% (18/52). ELT monotherapy led to ORR of 33.3% (7/21), 29% achieving HI-Platelets, and 24% bilineage responses. LEN monotherapy had 38% ORR (6/16) with all responders achieving HI-Erythroid. 15 patients received both ELT and LEN with ORR of 33.3%, 20% achieved HI-Erythroid, and 20% HI-Platelets with 13% bilineage responses. Median duration of response was 40 weeks for ELT (range 8-ongoing), 41 weeks (25-ongoing) for LEN, and 88 weeks (8.3-ongoing) for ELT/LEN. Non-hematological grade 3-4 treatment-related adverse events were infrequent. Among patients on ELT, 2 had major bleeding events, 1 had a reversible increase in peripheral blasts, and 1 developed marrow fibrosis after 6 years on ELT. Conclusion/discussion: ELT and LEN are well tolerated and effective in achieving hematological improvement in patients with low/intermediate-risk MDS.

Blood Banking/Transfusion Medicine (BB/TM) specialists oversee all aspects of blood component transfusions and are often involved with apheresis, coagulation, and cellular therapy services as well. This study characterizes the BB/TM workforce to determine the scholarly productivity in the first 3-5 years after obtaining board certification and the impact of job type, job location, and academic rank on scholarly productivity. Academic productivity was assessed among individuals passing the American Board of Pathology BB/TM board exam between 2016-2018 using the National Institutes of Health (NIH) Office of Portfolio Analysis tool, iCite. One hundred and twenty-eight BB/TM specialists were included in the analysis. The majority of BB/TM specialists work in academia, are located in the Great Lakes and Mid-Atlantic regions, and have a rank of Assistant Professor. Since passing the board exam, 76.5% (98/128) of BB/TM specialists have published papers, with 4.0 (IQR=1-8) total number of published papers per individual, and 791 total papers amongst the group. The median publications per individual per year since passing boards is 0.9 (IQR=0.2-2.3) the number of publications per year since passing boards for BB/TM specialists in academia significantly higher compared to other jobs at 1.33 (IQR, 0.5-2.89, Kruskal-Wallis p=0.03) per individual Assistant Professors and Associate Professors (1.3, IQR=0.4-2.7 and 1.4, IQR=0.6-3.3, Mann-Whitney test p>0.99). BB/TM specialists who passed the board exam between 2016-2018 are highly academically productive, especially those working in academia where publications are necessary for promotion. BB/TM physicians are an extensively trained and academically-minded group of practitioners.

Importance Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Objective Many therapies are used to treat COVID-19, the disease caused by the virus SARS-CoV-2, including convalescent plasma. The clinical utility of using 2 units of convalescent plasma for COVID-19 hospitalized patients is not fully understood. Our study aims to determine the safety and efficacy of treating hospitalized COVID-19 patients with 2 units of COVID-19 convalescent plasma (CCP). Method This was a retrospective study of Arkansas patients treated with CCP using the (US) Food and Drug Administration (FDA) emergency Investigational New Drug (eIND) mechanism from April 9, 2020, through August 9, 2020. It was a multicenter, statewide study in a low-resource setting, which are areas that lack funding for healthcare cost coverage on various levels including individual, family, or social. Adult patients (n = 165, volunteer sample) in Arkansas who were hospitalized with severe or life-threatening acute COVID-19 disease as defined by the FDA criteria were transfused with 2 units of CCP (250 mL/unit) using the FDA eIND mechanism. The primary outcome was 7- and 30-day mortality after the second unit of CCP. Results Unadjusted mortality was 12.1% at 7 days and 23.0% at 30 days. The unadjusted mortality was reduced to 7.7% if the first CCP unit was transfused on the date of diagnosis, 8.7% if transfused within 3 days of diagnosis, and 32.0% if transfused at or after 4 or more days of diagnosis. The risk of death was higher in patients that received low, negative, or missing titer CCP units in comparison to those that received higher titer units. Conclusion The provision of 2 units of CCP was associated with a reduction in mortality in patients treated with high titer units within 3 days of COVID-19 diagnosis. Given the results, CCP is a viable, low-cost therapy in resource-constrained states and countries.