Transfusing children with sickle cell disease using blood group genotyping when the pool of Black donors is limited.

BACKGROUND: Red blood cell transfusion is an effective treatment for patients with sickle cell disease (SCD). Alloimmunization can occur after a single transfusion, limiting further usage of blood transfusion. It is recommended to match for the ABO, D, C, E, and K antigens to reduce risks of alloimmunization. However, availability of compatible blood units can be challenging for blood providers with a limited number of Black donors. STUDY DESIGN AND METHODS: A prospective cohort of 205 pediatric patients with SCD was genotyped for the RH and FY genes. Transfusion and alloimmunization history were collected. Our capacity to find RhCE-matched donors was evaluated using a database of genotyped donors. RESULTS: Nearly 9.8% of patients carried a partial D variant and 5.9% were D-. Only 45.9% of RHCE alleles were normal, with the majority of variants affecting the RH5 (e) antigen. We found an alloimmunization prevalence of 20.7% and a Rh alloimmunization prevalence of 7.1%. Since Black donors represented only 1.40% of all blood donors in our province, D- Caucasian donors were mostly used to provide phenotype matched products. Compatible blood for patients with rare Rh variants was found only in Black donors. A donor with compatible RhCE could be identified for all patients. CONCLUSION: Although Rh-compatible donors were identified, blood units might not be available when needed and/or the extended phenotype or ABO group might not match the patient. A greater effort has to be made for the recruitment of Black donors to accommodate patients with SCD.

Management of a patient with sickle cell disease and multiple red blood cell alloantibodies in preparation for a hematopoietic stem cell transplantation.

BACKGROUND: Hematopoietic stem cell transplant (HSCT) is currently the only widely available curative option for patients with sickle cell disease (SCD). Alloimmunization in this population is frequent and can complicate transfusion management during the HSCT period. The case of a pediatric patient with severe SCD clinical phenotype, multiple alloantibodies (9), and hyperhemolysis syndrome who underwent haploidentical HSCT is described. STUDY DESIGN AND METHODS: The patient was known for an anti-e, despite RHCE*01.01 allele, which predicts a C- c+ E- weak e+ phenotype. Donors matching the patient's extended phenotype were targeted for RHCE genotyping. RESULTS: Donors homozygotes or heterozygotes for RHCE*01.01 were selected for compatibility analyses and ranked based on strength of reactions. Discordance between zygosity and strength of reactions was observed, as the most compatible donors were heterozygotes for RHCE*01.01. In total, the patient received seven RBC units from two different donors during HSCT process without transfusion reaction or development of new alloantibodies. Six months post-HSCT, his hemoglobin level is stable at around 120 g/L and his chimerism is 100%. DISCUSSION: This case highlights the complexity of transfusion management during HSCT of alloimmunized patients with SCD. Collecting sufficient compatible units requires early involvement of transfusion medicine teams and close communication with the local blood provider. Genotyping of donors self-identifying as Black is useful for identifying compatible blood for those patients but has some limitations. HSCT for heavily alloimmunized patients is feasible and safe with early involvement of transfusion medicine specialists. Further research on the clinical impact of genotypic matching is needed.

Incidence of acute haemolytic transfusion reaction among ABO-incompatible recipients transfused with A3 blood: A case series.

BACKGROUND AND OBJECTIVES: ABO antigens are among the most immunogenic, but the haemolytic risks of ABO incompatibilities involving a donor with a weak ABO phenotype are little documented. MATERIALS AND METHODS: This retrospective case series assessed the incidence of acute haemolytic transfusion reaction (AHTR) among ABO-incompatible recipients of A3 blood in Québec (Canada). Transfusion safety officers reported laboratory AHTR indicators measured ≤24 h pre- and post-transfusion. Because the AHTR case definition of Québec's Hemovigilance System (QHS) leaves significant room for clinical judgement, a two-step approach was used to assess potential cases: Step 1 consisted in a highly sensitive-but unspecific-initial screen that identified all candidate cases per QHS case definition, and Step 2 consisted in a detailed review of candidate cases by two haematologists. RESULTS: Nine donors initially typed as Group B (N = 1) or O (N = 8) were subsequently found to display an A3 B or A3 O phenotype. Eighty-one recipients received ABO-incompatible blood, including 53 (65.4%) with interpretable data. Of these, 29 (54.7%) were classified as candidate cases after Step 1. Following Step 2, no conclusive evidence of AHTR was found: Abnormal pre- versus post-transfusion changes appeared modest, within normal range, insufficient to ascertain AHTR, or were consistent with a pre-existing condition unrelated to AHTR. Two candidate cases had a QHS-reported transfusion reaction; both were unrelated to AHTR. CONCLUSION: In this case series, no conclusive evidence of serious AHTR was found among ABO-incompatible recipients who were inadvertently transfused with A3 blood.

Kinetic modeling of the adsorption and desorption of metallic ions present in effluents using the biosorbent obtained from Syagrus romanzoffiana.

In this study, the kinetic mechanism of adsorption and desorption, as well as the equilibrium isotherms, of four metallic ions (Cd2+, Cu2+, Ni2+, and Zn2+) mono and multicomponent were investigated. The biosorbent used was produced from Jerivá (Syagrus romanzoffiana-commonly known as queen palm) coconut. A kinetic model that considers macropore diffusion as a control step was solved. The finite volume method was used in the discretization of the equations, and the algorithm was implemented in the Fortran programming language. The equilibrium time for monocomponent adsorption was 5 min; for the multicomponent tests, equilibrium occurred instantly (less than 2 min of adsorption). The pseudo-second-order model presented the lowest mean of the sum of normalized errors (SNE) and represented the experimental data of mono and multicomponent adsorption and desorption. Single and multicomponent Langmuir model represented the adsorption isotherms. The maximum capacity of adsorption of metallic ions, both mono and multicomponent, was higher for copper, and the multicomponent adsorption proved to be antagonistic; the presence of co-ions in the solution reduced the removal of metals due to competition between these contaminants. The capture preference order was justified by the physicochemical properties of the ions, such as electron incompatibility and electronegativity. All these situations justified the maximum adsorption of Cu2+, followed by Zn2+, Cd2+, and Ni2+ in the mixture.

Comparison of Noninvasive Measurements of Intracranial with Tap Test Results in Patients with Idiopathic Normal Pressure Hydrocephalus.

Background: Normal pressure hydrocephalus is a disease directly related to the change in intracranial compliance and consequent repercussions in the brain parenchyma. Invasive monitoring of such parameters proves to be reliable especially for prognosis in neurocritical patients; however, it is not applicable in an outpatient service setting. The present study describes the comparison between the tap test results and the parameters obtained with a non-invasive sensor for monitoring intracranial compliance in patients with suspected NPH. Methods: Twenty-eight patients were evaluated before and after lumbar puncture of 50mL of CSF (the tap test), comprising clinical assessment, magnetic resonance imaging, physical therapy assessment using the Timed Up and Go test, Dynamic Gait Index, BERG test, neuropsychological assessment, and recording of non-invasive intracranial compliance data using the Brain4care® device in three different positions (lying, sitting, and standing) for 5 min each. The tap test results were compared to the Time to Peak and P2/P1 ratio parameters obtained by the device. Results: The group that had a positive Tap test result presented a median P2/P1 ratio greater than 1.0, suggesting a change in intracranial compliance. In addition, there was also a significant difference between patients with positive, negative, and inconclusive results, especially in the lying position. Conclusion: A non-invasive intracranial compliance device when used with the patient lying down and standing up obtained parameters that suggest correspondence with the result of the tap test.

Design of a phase 3, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of prucalopride in pediatric patients with functional constipation.

Background: A previous phase 3 trial of prucalopride in pediatric patients (6 months-18 years old) with functional constipation (FC) demonstrated no efficacy versus placebo. We designed an additional phase 3 trial to further assess the efficacy, long-term safety and tolerability of prucalopride in children and adolescents. Methods: This multicenter trial (ClinicalTrials.gov identifier: NCT04759833; EudraCT number: 2022-003221-22) comprises a 12-week, randomized, double-blind, placebo-controlled phase, followed by a 36-week, double-blind, safety extension phase. Approximately 240 toilet-trained patients aged 3-17 years will be randomized 1:1:1 to receive low- (0.04 mg/kg) or high-dose (0.08 mg/kg) prucalopride, or placebo once daily. Fifteen non-toilet-trained patients ≥6 months old with FC will be included in an exploratory efficacy and safety analysis. Discussion: The efficacy endpoints used in this study will differ from those used in adults and in the previous pediatric phase 3 trial; they have been adapted to be more suitable for a wider age range of pediatric patients. Both study phases will be longer than in the previous pediatric study, providing a longer time period in which to assess the efficacy and safety of prucalopride. Study participants will be identified using the modified Rome IV criteria for FC, instead of the Rome III criteria, and non-toilet-trained patients will be included, which will broaden the population of pediatric patients assessed. Patients will undergo fecal disimpaction before randomization and undergo standardized continuous behavioral therapy throughout the trial. This pediatric study of prucalopride will aim to demonstrate the efficacy and long-term safety of this treatment.

Modified truncated Hochberg procedure for multiple endpoints: An application in a confirmatory trial for pediatric functional constipation.

BACKGROUND: In confirmatory clinical trials, it is critical to have appropriate control of multiplicity for multiple comparisons or endpoints. When multiplicity-related issues arise from different sources (e.g., multiple endpoints, multiple treatment arms, multiple interim data-cuts and other factors), it can become complicated to control the family-wise type I error rate (FWER). Therefore, it is crucial for statisticians to fully understand the multiplicity adjustment methods and the objectives of the analysis regarding study power, sample size and feasibility in order to identify the proper multiplicity adjustment strategy. METHODS: In the context of multiplicity adjustment of multiple dose levels and multiple endpoints in a confirmatory trial, we proposed a modified truncated Hochberg procedure in combination with a fixed-sequence hierarchical testing procedure to strongly control the FWER. In this paper, we provided a brief review of the mathematical framework of the regular Hochberg procedure, the truncated Hochberg procedure and the proposed modified truncated Hochberg procedure. An ongoing phase 3 confirmatory trial for pediatric functional constipation was used as a real case application to illustrate how the proposed modified truncated Hochberg procedure will be implemented. A simulation study was conducted to demonstrate that the study was adequately powered and the FWER was strongly controlled. CONCLUSION: This work is expected to facilitate the understanding and selection of adjustment methods for statisticians.

A Review of the Cardiovascular Safety of Prucalopride in Patients With Chronic Idiopathic Constipation.

Prokinetic agents, specifically 5-hydroxytryptamine type 4 (5-HT 4 ) receptor agonists, have been shown to provide relief in chronic idiopathic constipation (CIC). The first-generation 5-HT 4 agonists were initially withdrawn from use owing to associations with serious cardiovascular (CV) events. This review summarizes CV safety data for prucalopride, a high-affinity 5-HT 4 agonist approved in the United States in 2018 for adults with CIC. No significant effects of prucalopride on CV safety were observed in animal models or early-phase clinical studies, including a thorough QT study at therapeutic (2 mg) or supratherapeutic (10 mg) doses. Among 1,750 patients with CIC who received prucalopride (2-4 mg) in 5 phase 3 studies, no trends in CV adverse events, electrocardiogram parameters, or blood pressure were documented; ≤1.0%-2.0% of patients had prolonged QT interval corrected for heart rate (HR) using Fridericia formula after placebo or prucalopride treatment, and low HR occurred in ≤6.1% and ≤3.3% of these patients, respectively. In two 24-month observational studies among 2,468 patients, changes in electrocardiogram parameters over time were minor, except at occasional time points when significant changes from baseline were reported for HR or QT interval. In a real-world European CV safety study among 35,087 patients (prucalopride, 5,715; polyethylene glycol 3350 [PEG3350], 29,372), results were consistent for no evidence of increased risk of major adverse CV events among patients treated with prucalopride vs PEG3350 (incidence rate ratio = 0.64; 95% confidence interval 0.36-1.14). Studies to date have not raised concerns regarding the impact of prucalopride treatment on CV parameters.

HLA and red blood cell antigen genotyping in SARS-CoV-2 convalescent plasma donors.

Aim: More data is required regarding the association between HLA allele and red blood cell (RBC) antigen expression in regard to SARS-CoV-2 infection and COVID-19 susceptibility. Methods: ABO, RhD, 37 other RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms in 90 Caucasian convalescent plasma donors. Results: The AB group was significantly increased (1.5×, p = 0.018) and some HLA alleles were found to be significantly overrepresented (HLA-B*44:02, C*05:01, DPB1*04:01, DRB1*04:01 and DRB1*07:01) or underrepresented (A*01:01, B51:01 and DPB1*04:02) in convalescent individuals compared with the local bone marrow registry population. Conclusion: Our study of infection-susceptible but non-hospitalized Caucasian COVID-19 patients contributes to the global understanding of host genetic factors associated with SARS-CoV-2 infection and severity.

Weak D type 42: Antigen density and risk of alloimmunization in the province of Québec.

BACKGROUND AND OBJECTIVES: A high proportion of suspected weak D patients referred to Héma-Québec were genotyped as weak D type 42 (368/2105, 17.5%). These patients are currently considered D with regard to RhD immunoprophylaxis in pregnancy and transfusion. The goal of this study was to retrospectively evaluate the risk of alloimmunization in weak D type 42 patients and to characterize their RhD surface molecule expression on red blood cells (RBCs) in comparison to other weak D types (1, 2 and 3). MATERIALS AND METHODS: A retrospective analysis using the weak D type 42 patients' medical data to verify potential anti-D alloimmunization events was conducted. Quantitative analyses using flow cytometry were also performed on RBCs to quantify the cell surface density of the D antigen. RESULTS: Data on 215 subjects with weak D type 42 were reviewed. None developed immune allo-anti-D; three had definite exposure to D+ red cells and 41 had possible exposure through pregnancy. Flow cytometry analysis showed that weak D types 1, 2, 3 and 42 had relative antigen densities of 2.7%, 2.2%, 8.1% and 3.6%, respectively, with R1R2 red cells referencing 100% density. The estimated antigen density range of weak D type 42 was 819-1104 sites per RBC. CONCLUSION: Our retrospective alloimmunization data analysis and antigen density study establish a basis for the consideration of a weak D type 42 individual as D+. This consideration would allow for a targeted reduction of RhD immunoprophylaxis in pregnancy and the unjustified use of D- units for transfusion.

Impact of Gd-153 scanning line source attenuation correction on downstream invasive testing.

BACKGROUND: Attenuation correction (AC) using hardware and software solutions has been shown to increase the specificity of SPECT MPI by decreasing false positive results and improving prognostic ability. Theoretically this should reduce downstream testing and unnecessary costs. We sought to assess the consequences of the use of Gd-153 scanning line source attenuation correction during SPECT myocardial perfusion imaging (MPI) on downstream invasive testing. METHODS: All patients who underwent a clinically indicated Tc-99m stress SPECT MPI study from 2013 to 2015 at five hospitals (2 with AC and 3 without) were retrospectively reviewed. Patient demographics, results of testing, subsequent coronary angiography within 3 months, and revascularization were recorded. The results of the MPI studies, downstream angiogram utilization, and results of angiography were compared and a propensity matched subgroup analysis was performed. RESULTS: A total of 9968 patients underwent SPECT MPI during the study time period (6106 performed with AC and 3862 without). Out of 3928 patients included in the propensity matched cohort, there was no difference in the proportion of abnormal MPI results between the two groups (31.5% vs 30.4%, P = 0.47), however, more patients underwent coronary angiography within 90 days in the AC group (10.6% vs 8.7%, P = 0.05). There was no significant difference in the proportion of patients with angiographically significant obstructive disease (53.4% vs 56.1%, P = 0.19), however, fewer patients in the AC group with obstructive coronary disease were revascularized (36.1% vs 46.8%, P = 0.04). The findings remained consistent after sub-group analysis in patients without known coronary disease. CONCLUSION: The use of scanning line source AC did not meaningfully influence the rate of abnormal MPI results or downstream invasive testing in this cohort. The clinical utility of scanning line source AC may be limited to facilitating stress-first imaging protocols.

Association between miR-146a and Tumor Necrosis Factor Alpha (TNF-α) in Stable Coronary Artery Disease.

Background and Objectives: Tumor necrosis factor alpha (TNF-α) is proatherogenic and associated with the risk of acute ischemic events, although the mechanisms that regulate TNF-α expression in stable coronary artery disease (SCAD) are not fully understood. We investigated whether metabolic, inflammatory, and epigenetic (microRNA (miRNA)) markers are associated with TNF-α expression in SCAD. Materials and Methods: Patients with SCAD were prospectively recruited and their metabolic and inflammatory profiles were assessed. TNF-α levels were assessed using an enzyme-linked immunosorbent assay. The relative expression of six circulating miRNAs associated with the regulation of inflammation and/or atherosclerosis was determined. Results: Of the 24 included patients with the mean age of 65 (9) years, 88% were male, and 54% were diabetic. The TNF-α levels were (median (interquartile range)) 1.0 (0.7-1.1) pg/mL. The percentage of glycosylated hemoglobin (r = 0.418, p = 0.042), serum triglyceride levels (r = 0.429, p = 0.037), and C-reactive protein levels (r = 0.407, p = 0.048) were positively correlated with TNF-α levels. Of the candidate miRNAs, miR-146a expression levels were negatively correlated with TNF-α levels (as indicated by r = 0.500, p = 0.035 for correlation between delta cycle threshold (ΔCt) miR-146a and TNF-α levels). In multivariate analysis, serum triglyceride levels and miR-146a expression levels were independently associated with TNF-α levels. miR-146 expression levels were not associated with metabolic or other inflammatory parameters and were negatively correlated with the number of coronary vessels with obstructive disease (as indicated by r = 0.556, p = 0.017 for correlation between ΔCt miR-146a and number of diseased vessels). Conclusions: miR-146a expression levels were negatively correlated with TNF-α levels in patients with SCAD, irrespective of other metabolic or inflammatory markers, and with the severity of coronary artery disease. The results add to the knowledge on the role of miR-146a in TNF-α-based inflammation in SCAD and support future research on the potential therapeutic use of miR-146a in such a clinical scenario.

High prevalence of weak D type 42 in a large-scale RHD genotyping program in the province of Quebec (Canada).

BACKGROUND: The determination of the RhD phenotype is crucial to avoid alloimmunization, especially in childbearing women. Following the 2015 recommendation from the Work Group on RHD Genotyping, a large-scale RHD genotyping program was implemented in the province of Quebec (Canada) and offered to women ≤45 years old with a serological weak D or discordant results. Since weak D type 42 was previously shown to be prevalent among French Canadians, genotyping for that variant was also performed. Our aim was to report the prevalence of the weak D alleles in the province of Quebec. STUDY DESIGN AND METHODS: A retrospective study of 2105 women with serological weak D referred to Hema-Quebec's immunohematology reference laboratory (IRL) between June 2016 and May 2020 was conducted. Results from the serological tests performed by the referring hospital were compiled and RHD were genotyped. RESULTS: Most patients presented at least one serological result ≤2+ before being referred to Hema-Quebec. Weak D type 42 was the most prevalent variant, representing 17.5% (368/2105) of all individuals tested. Only 15.3% (323/2105) of patients were weak D type 1, 3.3% (69/2105) were type 2, and 8.6% (180/2105) were type 3. Weak D type 42 is highly expressed in regions with low immigration rate and known for their founder effect. CONCLUSION: Our RHD genotyping program allowed for a better management of weak D. The province of Quebec presents a unique RHD genotype distribution. We confirmed that weak D type 42 is associated with a founder effect found in Caucasian French Canadians.

Circulating miRNAs Are Associated with the Systemic Extent of Atherosclerosis: Novel Observations for miR-27b and miR-146.

The mechanisms that regulate the systemic extent of atherosclerosis are not fully understood. We investigated whether the expression of circulating miRNAs is associated with the extent of stable atherosclerosis to a single territory or multiple territories (polyvascular) and with the severity of atherosclerosis in each territory. Ninety-four participants were prospectively recruited and divided into five age- and sex-matched groups: presenting no atherosclerosis, isolated coronary atherosclerosis, coronary and lower extremity atherosclerosis, coronary and carotid atherosclerosis, and atherosclerosis of the coronary, lower extremity, and carotid territories. The expression of six circulating miRNAs with distinct biological roles was assessed. The expression of miR-27b and miR-146 differed across groups (p < 0.05), showing a decrease in the presence of atherosclerosis, particularly in the three territories. miR-27b and miR-146 expression decreased in association with a higher severity of coronary, lower extremity, and carotid atherosclerosis. Polyvascular atherosclerosis involving the three territories was independently associated with a decreased miR-27b and miR-146 expression. Both miRNAs presented an area under the curve of ≥0.75 for predicting polyvascular atherosclerosis involving the three territories. To conclude, miR-27b and miR-146 were associated with the presence of severe polyvascular atherosclerosis and with the atherosclerosis severity in each territory. Both are potential biomarkers of severe systemic atherosclerosis.

Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity.

Cigarette smoking is a risk factor for the development of peripheral artery disease (PAD), although the proatherosclerotic mediators of cigarette smoking are not entirely known. We explored whether circulating microRNAs (miRNAs) are dysregulated in cigarette smokers and associated with the presence of PAD. Ninety-four participants were recruited, including 58 individuals without and 36 with PAD, 51 never smokers, 28 prior smokers, and 15 active smokers. The relative expression of six circulating miRNAs with distinct biological roles (miR-21, miR-27b, miR-29a, miR-126, miR-146, and miR-218) was assessed. Cigarette smoking was associated with the presence of PAD in multivariate analysis. Active smokers, but not prior smokers, presented miR-27b downregulation and higher leukocyte, neutrophil, and lymphocyte counts; miR-27b expression levels were independently associated with active smoking. Considering the metabolic and/or inflammatory abnormalities induced by cigarette smoking, miR-27b was independently associated with the presence of PAD and downregulated in patients with more extensive PAD. In conclusion, the atheroprotective miR-27b was downregulated in active smokers, but not in prior smokers, and miR-27b expression was independently associated with the presence of PAD. These unreported data suggest that the proatherogenic properties of cigarette smoking are mediated by a downregulation of miR-27b, which may be attenuated by smoking cessation.

Effects of neonatal exposure to methoxychlor on corpus luteum in gilts: A transcriptomic analysis.

This study investigated the effects of neonatal exposure to methoxychlor (MXC), a synthetic organochlorine used as an insecticide with estrogenic, antiestrogenic, and antiandrogenic activities, on luteal function in pigs. Piglets were injected subcutaneously with MXC (20 µg/kg body weight) or corn oil (control) between postnatal Days 1 and 10 (N = 5/group). Corpora lutea from sexually mature gilts were examined for luteal steroid and prostaglandin concentrations and processed for total RNA isolation and subsequent RNA sequencing. Intra-luteal concentrations of androstenedione and prostaglandin E2 were greater, while that of estrone was lower when compared to control. Fifty-three differentially expressed (DE) microRNAS (miRNAs) (p-adjusted <.05 and log2(fold change) ≥.5) and 359 DE genes (p-adjusted <.05 and log2(fold change) ≥1) were identified in luteal tissue in response to neonatal MXC treatment. MXC was found to affect the expression of genes related to lipogenesis, steroidogenesis, membrane transport, immune response, cell signaling and adhesion. These results suggest an earlier onset of structural luteolysis in pigs caused by MXC actions in neonates. Since negative correlation analysis showed the potential interactions of miRNAs with specific messenger RNAs, we propose that these miRNAs are potential mediators of the long-term MXC effect on the CL function in pigs.

Increased prevalence of AB group and FY*A red blood cell antigen in Caucasian SARS-CoV-2 convalescent plasma donors

IntroductionThe SARS-CoV-2 pandemic has put significant additional pressure on healthcare systems throughout the world. The identification of at-risk population beyond age, pre-existing medical conditions and socioeconomic status has been the subject of only a small part of the global COVID-19 research so far. To this day, more data is required regarding the association between HLA allele and red blood cell (RBC) antigens expression in regard to SARS-CoV-2 infection susceptibility and virus clearance capability, and COVID-19 susceptibility, severity, and duration. MethodsThe phenotypes for ABO and RhD, and the genotypes for 37 RBC antigens and HLA-A, B, C, DRB1, DQB1 and DPB1 were determined using high throughput platforms (Luminex and Next-generation Sequencing) in 90 Caucasian convalescent plasma donors. The results were compared to expected reference frequencies, local and international databases, and literature. ResultsThe AB group was significantly increased (1.5x, p=0.018) and a non-significant (2.2x, p=0.030) increase was observed for the FY*A allele frequency in the convalescent cohort (N=90) compared to reference frequencies. Some HLA alleles were found significantly overrepresented (HLA-B*44:02, C*05:01, DPB1*04:01, DRB1*04:01 and DRB1*07:01) or underrepresented (A*01:01, B51:01 and DPB1*04:02) in convalescent individuals compared to the local bone marrow registry population. ConclusionOur study of infection-susceptible but non-hospitalized Caucasian COVID-19 patients contributes to the global understanding of host genetic factors associated with SARS-CoV-2 infection susceptibility and severity of the associated disease.

Heart Rate and Neurological Outcomes in Patients Undergoing Targeted Temperature Management.

INTRODUCTION: There is a paucity of data evaluating the impact of heart rate (HR) during Targeted Temperature Management (TTM) and neurologic outcomes. Current resuscitation guidelines do not specify a HR goal during TTM. We sought to determine the relationship between HR and neurologic outcomes in a single-center registry dataset. METHODS: We retrospectively studied 432 consecutive patients who completed TTM (33°C) after cardiac arrest from 2008 to 2017. We evaluated the relationship between neurologic outcomes and HR during TTM. Pittsburgh Cerebral Performance Categories (CPC) at discharge were used to determine neurological recovery. Statistical analysis included chi square, Student's t-test and Mann-Whitney U. A logistic regression model was created to evaluate the strength of contribution of selected variables on the outcome of interest. RESULTS: Approximately 94,000 HR data points from 432 patients were retrospectively analyzed; the mean HR was 82.17 bpm over the duration of TTM. Favorable neurological outcomes were seen in 160 (37%) patients. The mean HR in the patients with a favorable outcome was lower than the mean HR of those with an unfavorable outcome (79.98 bpm vs 85.67 bpm p < 0.001). Patients with an average HR of 60-91 bpm were 2.4 times more likely to have a favorable neurological outcome compared to than HR's < 60 or > 91 (odds ratio [OR] = 2.36, 95% confidence interval [CI] 1.61-3.46, p < 0.001). Specifically, mean HR's in the 73-82 bpm range had the greatest rate of favorable outcomes (OR 3.56, 95% CI 1.95-6.50), p < 0.001. Administration of epinephrine, a history of diabetes mellitus and hypertension all were associated with worse neurological outcomes independent of HR. CONCLUSION: During TTM, mean HRs between 60-91 showed a positive association with favorable outcomes. It is unclear whether a specific HR should be targeted during TTM or if heart rates between 60-91 bpm might be a sign of less neurological damage.

An Observation of Racial and Gender Disparities in Congestive Heart Failure Admissions Using the National Inpatient Sample.

Background Congestive heart failure (CHF) is a frequent cause of inpatient admissions in the United States. The purpose of this study was to analyze the racial and gender disparities that occur in CHF admissions and determine the impact of these disparities on medical expenditure. Methods We analyzed the National Inpatient Sample (NIS) database from 2009 to 2014 for patients with a primary discharge diagnosis of CHF, and further stratified the cohort on the basis of race and sex. Multivariate analysis was performed to identify the association between CHF and total charges along with other variables such as mortality, length of stay (LOS), and number of procedures. Results There were a total of 5,491,050 admissions with a primary diagnosis of CHF from 977,850 in 2009 to 901,425 in 2014. Females accounted for 49.7%. Total charges for CHF admission were highest in Asians at an average cost of $59,668. African Americans had the lowest mortality rate at 1.75%, however, they also had an average age of admission of 63.47 years, compared to Caucasian at 76.76 (p<0.05). Total charges for males were $42,920 and $36,744 for females (p <0.05). Males also had more procedures at 1.16 vs 0.98 for females (p <0.05). Elixhauser mortality score was higher in males than females at 5.95 vs 5.42 (p <0.05). Conclusion Healthcare disparities exist in CHF admissions in both contexts of race and gender. Further studies are required to pinpoint the source of these differences not only to address mortality but also expenditure costs.