Effects of Interventions for Improving Awareness and Knowledge of Nonalcoholic Fatty Liver Disease Among Chinese Young Adults for Prevention of Liver Cancer-A Randomized Controlled Trial.

Chinese young adults (CYA), who are at an increasing risk of developing nonalcoholic fatty liver disease (NAFLD), which in turn increases the risk of liver cancer, are an ideal target population to deliver educational interventions to improve their awareness and knowledge of NAFLD and consequently reduce their risk of developing NAFLD. The purpose of this study was to determine the efficacy of two interventions to improve awareness and knowledge of NAFLD among CYA for the prevention of liver cancer. Between May and July 2021, 1373 undergraduate students aged 18 to 25 years in one university in China completed a web-based, self-administered survey distributed through WeChat app. One week after completion of the baseline survey, all eligible participants were randomly assigned to a pamphlet, a video intervention, or no intervention (control group), with follow-up assessments immediately and 1-month post-intervention. The 7-page pamphlet or 6.5-min video had information on NAFLD. Self-assessments included NAFLD awareness, lean NAFLD awareness, and knowledge scores of NAFLD. About 26% of participants had NAFLD awareness at baseline. Compared with controls, participants in both interventions showed significant improvement of awareness of NAFLD (pamphlet, + 46.0%; video, + 44.3%; control, + 18.7%; OR [95% CI], 3.13 [2.19-4.47] and 2.84 [1.98-4.08]), awareness of lean NAFLD (pamphlet, + 41.2%; video, + 43.0%; control, + 14.5%; OR [95% CI], 2.84 [1.62-4.99] and 2.61 [1.50-4.54]), and knowledge score of NAFLD (pamphlet, + 64.2%; video, + 68.9%; control, - 1.0%; OR [95% CI], 1.62 [1.47-1.80] and 1.67 [1.50-1.86]) at immediately post-intervention. Delivering NAFLD education through a pamphlet or video intervention was effective in improving the awareness and knowledge of NAFLD among CYA.

Disparities in Thyroid Cancer Diagnosis Based on Residence and Distance From Medical Facility.

Context: Rural-urban disparities have been reported in cancer care, but data are sparse on the effect of geography and location of residence on access to care in thyroid cancer. Objective: To identify impact of rural or urban residence and distance from treatment center on thyroid cancer stage at diagnosis. Methods: We evaluated 800 adults with differentiated thyroid cancer in the iCaRe2 bioinformatics/biospecimen registry at the Fred and Pamela Buffett Cancer Center. Participants were categorized into early and late stage using AJCC staging, and residence/distance from treating facility was categorized as short (≤ 12.5 miles), intermediate (> 12.5 to < 50 miles) or long (≥ 50 miles). Multivariable logistic regression was used to identify factors associated with late-stage diagnosis. Results: Overall, 71% lived in an urban area and 29% lived in a rural area. Distance from home to the treating facility was short for 224 (28%), intermediate for 231 (28.8%), and long for 345 (43.1%). All 224 (100%) short, 226 (97.8%) intermediate, and 120 (34.7%) long distances were for urban patients; in contrast, among rural patients, 5 (2.16%) lived intermediate and 225 (65.2%) lived long distances from treatment (P < .0001). Using eighth edition AJCC staging, the odds ratio of late stage at diagnosis for rural participants ≥ 55 years was 2.56 (95% CI, 1.08-6.14) (P = .03), and for those living ≥ 50 miles was 4.65 (95% CI, 1.28-16.93) (P = .0075). Results were similar using seventh edition AJCC staging. Conclusion: Older age at diagnosis, living in rural areas, and residing farther from the treatment center are all independently associated with late stage at diagnosis of thyroid cancer.

Development and Validation of a Questionnaire to Assess Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, among Chinese Young Adults.

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of valid, reliable, ready-to-use survey instruments for assessing awareness and knowledge of NAFLD in this population. The aims of this study were to develop, validate, and assess the reliability of a web-based, self-administered questionnaire evaluating awareness and knowledge of NAFLD among CYA. METHODS: Based on review of relevant literature, a draft questionnaire was initially developed. Face and content validity of the questionnaire was evaluated by an expert panel of seven gastroenterologists. The construct validity was tested through item analysis based on item response theory. Reliability assessment included test-retest for stability and test for internal consistency. Two pilot tests were conducted among 60 randomly selected students at Lanzhou University, China, through WeChat App. RESULTS: The content validity and clarity indexes were both greater than 0.85. Face validity was established by concluding that questions had no issue with feasibility, readability, clarity of wording, clarity of layout, and style. Response rates for two pilot tests were 96.7% (58 out of 60) and 98.3% (59 out of 60), respectively. Results testing the construct validity showed estimated amount of information obtained by the test between -3 and +3 range of ability was 97.57%. The test-retest reliability (Pearson's r) was 0.62. The internal consistency (KR20) was 0.92. CONCLUSIONS: This newly developed questionnaire is a reliable and valid instrument for assessing awareness and knowledge of NAFLD among this sample from CYA.

Factors Associated with Awareness and Knowledge of Nonalcoholic Fatty Liver Disease, a Liver Cancer Etiological Factor, Among Chinese Young Adults.

PURPOSE: Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), a liver cancer etiological factor, among Chinese young adults (CYA), there is a lack of study assessing awareness and knowledge of NAFLD among them. This study aimed to assess awareness and knowledge of NAFLD, and identify the factors associated with awareness and knowledge of NAFLD among CYA. We conducted a survey to assess awareness and knowledge of NAFLD among students who enrolled in one university undergraduate program in 2018, 2019, and 2020 through a newly developed web-based, self-administered questionnaire. The outcomes included awareness of NAFLD and knowledge score of NAFLD. We conducted unadjusted and adjusted analyses of associated factors with these outcomes. A total of 1373 students participated in the survey. Of all participants, 26.2% reported that they had heard of NAFLD, 7.7% reported that they had heard of lean NAFLD, and 11.1% received ≥ 20 points in the knowledge section of NAFLD. The mean and median scores were 9.35 (Std = 7.67) and 9 (range 0-27). Factors associated with having awareness and knowledge (≥ 20 points) of NAFLD included medical background, high medical knowledge level, and family history of NAFLD. There was low NAFLD awareness and knowledge among CYA aged 18 to 25 years. Our findings point to the need to develop an educational intervention for CYA to improve their NAFLD awareness and knowledge. Further studies should include information on physical activity and dietary habits to test whether NAFLD awareness and knowledge impact those habits.

Predictors of cancer risky and preventive behaviors among the Nebraska farmers population.

PURPOSE: Previous studies on cancer risk among agricultural producers have focused on occupational exposures, with only a few studies examining behavioral factors. The aim of this study was to understand cancer risky and preventative behaviors among the large farming population in Nebraska. METHODS: A statewide cross-sectional study of farmers in Nebraska aged 19 and older was conducted in 2019 (n = 782). Multivariable logistic regression was used to examine factors associated with being up to date on cancer screening and with cancer risky and preventive behaviors. FINDINGS: The 93.68% of the Nebraska farmers population do not meet the daily recommended consumption of fruits and vegetables, and 70.14% reported regular alcohol consumption. The proportion of adults up to date on cancer screening was 79.57% for breast, 67.55% for cervical, 85.54% for colorectal, and 46.05% for skin cancers. Compared to women, men had a higher odds of heavy alcohol consumption (aOR 2.96, 95% CI 1.94-4.56) and ever smoking 100 or more cigarettes (aOR 1.66, 95% CI 1.03-2.73). The odds of being current with skin cancer screening was higher among those with higher incomes (aOR 1.77, 95% CI 1.06-3.01). Compared to men aged 50-64, the odds of being current with prostate cancer screening was higher among men aged 65-74 (aOR: 2.65, 95% CI 1.10-7.31) and 75 and older (aOR: 7.73, 95% CI 2.03-51.73). CONCLUSIONS: Disparities in cancer screening and risk and preventive behaviors exist among farmers in Nebraska. The study highlights a need for continuing efforts to improve preventive cancer behaviors targeted to the farming population.

Cross-sectional Study of Colorectal Cancer Screening Barriers in a Latino-Serving Federally Qualified Health Center.

Compared to other races/ethnicities, the Latino population has a lower rate of adherence to colorectal cancer (CRC) screening guidelines. Previous studies have identified a variety of barriers to CRC screening in Latino populations but have not explored factors associated with barriers. The purpose of this study was to identify barriers to CRC screening and associated factors in a Midwest Latino population visiting an urban Federally Qualified Health Center (FQHC). We conducted a cross-sectional investigation of 68 Latinos at a FQHC from June to October 2017. We examined factors associated with scheduling, psychological, and financial barriers using t-test, ANOVA, and multiple linear regression analyses. Our participants reported low educational level, low income, and limited access to insurance or a primary care provider. Scheduling barriers are the highest barrier compared with psychological and financial barriers. Being married or coupled was the only predictor of higher scheduling barriers (P < .05). Being married or coupled was associated with higher psychological barriers in both univariate and multivariate analysis (P < .05). Higher education level was associated with higher psychological barriers in univariate (P < .05) but not multivariate analysis. Participants with lower vs. higher English proficiency had a higher financial barrier score in univariate (P < .05) but not multivariate analysis. Despite interventions targeting CRC screening barriers, including the provision of free at-home testing, perceived barriers persist. Bilingual patient navigators may help address needs for those with limited English proficiency to find and schedule free or reduced-fee colonoscopy services. People who are well educated are also at high risk of psychological barriers and should be targeted and given more education on the importance of CRC screening.

Awareness and knowledge of Colorectal Cancer Screening among Latinos in Omaha, Nebraska.

BACKGROUND: Colorectal cancer (CRC) screening rates remain low in Latino communities. We sought to determine the screening awareness and attitudes in Omaha, Nebraska. METHODS: We interviewed 150 Latinos at an urban Federally Qualified Health Center, June-October 2017. Chi-square or Fisher-exact tests and multiple logistic regression models were used for data analysis. RESULTS: Participants reported low educational attainment, low income, and limited access to insurance or a primary provider. Less than one-third of participants aged 50 + had ever heard of FOBT (32.6%) or colonoscopy (30.4%). For individuals 50+, access to a primary care provider (p = .03) and knowing the screening initiation age (p = .03) were associated with ever having a colonoscopy. Higher knowledge score was a strong predictor of any CRC screening. DISCUSSION: Knowledge predicted screening, suggesting interventions should aim to educate this population regarding CRC screening guidelines and options and work with stakeholders to make CRC screening more accessible.

Differential methylation patterns in lean and obese non-alcoholic steatohepatitis-associated hepatocellular carcinoma.

BACKGROUND: Nonalcoholic fatty liver disease affects about 24% of the world's population and may progress to nonalcoholic steatohepatitis (NASH), cirrhosis, and hepatocellular carcinoma (HCC). While more common in those that are obese, NASH-HCC can develop in lean individuals. The mechanisms by which HCC develops and the role of epigenetic changes in the context of obesity and normal weight are not well understood. METHODS: In this study, we used previously generated mouse models of lean and obese HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to evaluate methylation differences in HCC progression in lean versus obese mice. Differentially methylated regions were determined using reduced representation bisulfite sequencing. RESULTS: A larger number of differentially methylated regions (DMRs) were seen in NASH-HCC progression in the obese mice compared to the non-obese mice. No overlap existed in the DMRs with the largest methylation differences between the two models. In lean NASH-HCC, methylation differences were seen in genes involved with cancer progression and prognosis (including HCC), such as CHCHD2, FSCN1, and ZDHHC12, and lipid metabolism, including PNPLA6 and LDLRAP1. In obese NASH- HCC, methylation differences were seen in genes known to be associated with HCC, including RNF217, GJA8, PTPRE, PSAPL1, and LRRC8D. Genes involved in Wnt-signaling pathways were enriched in hypomethylated DMRs in the obese NASH-HCC. CONCLUSIONS: These data suggest that differential methylation may play a role in hepatocarcinogenesis in lean versus obese NASH. Hypomethylation of Wnt signaling pathway-related genes in obese mice may drive progression of HCC, while progression of HCC in lean mice may be driven through other signaling pathways, including lipid metabolism.

Predictors of behavioral cancer risk factors and preventive behaviors among Nebraskans.

BACKGROUND: The overall incidence rate of cancer in Nebraska is higher than the national average with cancer being the second leading cause of death in the state. Interventions are required to reduce the cancer burden; however, further research is first needed to identify behavioral cancer risk factors and preventive behaviors among Nebraskans that can be targeted. METHODS: A statewide cross-sectional survey of Nebraskans aged 19 and older was conducted in 2019 using an address-based sampling method (n = 1640). Multivariable logistic regression was used to examine factors associated with being up-to-date on cancer screening and with behavioral cancer risk factors and preventive behaviors. RESULTS: 93.42% of Nebraskans did not meet the daily recommended consumption of fruits and vegetables, and 71.51% did not meet weekly physical activity guidelines. The proportion of adults up to date on cancer screening was 64.57% for breast, 68.83% for cervical, 69.01% for colorectal, and 24.07% for skin cancers. Individuals 65-74 (OR: 3.40, 95% CI: 1.52-7.62) and 75 or older (OR: 3.30, 95% CI: 1.35-8.07) were more likely to be current with their colorectal cancer screening compared to ages 50-64. Hispanics were less likely to be current with mammograms (OR: 0.06, 95% CI: 0.01-0.71) and ever screened for cervical cancer (OR:0.13, 95% CI: 0.02-0.94) compared to Non-Hispanic Whites. CONCLUSIONS: Disparities in cancer screening and risk and preventive behaviors exist in Nebraska. IMPACT: The study highlights a need for continuing efforts to improve preventive cancer behaviors for the entire population as well as some high-risk populations in Nebraska.

Disparities in awareness of and willingness to participate in cancer clinical trials between African American and White cancer survivors.

BACKGROUND: Cancer clinical trials (CCTs) are essential for cancer care, yet the evidence is scarce when it comes to racial disparities in CCT participation among cancer survivors in the Midwest. This study aimed to 1) assess disparities in the awareness of and willingness to participate in CCTs between African American and White cancer survivors; and 2) compare perceptions about CCTs between the two racial groups. METHODS: The study was based on cross-sectional data from the survey "Minority Patient Participation in Cancer Clinical Trials" that collected information from 147 Black and White cancer survivors from Nebraska between 2015 and 2016. Chi-square tests and logistic regressions were used to assess differences between Black and White cancer survivors regarding their awareness, willingness, and perceptions associated with CCT participation. RESULTS: After adjusting for the effects of socio-demographic, health status, and psychosocial variables, Black cancer survivors were much less likely than White cancer survivors to be aware of CCTs (AOR 0.26; CI 0.08-0.81), to express willingness to participate in CCTs (AOR 0.03; CI 0.01, 0.32) and to actually participate in CCTs (AOR 0.13; CI 0.04-0.38). Black cancer survivors reported a lower level of trust in physicians and were less likely than White cancer survivors to believe that CCTs make a significant contribution to science. CONCLUSIONS: Relative to White cancer survivors, Black cancer survivors had much lower awareness of and willingness to participate in CCTs. Part of these differences might be related to the differential perception of CCTs, psychosocial factors, and trust in physicians between the two groups.

Relationships of serum CC16 levels with smoking status and lung function in COPD.

BACKGROUND: The club cell secretory protein (CC16) has anti-inflammatory and antioxidant effects, and low CC16 serum levels have been associated with both risk and progression of COPD, yet the interaction between smoking and CC16 on lung function outcomes remains unknown. METHODS: Utilizing cross-sectional data on United States veterans, CC16 serum concentrations were measured by ELISA and log transformed for analyses. Spirometry was conducted and COPD status was defined by post-bronchodilator FEV1/FVC ratio < 0.7. Smoking measures were self-reported on questionnaire. Multivariable logistic and linear regression were employed to examine associations between CC16 levels and COPD, and lung function with adjustment for covariates. Unadjusted Pearson correlations described relationships between CC16 level and lung function measures, pack-years smoked, and years since smoking cessation. RESULTS: The study population (N = 351) was mostly male, white, with an average age over 60 years. An interaction between CC16 and smoking status on FEV1/FVC ratio was demonstrated among subjects with COPD (N = 245, p = 0.01). There was a positive correlation among former smokers and negative correlation among current or never smokers with COPD. Among former smokers with COPD, CC16 levels were also positively correlated with years since smoking cessation, and inversely related with pack-years smoked. Increasing CC16 levels were associated with lower odds of COPD (ORadj = 0.36, 95% CI 0.22-0.57, Padj < 0.0001). CONCLUSIONS: Smoking status is an important effect modifier of CC16 relationships with lung function. Increasing serum CC16 corresponded to increases in FEV1/FVC ratio in former smokers with COPD versus opposite relationships in current or never smokers. Additional longitudinal studies may be warranted to assess relationship of CC16 with smoking cessation on lung function among subjects with COPD.

Differential progression of unhealthy diet-induced hepatocellular carcinoma in obese and non-obese mice.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) ranks first among liver diseases in Western countries. NAFLD is typically associated with obesity and diabetes, however it also develops in lean individuals without metabolic syndrome. The prevalence of lean NAFLD is 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD starts with excess liver fat accumulation (NAFL), progresses to nonalcoholic steatohepatitis (NASH), cirrhosis and hepatocellular carcinoma (HCC). The pathogenesis of lean NASH-HCC and how it differs from obese NASH-HCC is not well understood. METHODS: In this work, we generated a mouse model of lean and obese NASH-HCC using a choline deficient/high trans-fat/fructose/cholesterol diet and a choline supplemented/high trans-fat/fructose/cholesterol diet, respectively, to compare progression to NASH-HCC in lean versus obese mice. Comparisons were made at the organismal, histological, and molecular level by investigating fatty acid metabolism in the plasma of these mice. RESULTS: Obese mice showed more pronounced glucose intolerance and insulin resistance, higher levels of plasma cholesterol and triglycerides, and higher penetrance of NASH compared to lean mice. Despite the abnormal metabolic profile of obese mice, male obese and lean mice developed HCC with similar penetrance (53.3% and 53.8%, respectively), albeit lean mice showed faster tumor progression as evidenced by the larger tumor size and lower HCC-free survival. None of the female lean mice developed HCC, while 50% of female obese mice developed HCC. Both groups of mice showed a reduction in plasma polyunsaturated fatty acids (PUFAs), however, the levels were higher towards the endpoint in obese mice compared to lean mice. CONCLUSIONS: Unhealthy diet composition appears to drive progression to NASH-HCC rather than the organismal effects of obesity. PUFA levels may increase due to systemic inflammation in obese mice and act as suppressors of tumor progression, thus delaying HCC progression in obese mice compared to lean mice. These models could be used to further dissect the molecular pathogenesis of lean and obese NASH-HCC and address the mechanisms whereby PUFAs may be implicated in hepatocarcinogenesis.

Exposure to Toxicants Associated With Use and Transitions Between Cigarettes, e-Cigarettes, and No Tobacco.

Importance: Transitions between e-cigarettes and cigarettes are common among tobacco users, but empirical evidence on the health outcomes of switching tobacco products is scarce. Objectives: To examine changes in urinary biomarkers between baseline and 1-year follow-up among adult tobacco users switching between e-cigarettes and cigarettes. Design, Setting, and Participants: This cohort study used data from wave 1 (baseline, September 2013 to December 2014) and wave 2 (1-year follow-up, October 2014 to October 2015) of the Population Assessment of Tobacco and Health Study. A subset of the probability sample of US adults who voluntarily provided biospecimens at 2 waves was analyzed. Participants were divided into 3 mutually exclusive groups at baseline: exclusive cigarette smokers, exclusive e-cigarette users, and dual users. Data analysis was performed in 2021. Exposures: Harmful and potentially harmful constituents included nicotine metabolites, tobacco-specific nitrosamines (TSNAs; including 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol [NNAL]), metals, polycyclic aromatic hydrocarbons (PAHs), and volatile organic compounds (VOCs). Main Outcomes and Measures: Within-participant changes in 55 urinary biomarkers of exposure (BOEs) to harmful and potentially harmful constituents were examined using multivariable regression models. Results: Among 3211 participants (55.6% women, 68.3% White, 13.2% Black, and 11.8% Hispanic) at baseline, 21.9% of exclusive cigarette users, 42.8% of exclusive e-cigarette users, and 62.1% of dual users changed product use at follow-up (all percentages are weighted). There was a significant reduction in urine concentrations of TSNAs, PAHs, and VOCs when users transitioned from exclusive cigarette to exclusive e-cigarette use, with a 92% decrease in NNAL, from a mean of 168.4 pg/mg creatinine (95% CI, 102.3-277.1 pg/mg creatinine) to 12.9 pg/mg creatinine (95% CI, 6.4-25.7 pg/mg creatinine; P < .001). A similar panel of BOEs decreased when dual users transitioned to exclusive e-cigarette use; NNAL levels decreased by 96%, from a mean of 143.4 pg/mg creatinine (95% CI, 86.7-237.0 pg/mg creatinine) to 6.3 pg/mg creatinine (95% CI, 3.5-11.4 pg/mg creatinine; P < .001). Nicotine metabolites, TSNAs, PAHs, and VOCs significantly increased when baseline exclusive e-cigarette users transitioned to exclusive cigarette use or dual use. Switching from exclusive cigarette use to dual use was not associated with significant decreases in BOEs. Conclusions and Relevance: This national cohort study provides evidence on the potential harm reduction associated with transitioning from exclusive cigarette use or dual use to exclusive e-cigarette use. e-Cigarettes tend to supplement cigarettes through dual use instead of cessation at the population level. Continuous monitoring of BOE at the population level and assessment of BOE change by product transition are warranted, as well as defined adverse health outcomes.

Knowledge and Attitudes of Cypriots on Melanoma Prevention: Is there a Public Health Concern?

BACKGROUND: Melanoma is the deadliest type of skin cancer. It is the eighth most common cancer in males and the tenth in females in Cyprus, an island in the Mediterranean with a high ultraviolet (UV) index. Cyprus is expected to be strongly affected by climate change and consequently, melanoma will likely become an increasing public health problem. Melanoma prevention is possible; however, it is unknown if people living in Cyprus are aware of melanoma and prevention methods. To this end, we used a validated survey to evaluate the level of melanoma knowledge and factors associated with it in the Cypriot population. METHODS: We conducted a 47-item survey with sections on demographics, knowledge of melanoma and risk factors, attitudes toward relevant health practices, and protective behaviors among six hundred Cypriot residents from October 2015 to April 2016. RESULTS: Our results revealed that only 59% of participants check their skin for moles, 87% protect their skin from the sun during summer holidays, and 57% do not take measures to protect their skin from the sun during non-holiday periods. Protective behavior was positively associated with educational level (P=0.016) and district of residence (P<0.0001). Melanoma knowledge was positively associated with education level (P=0.002) and district of residence (P=0.004). Level of Concern was positively associated with age (P=0.026) and education level (P=0.041). CONCLUSIONS: There are gaps in melanoma knowledge and prevention practices in the study population. Further education on melanoma and its prevention should be specifically targeted to individuals of lower education levels as well as teenagers, such that protective behaviors for melanoma are adopted early in life.

Cross-sectional survey study of primary care clinics on evidence-based colorectal cancer screening intervention use.

PURPOSE: The purpose of this study was to examine differences between urban and rural primary care clinics in the use of colorectal cancer (CRC) screening methods and evidence-based interventions to promote CRC screening. METHODS: This was a cross-sectional survey of primary care clinics in Nebraska. Surveys in paper form were sent out and followed up with telephone interviews to nonrespondents. Of the 375 facilities, 263 (70.1%) responded to the survey. FINDINGS: Over 30% of urban clinics indicated that 80% or more of their patients were meeting the CRC guidelines compared to 18.3% of rural clinics (P = .03). Rural clinics were more likely than urban clinics to prefer the use of colonoscopy alone or in combination with stool tests (P = .02). The most common interventions for CRC screening included one-on-one patient education and use of computer-based pop-ups to remind providers. CONCLUSIONS: In conclusion, we found some important differences between rural and urban primary care clinics in the implementation of CRC screening. Given that there is evidence for differences in preference for CRC screening methods (colonoscopy vs stool-based tests) between rural and urban community members, it is important to assess the effectiveness of different types of CRC screening interventions by comparing rural and urban primary care clinic patient populations.

Impact of Proton Pump Inhibitor Use on the Effectiveness of Immune Checkpoint Inhibitors in Advanced Cancer Patients.

BACKGROUND: The gut microbiome plays a critical role in modulating the therapeutic effect of immune checkpoint inhibitors (ICIs). Proton pump inhibitors (PPIs) are commonly used in cancer patients and may affect the gut microbiome by altering gut pH. OBJECTIVE: To evaluate if concurrent use of PPI is associated with overall survival (OS) and progression-free survival (PFS) in patients with stage IV non-small-cell lung cancer (NSCLC), melanoma, renal cell carcinoma, transitional cell carcinoma, or head and neck squamous cell carcinoma. METHODS: This was a single-center retrospective cohort study of advanced cancer adult patients who received nivolumab or pembrolizumab between September 1, 2014, and August 31, 2019. Concomitant PPI exposure was defined as PPI use 0 to 30 days before or after initiation of ICIs. Treatment outcome was OS and PFS. RESULTS: A total of 233 patients were included in our study. Concomitant PPI use was not significantly associated with OS (hazard ratio [HR] = 1.22; 95% CI = 0.80-1.86) or PFS (HR = 1.05; 95% CI = 0.76-1.45) in patients with ICI use. The effect estimates were robust after adjusting for covariates in multivariate analysis and in patients with NSCLC. CONCLUSION AND RELEVANCE: Concomitant PPI use was not associated with the effectiveness of nivolumab or pembrolizumab. Certain predictors of survival outcomes related to PPI use in patients receiving immunotherapy, such as the time window and indication of PPI exposure and autoimmune disorders, should be explored in the future to better carve out the impact of PPI on the effectiveness of ICI use.

Gender Differences in Recommended Treatment Decisions among Breast Cancer Patients: A Study Using the National Cancer Database.

BACKGROUND: Previous studies have explored surgery refusal among female breast cancer patients. However, little attention has been given to other therapies in both females and males. The goal of this study was to determine the potential role of gender on recommended hormone therapy, chemotherapy, radiation therapy, and surgery refusal and to describe other determinants of refusal. MATERIALS AND METHODS: A retrospective study of the National Cancer Database (NCDB) between 2004 and 2016 was conducted. The outcome was whether patients accepted or refused the recommended treatment. We examined four different outcome variables (hormone therapy, chemotherapy, radiation therapy, and surgery) relation to gender and other factors. RESULTS: A total of 906,342 breast cancer patients met the eligibility criteria for hormone therapy, 1,228,132 for surgery, 596,229 for chemotherapy, and 858,050 for radiation therapy. The odds of refusing hormone therapy and surgery in males were 17% (AOR = 0.83; 95% CI: 0.75-0.92) and 33% (AOR=0.67; 95% CI: 0.50-0.90) lower compared to female patients, respectively. The odds of refusing radiation therapy were 14% higher in males compared to females (AOR=1.14; 95% CI:1.03-1.30). Older age and lack of insurance were significantly associated with each treatment refusal. CONCLUSION: Female patients tend to refuse hormone therapy and surgery compared to males. A marginally statistically significant gender differences was found for radiotherapy refusal. The providers and other stakeholders can utilize the current findings to identify the risk groups and barriers associated with refusal for each treatment and to develop interventions.

Reduction of Polyunsaturated Fatty Acids with Tumor Progression in a Lean Non-Alcoholic Steatohepatitis-Associated Hepatocellular Carcinoma Mouse Model.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the most common liver disease in Western countries. While obesity and diabetes are the hallmarks of NAFLD, it also develops in lean individuals in the absence of metabolic syndrome, with a prevalence of 7 percent in the U.S. and 25-30 percent in some Asian countries. NAFLD represents the spectrum of liver disease, starting with excess liver fat accumulation (NAFL) that can progress to nonalcoholic steatohepatitis (NASH), cirrhosis and ultimately hepatocellular carcinoma (HCC). To date, the pathogenesis of lean NASH-HCC is poorly understood and a mouse model is lacking. We aimed to develop a mouse model of lean NASH-HCC using a choline deficient and high trans-fat/sucrose/cholesterol diet to enable better understanding of its molecular pathogenesis. Methods: C57BL/6N mice were fed this diet starting at 4 weeks of age for 52 weeks and were compared to mice fed an isocaloric low fat control diet for the same duration. C57BL/6N mice were chosen instead of the C57BL/6J mice due to the high susceptibility of C57BL/6J mice to diet-induced obesity. The plasma and tumor fatty acid profile of these mice was also investigated. Results: Nearly 61% of the mice developed lean NASH-HCC. These mice showed reduction of plasma polyunsaturated fatty acids (PUFAs) (linolenic acids (α and γ, ω-3 and ω-6, respectively), eicosapentanoic acid (ω-3), docosahexanoic acid (ω-3), and linoleic acid (ω-6)) and increasing levels over time in mice with pre-malignant lesions. Conclusions: We developed a novel high penetrance diet-induced lean NASH-HCC mouse model. Plasma PUFA levels were reduced with tumor progression in parallel with reduced expression of genes controlling desaturase expression suggesting their potential use as biomarkers for lean NASH-HCC progression as well as chemopreventive molecules.

Development of an Integer-based Risk Score to Predict 90-Day Mortality After Hepatectomy in Patients With Hepatocellular Carcinoma.

BACKGROUND: The incidence of liver cancer has more than tripled since 1980. Hepatectomy represents the major curative treatment for liver cancer. The risk factors associated with 90-day mortality after hepatectomy are not well understood and there are currently no good prediction models for this outcome. The objectives of the current study were to identify risk factors of 90-day mortality after hepatectomy in patients with hepatocellular carcinoma and to develop an integer-based risk score using the National Cancer Database. METHODS: Hepatectomies recorded in the National Cancer Database during 2004-2012 were reviewed for 90-day mortality. Risk factors were identified by multivariate logistic regression models. An integer-based risk score was developed using the ß coefficients derived from the logistic regression model and tested for discriminatory ability. According to the total risk score, patients were grouped into 4 risk groups. RESULTS: The overall 90-day mortality was 10.2%. Ten risk factors were identified, which included sex, age, race/ethnicity, insurance status, education, annual hospital volume, stage, tumor grade, Charlson-Deyo Score, and surgical procedure. The risk of 90-day mortality was stratified into 4 groups. The calculated 90-day mortality rates were 2.47%, 5.88%, 12.58%, and 24.67% for low-risk, medium-risk, high-risk, and excessive-risk groups, respectively. An area under the receiver operating characteristic curve of 0.69 was obtained for model discrimination. CONCLUSIONS: The integer-based risk score we developed could easily quantify each patient's risk level and predict 90-day mortality after hepatectomy. The stratified risk score could be a useful addition to perioperative risk management and a tool to improve 90-day mortality after hepatectomy.

The impact of body mass index and sociodemographic factors on moderate-to-vigorous physical activity and sedentary behaviors of women with young children: A cross-sectional examination.

OBJECTIVES: Moderate-to-vigorous physical activity provides multiple benefits to women after childbirth. To achieve these benefits, the recommendation that adults obtain, 150 min of moderate-to-vigorous physical activity per week and reduce sedentary behaviors, also applies to women in the post-partum phase of the life span. However, research examining the moderate-to-vigorous physical activity and sedentary behaviors of women with young children (0-2 years) is limited. A greater understanding of these behaviors from a nationally representative sample is needed. Therefore, the primary objective of this study was to determine the levels of moderate-to-vigorous physical activity and sedentary behaviors of a nationally representative sample of women with young children within the United States. A secondary objective was to examine the influence of body mass index and sociodemographic factors on these behaviors. METHODS: Cross-sectional data from four cycles of the National Health and Nutrition Examination Survey (2007-2008, 2009-2010, 2011-2012, and 2013-2014) were used for analysis. Descriptive statistics were calculated and a generalized linear model was used to investigate associations between mean minutes of moderate-to-vigorous physical activity, sedentary activity, body mass index, and sociodemographic variables. DISCUSSION: Women with young children (n = 477) obtained 634 min in moderate-to-vigorous physical activity per week and this was positively associated with having a higher income (p < 0.001) and the number of children in the home (p < 0.001). In total, 62% of women were meeting the World Health Organization guidelines for aerobic activity. Lower odds of achieving guidelines was associated with being Black (p = 0.004), Mexican American (p = 0.009), or married (p = 0.042) compared with being White or not married. Finally, women accumulated ~5 h of sedentary activity per day, with higher levels associated with race (p = 0.005), education (p = 0.022), and number of children within the home (p < 0.001). Research efforts should continue to focus on strategies to help non-adhering women with young children achieve the physical activity recommendations and reduce time spent in sedentary behaviors.