The association between dietary factors and risk of rectal cancer in African Americans and Whites

Colorectal cancer (CRC), a commonly diagnosed malignancy in the U.S., refers to cancers of the colon and rectum. African-Americans have the highest incidence and mortality rates for CRC; many reasons for this disparity remain unknown. Diet is involved in the etiology of CRC. There is an abundance of literature on diet and CRC or colon cancer, while evidence is limited on the role of diet in rectal cancer specifically. This dissertation addresses these issues by examining the relationship between dietary factors and rectal cancer risk, and determining if these associations differ between whites and African-Americans. We used the North Carolina Colon Cancer Study-Phase II, which included 945 rectal cancer cases (including sigmoid and rectosigmoid) and 959 controls. The Diet History Questionnaire was used to assess dietary intake, and we examined the following dietary factors: macronutrients, micronutrients, food groups, and dietary patterns. For macronutrients, we observed no association between fat intake in whites or African-Americans; only a possible risk reduction in African-Americans with high intake of polyunsaturated fatty acids. In whites, protein (% energy) was associated with lower rectal cancer risk. In regards to the micronutrients, statistically significant inverse associations were observed in whites for most micronutrients, but only for selenium in African-Americans. Interestingly, micronutrient intake from dietary supplements did not provide additional risk reduction. Regarding food groups, non-whole grains and white potatoes appeared to elevate rectal cancer risk in whites, while fruits, vegetables, dairy, fish, and poultry were inversely related to risk. In African-Americans, high fruit intake was positively associated with risk for rectal cancer. We identified three dietary patterns in whites and African-Americans. The High fat/Meat/Potatoes pattern was similar in both race groups, and associated with elevated risk in whites. This work adds to the literature on the relationship between diet and rectal cancer, and suggests that these associations differ by race. It also provides information on the epidemiology of rectal cancer in African-Americans, for which evidence is lacking. Rectal cancer is preventable, partially by dietary modifications; therefore, it is necessary to examine the role of diet in the etiology of rectal cancer, especially in large racially diverse samples

Influence of Comorbidity on Racial Differences in Receipt of Surgery Among US Veterans With Early-Stage Non–Small-Cell Lung Cancer

It is unclear why racial differences exist in the frequency of surgery for lung cancer treatment. Comorbidity is an important consideration in selection of patients for lung cancer treatment, including surgery. To assess whether comorbidity contributes to the observed racial differences, we evaluated racial differences in the prevalence of comorbidity and their impact on receipt of surgery

Activation of Cytosolic Phospholipase A\u3csub\u3e2\u3c/sub\u3eα in Resident Peritoneal Macrophages by Listeria Monocytogenes Involves Listeriolysin O and TLR2

Eicosanoid production by macrophages is an early response to microbial infection that promotes acute inflammation. The intracellular pathogen Listeria monocytogenes stimulates arachidonic acid release and eicosanoid production from resident mouse peritoneal macrophages through activation of group IVA cytosolic phospholipase A2 (cPLA2α). The ability of wild type L. monocytogenes (WTLM) to stimulate arachidonic acid release is partially dependent on the virulence factor listeriolysin O; however, WTLM and L. monocytogenes lacking listeriolysin O (ΔhlyLM) induce similar levels of cyclooxygenase 2. Arachidonic acid release requires activation of MAPKs by WTLM and ΔhlyLM. The attenuated release of arachidonic acid that is observed in TLR2-/- and MyD88-/- macrophages infected with WTLM and ΔhlyLM correlates with diminished MAPK activation. WTLM but not ΔhlyLM increases intracellular calcium, which is implicated in regulation of cPLA2α. Prostaglandin E2, prostaglandin I 2, and leukotriene C4 are produced by cPLA 2α+/+ but not cPLA2α-/- macrophages in response to WTLM and ΔhlyLM. Tumor necrosis factor (TNF)-α production is significantly lower in cPLA2α +/+ than in cPLA2α-/- macrophages infected with WTLM and ΔhlyLM. Treatment of infected cPLA 2α+/+ macrophages with the cyclooxygenase inhibitor indomethacin increases TNFα production to the level produced by cPLA 2α-/- macrophages implicating prostaglandins in TNFα down-regulation. Therefore activation of cPLA2α in macrophages may impact immune responses to L. monocytogenes

Associations of Red Meat, Fat, and Protein Intake With Distal Colorectal Cancer Risk

Studies have suggested that red and processed meat consumption elevate the risk of colon cancer; however, the relationship between red meat, as well as fat and protein, and distal colorectal cancer (CRC) specifically is not clear. We determined the risk of distal CRC associated with red and processed meat, fat, and protein intakes in Whites and African Americans. There were 945 cases (720 White, 225 African American) of distal CRC and 959 controls (800 White, 159 African American). We assessed dietary intake in the previous 12 mo. Multivariate logistic regression analyses were used to obtain odds ratios (OR) and 95% confidence intervals (95% CI). There was no association between total, saturated, or monounsaturated fat and distal CRC risk. In African Americans, the OR of distal CRC for the highest category of polyunsaturated fat intake was 0.28 (95% CI = 0.08–0.96). The percent of energy from protein was associated with a 47% risk reduction in Whites (Q4 OR = 0.53, 95% CI = 0.37–0.77). Red meat consumption in Whites was associated with a marginally significant risk reduction (Q4 OR = 0.66, 95% CI = 0.43–1.00). Our results do not support the hypotheses that fat, protein, and red meat increase the risk of distal CRC

Dietary Patterns, Food Groups, and Rectal Cancer Risk in Whites and African-Americans

Associations between individual foods and nutrients and colorectal cancer have been inconsistent, and few studies have examined associations between food, nutrients, dietary patterns, and rectal cancer. We examined the relationship between food groups and dietary patterns and risk of rectal cancer in non-Hispanic Whites and African Americans

Antioxidant and DNA methylation-related nutrients and risk of distal colorectal cancer

To investigate the relationship between antioxidant nutrients (vitamins C and E, β-carotene, selenium) and DNA methylation-related nutrients (folate, vitamins B6 and B12) and distal colorectal cancer risk in whites and African Americans and to examine intakes from food only versus total (food plus dietary supplements) intakes

A Multi-Stage Process to Develop Quality Indicators for Community-Based Palliative Care Using interRAI Data

Background: Individuals receiving palliative care (PC) are generally thought to prefer to receive care and die in their homes, yet little research has assessed the quality of home- and community-based PC. This project developed a set of valid and reliable quality indicators (QIs) that can be generated using data that are already gathered with interRAI assessments-an internationally validated set of tools commonly used in North America for home care clients. The QIs can serve as decision-support measures to assist providers and decision makers in delivering optimal care to individuals and their families. Methods: The development efforts took part in multiple stages, between 2017-2021, including a workshop with clinicians and decision-makers working in PC, qualitative interviews with individuals receiving PC, families and decision makers and a modified Delphi panel, based on the RAND/ULCA appropriateness method. Results: Based on the workshop results, and qualitative interviews, a set of 27 candidate QIs were defined. They capture issues such as caregiver burden, pain, breathlessness, falls, constipation, nausea/vomiting and loneliness. These QIs were further evaluated by clinicians/decision makers working in PC, through the modified Delphi panel, and five were removed from further consideration, resulting in 22 QIs. Conclusions: Through in-depth and multiple-stakeholder consultations we developed a set of QIs generated with data already collected with interRAI assessments. These indicators provide a feasible basis for quality benchmarking and improvement systems for care providers aiming to optimize PC to individuals and their families

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Should rehabilitated hedgehogs be released in winter? A comparison of survival, nest use and weight change in wild and rescued animals

The rehabilitation of sick or injured wildlife and their subsequent release back into the wild is considered important, not only for the welfare of the individual animal but also for the conservation and management of endangered and threatened wildlife. The European hedgehog Erinaceus europaeus has declined by 25% in Britain over the last decade and is the most common mammal admitted to wildlife rehabilitation centres in Britain, with a large proportion of individuals admitted to gain body weight overwinter prior to release in the spring. Consequently, many thousands of hedgehogs are housed overwinter which incurs significant costs for rehabilitation centres, and has potentially animal welfare issues, such as, stress in captivity, reintroduction stress, increased mortality risk and impaired or altered behaviour. To determine if releasing rehabilitated hedgehogs during autumn and winter had an effect on their survival, body weight or nesting behaviour, we compared these factors between 34 rehabilitated hedgehogs with 23 wild hedgehogs across five sites in England over four different winters. Overwinter survival was high for both wild and rehabilitated hedgehogs, with a significant decrease in survival across both groups when hedgehogs became active post hibernation in spring. We found no differences in the survival rates up to 150 days post release, in weight change, or nest use between wild- and winter-released rehabilitated hedgehogs. Our results suggest that under the correct conditions, rehabilitated hedgehogs can be released successfully during winter, therefore avoiding or reducing time in captivity

Effect of Hydrocortisone on Mortality and Organ Support in Patients With Severe COVID-19: The REMAP-CAP COVID-19 Corticosteroid Domain Randomized Clinical Trial.

Importance: Evidence regarding corticosteroid use for severe coronavirus disease 2019 (COVID-19) is limited. Objective: To determine whether hydrocortisone improves outcome for patients with severe COVID-19. Design, Setting, and Participants: An ongoing adaptive platform trial testing multiple interventions within multiple therapeutic domains, for example, antiviral agents, corticosteroids, or immunoglobulin. Between March 9 and June 17, 2020, 614 adult patients with suspected or confirmed COVID-19 were enrolled and randomized within at least 1 domain following admission to an intensive care unit (ICU) for respiratory or cardiovascular organ support at 121 sites in 8 countries. Of these, 403 were randomized to open-label interventions within the corticosteroid domain. The domain was halted after results from another trial were released. Follow-up ended August 12, 2020. Interventions: The corticosteroid domain randomized participants to a fixed 7-day course of intravenous hydrocortisone (50 mg or 100 mg every 6 hours) (n = 143), a shock-dependent course (50 mg every 6 hours when shock was clinically evident) (n = 152), or no hydrocortisone (n = 108). Main Outcomes and Measures: The primary end point was organ support-free days (days alive and free of ICU-based respiratory or cardiovascular support) within 21 days, where patients who died were assigned -1 day. The primary analysis was a bayesian cumulative logistic model that included all patients enrolled with severe COVID-19, adjusting for age, sex, site, region, time, assignment to interventions within other domains, and domain and intervention eligibility. Superiority was defined as the posterior probability of an odds ratio greater than 1 (threshold for trial conclusion of superiority >99%). Results: After excluding 19 participants who withdrew consent, there were 384 patients (mean age, 60 years; 29% female) randomized to the fixed-dose (n = 137), shock-dependent (n = 146), and no (n = 101) hydrocortisone groups; 379 (99%) completed the study and were included in the analysis. The mean age for the 3 groups ranged between 59.5 and 60.4 years; most patients were male (range, 70.6%-71.5%); mean body mass index ranged between 29.7 and 30.9; and patients receiving mechanical ventilation ranged between 50.0% and 63.5%. For the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively, the median organ support-free days were 0 (IQR, -1 to 15), 0 (IQR, -1 to 13), and 0 (-1 to 11) days (composed of 30%, 26%, and 33% mortality rates and 11.5, 9.5, and 6 median organ support-free days among survivors). The median adjusted odds ratio and bayesian probability of superiority were 1.43 (95% credible interval, 0.91-2.27) and 93% for fixed-dose hydrocortisone, respectively, and were 1.22 (95% credible interval, 0.76-1.94) and 80% for shock-dependent hydrocortisone compared with no hydrocortisone. Serious adverse events were reported in 4 (3%), 5 (3%), and 1 (1%) patients in the fixed-dose, shock-dependent, and no hydrocortisone groups, respectively. Conclusions and Relevance: Among patients with severe COVID-19, treatment with a 7-day fixed-dose course of hydrocortisone or shock-dependent dosing of hydrocortisone, compared with no hydrocortisone, resulted in 93% and 80% probabilities of superiority with regard to the odds of improvement in organ support-free days within 21 days. However, the trial was stopped early and no treatment strategy met prespecified criteria for statistical superiority, precluding definitive conclusions. Trial Registration: ClinicalTrials.gov Identifier: NCT02735707