Circulating exosomes in the blood are promising tools for biomarker discovery in cancer. Due to their heterogeneity, different isolation methods may enrich distinct exosome cargos generating ...different omic profiles. In this study, we evaluated the effects of plasma exosome isolation methods on detectable multi-omic profiles in patients with non-small cell lung cancer (NSCLC), castration-resistant prostate cancer (CRPC), and healthy controls, and developed an algorithm to quantify exosome enrichment. Plasma exosomes were isolated from CRPC (n = 10), NSCLC (n = 14), and healthy controls (n = 10) using three different methods: size exclusion chromatography (SEC), lectin binding, and T-cell immunoglobulin domain and mucin domain-containing protein 4 (TIM4) binding. Molecular profiles were determined by mass spectrometry of extracted exosome fractions. Enrichment analysis of uniquely detected molecules was performed for each method with MetaboAnalyst. The exosome enrichment index (EEI) scores methods based on top differential molecules between patient groups. The lipidomic analysis detected 949 lipids using exosomes from SEC, followed by 246 from lectin binding and 226 from TIM4 binding. The detectable metabolites showed SEC identifying 191 while lectin binding and TIM4 binding identified 100 and 107, respectively. When comparing uniquely detected molecules, different methods showed preferential enrichment of different sets of molecules with SEC enriching the greatest diversity. Compared to controls, SEC identified 28 lipids showing significant difference in NSCLC, while only 1 metabolite in NSCLC and 5 metabolites in CRPC were considered statistically significant (FDR < 0.1). Neither lectin-binding- nor TIM4-binding-derived exosome lipids or metabolites demonstrated significant differences between patient groups. We observed the highest EEI from SEC in lipids (NSCLC: 871.33) which was also noted in metabolites. These results support that the size exclusion method of exosome extraction implemented by SBI captures more heterogeneous exosome populations. In contrast, lectin-binding and TIM4-binding methods bind surface glycans or phosphatidylserine moieties of the exosomes. Overall, these findings suggest that specific isolation methods select subpopulations which may significantly impact cancer biomarker discovery.
Background
Quantitative computed tomography (CT) assessment of visceral adiposity may be superior to body mass index (BMI) as a predictor of surgical morbidity. We sought to examine the association ...of CT measures of obesity and BMI with short-term postoperative outcomes in colon cancer patients.
Methods
In this retrospective study, 110 patients treated with colectomy for stage I–III colon cancer were classified as obese or non-obese by preoperative CT-based measures of adiposity or BMI obese: BMI ≥ 30 kg/m
2
, visceral fat area (VFA) to subcutaneous fat area ratio (
V
/
S
) ≥0.4, and VFA > 100 cm
2
. Postoperative morbidity and mortality rates were compared.
Results
Obese patients, by
V
/
S
and VFA but not BMI, were more likely to be male and have preexisting hypertension and diabetes. The overall complication rate was 25.5%, and there were no mortalities. Obese patients by VFA (with a trend for
V
/
S
but not BMI) were more likely to develop postoperative complications as compared to patients classified as non-obese: VFA (30.5 vs.10.7%,
p =
0.03),
V
/
S
(29.2 vs. 9.5%,
p
= 0.05), and BMI (32.4 vs. 21.9%,
p
= 0.23).
Conclusions
Elevated visceral obesity quantified by CT is associated with the presence of key metabolic comorbidities and increased postoperative morbidity and may be superior to BMI for risk stratification.
Objective: We aimed to identify patient-level demographic and behavioral characteristics associated with higher social isolation among patients with cancer throughout the coronavirus disease 2019 ...(COVID-19) pandemic. Method: Moffitt Cancer Center patients seen on or after January 1, 2015, had a last known alive vital status, a valid e-mail address, and were 18-89 years old, were emailed a survey regarding social isolation. We collected information on age, sex, race, ethnicity, marital status, smoking, self-reported cancer diagnosis, cancer treatment, and perceived life changes due to the COVID-19 pandemic. We calculated a COVID-19 risk mitigation score by summing the frequency of risk mitigation behaviors (e.g., mask wearing). Social isolation was assessed with the self-reported Patient-Reported Outcomes Measurement Information System (PROMIS) Social Isolation Short Form. Logistic regression models compared characteristics of participants reporting higher versus lower social isolation (T-scores >60 vs. ≤60). Results: Most participants (N = 9,579) were female (59.2%), White (93.0%), and non-Hispanic (92.5%). Participants at greater odds of higher social isolation were younger (per 10 years decrease odds ratio OR = 1.36, 95% confidence interval, CI 1.30, 1.43), female (vs. male OR = 1.54, 95% CI 1.36, 1.74), unmarried (vs. married OR = 1.83, 95% CI 1.62, 2.08), current smokers (vs. never OR = 2.38, 95% CI 1.88, 3.00), reporting more risk mitigation behaviors (per 1 SD; OR = 1.33, 95% CI 1.24, 1.42), and more perceived life changes (vs. little/no change; OR = 2.64, 95% CI 2.08, 3.35). Conclusions: We identified younger age, females, unmarried, current smokers, more risk mitigation behaviors, and more perceived life changes increased odds of social isolation for patients with cancer during the COVID-19 pandemic. This can inform identification of patients with cancer at higher risk of social isolation for targeted mitigation strategies.
The current literature on depression within HIV populations shows poorer outcomes for these individuals than those in the general population. To further these studies, I performed an analysis looking ...at the effects of formal and informal social support on an HIV population in the south. The data comes from a 2005 SAMHSA study of health outcomes of 320 HIV-positive individuals over a twelve month period. The individuals in this study were referred through an enhanced substance abuse program. Social support variables used included professional support, support from a partner, support from family and friends, and feelings of closeness to family and friends. Depression was measured in the study as the number of days depressed in the past 30 days. This variable was recoded into categories for the analysis in this paper. Regression analysis was used and findings showed variations in the effects of different forms of social support. Both formal and informal social support variables were found to have no significant effect on people living with HIV/AIDS. Race was found to be significant for levels of depression reported. Implications of this study could help to better future outcomes for individuals within this population.
Cannabis use is associated with altered processing of external (exteroceptive) and internal (interoceptive) sensory stimuli. However, little research exists on whether subjective experiences of these ...processes are altered in people who frequently use cannabis. Altered exteroception may influence externally oriented attention, whereas interoceptive differences have implications for intoxication, craving, and withdrawal states.
The goal of the current study was to investigate subjective experiences of exteroceptive sensory gating and interoception in people frequently using cannabis. We hypothesized subjective impairments in sensory gating and elevations in affect-related interoceptive awareness; furthermore, such deviations would relate to cannabis use patterns.
This cross-sectional study of community adults 18-40 years old included 72 individuals (50% female) who used cannabis at least twice a week (not intoxicated during study) and 78 individuals who did not use cannabis (60% female). Participants completed the Sensory Gating Inventory and the Multidimensional Assessment of Interoceptive Awareness-2 surveys. People using cannabis completed surveys on cannabis use patterns. Analyses tested group differences and associations with cannabis use.
People using cannabis reported impaired sensory gating (
= 0.37-0.44; all
values < 0.05) and elevations of interoceptive awareness related to detection and affect (
= 0.21-0.61; all
values < 0.05). Problematic cannabis use was associated with increased sensory gating impairments (
= 0.37,
< .05). Interoceptive awareness was unrelated to cannabis use variables.
These findings extend literature on subjective experiences of sensory processing in people using cannabis. Findings may inform inclusion of external attentional tendencies and internal bodily awareness in assessments of risk and novel treatment approaches.
Purpose
Colorectal cancer (CRC) incidence and mortality are increasing among young adults (YAs) aged 18–39. This study compared quality of life (QOL) between YA and older adult CRC survivors in the ...ColoCare Study.
Methods
Participants were grouped by age (years) as follows: 18–39 (YA), 40–49, 50–64, and 65 + . Functional QOL (physical, social, role, emotional, cognitive) and global QOL were assessed with the EORTC-QLQ-C30 at enrollment, 3, 6, and 12 months. Average scores were compared between groups over time using longitudinal mixed-effect modeling. Proportions with clinically meaningful QOL impairment were calculated using age-relevant thresholds and compared between groups over time using logistic regression with mixed effects.
Results
Participants (
N
= 1590) were
n
= 81 YAs,
n
= 196 aged 40–49,
n
= 627 aged 50–64, and
n
= 686 aged 65 + . Average physical function was better among YAs than participants aged 50–64 (
p
= 0.010) and 65 + (
p
< 0.001), and average social function was worse among YAs than aged 65 + (
p
= 0.046). Relative to YAs, all age groups were less likely to report clinically meaningful social dysfunction (aged 40–49 OR = 0.13, 95%CI = 0.06–0.29; aged 50–64 OR = 0.10, 95%CI = 0.05–0.21; aged 65 + OR = 0.07, 95%CI = 0.04–0.15) and role dysfunction (aged 40–49 OR = 0.36, 95%CI = 0.18–0.75; aged 50–64 OR = 0.41, 95%CI = 0.22–0.78; aged 65 + OR = 0.32, 95%CI = 0.17–0.61). Participants aged 40–49 were also less likely to report physical dysfunction (OR = 0.42, 95%CI = 0.19–0.93).
Conclusion
YA CRC survivors reported better physical and worse social function compared to older CRC survivors, and YA CRC survivors were more likely to report clinically meaningful social, role, and physical disfunction. Future work should further investigate QOL using age-relevant benchmarks to inform best practices for CRC survivorship care.
Trial registration
NCT02328677, registered December 2014.
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