Safely Identifying Emergency Department Patients With Acute Chest Pain for Early Discharge.

BACKGROUND: The HEART Pathway (history, ECG, age, risk factors, and initial troponin) is an accelerated diagnostic protocol designed to identify low-risk emergency department patients with chest pain for early discharge without stress testing or angiography. The objective of this study was to determine whether implementation of the HEART Pathway is safe (30-day death and myocardial infarction rate <1% in low-risk patients) and effective (reduces 30-day hospitalizations) in emergency department patients with possible acute coronary syndrome. METHODS: A prospective pre-post study was conducted at 3 US sites among 8474 adult emergency department patients with possible acute coronary syndrome. Patients included were ≥21 years old, investigated for possible acute coronary syndrome, and had no evidence of ST-segment-elevation myocardial infarction on ECG. Accrual occurred for 12 months before and after HEART Pathway implementation from November 2013 to January 2016. The HEART Pathway accelerated diagnostic protocol was integrated into the electronic health record at each site as an interactive clinical decision support tool. After accelerated diagnostic protocol integration, ED providers prospectively used the HEART Pathway to identify patients with possible acute coronary syndrome as low risk (appropriate for early discharge without stress testing or angiography) or non-low risk (appropriate for further in-hospital evaluation). The primary safety and effectiveness outcomes, death, and myocardial infarction (MI) and hospitalization rates at 30 days were determined from health records, insurance claims, and death index data. RESULTS: Preimplementation and postimplementation cohorts included 3713 and 4761 patients, respectively. The HEART Pathway identified 30.7% as low risk; 0.4% of these patients experienced death or MI within 30 days. Hospitalization at 30 days was reduced by 6% in the postimplementation versus preimplementation cohort (55.6% versus 61.6%; adjusted odds ratio, 0.79; 95% CI, 0.71-0.87). During the index visit, more MIs were detected in the postimplementation cohort (6.6% versus 5.7%; adjusted odds ratio, 1.36; 95% CI, 1.12-1.65). Rates of death or MI during follow-up were similar (1.1% versus 1.3%; adjusted odds ratio, 0.88; 95% CI, 0.58-1.33). CONCLUSIONS: HEART Pathway implementation was associated with decreased hospitalizations, increased identification of index visit MIs, and a very low death and MI rate among low-risk patients. These findings support use of the HEART Pathway to identify low-risk patients who can be safely discharged without stress testing or angiography. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02056964.

Mild cognitive impairment in long-term brain tumor survivors following brain irradiation.

INTRODUCTION: There is no accepted classification of cognitive impairment in cancer survivors. We assess the extent of mild cognitive impairment (MCI) syndrome in brain tumor survivors using criteria adapted from the National Institute on Aging and the Alzheimer's Association (NIA-AA). METHODS: We retrospectively reviewed the cognitive data of brain tumor survivors post-radiation therapy (RT) enrolled from 2008 to 2011 in a randomized trial of donepezil versus placebo for cognitive impairment. One hundred and ninety eight adult survivors with primary or metastatic brain tumors who were ≥ 6 months post RT were recruited at 24 sites in the United States. Cognitive function was assessed at baseline, 12 and 24 weeks post-randomization. For this analysis, we used baseline data to identify MCI and possible dementia using adapted NIA-AA criteria. Cases were subtyped into four groups: amnestic MCI-single domain (aMCI-sd), amnestic MCI-multiple domain (aMCI-md), non-amnestic MCI-single domain (naMCI-sd), and non-amnestic MCI-multiple domain (naMCI-md). RESULTS: One hundred and thirty one of 197 evaluable patients (66%) met criteria for MCI. Of these, 13% were classified as aMCI-sd, 58% as aMCI-md, 19% as naMCI-sd, and 10% as naMCI-md. Patients with poorer performance status, less education, lower household income and those not working outside the home were more likely to be classified as MCI. CONCLUSION: Two-thirds of post-RT brain tumor survivors met NIA-AA criteria for MCI. This taxonomy may be useful when applied to brain tumor survivors because it defines cognitive phenotypes that may be differentially associated with course, treatment response, and risk factor profiles.

Cognitive functioning following brain irradiation as part of cancer treatment: Characterizing better cognitive performance.

OBJECTIVE: Although brain radiation therapy (RT) impacts cognitive function, little is known about the subset of survivors with minimal cognitive deficits. This study compares the characteristics of patients receiving brain irradiation as part of cancer treatment with minimal cognitive deficits to those with poorer cognitive functioning. METHODS: Adults at least 6 months postbrain RT (N = 198) completed cognitive measures of attention, memory, and executive functions. Cognitive functioning was categorized into better- and poorer-performing groups, with better-performing survivors scoring no worse than 1.5 standard deviations below the published normative mean on all cognitive measures. Logistic regression was used to identify variables associated with better-performing group membership. RESULTS: Approximately 25% of the sample met the criteria for the better-performing group. In unadjusted analyses, RT type (whole brain irradiation and partial brain irradiation), sedating medications, and fatigue were independently associated with cognition. Sociodemographic and other clinical characteristics were not significant. In adjusted analyses, only fatigue remained significantly associated with group membership (OR = 1.05, 95% CI = 1.01-1.09, P = .009). CONCLUSIONS: There is a subgroup of survivors with minimal long-term cognitive deficits despite undergoing a full course of brain RT as part of cancer treatment. Lower fatigue had the strongest association with better cognitive performance. Interventions targeting cancer-related fatigue may help buffer the neurotoxic effects of brain RT.

Effect of a Digital Health Intervention on Receipt of Colorectal Cancer Screening in Vulnerable Patients: A Randomized Controlled Trial.

Background: Screening for colorectal cancer (CRC) reduces mortality, yet more than one third of age-eligible Americans are unscreened. Objective: To examine the effect of a digital health intervention, Mobile Patient Technology for Health-CRC (mPATH-CRC), on rates of CRC screening. Design: Randomized clinical trial. (ClinicalTrials.gov: NCT02088333). Setting: 6 community-based primary care practices. Participants: 450 patients (223 in the mPATH-CRC group and 227 in usual care) scheduled for a primary care visit and due for routine CRC screening. Intervention: An iPad application that displays a CRC screening decision aid, lets patients order their own screening tests, and sends automated follow-up electronic messages to support patients. Measurements: The primary outcome was chart-verified completion of CRC screening within 24 weeks. Secondary outcomes were ability to state a screening preference, intention to receive screening, screening discussions, and orders for screening tests. All outcome assessors were blinded to randomization. Results: Baseline characteristics were similar between groups; 37% of participants had limited health literacy, and 53% had annual incomes less than $20 000. Screening was completed by 30% of mPATH-CRC participants and 15% of those receiving usual care (logistic regression odds ratio, 2.5 [95% CI, 1.6 to 4.0]). Compared with usual care, more mPATH-CRC participants could state a screening preference, planned to be screened within 6 months, discussed screening with their provider, and had a screening test ordered. Half of mPATH-CRC participants (53%; 118 of 223) "self-ordered" a test via the program. Limitation: Participants were English speakers in a single health care system. Conclusion: A digital health intervention that allows patients to self-order tests can increase CRC screening. Future research should identify methods for implementing similar interventions in clinical care. Primary Funding Source: National Cancer Institute.

Natural genetic variation profoundly regulates gene expression in immune cells and dictates susceptibility to CNS autoimmunity.

Regulation of gene expression in immune cells is known to be under genetic control, and likely contributes to susceptibility to autoimmune diseases such as multiple sclerosis (MS). How this occurs in concert across multiple immune cell types is poorly understood. Using a mouse model that harnesses the genetic diversity of wild-derived mice, more accurately reflecting genetically diverse human populations, we provide an extensive characterization of the genetic regulation of gene expression in five different naive immune cell types relevant to MS. The immune cell transcriptome is shown to be under profound genetic control, exhibiting diverse patterns: global, cell-specific and sex-specific. Bioinformatic analysis of the genetically controlled transcript networks reveals reduced cell type specificity and inflammatory activity in wild-derived PWD/PhJ mice, compared with the conventional laboratory strain C57BL/6J. Additionally, candidate MS-GWAS (genome-wide association study candidate genes for MS susceptibility) genes were significantly enriched among transcripts overrepresented in C57BL/6J cells compared with PWD. These expression level differences correlate with robust differences in susceptibility to experimental autoimmune encephalomyelitis, the principal model of MS, and skewing of the encephalitogenic T-cell responses. Taken together, our results provide functional insights into the genetic regulation of the immune transcriptome, and shed light on how this in turn contributes to susceptibility to autoimmune disease.

Standardized Rehabilitation and Hospital Length of Stay Among Patients With Acute Respiratory Failure: A Randomized Clinical Trial.

IMPORTANCE: Physical rehabilitation in the intensive care unit (ICU) may improve the outcomes of patients with acute respiratory failure. OBJECTIVE: To compare standardized rehabilitation therapy (SRT) to usual ICU care in acute respiratory failure. DESIGN, SETTING, AND PARTICIPANTS: Single-center, randomized clinical trial at Wake Forest Baptist Medical Center, North Carolina. Adult patients (mean age, 58 years; women, 55%) admitted to the ICU with acute respiratory failure requiring mechanical ventilation were randomized to SRT (n=150) or usual care (n=150) from October 2009 through May 2014 with 6-month follow-up. INTERVENTIONS: Patients in the SRT group received daily therapy until hospital discharge, consisting of passive range of motion, physical therapy, and progressive resistance exercise. The usual care group received weekday physical therapy when ordered by the clinical team. For the SRT group, the median (interquartile range [IQR]) days of delivery of therapy were 8.0 (5.0-14.0) for passive range of motion, 5.0 (3.0-8.0) for physical therapy, and 3.0 (1.0-5.0) for progressive resistance exercise. The median days of delivery of physical therapy for the usual care group was 1.0 (IQR, 0.0-8.0). MAIN OUTCOMES AND MEASURES: Both groups underwent assessor-blinded testing at ICU and hospital discharge and at 2, 4, and 6 months. The primary outcome was hospital length of stay (LOS). Secondary outcomes were ventilator days, ICU days, Short Physical Performance Battery (SPPB) score, 36-item Short-Form Health Surveys (SF-36) for physical and mental health and physical function scale score, Functional Performance Inventory (FPI) score, Mini-Mental State Examination (MMSE) score, and handgrip and handheld dynamometer strength. RESULTS: Among 300 randomized patients, the median hospital LOS was 10 days (IQR, 6 to 17) for the SRT group and 10 days (IQR, 7 to 16) for the usual care group (median difference, 0 [95% CI, -1.5 to 3], P = .41). There was no difference in duration of ventilation or ICU care. There was no effect at 6 months for handgrip (difference, 2.0 kg [95% CI, -1.3 to 5.4], P = .23) and handheld dynamometer strength (difference, 0.4 lb [95% CI, -2.9 to 3.7], P = .82), SF-36 physical health score (difference, 3.4 [95% CI, -0.02 to 7.0], P = .05), SF-36 mental health score (difference, 2.4 [95% CI, -1.2 to 6.0], P = .19), or MMSE score (difference, 0.6 [95% CI, -0.2 to 1.4], P = .17). There were higher scores at 6 months in the SRT group for the SPPB score (difference, 1.1 [95% CI, 0.04 to 2.1, P = .04), SF-36 physical function scale score (difference, 12.2 [95% CI, 3.8 to 20.7], P = .001), and the FPI score (difference, 0.2 [95% CI, 0.04 to 0.4], P = .02). CONCLUSIONS AND RELEVANCE: Among patients hospitalized with acute respiratory failure, SRT compared with usual care did not decrease hospital LOS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00976833.

Tumor-induced loss of mural Connexin 43 gap junction activity promotes endothelial proliferation.

BACKGROUND: Proper functional association between mural cells and endothelial cells (EC) causes EC of blood vessels to become quiescent. Mural cells on tumor vessels exhibit decreased attachment to EC, which allows vessels to be unstable and proliferative. The mechanisms by which tumors prevent proper association between mural cells and EC are not well understood. Since gap junctions (GJ) play an important role in cell-cell contact and communication, we investigated whether loss of GJ plays a role in tumor-induced mural cell dissociation. METHODS: Mural cell regulation of endothelial proliferation was assessed by direct co-culture assays of fluorescently labeled cells quantified by flow cytometry or plate reader. Gap junction function was assessed by parachute assay. Connexin 43 (Cx43) protein in mural cells exposed to conditioned media from cancer cells was assessed by Western and confocal microscopy; mRNA levels were assessed by quantitative real-time PCR. Expression vectors or siRNA were utilized to overexpress or knock down Cx43. Tumor growth and angiogenesis was assessed in mouse hosts deficient for Cx43. RESULTS: Using parachute dye transfer assay, we demonstrate that media conditioned by MDA-MB-231 breast cancer cells diminishes GJ communication between mural cells (vascular smooth muscle cells, vSMC) and EC. Both protein and mRNA of the GJ component Connexin 43 (Cx43) are downregulated in mural cells by tumor-conditioned media; media from non-tumorigenic MCF10A cells had no effect. Loss of GJ communication by Cx43 siRNA knockdown, treatment with blocking peptide, or exposure to tumor-conditioned media diminishes the ability of mural cells to inhibit EC proliferation in co-culture assays, while overexpression of Cx43 in vSMC restores GJ and endothelial inhibition. Breast tumor cells implanted into mice heterozygous for Cx43 show no changes in tumor growth, but exhibit significantly increased tumor vascularization determined by CD31 staining, along with decreased mural cell support detected by NG2 staining. CONCLUSIONS: Our data indicate that i) functional Cx43 is required for mural cell-induced endothelial quiescence, and ii) downregulation of Cx43 GJ by tumors frees endothelium to respond to angiogenic cues. These data define a novel and important role for maintained Cx43 function in regulation of vessel quiescence, and suggest its loss may contribute to pathological tumor angiogenesis.

Trajectories of Posttraumatic Growth and Associated Characteristics in Women with Breast Cancer.

BACKGROUND: Cancer survivors may experience posttraumatic growth (PTG), positive psychological changes resulting from highly stressful events; however, the longitudinal course of PTG is poorly understood. PURPOSE: The purpose of the present study was to determine trajectories of PTG in breast cancer survivors and associated characteristics. METHODS: Women (N = 653) participating in a longitudinal observational study completed questionnaires within 8 months of breast cancer diagnosis and 6, 12, and 18 months later. Group-based modeling identified PTG trajectories. Chi-square tests and ANOVA detected group differences in demographic, medical, and psychosocial variables. RESULTS: Six trajectory groups emerged. Three were stable at different levels of PTG, two increased modestly, and one increased substantially over time. Trajectory groups differed by age, race, receipt of chemotherapy, illness intrusiveness, depressive symptoms, active-adaptive coping, and social support. CONCLUSIONS: This first examination of PTG trajectories in US cancer survivors elucidates heterogeneity in longitudinal patterns of PTG. Future research should determine whether other samples exhibit similar trajectories and whether various PTG trajectories predict mental and physical health outcomes.

Disparities in barriers to follow-up care between African American and White breast cancer survivors.

PURPOSE: Despite recommendations for breast cancer survivorship care, African American women are less likely to receive appropriate follow-up care, which is concerning due to their higher mortality rates. This study describes differences in barriers to follow-up care between African American and White breast cancer survivors. METHODS: We conducted a mailed survey of women treated for non-metastatic breast cancer in 2009-2011, 6-24 months post-treatment (N = 203). Survivors were asked about 14 potential barriers to follow-up care. We used logistic regression to explore associations between barriers and race, adjusting for covariates. RESULTS: Our participants included 31 African American and 160 White survivors. At least one barrier to follow-up care was reported by 62 %. Compared to White survivors, African Americans were more likely to identify barriers related to out-of-pocket costs (28 vs. 51.6 %, p = 0.01), other health care costs (21.3 vs. 45.2 %, p = 0.01), anxiety/worry (29.4 vs. 51.6 %, p = 0.02), and transportation (4.4 vs. 16.1 %, p = 0.03). After adjustment for covariates, African Americans were three times as likely to report at least one barrier to care (odds ratio (OR) = 3.3, 95 % confidence interval (CI) = 1.1-10.1). CONCLUSIONS: Barriers to care are common among breast cancer survivors, especially African American women. Financial barriers to care may prevent minority and underserved survivors from accessing follow-up care. Enhancing insurance coverage or addressing out-of-pocket costs may help address financial barriers to follow-up care among breast cancer survivors. Psychosocial care aimed at reducing fear of recurrence may also be important to improve access among African American breast cancer survivors.

Rural-urban disparities in health status among US cancer survivors.

BACKGROUND: Although rural residents are more likely to be diagnosed with more advanced cancers and to die of cancer, little is known about rural-urban disparities in self-reported health among survivors. METHODS: The authors identified adults who had a self-reported history of cancer from the National Health Interview Survey (2006-2010). Rural-urban residence was defined using US Census definitions. Logistic regression with weighting to account for complex sampling was used to assess rural-urban differences in health status after accounting for differences in demographic characteristics. RESULTS: Of the 7804 identified cancer survivors, 20.8% were rural residents. This translated to a population of 2.8 million rural cancer survivors in the United States. Rural survivors were more likely than urban survivors to be non-Hispanic white (P < .001), to have less education (P < .001), and to lack health insurance (P < .001). Rural survivors reported worse health in all domains. After adjustment for sex, race/ethnicity, age, marital status, education, insurance, time since diagnosis, and number of cancers, rural survivors were more likely to report fair/poor health (odds ratio, 1.39; 95% confidence interval, 1.20-1.62), psychological distress (odds ratio, 1.23; 95% confidence interval, 1.00-1.50), ≥2 noncancer comorbidities (odds ratio, 1.15; 95% confidence interval, 1.01-1.32), and health-related unemployment (odds ratio, 1.66; 95% confidence interval, 1.35-2.03). CONCLUSIONS: The current results provide the first estimates of the proportion and number of US adult cancer survivors who reside in rural areas. Rural cancer survivors are at greater risk for a variety of poor health outcomes, even many years after their cancer diagnosis, and should be a target for interventions to improve their health and well being.

Age-related longitudinal changes in depressive symptoms following breast cancer diagnosis and treatment.

Younger women being treated for breast cancer consistently show greater depression shortly after diagnosis than older women. In this longitudinal study, we examine whether these age differences persist over the first 26 months following diagnosis and identify factors related to change in depressive symptoms. A total of 653 women within 8 months of a first time breast cancer diagnosis completed questionnaires at baseline and three additional timepoints (6, 12, and 18 months after baseline) on contextual/patient characteristics, symptoms, and psychosocial variables. Chart reviews provided cancer and treatment-related data. The primary outcome was depressive symptomatology assessed by the Beck Depression Inventory. Among women younger than age 65, depressive symptoms were highest soon after diagnosis and significantly decreased over time. Depressive symptoms remained stable and low for women aged 65 and older. Age was no longer significantly related to depressive symptoms in multivariable analyses controlling for a wide range of covariates. The primary factors related to levels of and declines in depressive symptomatology were the ability to pay for basics; completing chemotherapy with doxorubicin; and decreases in pain, vasomotor symptoms, illness intrusiveness, and passive coping. Increased sense of meaning/peace and social support were related to decreased depression. Interventions to reduce symptoms and illness intrusiveness, improve a sense of meaning and peace, and increase social support, may help reduce depression and such interventions may be especially relevant for younger women.

Rural-urban differences in health behaviors and implications for health status among US cancer survivors.

PURPOSE: Rural US adults have increased risk of poor outcomes after cancer, including increased cancer mortality. Rural-urban differences in health behaviors have been identified in the general population and may contribute to cancer health disparities, but have not yet been examined among US survivors. We examined rural-urban differences in health behaviors among cancer survivors and associations with self-reported health and health-related unemployment. METHODS: We identified rural (n = 1,642) and urban (n = 6,162) survivors from the cross-sectional National Health Interview Survey (2006-2010) and calculated the prevalence of smoking, physical activity, overweight/obesity, and alcohol consumption. Multivariable models were used to examine the associations of fair/poor health and health-related unemployment with health behaviors and rural-urban residence. RESULTS: The prevalence of fair/poor health (rural 36.7 %, urban 26.6 %), health-related unemployment (rural 18.5 %, urban 10.6 %), smoking (rural 25.3 %, urban 15.8 %), and physical inactivity (rural 50.7 %, urban 38.7 %) was significantly higher in rural survivors (all p < .05); alcohol consumption was lower (rural 46.3 %, urban 58.6 %), and there were no significant differences in overweight/obesity (rural 65.4 %, urban 62.6 %). All health behaviors were significantly associated with fair/poor health and health-related unemployment in both univariate and multivariable models. After adjustment for behaviors, rural survivors remained more likely than urban survivors to report fair/poor health (OR = 1.21, 95 % CI 1.03-1.43) and health-related unemployment (OR = 1.49, 95 % CI 1.18-1.88). CONCLUSIONS: Rural survivors may need tailored, accessible health promotion interventions to address health-compromising behaviors and improve outcomes after cancer.

Racial/Ethnic disparities in health care receipt among male cancer survivors.

OBJECTIVES: We examined racial/ethnic disparities in health care receipt among a nationally representative sample of male cancer survivors. METHODS: We identified men aged 18 years and older from the 2006-2010 National Health Interview Survey who reported a history of cancer. We assessed health care receipt in 4 self-reported measures: primary care visit, specialist visit, flu vaccination, and pneumococcal vaccination. We used hierarchical logistic regression modeling, stratified by age (< 65 years vs ≥ 65 years). RESULTS: In adjusted models, older African American and Hispanic survivors were approximately twice as likely as were non-Hispanic Whites to not see a specialist (odds ratio [OR] = 1.78; 95% confidence interval [CI] = 1.19, 2.68 and OR = 2.09; 95% CI = 1.18, 3.70, respectively), not receive the flu vaccine (OR = 2.21; 95% CI = 1.45, 3.37 and OR = 2.20; 95% CI = 1.21, 4.01, respectively), and not receive the pneumococcal vaccine (OR = 2.24; 95% CI = 1.54, 3.24 and OR = 3.10; 95% CI = 1.75, 5.51, respectively). CONCLUSIONS: Racial/ethnic disparities in health care receipt are evident among older, but not younger, cancer survivors, despite access to Medicare. These survivors may be less likely to see specialists, including oncologists, and receive basic preventive care.

Predictors of posttraumatic growth in women with breast cancer.

OBJECTIVE: Posttraumatic growth (PTG) is defined as 'positive psychological change experienced as a result of a struggle with highly challenging life circumstances'. The current study examined change in PTG over 2 years following breast cancer diagnosis and variables associated with PTG over time. METHODS: Women recently diagnosed with breast cancer completed surveys within 8 months of diagnosis and 6, 12, and 18 months later. Linear mixed effects models were used to assess the longitudinal effects of demographic, medical, and psychosocial variables on PTG as measured by the Posttraumatic Growth Inventory (PTGI). RESULTS: A total of 653 women were accrued (mean age = 54.9, SD = 12.6). Total PTGI score increased over time mostly within the first few months following diagnosis. In the longitudinal model, greater PTGI scores were associated with education level, longer time since diagnosis, greater baseline level of illness intrusiveness, and increases in social support, spirituality, use of active-adaptive coping strategies, and mental health. Findings for the PTGI domains were similar to those for the total score except for the Spiritual Change domain. CONCLUSION: PTG develops relatively soon after a breast cancer diagnosis and is associated with baseline illness intrusiveness and increases in social support, spirituality, use of active-adaptive coping strategies, and mental health.

A retrospective review of the metabolic syndrome in women diagnosed with breast cancer and correlation with estrogen receptor.

Women diagnosed with obesity and breast cancer have an increased risk of recurrence and death (Protani et al., Breast Cancer Res Treat 123:627-635, 1). Obesity is associated with the metabolic syndrome--a pathophysiologically distinct inflammatory process comprised of central obesity, insulin resistance, hypertension, and atherogenic dyslipidemia. The relationship of obesity as a risk factor for breast cancer is complex with a protective effect for younger women in contrast to a risk for older women (Kabat et al., Cancer Epidemiol Biomarkers Prev 18:2046-2053, 2; Ursin et al., Epidemiology 6:137-141, 3). The metabolic syndrome has been associated with the risk of cancer, and pro-inflammatory circulating factors may be associated with risk of more aggressive breast cancer (Capasso et al., Cancer Biol Ther 10:1240-1243, 4; Healy et al., Clin Oncol (R Coll Radiol) 22:281-288, 5; Laukkanen et al., Cancer Epidemiol Biomarkers Prev 13:1646-1650, 6). We conducted a retrospective review of 860 breast cancer patients to determine the relationship between estrogen receptor status and the metabolic syndrome. We collected the relevant metabolic diagnoses, medications, physical findings, and laboratory values and adapted the National Cholesterol Education Program criteria to define the metabolic syndrome retrospectively. No relationship was found between estrogen receptor status and the individual components of the metabolic syndrome. Based on findings in the medical records, 15% of the women with breast cancer had the metabolic syndrome, and 26% of the women were considered obese, 16% hyperglycemic, 54% hypertensive, and 30% dyslipidemic. The metabolic syndrome was associated with advanced age and African-American race (P < 0.001). When adjusted for age, race, and stage, the metabolic syndrome was marginally associated with estrogen receptor-positive tumors (P = 0.054). Our findings do not support the concern that the metabolic syndrome may contribute to more biologically aggressive breast cancer.

Phase II study of Ginkgo biloba in irradiated brain tumor patients: effect on cognitive function, quality of life, and mood.

UNLABELLED: Ginkgo biloba has been reported to improve cognitive function in older adults and patients with Alzheimer's disease and multi-infarct dementia. We conducted an open-label phase II study of this botanical product in symptomatic irradiated brain tumor survivors. Eligibility criteria included: life expectancy ≥30 weeks, partial or whole brain radiation ≥6 months before enrollment, no imaging evidence of tumor progression in previous 3 months, or stable or decreasing steroid dose, and no brain tumor treatment planned while on study. The Ginkgo biloba dose was 120 mg/day (40 mg t.i.d.) for 24 weeks followed by a 6-week washout period. Assessments performed at baseline, 12, 24 (end of treatment), and 30 weeks (end of washout) included KPS, Functional Assessment of Cancer Therapy-Brain (FACT-Br), Profile of Mood States, Mini-Mental Status Exam, Trail Making Test Parts A (TMT-A) and B (TMT-B), Digit Span Test, Modified Rey Osterrieth Complex Figure (ROCF), California Verbal Learning Test Part II, and the F-A-S Test. RESULTS: Of the 34 patients enrolled on study, 23 (68 %) completed 12 weeks of treatment and 19 (56 %) completed 24 weeks of treatment. There were significant improvements at 24 weeks in: executive function (TMT-B) (p = 0.007), attention/concentration (TMT-A) (p = 0.002), and non-verbal memory (ROCF-immediate/delayed recall) (p = 0.001/0.002), mood (p = 0.002), FACT-Br subscale (p = 0.001), and the FACT physical subscale (p = 0.003). CONCLUSIONS: Some improvement in quality of life and cognitive function were noted with Ginkgo biloba. However, treatment with Ginkgo biloba was associated with a high dropout rate.

Breast cancer subtype affects patterns of failure of brain metastases after treatment with stereotactic radiosurgery.

We investigate the variance in patterns of failure after Gamma Knife™ radiosurgery (GKRS) for patients with brain metastases based on the subtype of the primary breast cancer. Between 2000 and 2010, 154 breast cancer patients were treated with GKRS for brain metastases. Tumor subtypes were approximated based on hormone receptor (HR) and HER2 status of the primary cancer: Luminal A/B (HR+/HER2(-)); HER2 (HER2+/HR(-)); Luminal HER2 (HR+/HER2+), Basal (HR(-)/HER2(-)), and then based on HER2 status alone. The median follow-up period was 54 months. Kaplan-Meier method was used to estimate survival times. Multivariable analysis was performed using Cox regression models. Median number of lesions treated was two (range 1-15) with a median dose of 20 Gy (range 9-24 Gy). Median overall survival (OS) was 7, 9, 11 and 22 months for Basal, Luminal A/B, HER2, and Luminal HER2, respectively (p = 0.001), and was 17 and 8 months for HER2+ and HER(-) patients, respectively (p < 0.001). Breast cancer subtype did not predict time to local failure (p = 0.554), but did predict distant brain failure rate (76, 47, 47, 36 % at 1 year for Basal, Luminal A/B, HER2, and Luminal HER2 respectively, p < 0.001). An increased proportion of HER2+ patients experienced neurologic death (46 vs 31 %, p = 0.066). Multivariate analysis revealed that HER2+ patients (p = 0.007) independently predicted for improved survival. Women with basal subtype have high rates of distant brain failure and worsened survival. Our data suggest that differences in biologic behavior of brain metastasis occur across breast cancer subtypes.

Differences in arachidonic acid levels and fatty acid desaturase (FADS) gene variants in African Americans and European Americans with diabetes or the metabolic syndrome.

Over the past 50 years, increases in dietary n-6 PUFA, such as linoleic acid, have been hypothesised to cause or exacerbate chronic inflammatory diseases. The present study examines an individual's innate capacity to synthesise n-6 long-chain PUFA (LC-PUFA) with respect to the fatty acid desaturase (FADS) locus in Americans of African and European descent with diabetes or the metabolic syndrome. Compared with European Americans (EAm), African Americans (AfAm) exhibited markedly higher serum levels of arachidonic acid (AA) (EAm 7·9 (sd 2·1), AfAm 9·8 (sd 1·9) % of total fatty acids; P < 2·29 × 10⁻9) and the AA:n-6-precursor fatty acid ratio, which estimates FADS1 activity (EAm 5·4 (sd 2·2), AfAm 6·9 (sd 2·2); P = 1·44 × 10⁻5). In all, seven SNP mapping to the FADS locus revealed strong association with AA, EPA and dihomo-γ-linolenic acid (DGLA) in the EAm. Importantly, EAm homozygous for the minor allele (T) had significantly lower AA levels (TT 6·3 (sd 1·0); GG 8·5 (sd 2·1); P = 3·0 × 10⁻5) and AA:DGLA ratios (TT 3·4 (sd 0·8), GG 6·5 (sd 2·3); P = 2·2 × 10⁻7) but higher DGLA levels (TT 1·9 (sd 0·4), GG 1·4 (sd 0·4); P = 3·3 × 10⁻7) compared with those homozygous for the major allele (GG). Allele frequency patterns suggest that the GG genotype at rs174537 (associated with higher circulating levels of AA) is much higher in AfAm (0·81) compared with EAm (0·46). Similarly, marked differences in rs174537 genotypic frequencies were observed in HapMap populations. These data suggest that there are probably important differences in the capacity of different populations to synthesise LC-PUFA. These differences may provide a genetic mechanism contributing to health disparities between populations of African and European descent.

Effects of liquid type, delivery method, and bolus volume on penetration-aspiration scores in healthy older adults during flexible endoscopic evaluation of swallowing.

OBJECTIVES: The type of liquid (eg, water or milk) that should be used during flexible endoscopic evaluation of swallowing (FEES) has received little investigation. Aspiration may vary as a function of the thin liquid type used during FEES. METHODS: We measured the effects of liquid type (water, skim milk, 2% milk, and whole milk; all dyed with green food coloring), delivery method (cup and straw), and bolus volume (5, 10, 15, and 20 mL) on Penetration-Aspiration Scale (PAS) scores in 14 healthy older adults (mean, 75 years; range, 69 to 85 years). Each participant generated 32 swallows. RESULTS: The PAS scores differed significantly by liquid type (p = 0.003) and by bolus volume (p = 0.017), but not by delivery method (p = 0.442). The PAS scores were significantly greater for 2% milk and whole milk than for skim milk and water (p < 0.05), and for 20 mL versus smaller volumes. Penetration and aspiration were observed on 113 (25%) and 15 (3%) of 448 swallows, respectively. CONCLUSIONS: These findings suggest that both milk and water should be used during FEES for an accurate assessment of aspiration status.