Factors Associated With Geographic Disparities in Gastrointestinal Cancer Mortality in the United States.

BACKGROUND & AIMS: Significant geographic variability in gastrointestinal (GI) cancer-related death has been reported in the United States. We aimed to evaluate both modifiable and nonmodifiable factors associated with intercounty differences in mortality due to GI cancer. METHODS: Data from the Centers for Disease Control and Prevention's Wide-ranging Online Data for Epidemiologic Research platform were used to calculate county-level mortality from esophageal, gastric, pancreatic, and colorectal cancers. Multivariable linear regression models were fit to adjust for county-level covariables, considering both patient (eg, sex, race, obesity, diabetes, alcohol, and smoking) and structural factors (eg, specialist density, poverty, insurance prevalence, and colon cancer screening prevalence). Intercounty variability in GI cancer-related mortality explained by these covariables was expressed as the multivariable model R2. RESULTS: There were significant geographic disparities in GI cancer-related county-level mortality across the US from 2010-2019 with the ratio of mortality between 90th and 10th percentile counties ranging from 1.5 (pancreatic) to 2.1 (gastric cancer). Counties with the highest 5% mortality rates for gastric, pancreatic, and colorectal cancer were primarily in the Southeastern United States. Multivariable models explained 43%, 61%, 14%, and 39% of the intercounty variability in mortality rates for esophageal, gastric, pancreatic, and colorectal cancer, respectively. Cigarette smoking and rural residence (independent of specialist density) were most strongly associated with GI cancer-related mortality. CONCLUSIONS: Both patient and structural factors contribute to significant geographic differences in mortality from GI cancers. Our findings support continued public health efforts to reduce smoking use and improve care for rural patients, which may contribute to a reduction in disparities in GI cancer-related death.

Impact of major hepatocellular carcinoma policy changes on liver transplantation for hepatocellular carcinoma in the United States.

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 percentage of transplants for HCC without an increase in waitlist mortality. The impact is not uniform across geographic areas.

Demographics, distance to gastrointestinal specialists, and social deprivation are associated with advanced stage of gastrointestinal cancer diagnosis.

Background: Gastrointestinal (GI) luminal cancers can be detected at early stages by endoscopic procedures. Place-based factors, such as social deprivation and distance to specialist care, are under-investigated with regard to the stage of diagnosis. Methods: This was a retrospective cohort study among persons ≥18 years of age in the Florida Cancer Data System, a population-based cancer incidence registry. We included persons diagnosed with esophageal cancer, gastric canceror colorectal cancer, with at least 1 measure of geographic location during the period January 1, 1981, to December 31, 2016. Multivariate multinomial logistic regression was used to identify factors associated with the stage of diagnosis, including social deprivation and proximity to GI care. Results: Among 379,054 persons, the median age was 71 years, and 54% were male. Distant stage disease was significantly less likely than local stage in those of non-Hispanic/Latino ethnicity (odds ratio [OR] 0.92, 95% confidence interval [CI] 0.89-0.94, P<0.001). Distant disease was more likely in African Americans (OR 1.30, 95%CI 1.26-1.34) and Asians (OR 1.41, 95%CI 1.27-1.56, P<0.001), with each 5-min increase in travel time to specialists, (OR 1.02, 95%CI 1.01-1.02, P<0.001), and with each 10-point increase in Social Deprivation Index (OR 1.01, 95%CI 1.01-1.02, P<0.001). Conclusions: A greater distance from care and living in areas with increased deprivation are associated with an advanced stage of diagnosis and should be recipients of policy-driven efforts to improve access to care. That the strongest risk factors include minority race and ethnicity underlines the complexity of healthcare disparities.

30-Day Readmissions and Coordination of Care Following Endoscopic Transsphenoidal Pituitary Surgery: Experience with 409 Patients.

Objective The study aimed to (1) quantify readmission rates and common causes of readmission following endoscopic transsphenoidal pituitary surgery (ETPS); (2) identify risk factors that may predict readmission within 30 days; (3) assess postoperative care coordination with endocrinology follow-up; and (4) identify patients for whom targeted interventions may reduce 30-day readmissions. Methods Retrospective quality improvement review of patients with pituitary adenoma who underwent ETPS from December 2010 to 2018 at a single tertiary care center. Results A total of 409 patients were included in the study, of which 57 (13.9%) were readmitted within 30 days. Hyponatremia was the most common cause of readmission (4.2%) followed by pain/headache (3.9%), cerebrospinal fluid leak (3.4%), epistaxis (2.7%), hypernatremia (1.2%), and adrenal insufficiency (1.2%). Patients with hyponatremia were readmitted significantly earlier than other causes (4.3 ± 2.2 vs. 10.6 ± 10.9 days from discharge, p = 0.032). Readmitted patients had significantly less frequent outpatient follow-up with an endocrinologist than the nonreadmitted cohort (56.1 vs. 70.5%, p = 0.031). Patients who had outpatient follow-up with an endocrinologist were at lower risk of readmission compared with those without (odds ratio: 0.46; 95% confidence interval: 0.24-0.88). Conclusion Delayed hyponatremia is one of the most common causes of 30-day readmission following ETPS. Postoperative follow-up with an endocrinologist may reduce risk of 30-day readmission following ETPS. Implications for Clinical Practice A multidisciplinary team incorporating otolaryngologist, neurosurgeons, and endocrinologist may identify patients at risk of 30-day readmissions. Protocols checking serum sodium within 1 week of surgery in conjunction with endocrinologist to tailor fluid restriction may reduce readmissions from delayed hyponatremia.

Genomics, Epigenetics, and Hearing Loss in Neurofibromatosis Type 2.

OBJECTIVES: In this review, we discuss current knowledge about the genetics and epigenetics of vestibular schwannoma (VS) in relation to hearing loss. A multistep and sequential genetic algorithm suitable for the identification of Neurofibromatosis Type 2 (NF2) constitutional and somatic mutations is discussed. DATA SOURCES, STUDY SELECTION: A review was performed of the English literature from 1990 to 2019 using PubMed regarding genetics and epigenetics of vestibular schwannoma and NF2. CONCLUSION: NF2 is a genetic disorder characterized by NF2 mutations that affect the function of a tumor suppressor called merlin. In particular, individuals with NF2 develop bilateral VS that can lead to hearing loss and even deafness. Recent advances in genetic and epigenetic studies have improved our understanding of the genotype-phenotype relationships that affect hearing in NF2 patients. Specific constitutional NF2 mutations including particular truncating, deletion, and missense mutations have been associated with poorer hearing outcomes and more severe clinical manifestations. Epigenetic events, such as DNA methylation and histone modifications, also contribute to the development and progression of hearing loss in NF2 patients. Furthermore, the accumulation of multiple NF2 and non-NF2 genetic and epigenetic abnormalities at the level of the tumor may contribute to worse hearing outcomes. Understanding genetic and epigenetic signatures in individual NF2 patients and particularly in each VS will allow us to develop novel gene therapies and precision medicine algorithms to preserve hearing in NF2 individuals.

Association of Socioeconomic Status, Race and Insurance Status with Chronic Rhinosinusitis Patient-Reported Outcome Measures.

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.

Parasex Generates Phenotypic Diversity de Novo and Impacts Drug Resistance and Virulence in Candida albicans.

Candida albicans 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 C. albicans 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 Galleria mellonella 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 de novo 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 de novo, and that this process has important consequences for both virulence and drug resistance in C. albicans populations.