BackgroundHuman noroviruses (NoVs) are the primary cause of acute gastroenteritis and are characterized by antigenic variation between genogroups and genotypes and antigenic drift of strains within the predominant GII.4 genotype. In the context of this diversity, an effective NoV vaccine must elicit broadly protective immunity. We used an antibody (Ab) binding blockade assay to measure the potential cross-strain protection provided by a multivalent NoV virus-like particle (VLP) candidate vaccine in human volunteers.Methods and FindingsSera from ten human volunteers immunized with a multivalent NoV VLP vaccine (genotypes GI.1/GII.4) were analyzed for IgG and Ab blockade of VLP interaction with carbohydrate ligand, a potential correlate of protective immunity to NoV infection and illness. Immunization resulted in rapid rises in IgG and blockade Ab titers against both vaccine components and additional VLPs representing diverse strains and genotypes not represented in the vaccine. Importantly, vaccination induced blockade Ab to two novel GII.4 strains not in circulation at the time of vaccination or sample collection. GII.4 cross-reactive blockade Ab titers were more potent than responses against non-GII.4 VLPs, suggesting that previous exposure history to this dominant circulating genotype may impact the vaccine Ab response. Further, antigenic cartography indicated that vaccination preferentially activated preexisting Ab responses to epitopes associated with GII.4.1997. Study interpretations may be limited by the relevance of the surrogate neutralization assay and the number of immunized participants evaluated.ConclusionsVaccination with a multivalent NoV VLP vaccine induces a broadly blocking Ab response to multiple epitopes within vaccine and non-vaccine NoV strains and to novel antigenic variants not yet circulating at the time of vaccination. These data reveal new information about complex NoV immune responses to both natural exposure and to vaccination, and support the potential feasibility of an efficacious multivalent NoV VLP vaccine for future use in human populations.Trial RegistrationClinicalTrials.gov NCT01168401

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Background Racial and ethnic disparities contribute to differences in access and outcomes for patients undergoing heart transplantation. We evaluated contemporary outcomes for heart transplantation stratified by race and ethnicity as well as the new 2018 allocation system. Methods and Results Adult heart recipients from 2011 to 2020 were identified in the United Network for Organ Sharing database and stratified into 3 groups: Black, Hispanic, and White. We analyzed recipient and donor characteristics, and outcomes. Among 32 353 patients (25% Black, 9% Hispanic, 66% White), Black and Hispanic patients were younger, more likely to be women and have diabetes mellitus or renal disease (all, P <0.05). Over the study period, the proportion of Black and Hispanic patients listed for transplant increased: 21.7% to 28.2% ( P =0.003) and 7.7% to 9.0% ( P =0.002), respectively. Compared with White patients, Black patients were less likely to undergo transplantation (adjusted hazard ratio [aHR], 0.87; CI, 0.84–0.90; P <0.001), but had a higher risk of post‐transplant death (aHR, 1.14; CI, 1.04–1.24; P =0.004). There were no differences in transplantation likelihood or post‐transplant mortality between Hispanic and White patients. Following the allocation system change, transplantation rates increased for all groups ( P <0.05). However, Black patients still had a lower likelihood of transplantation than White patients (aHR, 0.90; CI, 0.79–0.99; P =0.024). Conclusions Although the proportion of Black and Hispanic patients listed for cardiac transplantation have increased, significant disparities remain. Compared with White patients, Black patients were less likely to be transplanted, even with the new allocation system, and had a higher risk of post‐transplantation death.

OBJECTIVES The effectiveness of proximal thoracic aortic aneurysm (TAA) surgery in preventing acute aortic syndromes, such as dissection and rupture, is unknown at the populational level. This study evaluated trends in acute aortic syndrome operation incidence relative to proximal aortic surgical volume in the USA. METHODS A retrospective analysis of the National Inpatient Sample in 2005–2014 was performed. Acute aortic syndrome and TAA were identified with International Classification of Diseases, 9th edition diagnosis codes. Proximal aortic surgery was defined as the diagnosis of acute aortic syndrome or TAA with an aortic procedure and either cardioplegia, cardiopulmonary bypass or other cardiac operation. Annual rates of acute aortic syndrome surgery and proximal thoracic aneurysm surgery were adjusted for US population. Trends were evaluated using linear regression. RESULTS We identified 38 442 operations for acute aortic diagnoses and 74 953 operations for TAAs. Case volume for acute aortic syndromes increased from 0.93 to 1.63 per 100 000 (P = 0.001), and aneurysm surgery increased from 1.75 to 3.19 per 100 000 (P &lt; 0.001). Patient and hospital characteristics differed between acute aortic and aneurysm operations, with black patients being most notably underrepresented in the aneurysm population (4.9% vs 17.0%, P &lt; 0.001). CONCLUSIONS Acute aortic syndrome operative volume increased from 2005 to 2014 despite increasing rates of proximal aortic aneurysm surgery. Patient characteristic discrepancies were observed between the 2 groups of hospitalizations, highlighting the need for continued efforts to minimize sociodemographic disparities.