Birth Prevalence of Sickle Cell Disease and County-Level Social Vulnerability - Sickle Cell Data Collection Program, 11 States, 2016-2020.

Sickle cell disease (SCD) remains a public health priority in the United States because of its association with complex health needs, reduced life expectancy, lifelong disabilities, and high cost of care. A cross-sectional analysis was conducted to calculate the crude and race-specific birth prevalence for SCD using state newborn screening program records during 2016-2020 from 11 Sickle Cell Data Collection program states. The percentage distribution of birth mother residence within Social Vulnerability Index quartiles was derived. Among 3,305 newborns with confirmed SCD (including 57% with homozygous hemoglobin S or sickle ß-null thalassemia across 11 states, 90% of whom were Black or African American [Black], and 4% of whom were Hispanic or Latino), the crude SCD birth prevalence was 4.83 per 10,000 (one in every 2,070) live births and 28.54 per 10,000 (one in every 350) non-Hispanic Black newborns. Approximately two thirds (67%) of mothers of newborns with SCD lived in counties with high or very high levels of social vulnerability; most mothers lived in counties with high or very high levels of vulnerability for racial and ethnic minority status (89%) and housing type and transportation (64%) themes. These findings can guide public health, health care systems, and community program planning and implementation that address social determinants of health for infants with SCD. Implementation of tailored interventions, including increasing access to transportation, improving housing, and advancing equity in high vulnerability areas, could facilitate care and improve health outcomes for children with SCD.

Evaluating threshold for donor fraction cell-free DNA using clinically available assay for rejection in pediatric and adult heart transplantation.

BACKGROUND: The aims of the study were to assess the performance of a clinically available cell-free DNA (cfDNA) assay in a large cohort of pediatric and adult heart transplant recipients and to evaluate performance at specific cut points in detection of rejection. METHODS: Observational, non-interventional, prospective study enrolled pediatric and adult heart transplant recipients from seven centers. Biopsy-associated plasma samples were used for cfDNA measurements. Pre-determined cut points were tested for analytic performance. RESULTS: A total of 487 samples from 160 subjects were used for the analysis. There were significant differences for df-cfDNA values between rejection [0.21% (IQR 0.12-0.69)] and healthy samples [0.05% (IQR 0.01-0.14), p < .0001]. The pediatric rejection group had a median df-cfDNA value of 0.93% (IQR 0.28-2.84) compared to 0.09% (IQR 0.04-0.23) for healthy samples, p = .005. Overall negative predictive value was 0.94 while it was 0.99 for pediatric patients. Cut points of 0.13% and 0.15% were tested for various types of rejection profiles and were appropriate to rule out rejection. CONCLUSION: The study suggests that pediatric patients with rejection show higher levels of circulating df-cfDNA compared to adults and supports the specific cut points for clinical use in pediatric and adult patients with overall acceptable performance.

Acute care utilization among individuals with sickle cell disease and related cardiopulmonary and renal complications.

Cardiopulmonary and renal end organ (CPR) complications are associated with early mortality among individuals with sickle cell disease (SCD). However, there is limited knowledge regarding acute care utilization for individuals with SCD and CPR complications. Our objective was to determine the prevalence of CPR complications in a state specific SCD population and compare acute care utilization among individuals with and without CPR complications. We leveraged 2017-2020 data for individuals with SCD identified by the Sickle Cell Data Collection program in Wisconsin. The prevalence of CPR complications is determined for distinct age groups. Generalized linear models adjusted for age compared the rate of acute care visits/person/year among individuals who had cardiopulmonary only, renal only, both cardiopulmonary and renal, or no CPR complications. There were 1378 individuals with SCD, 52% females, mean (SD) age 28.3 (18.5) years; 48% had at least one CPR complication during the study period. The prevalence of CPR complications was higher in adults (69%) compared to pediatric (15%) and transition (51%) groups. Individuals with SCD and cardiopulmonary complications had higher acute visit rates than those without CPR complications (5.4 (IQR 5.0-5.8) vs 2.4 (IQR 2.1-2.5), p <0.001)). Acute care visit rates were similar between individuals with SCD who had renal only complications and no CPR complications (2.7 (IQR 2.5-3.0) vs 2.4 (2.1-2.5), p = 0.24). The high acute care visit rates, especially for those with cardiopulmonary complications, warrant further investigation to understand risk factors for CPR complications, the underlying reasons and identify effective disease management strategies.

Corrigendum: Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8+ T cell repertoire response to influenza vaccination.

[This corrects the article DOI: 10.3389/fimmu.2024.1306490.].

Patients with juvenile idiopathic arthritis have decreased clonal diversity in the CD8+ T cell repertoire response to influenza vaccination.

Recurrent exposures to a pathogenic antigen remodel the CD8+ T cell compartment and generate a functional memory repertoire that is polyclonal and complex. At the clonotype level, the response to the conserved influenza antigen, M158-66 has been well characterized in healthy individuals, but not in patients receiving immunosuppressive therapy or with aberrant immunity, such as those with juvenile idiopathic arthritis (JIA). Here we show that patients with JIA have a reduced number of M158-66 specific RS/RA clonotypes, indicating decreased clonal richness and, as a result, have lower repertoire diversity. By using a rank-frequency approach to analyze the distribution of the repertoire, we found several characteristics of the JIA T cell repertoire to be akin to repertoires seen in healthy adults, including an amplified RS/RA-specific antigen response, representing greater clonal unevenness. Unlike mature repertoires, however, there is more fluctuation in clonotype distribution, less clonotype stability, and more variable IFNy response of the M158-66 specific RS/RA clonotypes in JIA. This indicates that functional clonal expansion is altered in patients with JIA on immunosuppressive therapies. We propose that the response to the influenza M158-66 epitope described here is a general phenomenon for JIA patients receiving immunosuppressive therapy, and that the changes in clonal richness and unevenness indicate a retarded and uneven generation of a mature immune response.

The Burden of Neonatal Abstinence Syndrome, Opioids, and COVID-19 in Wisconsin.

INTRODUCTION: Wisconsin experienced overlapping and accelerating epidemics of opioid use and COVID-19 after March 2020. We hypothesized that Wisconsin neonatal abstinence syndrome rates increased after March 2020 alongside other markers of opioid burden. METHODS: Retrospective cohort analysis examined deidentified Wisconsin census, birth certificate, death certificate, hospital discharge, Prescription Drug Monitoring Program, emergency medical service run, and COVID-19 diagnosis records spanning January 1, 2019, through December 31, 2021. January 2019 through March 2020 was considered before the onset of COVID-19 (pre); April 2020 through December 2021 was considered post-onset of COVID-19 (post). Wisconsin Department of Health Services guidelines defined 5 Wisconsin regions. Rates pre- to post-onset were compared with P values < 0.05 considered statistically significant. RESULTS: Of 1362 patients, 83.3% completed a COVID-19 vaccination series. Younger patients had increased odds of not completing a COVID-19 vaccination series (mean [SD] 46.7 [14.7] vs 54.3 [15.8]; OR 1.03; 95% CI, 1.02-1.04; P < 0.001). Those who identified as non-White (1.88; 95% CI, 1.16-3.04; P = 0.010) or current smoker (1.85, 95% CI, 1.85-2.79; P = 0.004) had increased odds of not completing a COVID-19 vaccination series. Those who resided in rural ZIP codes (1.81; 95% CI, 1.35-2.43; P < 0.001), had not received a 2019-2020 influenza vaccine (5.13; 95% CI, 3.79-6.96; P < 0.001), or had lower comorbidity scores (2.95; 95% CI, 1.98-4.41; P < 0.001) had higher odds of not completing a COVID-19 vaccination series. CONCLUSIONS: Opioid-associated morbidity and mortality increased in Wisconsin during the study period, including among females age 15 to 44 years. Despite increased opioid burden, neonatal abstinence syndrome incidence decreased in the Southeastern Region. Ongoing neonatal abstinence syndrome and opioid analysis may benefit from region-based contextualization.