Impaired Cellular and Antibody immunity after COVID-19 in Chronically Immunosuppressed Transplant Recipients.

Assessment of cellular immunity to the SARS-CoV-2 coronavirus is of great interest in chronically immunosuppressed transplant recipients (Tr), who are predisposed to infections and vaccination failures. We evaluated CD154-expressing T-cells induced by spike (S) antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed Tr who were sampled pre-pandemic, compared with healthy NT (p=0.02), b) lower in Tr COVID-19 patients compared with healthy Tr (p<0.0001) and were accompanied by lower S-reactive B-cell frequencies (p<0.05), c) lower in Tr with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr. Among Tr with COVID-19, cytomegalovirus co-infection occurred in 34%; further, incidence of anti-receptor-binding-domain IgG (p=0.011) was lower compared with NT COVID-19 patients. Healthy unexposed Tr exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 impairs anti-S T-cell and antibody and predisposes to CMV co-infection in transplant recipients.

Comparative analysis of all-terrain vehicles, motorcycle and automobile-related trauma in a rural border community of the USA.

INTRODUCTION: There is widespread use of all-terrain vehicles (ATVs) in the USA for both work-related and recreational activities. In this study, we aimed to determine the difference in injury severity, Glasgow Coma scales and length of stay between ATV-related injuries and injuries sustained from motorcycles (MOTOs) and automobiles (AUTOs). METHODS: We retrospectively analysed ATV, MOTO and AUTO injuries from a Level 2 Trauma Center between 01 January 2015 and 31 August 2020. Proportional odds regression analyses, as well as multivariable regression models, were used to analyse the data. RESULTS: There were significantly more male and paediatric patients that suffered ATV-related injuries compared with MOTO or AUTO injuries. Victims of ATV-related injuries were also more likely to have open fractures. Paediatric patients were less likely to sustain an injury from either AUTO or MOTO accidents compared with ATV accidents. Patients with no drug use during injury and those who used protective equipment such as seat belts and child seats were significantly associated with lower Injury Severity Scores and higher Glasgow Coma Scale scores, indicating less severe injuries. DISCUSSION: Paediatric patients are very likely to suffer sequela and long-term disability due to the severity of ATV-related injuries. Public awareness campaigns to educate our population, especially our youth, about the danger of ATV use are highly needed.

Impact of accountable care organizations on acute cholecystitis outcomes in the Rio Grande Valley.

BACKGROUND: Accountable care organizations through the Affordable Care Act are to improve Medicare beneficiaries' health while reducing costs. We hypothesize that this model may shift care, disease burden, and costs to nonaffiliated hospital facilities in patients with acute cholecystitis. METHODS: A retrospective difference-in-differences analysis was performed to compare severity, postoperative complications, diagnostic modality, length of stay, and costs in patients with acute cholecystitis from a post-accountable care organization implementation period (January 2014 through December 2015) to a pre-accountable care organization period (January 2011 through December 2012). RESULTS: Analysis of 400 patients with acute cholecystitis revealed the post-accountable care organization patients had significantly (P < .0001) higher disease severity (14.4% vs 8.4%), emergency admissions (90.1 vs 74.2%), computed tomography scans (55.5% vs 27.8%), prolonged length of stay (5.2 vs 3.9 days), and a 30% (P < .0003) increase in total costs. CONCLUSION: These data are consistent with the hypothesis that the introduction of accountable care organizations resulted in a higher morbidity, more emergency admissions, more extensive management, a prolonged length of stay, and increased cost in patients with acute cholecystitis. These data support the position that accountable care organizations may shift costs from the primary care setting to nonaffiliated accountable care organization hospitals, provide a lesser level of care, and thus potentially failing their primary mandates.

Immune Response in Severe and Non-Severe Coronavirus Disease 2019 (COVID-19) Infection: A Mechanistic Landscape.

The mechanisms underlying the immune remodeling and severity response in coronavirus disease 2019 (COVID-19) are yet to be fully elucidated. Our comprehensive integrative analyses of single-cell RNA sequencing (scRNAseq) data from four published studies, in patients with mild/moderate and severe infections, indicate a robust expansion and mobilization of the innate immune response and highlight mechanisms by which low-density neutrophils and megakaryocytes play a crucial role in the cross talk between lymphoid and myeloid lineages. We also document a marked reduction of several lymphoid cell types, particularly natural killer cells, mucosal-associated invariant T (MAIT) cells, and gamma-delta T (γδT) cells, and a robust expansion and extensive heterogeneity within plasmablasts, especially in severe COVID-19 patients. We confirm the changes in cellular abundances for certain immune cell types within a new patient cohort. While the cellular heterogeneity in COVID-19 extends across cells in both lineages, we consistently observe certain subsets respond more potently to interferon type I (IFN-I) and display increased cellular abundances across the spectrum of severity, as compared with healthy subjects. However, we identify these expanded subsets to have a more muted response to IFN-I within severe disease compared to non-severe disease. Our analyses further highlight an increased aggregation potential of the myeloid subsets, particularly monocytes, in COVID-19. Finally, we provide detailed mechanistic insights into the interaction between lymphoid and myeloid lineages, which contributes to the multisystemic phenotype of COVID-19, distinguishing severe from non-severe responses.

An Effective Model for Establishing a Collaborative for the Treatment of COVID-19 in the Rio Grande Valley.

The DHR Health Institute for Research and Development spearheaded a region-wide initiative to establish a Rio Grande Valley (RGV) Collaborative for early diagnosis, prevention, and treatment of COVID-19. The Collaborative was established on March 23, 2020, to conserve resources and provide the best clinical care in the face of an imminent regional health crisis in an underserved community, predominantly of Hispanic heritage with some of the highest rates of chronic diseases in the United States. The use of plasma obtained from convalesced SARS-CoV-2-infected donors was approved by the FDA and the RGV Collaborative took this as its initial challenge. To date, over 2,200 patients with severe and life-threatening COVID-19 have successfully received transfusion of convalescent plasma in various health care facilities in the RGV. The RGV Collaborative is a unique model for creating an effective public health strategy for the delivery of quality clinical care, especially in underserved communities.

Impaired T-cell and antibody immunity after COVID-19 infection in chronically immunosuppressed transplant recipients.

Assessment of T-cell immunity to the COVID-19 coronavirus requires reliable assays and is of great interest, given the uncertain longevity of the antibody response. Some recent reports have used immunodominant spike (S) antigenic peptides and anti-CD28 co-stimulation in varying combinations to assess T-cell immunity to SARS-CoV-2. These assays may cause T-cell hyperstimulation and could overestimate antiviral immunity in chronically immunosuppressed transplant recipients, who are predisposed to infections and vaccination failures. Here, we evaluate CD154-expressing T-cells induced by unselected S antigenic peptides in 204 subjects-103 COVID-19 patients and 101 healthy unexposed subjects. Subjects included 72 transplanted and 130 non-transplanted subjects. S-reactive CD154+T-cells co-express and can thus substitute for IFNγ (n=3). Assay reproducibility in a variety of conditions was acceptable with coefficient of variation of 2-10.6%. S-reactive CD154+T-cell frequencies were a) higher in 42 healthy unexposed transplant recipients who were sampled pre-pandemic, compared with 59 healthy non-transplanted subjects (p=0.02), b) lower in Tr COVID-19 patients compared with healthy transplant patients (p<0.0001), c) lower in Tr patients with severe COVID-19 (p<0.0001), or COVID-19 requiring hospitalization (p<0.05), compared with healthy Tr recipients. S-reactive T-cells were not significantly different between the various COVID-19 disease categories in NT recipients. Among transplant recipients with COVID-19, cytomegalovirus co-infection occurred in 34%; further, CMV-specific T-cells (p<0.001) and incidence of anti-receptor-binding-domain IgG (p=0.011) were lower compared with non-transplanted COVID-19 patients. Healthy unexposed transplant recipients exhibit pre-existing T-cell immunity to SARS-CoV-2. COVID-19 infection leads to impaired T-cell and antibody responses to SARS-CoV-2 and increased risk of CMV co-infection in transplant recipients.

Diabetes and Its Effect on Abdominal Aortic Aneurysm Growth Rate in Hispanic Patients.

BACKGROUND: The growth rate of abdominal aortic aneurysms (AAA) can vary depending on age, baseline diameter, blood pressure, race, and history of smoking. Paradoxically, previous studies show evidence of a protective effect of diabetes on the rate of AAA expansion despite its well-established role in the morbidity and mortality of cardiovascular disease. This study aims to investigate the impact diabetes plays on AAA growth within a Hispanic population. METHODS: Data were collected from patients who were predominantly Mexican-American at a single hospital site. Baseline and follow-up measures for AAA diameter were obtained from serial imaging studies. Demographics, medical history, the presence of type 2 diabetes, and medication use were extracted from hospital records. Linear mixed-effects growth models were used to calculate the overall AAA growth rate and to assess the difference in AAA growth rate between demographics, comorbidities, and medication use. RESULTS: The study comprised 201 patients (70.4% male) with a mean baseline age of 79.1 years, of whom 43.2% were diabetic. The average monthly AAA growth rate across all study participants was 0.15 mm (SE = 0.02 mm). Independently, the average AAA expansion rate for the diabetic and nondiabetic groups was 0.07 mm (SE = 0.04 mm) and 0.21 mm (SE = 0.03 mm) per month, respectively. This demonstrates a 65% lower linear AAA expansion rate per month in patients with diabetes. CONCLUSIONS: This study confirms a difference of AAA physiology between diabetics and nondiabetics in the Hispanic community. The observed significant difference in AAA growth rate may be a combination of factors associated with race/ethnicity, prevalence of diabetes mellitus, and low compliance with diabetic control exhibited in the Mexican-American population.

The effect of Hispanic ethnicity on surgical outcomes: An analysis of the NSQIP database.

BACKGROUND: Existing literature has shown racial/ethnic disparities between white and black surgical populations, however, surgical outcomes for Hispanic patients are limited in both scope and quantity. METHODS: Data from the American College of Surgeons National Surgical Quality Improvement Program from 2007 to 2015 was used to analyze surgical outcomes in approximately 3.5 million patients. RESULTS: Overall, Hispanics experienced lower odds of mortality compared to non-Hispanic White, non-Hispanic Black, and non-Hispanic American Indian or Alaska Native patients (all P < 0.0001). No difference was found in mortality odds between Hispanics and non-Hispanic Asian or Native Hawaiian patients. Hispanics experienced minimal disparities in complications as compared to non-Hispanic White and non-Hispanic Black but had a higher rate of select complications when compared to Non-Hispanic Asian, Native Hawaiian, or Pacific Islander. CONCLUSION: Hispanics, in general, had lower odds of 30-day postoperative mortality and major morbidity compared to most of the races/ethnicities included in the ACS NSQIP database.

Prevalence of Aflatoxin-Associated TP53R249S Mutation in Hepatocellular Carcinoma in Hispanics in South Texas.

We aimed to determine whether aflatoxin dietary exposure plays a role in the high incidence of hepatocellular carcinoma (HCC) observed among Hispanics in South Texas. We measured TP53R249S somatic mutation, hallmark of aflatoxin etiology in HCC, using droplet digital PCR and RFLP. TP53R249S mutation was detected in 3 of 41 HCC tumors from Hispanics in South Texas (7.3%). We also measured TP53R249S mutation in plasma cell-free DNA (cfDNA) from 218 HCC patients and 96 Hispanic subjects with advanced fibrosis or cirrhosis, from South Texas. The mutation was detected only in Hispanic and Asian HCC patients, and patients harboring TP53R249S mutation were significantly younger and had a shorter overall survival. The mutation was not detected in any Hispanic subject with advanced fibrosis or cirrhosis. Genes involved in cell-cycle control of chromosomal replication and in BRCA1-dependent DNA damage response were enriched in HCCs with TP53R249S mutation. The E2F1 family members, E2F1 and E2F4, were identified as upstream regulators. TP53R249S mutation was detected in 5.7% to 7.3% of Hispanics with HCC in South Texas. This mutation was associated with a younger age and worse prognosis. TP53R249S was however not detected in Hispanics in South Texas with cirrhosis or advanced fibrosis. Aflatoxin exposure may contribute to a small number of HCCs in Hispanics in South Texas, but the detection of TP53R249S mutation in plasma cfDNA is not a promising biomarker of risk assessment for HCC in subjects with cirrhosis or advanced fibrosis in this population. Cancer Prev Res; 11(2); 103-12. ©2017 AACR.

Pediatric Nonalcoholic Fatty Liver Disease: the Rise of a Lethal Disease Among Mexican American Hispanic Children.

Hispanic children of Mexican origin have a high incidence of NAFLD. Susceptibility has been linked to a combination of factors including an increasing epidemic of obesity in children and adolescents, an allele substitution in the PNPLA3 gene that reduces hepatic lipid catabolism, and an altered microbiome that may increase hepatic endotoxins. The combination of NAFLD and portal vein toxins secondary to an indigenous gut microbiome appear to lead to the early occurrence of NASH, which progresses to cirrhosis and early hepatocellular carcinoma. Early detection and treatment of hepatic changes are needed. Given the success of gastric bypass in reducing body weight, modifying the gut microbiome, and improving NAFLD/NASH in adults, a trial of gastric bypass in predisposed pediatric candidates should be undertaken.