Rationale and design of the Exercise Intensity Trial (EXCITE): A randomized trial comparing the effects of moderate versus moderate to high-intensity aerobic training in women with operable breast cancer

<p>Abstract</p> <p>Background</p> <p>The Exercise Intensity Trial (EXcITe) is a randomized trial to compare the efficacy of supervised moderate-intensity aerobic training to moderate to high-intensity aerobic training, relative to attention control, on aerobic capacity, physiologic mechanisms, patient-reported outcomes, and biomarkers in women with operable breast cancer following the completion of definitive adjuvant therapy.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 174 postmenopausal women (58 patients/study arm) with histologically confirmed, operable breast cancer presenting to Duke University Medical Center (DUMC) will be enrolled in this trial following completion of primary therapy (including surgery, radiation therapy, and chemotherapy). After baseline assessments, eligible participants will be randomized to one of two supervised aerobic training interventions (moderate-intensity or moderate/high-intensity aerobic training) or an attention-control group (progressive stretching). The aerobic training interventions will include 150 mins.wk^-1of supervised treadmill walking per week at an intensity of 60%-70% (moderate-intensity) or 60% to 100% (moderate to high-intensity) of the individually determined peak oxygen consumption (VO_2peak) between 20-45 minutes/session for 16 weeks. The progressive stretching program will be consistent with the exercise interventions in terms of program length (16 weeks), social interaction (participants will receive one-on-one instruction), and duration (20-45 mins/session). The primary study endpoint is VO_2peak, as measured by an incremental cardiopulmonary exercise test. Secondary endpoints include physiologic determinants that govern VO_2peak, patient-reported outcomes, and biomarkers associated with breast cancer recurrence/mortality. All endpoints will be assessed at baseline and after the intervention (16 weeks).</p> <p>Discussion</p> <p>EXCITE is designed to investigate the intensity of aerobic training required to induce optimal improvements in VO_2peakand other pertinent outcomes in women who have completed definitive adjuvant therapy for operable breast cancer. Overall, this trial will inform and refine exercise guidelines to optimize recovery in breast and other cancer survivors following the completion of primary cytotoxic therapy.</p> <p>Trial Registration</p> <p>NCT01186367</p

Chronic recurrent Gorham-Stout syndrome with cutaneous involvement

Type IV osteolysis or Gorham-Stout syndrome is a rare condition characterized by recurrent vascular tumors that disrupt normal anatomical architecture. Gorham-Stout syndrome is most commonly associated with the skeletal system with resulting replacement of bone with scar tissue following tumor regression. The loss of entire bones has given Gorham-Stout syndrome the moniker vanishing bone disease. Natural progression of Gorham-Stout syndrome is characterized by spontaneous disease resolution. However, rare variants of recurrent, progressive, and/or systemic disease have been reported. We present a patient with a history of recurrent Gorham- Stout disease refractory to all treatment options considered. In addition to skeletal disease, our patient had soft tissue and cutaneous involvement, thus reflecting the more aggressive disease variant. Previous surgical attempts to control disease had been ineffective and the patient was referred to us for radiation therapy. Treatment with external beam radiation therapy resulted in good local control and symptom palliation, but full disease resolution was never accomplished. In addition to presentation of this patient, a review of the literature on etiological hypotheses and past/future treatment options was conducted and is included

Concomitant treatment of brain metastasis with Whole Brain Radiotherapy [WBRT] and Temozolomide [TMZ] is active and improves Quality of Life

BACKGROUND: Brain metastases (BM) represent one of the most frequent complications related to cancer, and their treatment continues to evolve. We have evaluated the activity, toxicity and the impact on Quality of Life (QoL) of a concomitant treatment with whole brain radiotherapy (WBRT) and Temozolomide (TMZ) in patients with brain metastases from solid tumors in a prospective Simon two stage study. METHODS: Fifty-nine patients were enrolled and received 30 Gy WBRT with concomitant TMZ (75 mg/m2/day) for ten days, and subsequently TMZ (150 mg/m2/day) for up to six cycles. The primary end points were clinical symptoms and radiologic response. RESULTS: Five patients had a complete response, 21 patients had a partial response, while 18 patients had stable disease. The overall response rate (45%) exceeded the target activity per study design. The median time to progression was 9 months. Median overall survival was 13 months. The most frequent toxicities included grade 3 neutropenia (15%) and anemia (13%), and only one patient developed a grade 4 thrombocytopenia. Age, Karnofsky performance status, presence of extracranial metastases and the recursive partitioning analysis (RPA) were found to be predictive factors for response in patients. Overall survival (OS) and progression-free survival (PFS) were dependent on age and on the RPA class. CONCLUSION: We conclude that this treatment is well tolerated, with an encouraging objective response rate, and a significant improvement in quality of life (p < 0.0001) demonstrated by FACT-G analysis. All patients answered the questionnaires and described themselves as 'independent' and able to act on their own initiatives. Our study found a high level of satisfaction for QoL, this provides useful information to share with patients in discussions regarding chemotherapy treatment of these lesions

Probabilistic Computation in Human Perception under Variability in Encoding Precision

A key function of the brain is to interpret noisy sensory information. To do so optimally, observers must, in many tasks, take into account knowledge of the precision with which stimuli are encoded. In an orientation change detection task, we find that encoding precision does not only depend on an experimentally controlled reliability parameter (shape), but also exhibits additional variability. In spite of variability in precision, human subjects seem to take into account precision near-optimally on a trial-to-trial and item-to-item basis. Our results offer a new conceptualization of the encoding of sensory information and highlight the brain’s remarkable ability to incorporate knowledge of uncertainty during complex perceptual decision-making

Hyperthymic affective temperament and hypertension are independent determinants of serum brain-derived neurotrophic factor level

BACKGROUND: Brain-derived neurotrophic factor (BDNF) has neuroprotective, proangiogenic and myogenic effects and, therefore, possibly acts as a psychosomatic mediator. Here, we measured serum BDNF (seBDNF) level in hypertensive patients (HT) and healthy controls (CONT) and its relation to affective temperaments, depression and anxiety scales, and arterial stiffness parameters. METHODS: In this cross-sectional study, affective temperaments, anxiety, and depression were studied with questionnaires (TEMPS-A, HAM-A, and BDI, respectively). SeBDNF level and routine laboratory parameters were measured as well. Arterial stiffness was evaluated with a tonometric method. RESULTS: Allover, 151 HT, and 32 CONT subjects were involved in the study. SeBDNF level was significantly higher in HT compared to CONT (24880 +/- 8279 vs 21202.6 +/- 6045.5 pg/mL, p < 0.05). In the final model of regression analysis, hyperthymic temperament score (Beta = 405.8, p = 0.004) and the presence of hypertension (Beta = 6121.2, p = 0.001) were independent determinants of seBDNF. In interaction analysis, it was found that in HT, a unit increase in hyperthymic score was associated with a 533.3 (95 %CI 241.3-825.3) pg/mL higher seBDNF. This interaction was missing in CONT. CONCLUSIONS: Our results suggest a complex psychosomatic involvement of BDNF in the pathophysiology of hypertension, where hyperthymic affective temperament may have a protective role. BDNF is not likely to have an effect on large arteries

Identification of mRNAs differentially-expressed between benign and malignant breast tumour cells

Two suppression subtracted cDNA libraries have been constructed, one containing cDNAs to mRNAs present at a higher level in a benign human breast tumour-derived cell line relative to the malignant mammary cell line, MCF-7, and the other containing cDNAs present at a higher level in the MCF-7 cells relative to the benign cells. Randomly-picked cloned DNAs have been sequenced yielding 29 and 128 different cDNAs from the benign and malignant libraries, respectively. Using reverse Northern hybridisation, 76% and 83% of the cDNAs were differentially expressed by greater than two-fold, whilst 14% and 11% of cDNAs in the respective libraries were differentially expressed by more than 15-fold. Amongst these were oestrogen-responsive cDNAs and expressed sequence tags. One such oestrogen-responsive expressed sequence tag, M41, is transcribed from a gene located on chromosome 21q22.3, within an intron of a larger gene. The M41 gene contains oestrogen response elements, one of which is associated with alu repeats. M41 mRNA is expressed at a statistically significantly higher level in human breast cancer specimens than in normal human breast and benign lesions. In carcinomas, its up-regulation is associated with the development of the malignant cell

A Hierarchical Probabilistic Model for Rapid Object Categorization in Natural Scenes

Humans can categorize objects in complex natural scenes within 100–150 ms. This amazing ability of rapid categorization has motivated many computational models. Most of these models require extensive training to obtain a decision boundary in a very high dimensional (e.g., ∼6,000 in a leading model) feature space and often categorize objects in natural scenes by categorizing the context that co-occurs with objects when objects do not occupy large portions of the scenes. It is thus unclear how humans achieve rapid scene categorization

Ventral and dorsal striatal dopamine efflux and behavior in rats with simple vs. co-morbid histories of cocaine sensitization and neonatal ventral hippocampal lesions

xposing animal models of mental illness to addictive drugs provides an approach to understanding the neural etiology of dual diagnosis disorders. Previous studies have shown that neonatal ventral hippocampal lesions (NVHL) in rats produce features of both schizophrenia and addiction vulnerability. Objective This study investigated ventral and dorsal striatal dopamine (DA) efflux in NVHL rats combined with behavioral sensitization to cocaine. Methods Adult NVHL vs. SHAM-operated rats underwent a 5-day injection series of cocaine (15 mg/kg/day) vs. saline. One week later, rats were cannulated in nucleus accumbens SHELL, CORE, or caudate–putamen. Another week later, in vivo microdialysis sampled DA during locomotor testing in which a single cocaine injection (15 mg/kg) was delivered. Results NVHLs and cocaine history significantly increased behavioral activation approximately 2-fold over SHAM-saline history rats. DA efflux curves corresponded time dependently with the cocaine injection and locomotor curves and varied significantly by striatal region: Baseline DA levels increased 5-fold while cocaine-stimulated DA efflux decreased by half across a ventral to dorsal striatal gradient. However, NVHLs, prior cocaine history, and individual differences in behavior were not underpinned by differential DA efflux overall or within any striatal region.Conclusion Differences in ventral/dorsal striatal DA efflux are not present in and are not required for producing differential levels of acute cocaine-induced behavioral activation in NVHLs with and without a behaviorally sensitizing cocaine history. These findings suggest other neurotransmitter systems, and alterations in striatal network function post-synaptic to DA transmission are more important to understanding the interactive effects of addictive drugs and mental illness

Spiritual Well-Being and Depression in Patients with Heart Failure

BACKGROUND: In patients with chronic heart failure, depression is common and associated with poor quality of life, more frequent hospitalizations, and higher mortality. Spiritual well-being is an important, modifiable coping resource in patients with terminal cancer and is associated with less depression, but little is known about the role of spiritual well-being in patients with heart failure. OBJECTIVE: To identify the relationship between spiritual well-being and depression in patients with heart failure. DESIGN: Cross-sectional study. PARTICIPANTS: Sixty patients aged 60 years or older with New York Heart Association class II–IV heart failure. MEASUREMENTS: Spiritual well-being was measured using the total scale and 2 subscales (meaning/peace, faith) of the Functional Assessment of Chronic Illness Therapy—Spiritual Well-being scale, depression using the Geriatric Depression Scale—Short Form (GDS-SF). RESULTS: The median age of participants was 75 years. Nineteen participants (32%) had clinically significant depression (GDS-SF > 4). Greater spiritual well-being was strongly inversely correlated with depression (Spearman’s correlation −0.55, 95% confidence interval −0.70 to −0.35). In particular, greater meaning/peace was strongly associated with less depression (r = −.60, P < .0001), while faith was only modestly associated (r = −.38, P < .01). In a regression analysis accounting for gender, income, and other risk factors for depression (social support, physical symptoms, and health status), greater spiritual well-being continued to be significantly associated with less depression (P = .05). Between the 2 spiritual well-being subscales, only meaning/peace contributed significantly to this effect (P = .02) and accounted for 7% of the variance in depression. CONCLUSIONS: Among outpatients with heart failure, greater spiritual well-being, particularly meaning/peace, was strongly associated with less depression. Enhancement of patients’ sense of spiritual well-being might reduce or prevent depression and thus improve quality of life and other outcomes in this population

Randomised controlled trial of a home-based physical activity intervention in breast cancer survivors

Background: To improve adherence to physical activity (PA), behavioural support in the form of behavioural change counselling may be necessary. However, limited evidence of the effectiveness of home-based PA combined with counselling in breast cancer patients exists. The aim of this current randomised controlled trial with a parallel group design was to evaluate the effectiveness of a home-based PA intervention on PA levels, anthropometric measures, health-related quality of life (HRQoL), and blood biomarkers in breast cancer survivors. Methods: Eighty post-adjuvant therapy invasive breast cancer patients (age = 53.6 ± 9.4 years; height = 161.2 ± 6.8 cm; mass = 68.7 ± 10.5 kg) were randomly allocated to a 6-month home-based PA intervention or usual care. The intervention group received face-to-face and telephone PA counselling aimed at encouraging the achievement of current recommended PA guidelines. All patients were evaluated for our primary outcome, PA (International PA Questionnaire) and secondary outcomes, mass, BMI, body fat %, HRQoL (Functional assessment of Cancer Therapy-Breast), insulin resistance, triglycerides (TG) and total (TC), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) cholesterol were assessed at baseline and at 6-months. Results: On the basis of linear mixed-model analyses adjusted for baseline values performed on 40 patients in each group, total, leisure and vigorous PA significantly increased from baseline to post-intervention in the intervention compared to usual care (between-group differences, 578.5 MET-min∙wk−1, p = .024, 382.2 MET-min∙wk−1, p = .010, and 264.1 MET-min∙wk−1, p = .007, respectively). Both body mass and BMI decreased significantly in the intervention compared to usual care (between-group differences, −1.6 kg, p = .040, and −.6 kg/m2, p = .020, respectively). Of the HRQoL variables, FACT-Breast, Trial Outcome Index, functional wellbeing, and breast cancer subscale improved significantly in the PA group compared to the usual care group (between-group differences, 5.1, p= .024; 5.6, p = .001; 1.9 p = .025; and 2.8, p=.007, respectively). Finally, TC and LDL-C was significantly reduced in the PA group compared to the usual care group (between-group differences, −.38 mmol∙L−1, p=.001; and −.3 mmol∙L−1, p=.023, respectively). Conclusions: We found that home-based PA resulted in significant albeit small to moderate improvements in selfreported PA, mass, BMI, breast cancer specific HRQoL, and TC and LDL-C compared with usual care