Search

Background and Objectives: Deterioration in pulmonary function is associated with greater disability and mortality in older adults. Dietary antioxidants are implicated in lung health, but the relationship between major dietary antioxidants, such as serum carotenoids, and pulmonary function have not been well characterized. Serum carotenoids are considered the most reliable indicator of fruit and vegetable intake. Subjects and Methods: We examined the relationship between serum α-carotene, β-carotene, β-cryptoxanthin, lutein/zeaxanthin, and lycopene with pulmonary function (forced expiratory volume in one second [FEV] and forced vital capacity [FVC]) in a population-based sample of 631 moderately to severely disabled community-dwelling older women (Women's Health and Aging Study I) in Baltimore, Maryland, USA. Results: Higher serum α-carotene and β-carotene concentrations were positively associated with both FEV and FVC, respectively (all P < 0.05), in separate multivariate linear regression models adjusting for age, race, education, cognition, anemia, inflammation, and chronic diseases. Total serum carotenoids were associated with FEV1 (P = 0.08) and FVC (P = 0.06), respectively, in similar models. No association was found between β-cryptoxanthin, lutein/zeaxanthin, and lycopene, and FEV or FVC. Conclusions: Higher serum α-carotene and β-carotene concentrations, which reflect greater intake of orange and dark green leafy fruits and vegetables, were associated with better pulmonary function among older community-dwelling women.function may lead to food avoidance and to a higher incidence of digestive complaints. [ABSTRACT FROM AUTHOR]

Re-irradiation (re-RT) for recurrent head and neck cancer (rHNC) after prior HNC RT is clinically challenging given prior radiation of nearby organs at risk (OARs). We describe clinical outcomes and toxicity of pencil beam scanning proton therapy (PBS-PT) for recurrent HNC, and report genomic alterations associated with patterns of failure to improve clinical decision making. We performed a retrospective analysis of rHNC patients treated at a single institution with PBS-PT. Baseline demographic, disease and treatment characteristics were recorded. Clinical outcomes were estimated using the Kaplan-Meier method. Univariable (UVA) and multivariable analyses (MVA) were performed to assess patient, disease, and treatment related factors. Acute and late grade 3+ toxicities were assessed per CTCAE v5.0. Next generation sequencing (NGS) and genomic analyses were performed on available samples. Eighty-nine patients treated with PBS-PT for rHNC between 2016 and 2022 with a median follow-up of 12 months (range 0-71) were included. The 1- and 2-year local control rates were 80.8% (95% CI: 70.8-90.8) and 66.2% (95% CI: 50.7-81.7) and 1- and 2-year distant metastasis free survival (DMFS) were 41.0% (95% CI: 30.0-52.0) and 26.3% (95% CI: 15.7-36.9). Median overall survival (OS) was 13 months (95% CI: 9.3-16.7). On UVA and MVA, smaller gross tumor volume was associated with improved OS (HR 1.002, p=.004), DMFS (HR 1.002, p=0.004) and progression free survival (PFS) (HR 1.002, p=0.014). There were 35 late grade 3 or higher toxicity events (30.3%), including one patient that suffered late grade 5 osteoradionecrosis resulting in sepsis. Patients with higher candidate gene specific mutation burden (genes with odds-ratio >2, p<0.05) had inferior PFS. In addition, TP53, NOTCH4 and ARID1B mutations were associated with inferior DMFS (OR>2, p<0.05). Of the top 28 highly mutated genes (mutated in ≥ 3 samples in either group, odd ratio>2), TP53 was the most frequently mutated gene in DMFS alive group with Met(78%), followed by NOTCH4(52%), ARID1B (33%). please see table table1b. Pencil beam scanning proton therapy re-irradiation is effective at achieving local control for recurrent head and neck cancer and is associated with a favorable toxicity profile. Distant metastases comprise the major failure pattern for this patient population and are associated with TP53, NOTCH4 , and ARID1B somatic mutations. Validation of these findings may provide rationale for the inclusion of genomic alterations in the clinical decision process. [ABSTRACT FROM AUTHOR]

Context: The relationship of fibroblast growth factor 21 (FGF21) with glucose metabolism and insulin resistance has not been well characterized in community-dwelling adults., Objective: The objective of the study was to examine the relationship of FGF21 with glucose metabolism and insulin resistance., Design: Serum FGF21, fasting plasma glucose (FPG), glucose tolerance, and insulin resistance were measured in a cross-sectional study, 2002-2007., Setting: The study was the Baltimore Longitudinal Study of Aging, a natural history cohort study of aging in community-dwelling men and women., Participants: Seven hundred adults, mean age 63.3 yr, participated in the study., Main Outcome Measures: FPG, 2-h plasma glucose, homeostasis model of insulin resistance, whole-body insulin sensitivity (Matsuda index), glucose area under the curve (AUC), and insulin AUC were measured., Results: Overall, the median (25th and 75th percentiles) FGF21 concentration was 225 (126, 370) pg/ml. The proportion of adults with normal, impaired, and diabetic FPG was 77.0, 21.4, and 1.6%, and those with normal, impaired, and diabetic 2-h plasma glucose was 76.7, 19.1, and 4.1%, respectively. Log serum FGF21 (picograms per milliliter), per 1 sd increase, was associated with an FPG (odds ratio 1.43, 95% confidence interval 1.15, 1.77, P = 0.001) and with 2-h plasma glucose (odds ratio 1.39, 95% confidence interval 1.12, 1.73, P = 0.003), in respective multivariate, ordered logistic regression models, adjusted for potential confounders. Serum FGF21 (picograms per milliliter) was associated with the homeostasis model of insulin resistance, the Matsuda index, glucose AUC, and insulin AUC (all P < 0.0001) in respective multivariable linear regression models adjusted for potential confounders., Conclusions: Higher serum FGF21 concentrations were associated with abnormal glucose metabolism and insulin resistance in community-dwelling adults.

A high dietary intake of fruit and vegetables has been shown to be protective for health. Neighborhood socioeconomic differences may influence the consumption of carotenoid-rich foods, as indicated by serum carotenoid concentrations. To test this hypothesis, we examined the relationship between neighborhood socioeconomic status (SES) and serum carotenoid concentrations in a population-based sample of community-dwelling women, aged 70-79 y, who participated in the Women's Health and Aging Study II in Baltimore, Maryland. Neighborhood socioeconomic Z-scores were derived from characteristics of the census block of the participants. Serum carotenoid concentrations were measured at baseline and at 18, 36, 72, 98, and 108 mo follow-up visits. Neighborhood Z-scores were positively associated with serum α-carotene (P = 0.0006), β-carotene (P = 0.07), β-cryptoxanthin (P = 0.03), and lutein+zeaxanthin (P = 0.004) after adjusting for age, race, BMI, smoking, inflammation, and season. There was no significant association between neighborhood Z-score and serum lycopene. Older, community-dwelling women from neighborhoods with lower SES have lower serum carotenoid concentrations, which reflect a lower consumption of carotenoid-rich fresh fruits and vegetables.

Objectives: To determine whether oxidative stress, as implied by oxidative damage to proteins, is associated with greater mortality in older women living in the community., Design: Longitudinal., Setting: Women's Health and Aging Study I, Baltimore, Maryland., Participants: Seven hundred forty-six moderately to severely disabled women, aged 65 and older, with baseline measures of serum protein carbonyls., Measurements: Serum protein carbonyls, which consist of chemically stable aldehyde and ketone groups produced on protein side chains when they are oxidized, were measured using enzyme-linked immunosorbent assay. Multivariate logistic regression was used to adjust for potential confounders., Results: During 5 years of follow-up, 202 (27.1%) participants died. Geometric mean serum protein carbonyls were 0.091 nmol/mg in women who died and 0.083 nmol/mg in those who survived (P=.02). Log(e) protein carbonyls (nmol/mg) were associated with greater risk of mortality (hazards ratio=1.34, 95% confidence interval=1.01-1.79, P=.04) in a multivariate Cox proportional hazards model adjusting for age, current smoking, and body mass index., Conclusion: Greater oxidative stress, as indicated by elevated serum protein carbonyl concentrations, was associated with greater risk of death in older women living in the community who were moderately to severely disabled. Prevention of oxidative stress may reduce the risk of mortality.