is a diploid fungus that is a frequent cause of mucosal and systemic infections in humans. This species exhibits an unusual parasexual cycle in which mating produces tetraploid cells that undergo a nonmeiotic program of concerted chromosome loss to return to a diploid or aneuploid state. In this work, we used a multipronged approach to examine the capacity of parasex to generate diversity in First, we compared the phenotypic properties of 32 genotyped progeny and observed wide-ranging differences in fitness, filamentation, biofilm formation, and virulence. Strikingly, one parasexual isolate displayed increased virulence relative to parental strains using a model of infection, establishing that parasex has the potential to enhance pathogenic traits. Next, we examined parasexual progeny derived from homothallic, same-sex mating events, and reveal that parasex can generate diversity from identical parental strains. Finally, we generated pools of parasexual progeny and examined resistance of these pools to environmental stresses. Parasexual progeny were generally less fit than control strains across most test conditions, but showed an increased ability to grow in the presence of the antifungal drug fluconazole (FL). FL-resistant progeny were aneuploid isolates, often being diploid strains trisomic for both Chr3 and Chr6. Passaging of these aneuploid strains frequently led to loss of the supernumerary chromosomes and a concomitant decrease in drug resistance. These experiments establish that parasex generates extensive phenotypic diversity, and that this process has important consequences for both virulence and drug resistance in populations.

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Objective Disparities in health and health care access are widely prevalent. However, disparities among patients with chronic rhinosinusitis (CRS) are poorly understood. We investigated if CRS severity at presentation according to socioeconomic factors. Study Design Cross-sectional study. Setting Tertiary rhinology center. Subjects and Methods Three hundred prospectively recruited patients presenting with CRS were included. Outcome variables included CRS symptomatology, as reflected by the 22-item Sinonasal Outcome Test (SNOT-22); general health status, as reflected by the EuroQol 5-dimensional visual analog scale (EQ-5D VAS); and CRS-related antibiotic and systemic corticosteroid use. Race/ethnicity, zip code income bracket, education level, and insurance status were used as predictor variables. Regression, controlling for clinical and demographic characteristics, was used to determine associations between predictor and outcome variables. Results Mean SNOT-22 score was 33.8 (SD, 23.2), and mean EQ-5D VAS score was 74.2 (SD, 18.9). On multivariable analysis, presenting SNOT-22 and EQ-5D VAS scores were not associated with nonwhite patient race/ethnicity ( P = .634 and P = .866), education ( P = .106 and P = .586), or the percentage of households in zip code with incomes <$50,000 per year ( P = .917 and P = .979, respectively). SNOT-22 scores did not differ by insurance type, but patients receiving Medicare reported worse general health status. Use of oral antibiotics or oral steroids for CRS was not associated with predictor variables. Conclusion Patients with CRS presented to a tertiary rhinology center with similar metrics for CRS severity and pre-presentation medical management regardless of race/ethnicity, education status, or zip code income level. Patients with Medicare had worse general health status. Further research should investigate potential disparities in diagnosis of CRS, specialist referral, and treatment outcomes.

Since its inception in 2002, Model for End-Stage Liver Disease (MELD)based allocation has undergone a series of revisions, especially with respect to exception points. Hepatocellular carcinoma (HCC) is the most common indication for MELD exceptions, and as a result of higher transplant proportions and lower waitlist mortality, a series of policy changes have been implemented to deprioritize HCC transplants. We examined the impact of HCC exception policy changes on transplant and waitlist mortality rates. We evaluated Organ Procurement and Transplantation Network/United Network for Organ Sharing data on adult patients from January 1, 2005, to June 4, 2021, focusing on waitlist mortality and deceased donor liver transplantation (DDLT) proportions. The data were divided into four policy eras: (1) MELD 22 points at waitlisting with an increase in points every 3 months (i.e., elevator) (January 2005-October 2015), (2) delay and cap at MELD 34 points (October 2015-May 2019), (3) delay and fixed exceptions based on donor service area (DSA) median MELD at transplantation minus three (MMaT-3; May 2019-February 2020), and (4) delay and fixed exceptions based on the MMaT-3 of centers within 250 nautical miles (i.e., acuity circles; February 2020-June 2021). We evaluated (a) changes in the proportions of DDLTs for patients with HCC exceptions within each era nationally and by DSA and (b) waitlist mortality in the three recent policy eras, focusing on mortality in the 6 months after the 6-month delay period. The percentage of adult DDLT with HCC exceptions decreased through the four eras: 22.9% (n = 14,049), 17.9% (n = 4598), 14.3% (n = 851), and 12.4% (n = 1425), respectively. Of the 51 DSAs analyzed, the annual percent change in DDLTs for patients with HCC exceptions was negative (i.e., decreased) in 47 (92.2%). Waitlist mortality remained stable. All HCC policy implementations led to a decrease in the SEE EDITORIAL ON PAGE 1821How to cite this article: Shah RH, Chyou D, Goldberg DS. Impact of major hepatocellular carcinoma policy changes on liver transplantation for hepatocellular carcinoma in the United States.