A Perspective Review on Diet Quality, Excess Adiposity, and Chronic Psychosocial Stress and Implications for Early-Onset Colorectal Cancer.

Colorectal cancer (CRC) is the third most common cancer worldwide. Although the overall incidence of CRC has been decreasing over the past 40 y, early-onset colorectal cancer (EOCRC), which is defined as a CRC diagnosis in patients aged >50 y has increased. In this Perspective, we highlight and summarize the association between diet quality and excess adiposity, and EOCRC. We also explore chronic psychosocial stress (CPS), a less investigated modifiable risk factor, and EOCRC. We were able to show that a poor-quality diet, characterized by a high intake of sugary beverages and a Western diet pattern (high intake of red and processed meats, refined grains, and foods with added sugars) can promote risk factors associated with EOCRC development, such as an imbalance in the composition and function of the gut microbiome, presence of chronic inflammation, and insulin resistance. Excess adiposity, particularly obesity onset in early adulthood, is a likely contributor of EOCRC. Although the research is sparse examining CPS and CRC/EOCRC, we describe likely pathways linking CPS to tumorigenesis. Although additional research is needed to understand what factors are driving the uptick in EOCRC, managing body weight, improving diet quality, and mitigating psychosocial stress, may play an important role in reducing an individual's risk of EOCRC.

Utilizing public health data to geotarget hepatitis C virus elimination approaches in urban and rural Michigan.

Using Michigan public health data, we assessed geographical access to specialist providers for hepatitis C virus (HCV) treatment in urban and rural areas in Michigan and explored correlates of HCV in these areas to help inform HCV elimination planning and resource allocations. We found higher HCV incidence in urban areas, lower treatment specialist access in rural areas, but few correlates of HCV across adult populations in both areas. State and local HCV elimination planning should include population-based screening among all adults and address geographical barriers to care.

Increased Driving Distance to Screening Colonoscopy Negatively Affects Bowel Preparation Quality: an Observational Study.

BACKGROUND: To prepare for colonoscopy, patients must consume a bowel purgative and travel from their home to the site of their procedure. The timing of bowel purgative ingestion predicts bowel preparation quality. Currently, it is not known if driving distance impacts bowel preparation quality or adenoma detection. OBJECTIVE: This study investigates the effect of driving distance on bowel preparation and adenoma detection. DESIGN: This is a cross-sectional retrospective analysis of outpatient screening colonoscopy procedures that were completed at an academic medical center. PARTICIPANTS: A total of 5089 patients who completed screening colonoscopy across 3 procedure units were analyzed. MAIN MEASURES: Description of bowel preparation was dichotomized to either adequate or inadequate. Patient residential addresses were converted into geographic coordinates for geospatial analysis of driving distance to their colonoscopy site. KEY RESULTS: Median driving distance was 13.1 miles. Eighty-nine percent of patients had an adequate bowel preparation. The rate of adenoma detection was 37%. On multivariable logistic regression adjusting for age, sex, race, insurance, endoscopist, and site, increasing driving distance (10-mile increments) was negatively associated with adequate bowel preparation (odds ratio = 0.91; 95% confidence interval 0.85 to 0.97), while adenoma detection was positively associated with adequate bowel preparation (odds ratio = 1.53; 95% confidence interval 1.24 to 1.88) but not with driving distance (odds ratio = 1.02; 95% confidence interval 0.98 to 1.06). Driving distances of 30 miles or less were associated with adequate bowel preparation (odds ratio = 1.37; 95% confidence interval 1.09 to 1.72). CONCLUSIONS: Increasing driving distance to screening colonoscopy was negatively associated with adequate bowel preparation but not adenoma detection. Among an academic medical center population, the likelihood of adequate bowel preparation was highest in patients traveling 30 miles or less to their screening colonoscopy. Patient driving distance to colonoscopy is an important consideration in optimizing screening colonoscopy quality.

Microbial methionine transporters and biotechnological applications.

Methionine (Met) is an essential amino acid with commercial value in animal feed, human nutrition, and as a chemical precursor. Microbial production of Met has seen intensive investigation towards a more sustainable alternative to the chemical synthesis that currently meets the global Met demand. Indeed, efficient Met biosynthesis has been achieved in genetically modified bacteria that harbor engineered enzymes and streamlined metabolic pathways. Very recently, the export of Met as the final step during its fermentative production has been studied and optimized, primarily through identification and expression of microbial Met efflux transporters. In this mini-review, we summarize the current knowledge on four families of Met export and import transporters that have been harnessed for the production of Met and other valuable biomolecules. These families are discussed with respect to their function, gene regulation, and biotechnological applications. We cover methods for identification and characterization of Met transporters as the basis for the further engineering of these proteins and for exploration of other solute carrier families. The available arsenal of Met transporters from different species and protein families provides blueprints not only for fermentative production but also synthetic biology systems, such as molecular sensors and cell-cell communication systems. KEY POINTS: • Sustainable production of methionine (Met) using microbes is actively explored. • Met transporters of four families increase production yield and specificity. • Further applications include other biosynthetic pathways and synthetic biology.

Design of a Remote Time-Restricted Eating and Mindfulness Intervention to Reduce Risk Factors Associated with Early-Onset Colorectal Cancer Development among Young Adults.

Early-onset colorectal cancer (EOCRC) is defined as a diagnosis of colorectal cancer (CRC) in individuals younger than 50 years of age. While overall CRC rates in the United States (US) decreased between 2001 and 2018, EOCRC rates have increased. This research project aims to evaluate the feasibility and acceptability of Time-Restricted Eating (TRE), Mindfulness, or TRE combined with Mindfulness among young to middle-aged adults at risk of EOCRC. Forty-eight participants will be randomly assigned to one of four groups: TRE, Mindfulness, TRE and Mindfulness, or Control. Data on feasibility, adherence, and acceptability will be collected. Measures assessed at baseline and post-intervention will include body weight, body composition, dietary intake, physical activity, sleep behavior, circulating biomarkers, hair cortisol, and the gut microbiome. The effects of the intervention on the following will be examined: (1) acceptability and feasibility; (2) body weight, body composition, and adherence to TRE; (3) circulating metabolic, inflammation, and oxidative stress biomarkers; (4) intestinal inflammation; and (5) the gut microbiome. TRE, combined with Mindfulness, holds promise for stress reduction and weight management among individuals at risk of EOCRC. The results of this pilot study will inform the design and development of larger trials aimed at preventing risk factors associated with EOCRC.

Mi-CARE: Comparing Three Evidence-Based Interventions to Promote Colorectal Cancer Screening among Ethnic Minorities within Three Different Clinical Contexts.

Multiple evidence-based interventions (EBIs) have been developed to improve the completion of colorectal cancer (CRC) screening within Federally Qualified Health Centers (FQHCs) and other safety net settings in marginalized communities. Little effort has been made, however, to evaluate their relative effectiveness across different clinical contexts and populations. To this end, we tested the relative effectiveness of three EBIs (mailed birthday cards, lay navigation, and provider-delivered education) among a convenience sample of 1252 patients (aged 50-75 years old, who were due for CRC screening and scheduled for a visit at one of three clinics within a network of Federally Qualified Health Centers (FQHCs) in the United States. To be eligible for the study, patients had to identify as African American (AA) or Latino American (LA). We compared the effects of the three EBIs on CRC screening completion using logistic regression. Overall, 20% of the study population, an increase from a baseline of 13%, completed CRC screening. Clinical demographics appeared to influence the effectiveness of the EBIs. Mailed birthday reminders appeared to be the most effective within the multi-ethnic clinic (p = 0.03), provider-delivered education within the predominantly LA clinic (p = 0.02), and lay navigation within the predominantly AA clinic (p = 0.03). These findings highlight the importance of understanding clinical context when selecting which evidence-based interventions to deploy.

Interventions to improve care related to colorectal cancer among racial and ethnic minorities: a systematic review.

OBJECTIVE: To systematically review the literature to identify interventions that improve minority health related to colorectal cancer care. DATA SOURCES: MEDLINE, PsycINFO, CINAHL, and Cochrane databases, from 1950 to 2010. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS, AND INTERVENTIONS: Interventions in US populations eligible for colorectal cancer screening, and composed of ≥50 % racial/ethnic minorities (or that included a specific sub-analysis by race/ethnicity). All included studies were linked to an identifiable healthcare source. The three authors independently reviewed the abstracts of all the articles and a final list was determined by consensus. All papers were independently reviewed and quality scores were calculated and assigned using the Downs and Black checklist. RESULTS: Thirty-three studies were included in our final analysis. Patient education involving phone or in-person contact combined with navigation can lead to modest improvements, on the order of 15 percentage points, in colorectal cancer screening rates in minority populations. Provider-directed multi-modal interventions composed of education sessions and reminders, as well as pure educational interventions were found to be effective in raising colorectal cancer screening rates, also on the order of 10 to 15 percentage points. No relevant interventions focusing on post-screening follow up, treatment adherence and survivorship were identified. LIMITATIONS: This review excluded any intervention studies that were not tied to an identifiable healthcare source. The minority populations in most studies reviewed were predominantly Hispanic and African American, limiting generalizability to other ethnic and minority populations. CONCLUSIONS AND IMPLICATIONS OF KEY FINDINGS: Tailored patient education combined with patient navigation services, and physician training in communicating with patients of low health literacy, can modestly improve adherence to CRC screening. The onus is now on researchers to continue to evaluate and refine these interventions and begin to expand them to the entire colon cancer care continuum.

Spatial access to primary care providers and colorectal cancer-specific survival in Cook County, Illinois.

BACKGROUND: Spatial access to primary care has been associated with late-stage and fatal breast cancer, but less is known about its relation to outcomes of other screening-preventable cancers such as colorectal cancer. This population-based retrospective cohort study examined whether spatial access to primary care providers associates with colorectal cancer-specific survival. METHODS: Approximately 26 600 incident colorectal cancers diagnosed between 2000 and 2008 in adults residing in Cook County, Illinois were identified through the state cancer registry and georeferenced to the census tract of residence at diagnosis. An enhanced two-step floating catchment area method measured tract-level access to primary care physicians (PCPs) in the year of diagnosis using practice locations obtained from the American Medical Association. Vital status and underlying cause of death were determined using the National Death Index. Fine-Gray proportional subdistribution hazard models analyzed the association between tract-level PCP access scores and colorectal cancer-specific survival after accounting for tract-level socioeconomic status, case demographics, tumor characteristics, and other factors. RESULTS: Increased tract-level access to PCPs was associated with a lower risk of death from colorectal cancer (hazard ratio [HR], 95% confidence interval [CI]) = 0.87 [0.79, 0.96], P = .008, highest vs lowest quintile), especially among persons diagnosed with regional-stage tumors (HR, 95% CI = 0.80 [0.69, 0.93], P = .004, highest vs lowest quintile). CONCLUSIONS: Spatial access to primary care providers is a predictor of colorectal cancer-specific survival in Cook County, Illinois. Future research is needed to determine which areas within the cancer care continuum are most affected by spatial accessibility to primary care such as referral for screening, accessibility of screening and diagnostic testing, referral for treatment, and access to appropriate survivorship-related care.

Geographic variation in spatial accessibility of U.S. healthcare providers.

BACKGROUND: Growing physician maldistribution and population demographic shifts have contributed to large geographic variation in healthcare access and the emergence of advanced practice providers as contributors to the healthcare workforce. Current estimates of geographic accessibility of physicians and advanced practice providers rely on outdated "provider per capita" estimates that have shortcomings. PURPOSE: To apply state of the art methods to estimate spatial accessibility of physician and non-physician clinician groups and to examine factors associated with higher accessibility. METHODS: We used a combination of provider location, medical claims, and U.S. Census data to perform a national study of health provider accessibility. The National Plan and Provider Enumeration System was used along with Medicare claims to identify providers actively caring for patients in 2014 including: primary care physicians (i.e., internal medicine and family medicine), specialists, nurse practitioners, and chiropractors. For each U.S. ZIP code tabulation area, we estimated provider accessibility using the Variable-distance Enhanced 2 step Floating Catchment Area method and performed a Getis-Ord Gi* analysis for each provider group. Generalized linear models were used to examine associations between population characteristics and provider accessibility. RESULTS: National spatial patterns of the provider groups differed considerably. Accessibility of internal medicine most resembled specialists with high accessibility in urban locales, whereas relative higher accessibility of family medicine physicians was concentrated in the upper Midwest. In our adjusted analyses independent factors associated with higher accessibility were very similar between internal medicine physicians and specialists-presence of a medical school in the county was associated with approximately 70% higher accessibility and higher accessibility was associated with urban locales. Nurse practitioners were similar to family medicine physicians with both having higher accessibility in rural locales. CONCLUSIONS: The Variable-distance Enhanced 2 step Floating Catchment Area method is a viable approach to measure spatial accessibility at the national scale.

Is the risk of concomitant invasive esophageal cancer in high-grade dysplasia in Barrett's esophagus overestimated?

BACKGROUND & AIMS: Recent studies have claimed long neoplasia-free survival rates with endoscopic mucosal resection of high-grade dysplasia (HGD) in Barrett's esophagus (BE). However, reports have contended that approximately 40% of patients who have esophagectomy for HGD have occult invasive cancer. The aim of this study was to use explicit criteria to determine the true prevalence of invasive adenocarcinoma in reports of patients who had esophagectomy for HGD in BE. METHODS: Studies reporting rates of esophageal cancer in patients who underwent esophagectomy for HGD in BE were gathered using MEDLINE and PUBMED. We defined invasive esophageal adenocarcinoma (IEAC) as tumor with submucosal invasion or beyond. Intramucosal carcinoma (IMC) was not considered IEAC. RESULTS: Twenty-three articles were selected for analysis. Most investigators reported rates of invasive cancer in the esophagectomy specimen, and the pooled average was 39.9% among the 441 patients who underwent an esophagectomy for HGD. Reported rates varied from 0% to 73%. A total of 267 patients had American Joint Committee on Cancer stage 0 postoperatively, 132 patients had stage I, 23 patients had stage IIa, 10 patients had stage IIb, and 9 patients had stage III. Fourteen studies provided differentiation between intramucosal and submucosal invasion. Among 213 patients, only 12.7% had IEAC, whereas 87.3% had HGD or IMC. The IEAC rate of 11% among patients with visible lesions is greater than the rate of 3% among patients with no visible lesion. CONCLUSIONS: By using strict pathologic definitions of invasive disease, the present study indicates the true prevalence of IEAC in BE and HGD may have been overestimated significantly. Separating IMC from IEAC is clinically relevant because endoscopic techniques potentially may treat IMC.

Evaluating screening colonoscopy quality in an uninsured urban population following patient navigation.

Patient navigation (PN) increases screening colonoscopy completion in minority and uninsured populations. However, colonoscopy quality is under-reported in the setting of PN and quality indicators have often failed to meet benchmark standards. This study investigated screening colonoscopy quality indicators after year-one of a PN initiative targeting the medically uninsured. This was a retrospective analysis of 296 outpatient screening colonoscopies. Patients were 45 to 75 years of age with no history of bowel cancer, inflammatory bowel disease, or colorectal surgery. The screening colonoscopy quality indicators: adenoma detection rate (ADR), cecal intubation rate (CIR), and bowel preparation quality were compared in 89 uninsured Federally Qualified Health Center (FQHC) patients who received PN and 207 University Hospital patients who received usual care. The FQHC PN and University Hospital cohorts were similar in female sex (69% vs. 70%; p = 0.861) and African American race (61% vs. 61%; p = 0.920). The FQHC PN cohort was younger (57 years vs. 60 years; p < 0.001). There was no difference in ADR (33% vs. 32%; p = 0.971) or CIR (96% vs. 95%; p = 0.900) comparing the FQHC PN and University Hospital cohorts. The FQHC PN patients had a greater likelihood of an optimal bowel preparation on multivariate logistic regression (odds ratio 4.17; 95% confidence interval 1.07 to 16.20). Uninsured FQHC patients who received PN were observed to have intra-procedure quality indicators that exceeded bench-mark standards for high-quality screening colonoscopy and were equivalent to those observed in an insured University Hospital patient population.

Knowledge of Polyp History and Recommended Follow-Up Among a Predominately African American Patient Population and the Impact of Patient Navigation.

BACKGROUND AND AIMS: Colorectal screening (CRS) rates in minority and uninsured populations have increased through patient navigation (PN) interventions. However, patient knowledge of colonoscopy results and follow-up recommendations has not been described in an African American (AA) population or following PN. Our objectives were to determine patient knowledge of colonoscopy results and follow-up recommendations within an AA patient population and to compare post-colonoscopy knowledge among patients who received either PN or usual care. METHODS: This is a prospective observational study of patients who completed a screening colonoscopy in 2014. A semi-structured telephone survey was completed by 96 participants (69 % AA, 78 % female, and mean age 63 years). The survey assessed patient recall of polyp results and follow-up recommendations. Responses were compared with the medical record. RESULTS: Of 96 patients surveyed (response rate, 68 %), 83 % accurately reported if polyps were detected and 66 % accurately reported their recommended follow-up. The identification of adenomatous polyps on colonoscopy was a predictor of accurate recall of colonoscopy results and follow-up recommendations. Uninsured patients who completed PN (18 of 96) were more likely to accurately report polyp results (100 vs. 80 %; P = 0.036), but the rates of accurate follow-up recall were not statistically significant (44 vs. 71 %; P = 0.053) when compared to usual care patients. CONCLUSIONS: In an AA population, post-colonoscopy polyp recall rates were similar to those described in white populations. Uninsured patients who completed PN were more likely than insured usual care patients to accurately report the presence of polyps on colonoscopy.

Are We Missing the Mark? The Implementation of Community Based Participatory Education in Cancer Disparities Curriculum Development.

OBJECTIVE: The Chicago south side, even more so than national populations, continues to be burdened with widening gaps of disparities in cancer outcomes. Therefore, Chicago community members were engaged in addressing the following content areas for a cancer disparities curriculum: (1) the south side Chicago community interest in participating in curriculum design, (2) how community members should be involved in designing cancer disparities curriculum, and (3) what community members believe the curriculum should address to positively impact their community. METHODS: Eighty-six community members from 19 different zip code areas of Chicago attended the deliberative session. A survey composed of three quantitative and three short-answer content questions was analyzed. RESULTS: The majority of participants were from the south side of Chicago (62 %) and females (86 %). Most, 94 %, believed community members should be involved in cancer disparities curriculum development. Moreover, 56 % wanted to be involved in designing the curriculum, and 61 % reported an interest in taking a course in cancer disparities. Three categorical themes were derived from the qualitative questions: (1) community empowerment through disparities education-"a prescription for change," (2) student skill development in community engagement and advocacy training, and (3) community expression of shared experiences in cancer health disparities. CONCLUSION: The community provided valuable input for curricular content and has an interest in collaborating on cancer disparities curriculum design. Community participation must be galvanized to improve disparities curricular development and delivery to successfully address the challenges of eliminating disparities in health.

Modulation of leukocyte recruitment and IL-8 expression by the membrane attack complex of complement (C5b-9) in a rabbit model of antigen-induced arthritis.

The complement system is thought to be a major physiological mediator of injury in a number of diseases including rheumatoid arthritis (RA). The membrane attack complex (MAC) of complement has been detected in RA tissue, suggesting that the MAC may be relevant to the pathogenesis of the disease. Deposition of sublytic concentrations of the MAC has been shown to promote the expression of proinflammatory mediators. In the present study, we utilized rabbits deficient in the complement protein C6 to elucidate the role of the MAC in mediating the pathogenesis of antigen-induced arthritis. Swelling, leukocyte accumulation, IL-8 expression, proteoglycan, and hydroxyproline content were assessed. Analysis of synovial tissue demonstrated a significant decrease in leukocyte influx and a parallel decrease in tissue associated IL-8 in joints of C6-deficient animals as compared to C6-sufficient animals. However, this did not correlate with the preservation of connective tissue. The results derived from this study provide evidence that the MAC has an important function in mediating leukocyte recruitment in antigen-induced arthritis but does not play a direct role in connective tissue breakdown.

A resident-led quality improvement initiative to improve obesity screening.

Instruction on quality improvement (QI) methods is required as part of residency education; however, there is limited evidence regarding whether internal medicine residents can improve patient care using these methods. Because obesity screening is not done routinely in clinical practice, residents aimed to improve screening using QI techniques. Residents streamlined body mass index (BMI) documentation, created educational materials about obesity, and launched an obesity screening QI initiative in a residency clinic. Residents designed plan-do-study-act cycles focused on increasing awareness and maintaining improvements in screening over a 1-year period. Documentation rates were collected at baseline, 2 weeks, 6 months, and 1 year post-intervention. At 1 year, obesity treatment rates also were collected. BMI documentation rates after 1 year were higher than baseline (43% vs 4%, P < .0001). In obese patients, BMI documentation was associated with lifestyle counseling (34% vs 14%, P < .01). An internal medicine resident-led QI project targeting obesity can improve screening.

The influence of age on T cell generation and TCR diversity.

The ability to mount protective immune responses depends on the diversity of T cells. T cell diversity may be compromised by the declining thymic output of new T cells. The aging process imposes a threat to diversity, because thymic function deteriorates. In this study we have examined the relationship between thymic production, homeostatic T cell proliferation and TCR beta-chain diversity in young (approximately 25 years), middle-aged ( approximately 60 years), and elderly adults (approximately 75 years). TCR excision circles (TREC) as a marker of thymic output exponentially decreased by >95% between 25 and 60 years of age. The frequency of Ki67(+) cycling CD4 T cells remained steady, and surprisingly, the diversity of the naive CD4 T cell repertoire was maintained at approximately 2 x 10(7) different TCR beta-chains. After the age of 70 years, TRECs only slightly declined, but homeostatic proliferation doubled. The diversity of the T cell pool drastically contracted to 200,000 TCR beta-chains. Also, the phenotypic distinction between naive and memory CD4 T cells became fuzzy. The collapse in CD4 T cell diversity during the seventh and eighth decades indicates substantial T cell loss and implies that therapeutic measures to improve vaccine responses will have to include strategies for T cell replenishment.