Differences in microenvironment of lung cancer and pleural effusions by single-cell RNA sequencing.

BACKGROUND: Direct comparison of tumor microenvironment of matched lung cancer biopsies and pleural effusions (PE) from the same patients is critical in understanding tumor biology but has not been performed. This is the first study to compare the lung cancer and PE microenvironment by single-cell RNA sequencing (scRNA-seq). METHODS: Matched lung cancer biopsies and PE were obtained prospectively from ten patients. We isolated CD45+ cells and performed scRNA-seq to compare the biopsies and PE. RESULTS: PE had a higher proportion of CD4+ T cells but lower proportion of CD8+ T cells (False detection rate, FDR = 0.0003) compared to biopsies. There was a higher proportion of naïve CD4+ T cells (FDR = 0.04) and naïve CD8+ T cells (FDR = 0.0008) in PE vs. biopsies. On the other hand, there was a higher proportion of Tregs (FDR = 0.04), effector CD8+ (FDR = 0.006), and exhausted CD8+ T cells (FDR = 0.01) in biopsies. The expression of inflammatory genes in T cells was increased in biopsies vs. PE, including TNF, IFN-É£, IL-1R1, IL-1R2, IL-2, IL-12RB2, IL-18R1, and IL-18RAP (FDR = 0.009, 0.013, 0.029, 0.043, 0.009, 0.013, 0.004, and 0.003, respectively). The gene expression of exhaustion markers in T cells was also increased in tumor biopsies including PDCD1, CTLA4, LAG 3, HAVCR2, TIGIT, and CD160 (FDR = 0.008, 0.003, 0.002, 0.011, 0.006, and 0.049, respectively). CONCLUSIONS: There is a higher proportion of naïve T cells and lower proportion of exhausted T cells and Tregs in PE compared to lung cancer biopsies, which can be leveraged for prognostic and therapeutic applications.

Impact of FDA's HCT/P ZIKV Recommendations on Cord Blood Unit Eligibility and Utilization in a Large Public Cord Blood Bank.

BACKGROUND: Cord blood units (CBUs) that are ineligible for licensure due to incomplete compliance with FDA recommendations may be used for hematopoietic stem cell transplantation under urgent medical need and an Investigational Drug Application. The largest reason for CBU donor ineligibility is Zika virus (ZIKV) risk. The study's objective was to analyze the impact of current FDA recommendations for ZIKA risk on a large public cord blood bank and propose updated recommendations. METHODS: We performed a retrospective analysis of Carolinas Cord Blood Bank (CCBB), an FDA licensed public CBB, using data from January 1, 2016 to November 21, 2023 and compared FDA recommendations for transfusion transmitted infections (TTI) for blood products and relevant communicable disease agents or diseases for human cell, tissue, or cellular or tissue-based products (HCT/Ps). RESULTS: CCBB: 9057 (84.3% licensed) CBUs were banked. 984/1682 (58.5%) of unlicensed CBUs had ZIKV risk. 22.0% of CBUs with ZIKV risk were from Hispanic parents, compared to 16.1% of all units. 31 of IND CBUs (11 due to ZIKV risk without reported ZIKV transmission) were safely infused. FDA Guidance: HCT/P ZIKV, HIV, and vCJD recommendations have not been updated since 2018 in contrast to FDA removal of ZIKV as a relevant TTI in 2021 and updating HIV and vCJD guidance related to TTI in 2023 and 2022, respectively. DISCUSSION: The FDA should consider new data to revise the HCT/P donor eligibility recommendations, which will increase the number of eligible HCT/P donors, and potentially improve access to therapies for a more diverse patient population.

Contemporary management of major haemorrhage in critical care.

Haemorrhagic shock is frequent in critical care settings and responsible for a high mortality rate due to multiple organ dysfunction and coagulopathy. The management of critically ill patients with bleeding and shock is complex, and treatment of these patients must be rapid and definitive. The administration of large volumes of blood components leads to major physiological alterations which must be mitigated during and after bleeding. Early recognition of bleeding and coagulopathy, understanding the underlying pathophysiology related to specific disease states, and the development of individualised management protocols are important for optimal outcomes. This review describes the contemporary understanding of the pathophysiology of various types of coagulopathic bleeding; the diagnosis and management of critically ill bleeding patients, including major haemorrhage protocols and post-transfusion management; and finally highlights recent areas of opportunity to better understand optimal management strategies for managing bleeding in the intensive care unit (ICU).

Local manufacturing processes contribute to variability in human mesenchymal stromal cell expansion while growth media supplements contribute to variability in gene expression and cell function: a Biomedical Excellence for Safer Transfusion (BEST) collaborative study.

BACKGROUND AIMS: Culture-derived mesenchymal stromal cells (MSCs) exhibit variable characteristics when manufactured using different methods, source material and culture media. The purpose of this multicenter study was to assess the impact on MSC expansion, gene expression and other characteristics when different laboratories expanded MSCs from cultures initiated with bone marrow-MSC aliquots derived from the same donor source material yet with different growth media. METHODS: Eight centers expanded MSCs using four human platelet lysate (HPL) and one fetal bovine serum (FBS) products as media supplements. The expanded cells were taken through two passages then assessed for cell count, viability, doubling time, immunophenotype, cell function, immunosuppression and gene expression. Results were analyzed by growth media and by center. RESULTS: Center methodologies varied by their local seeding density, feeding regimen, inoculation density, base media and other growth media features (antibiotics, glutamine, serum). Doubling times were more dependent on center than on media supplements. Two centers had appropriate immunophenotyping showing all MSC cultures were positive for CD105, CD73, CD90 and negative for CD34, CD45, CD14, HLA-DR. MSCs cultured in media supplemented with FBS compared with HPL featured greater T-cell inhibition potential. Gene expression analysis showed greater impact of the type of media supplement (HPL versus FBS) than the manufacturing center. Specifically, nine genes were decreased in expression and six increased when combining the four HPL-grown MSCs versus FBS (false discovery rate [FDR] <0.01), however, without significant difference between different sources of HPL (FDR <0.01). CONCLUSIONS: Local manufacturing process plays a critical role in MSC expansion while growth media may influence function and gene expression. All HPL and FBS products supported cell growth.

Blood and Its Components.

This JAMA Insights summarizes best clinical practices for use of whole blood, plasma, cryoprecipitate, platelets, and red blood cells in the process of blood transfusion.

The potential cost-effectiveness of novel cord blood therapies in children with autism spectrum disorder.

OBJECTIVE: To model the long-term clinical and economic outcomes of potential cord blood therapy in autism spectrum disorder (ASD). STUDY DESIGN: Markov microsimulation of ASD over the lifespan was used to compare two strategies: 1) standard of care (SOC), including behavioral and educational interventions, and 2) novel cord blood (CB) intervention in addition to SOC. Input data reflecting behavioral outcomes included baseline Vineland Adaptive Behavior Scale (VABS-3), monthly VABS-3 changes, and CB intervention efficacy on adaptive behavior based on a randomized, placebo-controlled trial (DukeACT). Quality-adjusted life-years (QALYs) were correlated to VABS-3. Costs for children with ASD ($15,791, ages 2-17 years) and adults with ASD ($56,559, ages 18+ years), and the CB intervention (range $15,000-45,000) were incorporated. Alternative CB efficacy and costs were explored. RESULTS: We compared model-projected results to published data on life-expectancy, mean VABS-3 changes, and lifetime costs. Undiscounted lifetime QALYs in the SOC and CB strategies were 40.75 and 40.91. Discounted lifetime costs in the SOC strategy were $1,014,000, and for CB ranged from $1,021,000-$1,058,000 with CB intervention cost ($8,000-$45,000). At $15,000 cost, CB was borderline cost-effective (ICER = $105,000/QALY). In one-way sensitivity analysis, CB cost and efficacy were the most influential parameters on CB ICER. CB intervention was cost-effective at costs<$15,000 and efficacies ≥2.0. Five-year healthcare payer projected budgetary outlays at a $15,000 CB cost were $3.847B. CONCLUSIONS: A modestly effective intervention designed to improve adaptive behavior in autism can be cost-effective under certain circumstances. Intervention cost and efficacy most affected the cost-effectiveness results and should be targeted to increase economic efficiency.

Feasibility Study of Cord Tissue Derived Mesenchymal Stromal Cells in COVID-19-Related Acute Respiratory Distress Syndrome.

BACKGROUND: Treatment options for patients with COVID-19-related acute respiratory distress syndrome (ARDS) are desperately needed. Allogeneic human umbilical cord derived mesenchymal stromal cells (hCT-MSCs) have potential therapeutic benefits in these critically ill patients, but feasibility and safety data are lacking. MATERIALS AND METHODS: In this phase I multisite study, 10 patients with COVID-19-related ARDS were treated with 3 daily intravenous infusions of hCT-MSCs (1 million cells/kg, maximum dose 100 million cells). The primary endpoint assessed safety. RESULTS: Ten patients (7 females, 3 males; median age 62 years (range 39-79)) were enrolled at 2 sites and received a total of 30 doses of study product. The average cell dose was 0.93 cells/kg (range 0.56-1.45 cells/kg and total dose range 55-117 million cells) with 5/30 (17%) of doses lower than intended dose. Average cell viability was 85% (range 63%-99%) with all but one meeting the >70% release criteria. There were no infusion-related reactions or study-related adverse events, 28 non-serious adverse events in 3 unique patients, and 2 serious adverse events in 2 unique patients, which were expected and unrelated to the study product. Five patients died: 3 by day 28 and 5 by day 90 of the study (median 27 days, range 7-76 days). All deaths were determined to be unrelated to the hCT-MSCs. CONCLUSION: We were able to collect relevant safety outcomes for the use of hCT-MSCs in patients with COVID-19-related ARDS. Future studies to explore their safety and efficacy are warranted.

Expanding the platelet inventory to mitigate the impact of severe shortages.

The platelet collection and distribution system, based on volunteer nonremunerated donors, apheresis platelet collections, and primarily 1-directional distribution of platelets for up to 5-day room temperature storage at hospitals, typically performs well and provides therapeutic support for hundreds of thousands of patients annually. However, direct and indirect effects of the coronavirus disease 2019 pandemic, particularly during the Omicron wave, produced dramatic systemic failures and severe shortages. We propose 4 initiatives to reinforce the existing platelet pipeline and buffer the platelet supply against future unexpected disruptions.

Blood donation motivators and barriers reported by young, first-time whole blood donors: Examining the association of reported motivators and barriers with subsequent donation behavior and potential sex, race, and ethnic group differences.

BACKGROUND: A greater understanding of young, first-time donor motivators and barriers is needed to address the ongoing challenge of retaining these essential donors. STUDY DESIGN AND METHODS: Structured interviews conducted with 508 young, first-time whole blood donors [66.1% female; Mean Age = 19.4 (SD = 2.5) years] were coded to identify reported motivators and barriers. Reported motivators and barriers were then examined for their association with attempted donation behavior over a 14-month follow-up, and for potential sex, race, and ethnic group differences in the frequency of endorsement. RESULTS: Prosocial motivation (e.g., altruism) was the most commonly reported motivator and fear (e.g., fainting, needles) was the most commonly reported barrier. Donation behavior was unrelated to reported motivators, but was significantly related to four reported barriers including fear of fainting/dizziness, fear of needles/pain, having personal commitments that conflict with donating, and perceiving oneself as unsuited to donate for health reasons. Sex, racial, and ethnic differences were noted with respect to the percentages of donors reporting several donation-related motivators and barriers. CONCLUSION: The present findings identify donation-related barriers that could be important targets to address in the effort to encourage new young donors and to retain these new donors for the long term. Importantly, these data also highlight the importance of considering individual differences in donor motivation as a function of sex, race, and ethnicity.

A randomized trial of blood donor iron repletion on red cell quality for transfusion and donor cognition and well-being.

Although altruistic regular blood donors are vital for the blood supply, many become iron deficient from donation-induced iron loss. The effects of blood donation-induced iron deficiency on red cell transfusion quality or donor cognition are unknown. In this double-blind, randomized trial, adult iron-deficient blood donors (n = 79; ferritin < 15 µg/L and zinc protoporphyrin >60 µMol/mol heme) who met donation qualifications were enrolled. A first standard blood donation was followed by the gold-standard measure for red cell storage quality: a 51-chromium posttransfusion red cell recovery study. Donors were then randomized to intravenous iron repletion (1 g low-molecular-weight iron dextran) or placebo. A second donation ∼5 months later was followed by another recovery study. Primary outcome was the within-subject change in posttransfusion recovery. The primary outcome measure of an ancillary study reported here was the National Institutes of Health Toolbox-derived uncorrected standard Cognition Fluid Composite Score. Overall, 983 donors were screened; 110 were iron-deficient, and of these, 39 were randomized to iron repletion and 40 to placebo. Red cell storage quality was unchanged by iron repletion: mean change in posttransfusion recovery was 1.6% (95% confidence interval -0.5 to 3.8) and -0.4% (-2.0 to 1.2) with and without iron, respectively. Iron repletion did not affect any cognition or well-being measures. These data provide evidence that current criteria for blood donation preserve red cell transfusion quality for the recipient and protect adult donors from measurable effects of blood donation-induced iron deficiency on cognition. This trial was registered at www.clinicaltrials.gov as NCT02889133 and NCT02990559.

Clinical Practice Guidelines From the Association for the Advancement of Blood and Biotherapies (AABB): COVID-19 Convalescent Plasma.

DESCRIPTION: Coronavirus disease 2019 convalescent plasma (CCP) has emerged as a potential treatment of COVID-19. However, meta-analysis data and recommendations are limited. The Association for the Advancement of Blood and Biotherapies (AABB) developed clinical practice guidelines for the appropriate use of CCP. METHODS: These guidelines are based on 2 living systematic reviews of randomized controlled trials (RCTs) evaluating CCP from 1 January 2019 to 26 January 2022. There were 33 RCTs assessing 21 916 participants. The results were summarized using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. An expert panel reviewed the data using the GRADE framework to formulate recommendations. RECOMMENDATION 1 (OUTPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for outpatients with COVID-19 who are at high risk for disease progression (weak recommendation, moderate-certainty evidence). RECOMMENDATION 2 (INPATIENT): The AABB recommends against CCP transfusion for unselected hospitalized persons with moderate or severe disease (strong recommendation, high-certainty evidence). This recommendation does not apply to immunosuppressed patients or those who lack antibodies against SARS-CoV-2. RECOMMENDATION 3 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 who do not have SARS-CoV-2 antibodies detected at admission (weak recommendation, low-certainty evidence). RECOMMENDATION 4 (INPATIENT): The AABB suggests CCP transfusion in addition to the usual standard of care for hospitalized patients with COVID-19 and preexisting immunosuppression (weak recommendation, low-certainty evidence). RECOMMENDATION 5 (PROPHYLAXIS): The AABB suggests against prophylactic CCP transfusion for uninfected persons with close contact exposure to a person with COVID-19 (weak recommendation, low-certainty evidence). GOOD CLINICAL PRACTICE STATEMENT: CCP is most effective when transfused with high neutralizing titers to infected patients early after symptom onset.

Evaluation of amotosalen and UVA pathogen-reduced apheresis platelets after 7-day storage.

BACKGROUND: Amotosalen/UVA pathogen-reduced platelet components (PRPCs) with storage up to 7 days are standard of care in France, Switzerland, and Austria. PRPCs provide effective hemostasis with reduced risk of transfusion-transmitted infections and transfusion-associated graft versus host disease, reduced wastage and improved availability compared with 5-day-stored PCs. This study evaluated the potency of 7-day PRPCs by in vitro characterization and in vivo pharmacokinetic analysis of autologous PCs. STUDY DESIGN AND METHODS: The in vitro characteristics of 7-day-stored apheresis PRPCs suspended in 100% plasma or 65% platelet additive solution (PAS-3)/35% plasma, thrombin generation, and in vivo radiolabeled post-transfusion recovery and survival of 7-day-stored PRPCs suspended in 100% plasma were compared with either 7-day-stored or fresh autologous conventional platelets. RESULTS: PRPCs after 7 days of storage maintained pH, platelet dose, in vitro physiologic characteristics, and thrombin generation when compared to conventional 7-day PCs. In vivo, the mean post-transfusion survival was 151.4 ± 20.1 h for 7-day PRPCs in 100% plasma (Test) versus 209.6 ± 13.9 h for the fresh autologous platelets (Control), (T-ΔC: 72.3 ± 8.8%: 95% confidence interval [CI]: 68.5, 76.1) and mean 24-h post-transfusion recovery 37.6 ± 8.4% for Test versus 56.8 ± 9.2% for Control (T-ΔC: 66.2 ± 11.2%; 95% CI: 61.3, 71.1). DISCUSSION: PRPCs collected in both 100% plasma as well as 65% PAS-3/35% plasma and stored for 7 days retained in vitro physiologic characteristics. PRPCs stored in 100% plasma for 7 days retained in vivo survival. Lower in vivo post-radiolabeled autologous platelet recovery is consistent with reported reduced count increments for allogenic transfusion.

Blood donor eligibility criteria for medical conditions: A BEST collaborative study.

BACKGROUND AND OBJECTIVES: Donor eligibility questions and criteria for medical conditions vary between blood centres, suggesting that they are based more on local regulations or experience, rather than on published data, which are limited. As the donor population ages, medical conditions become more common. We assessed donor health assessment criteria at blood centre members of the Biomedical Excellence for Safer Transfusion (BEST) Collaborative. Our aim was to compare eligibility criteria and determine their underlying basis. MATERIALS AND METHODS: A REDCap survey was sent to blood centre participants, based on medical conditions of greatest interest suggested by the Donor Studies Team of the BEST Collaborative. Participants were asked about current donor health assessment questions, deferral criteria and the basis for their deferral policy (donor risk, recipient risk or both) for 20 medical conditions. RESULTS: Complete responses were received from 26 blood donor centres (24 separate responses) representing a combination of hospital-based centres, large regional centres and community/national blood centres in 14 different countries. Most centres specifically ask about heart and lung conditions, whereas fewer than half inquire about kidney, gastrointestinal or neurological conditions. North American blood centres tended to be less restrictive, while regulatory restrictions are more prevalent in Europe. Most participants felt that the criteria were based on regulatory requirements or experience, rather than on published data. CONCLUSION: There is considerable variability in criteria by region. Ideally, criteria would be more evidence-based rather than based on regulatory requirements or experience. Deferral criteria must balance donor and recipient safety and maintain an adequate blood supply.

COVID-19 convalescent plasma.

As the coronavirus disease (COVID-19) pandemic led to a global health crisis, there were limited treatment options and no prophylactic therapies for those exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Convalescent plasma is quick to implement, potentially provides benefits, and has a good safety profile. The therapeutic potential of COVID-19 convalescent plasma (CCP) is likely mediated by antibodies through direct viral neutralization and Fc-dependent functions such as a phagocytosis, complement activation, and antibody-dependent cellular cytotoxicity. In the United States, CCP became one of the most common treatments with more than a half million units transfused despite limited efficacy data. More than a dozen randomized trials now demonstrate that CCP does not provide benefit for those hospitalized with moderate to severe disease. However, similar to other passive antibody therapies, CCP is beneficial for early disease when provided to elderly outpatients within 72 hours after symptom onset. Only high-titer CCP should be transfused. CCP should also be considered for immunosuppressed patients with COVID-19. CCP collected in proximity, by time and location, to the patient may be more beneficial because of SARS-CoV-2 variants. Additional randomized trial data are still accruing and should be incorporated with other trial data to optimize CCP indications.

Access to and safety of COVID-19 convalescent plasma in the United States Expanded Access Program: A national registry study.

BACKGROUND: The United States (US) Expanded Access Program (EAP) to coronavirus disease 2019 (COVID-19) convalescent plasma was initiated in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19. While randomized clinical trials were in various stages of development and enrollment, there was an urgent need for widespread access to potential therapeutic agents. The objective of this study is to report on the demographic, geographical, and chronological characteristics of patients in the EAP, and key safety metrics following transfusion of COVID-19 convalescent plasma. METHODS AND FINDINGS: Mayo Clinic served as the central institutional review board for all participating facilities, and any US physician could participate as a local physician-principal investigator. Eligible patients were hospitalized, were aged 18 years or older, and had-or were at risk of progression to-severe or life-threatening COVID-19; eligible patients were enrolled through the EAP central website. Blood collection facilities rapidly implemented programs to collect convalescent plasma for hospitalized patients with COVID-19. Demographic and clinical characteristics of all enrolled patients in the EAP were summarized. Temporal patterns in access to COVID-19 convalescent plasma were investigated by comparing daily and weekly changes in EAP enrollment in response to changes in infection rate at the state level. Geographical analyses on access to convalescent plasma included assessing EAP enrollment in all national hospital referral regions, as well as assessing enrollment in metropolitan areas and less populated areas that did not have access to COVID-19 clinical trials. From April 3 to August 23, 2020, 105,717 hospitalized patients with severe or life-threatening COVID-19 were enrolled in the EAP. The majority of patients were 60 years of age or older (57.8%), were male (58.4%), and had overweight or obesity (83.8%). There was substantial inclusion of minorities and underserved populations: 46.4% of patients were of a race other than white, and 37.2% of patients were of Hispanic ethnicity. Chronologically and geographically, increases in the number of both enrollments and transfusions in the EAP closely followed confirmed infections across all 50 states. Nearly all national hospital referral regions enrolled and transfused patients in the EAP, including both in metropolitan and in less populated areas. The incidence of serious adverse events was objectively low (<1%), and the overall crude 30-day mortality rate was 25.2% (95% CI, 25.0% to 25.5%). This registry study was limited by the observational and pragmatic study design that did not include a control or comparator group; thus, the data should not be used to infer definitive treatment effects. CONCLUSIONS: These results suggest that the EAP provided widespread access to COVID-19 convalescent plasma in all 50 states, including for underserved racial and ethnic minority populations. The study design of the EAP may serve as a model for future efforts when broad access to a treatment is needed in response to an emerging infectious disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT#: NCT04338360.

Promoting awareness of donation-related iron depletion among high risk blood donors.

BACKGROUND: The potential for iron deficiency is a known blood donor health concern and suggests the need to inform donors about the potential risks of low iron levels as well as strategies to address these risks. STUDY DESIGN AND METHODS: Frequent (n = 904) and young (n = 629) donors were randomly assigned within risk group to either a control (n = 548) or an intervention (n = 985) group. The control group answered questions at baseline and 6-month follow-up regarding their awareness of the risk of donation-related iron depletion and whether they were taking actions to address their iron status. The intervention group answered the same questions at baseline and follow-up, but after completing the baseline survey, they received information regarding their risk of iron depletion and behaviors they could adopt to mitigate this risk. Intervention group participants were also offered the opportunity to develop an action plan to help them supplement their iron intake. RESULTS: The intervention enhanced overall awareness of donation-related iron loss (OR = 1.5, 95% CI 1.171-1.864, p = .001), with no negative impact on retention. Reported iron health behaviors (iron supplementation, speaking with a doctor) showed significant increases when action planning was paired with the educational information. CONCLUSION: These findings suggest that it is possible to increase awareness of donation-related risk for iron depletion without negatively influencing retention, and combining education with encouragement to develop an action plan may increase the likelihood of both retention and behavioral changes to promote healthy iron levels.

Fear is associated with attrition of first-time whole blood donors: A longitudinal examination of donor confidence and attitude as potential mediators.

BACKGROUND: Elevated fear and anxiety regarding donation-related stimuli (e.g., needles, pain, blood, fainting) has been associated with reduced blood donor recruitment and retention. The present longitudinal study tests the notion that this inverse relationship may be accounted for by lower donation confidence and more negative donation attitudes among fearful first-time donors. STUDY DESIGN AND METHODS: In a sample of 1479 first-time whole blood donors [67.9% female; mean age = 19.3 (standard deviation (SD) = 2.5) years], path analyses were conducted to examine relationships among donor ratings of fear of blood draw and donation anxiety obtained approximately 1 week after donation, donation confidence and attitudes assessed approximately 6 weeks later, and donation attempts over the 14 months following the original donation. RESULTS: Path analyses indicated that both fear of blood draws and donation anxiety were associated with fewer attempted donations, and that these effects were indirectly mediated by a combination of lower donor confidence and more negative donation attitudes. CONCLUSION: Because retention of new blood donors is essential to maintain a healthy blood supply, the results of the present study suggest that first-time donors should be assessed for fear and anxiety so that appropriate strategies can be provided to address their concerns, bolster their confidence and attitudes, and ultimately promote their long-term retention.

Blood transfusions in gunshot-wound-related emergency department visits and hospitalizations in the United States.

BACKGROUND: The United States (US) leads all high-income countries in gunshot wound (GSW) deaths. However, previous US studies have not evaluated the national blood transfusion utilization patterns in hospitalized GSW patients. METHODS: Data from 2016 to 2017 were analyzed from the Nationwide Emergency Department Sample (NEDS) and Nationwide Inpatient Sample (NIS), the largest all-payer emergency department (ED) and inpatient databases, respectively. Using stratified probability sampling, weights were applied to generate nationally representative estimates. Multivariable Poisson-regression models were used to estimate prevalence ratios (PR) of blood transfusion. RESULTS: There were 168,315 ED visits and 58,815 hospitalizations (age = 18-90 years) following a GSW. The majority of hospitalizations were men (88.5%), age 18-24 years (31.8%), and assault-related GSW (51.3%). Blacks had the largest proportion (48.7%) overall of all GSW hospitalizations; Whites accounted for the highest proportion of intentional self-harm injuries (72.4%). Blood transfusions occurred in 12.7% of hospitalizations (12.0% red blood cell [RBC], 4.9% plasma, and 2.5% platelet transfusions). Only 1.9% of cases were associated with transfusion of all three blood components. Hospitalizations with major/extreme severity of illness had significantly higher prevalence of transfusion versus those with mild/moderate severity [crude PR = 4.79 (95%CI:4.15-5.33, p < .001)]. Overall, 8.2% of hospitalizations with GSW died, of whom 26.8% required blood transfusions, which was significantly higher than survivors [crude PR = 2.34 (95%CI:2.10-2.61, p < .001)]. The vast majority (95%) of the transfusions among those who died were within 48 h since admission. CONCLUSIONS: Gun-related violence is a public health emergency in the US, and GSWs are a source of significant mortality, blood utilization, and health care costs.