Assessing the performance of different outcomes for tumor growth studies with animal models.

The consistency of reporting results for patient-derived xenograft (PDX) studies is an area of concern. The PDX method commonly starts by implanting a derivative of a human tumor into a mouse, then comparing the tumor growth under different treatment conditions. Currently, a wide array of statistical methods (e.

Maintaining serum ionized calcium during brisk walking attenuates the increase in bone resorption in older adults.

Background: Endurance exercise can cause a decrease in serum ionized calcium (iCa) and increases in parathyroid hormone (PTH) and bone resorption, reflected by serum carboxy-terminal collagen crosslinks (CTX). We developed a calcium clamp to prevent the decrease in iCa during exercise, which attenuated increases in PTH and CTX during vigorous cycling in young men. The goal was to determine whether this occurs in older adults during brisk walking.

Testing Cancer Immunotherapy in a Human Immune System Mouse Model: Correlating Treatment Responses to Human Chimerism, Therapeutic Variables and Immune Cell Phenotypes.

Over the past decade, immunotherapies have revolutionized the treatment of cancer. Although the success of immunotherapy is remarkable, it is still limited to a subset of patients. More than 1500 clinical trials are currently ongoing with a goal of improving the efficacy of immunotherapy through co-administration of other agents.

Group sequential designs for clinical trials with bivariate endpoints.

Although all clinical trials are designed and monitored using more than one endpoint, methods are needed to assure that decision criteria are chosen to reflect the clinically relevant tradeoffs that assure the trial's scientific integrity. This article presents a framework for the design and monitoring clinical trials in a bivariate outcome space. The framework uses a rectangular hyperbola to define a bivariate null curve that divides outcome space into regions of benefit and lack of benefit.

Self-Efficacy and Social Support are Associated with Disability for Ambulatory Prosthesis Users After Lower-Limb Amputation.

Background: Interventions targeting psychosocial factors may improve rehabilitation outcomes for prosthesis users after lower-limb amputation (LLA), but there is a need to identify targeted factors for minimizing disability.

Objective: To identify psychosocial factors related to disability for prosthesis users after LLA in middle age or later.

Design: Cross-sectional study.

Decline in endothelial function across the menopause transition in healthy women is related to decreased estradiol and increased oxidative stress.

Endothelial function declines progressively across stages of the menopause transition; however, the mechanisms contributing to this decline are unknown. We hypothesized that differences in endothelial function among pre-, peri, and postmenopausal women are related to differences in estradiol and oxidative stress. Brachial artery flow-mediated dilation (FMD) was measured in 87 healthy women categorized by menopause stage (24 premenopausal, 17 early and 21 late perimenopausal, and 25 postmenopausal) before and after 3 days of ovarian hormone suppression (gonadotropin releasing hormone antagonist [GnRH]) alone, and an additional 3 days of GnRH with concurrent transdermal estradiol or placebo add-back treatment.

Quality of life and the negative impact of comorbidities in long-term colorectal cancer survivors: a population-based comparison.

Purpose: Colorectal cancer (CRC) is the third most common cancer in the USA. The objective of this study was to compare quality of life (QoL) across long-term colorectal cancer survivors and unaffected matched controls while adjusting for comorbidities.

Methods: The National Cancer Institute (NCI)-funded Colon Cancer Family Registry (CCFR) was used to randomly select and recruit CRC survivors (≥ 5 years from diagnosis) and matched controls for a cross-sectional survey.

Biobehavioral Intervention Targeting Physical Activity Behavior Change for Older Veterans after Nontraumatic Amputation: A Randomized Controlled Trial.

Background: Lower-limb amputation (LLA) due to non-traumatic vascular etiology is linked to extremely low physical activity and high disability.

Objective: To test the feasibility of a biobehavioral intervention designed to promote physical activity.

Design: A randomized, single-blind feasibility trial with a crossover design.

Effects of resveratrol or estradiol on postexercise endothelial function in estrogen-deficient postmenopausal women.

Regular exercise enhances endothelial function in older men, but not consistently in estrogen-deficient postmenopausal women. Estradiol treatment improves basal endothelial function and restores improvements in endothelial function (flow-mediated dilation, FMD) to aerobic exercise training in postmenopausal women; however, estradiol treatment is controversial. Resveratrol, an estrogen receptor ligand, enhances exercise training effects on cardiovascular function and nitric oxide (NO) release in animal models, but impairs exercise training effects in men.

EPIDEMIOLOGY of NECK INJURIES ACCOMPANYING SPORT CONCUSSIONS in YOUTH OVER a 13-YEAR PERIOD IN a COMMUNITY-BASED HEALTHCARE SYSTEM.

Background: The same trauma that produces concussion may also produce neck injury. The signs of concussion and neck injury are similar, and symptoms after acceleration-deceleration trauma to the head-neck complex do not accurately discriminate between them. Research on the epidemiology of neck injury among sport-concussed youth is sparse.

A Randomized Phase II Trial of Pioglitazone for Lung Cancer Chemoprevention in High-Risk Current and Former Smokers.

Lung cancer chemoprevention, especially in high-risk former smokers, has great potential to reduce lung cancer incidence and mortality. Thiazolidinediones prevent lung cancer in preclinical studies, and diabetics receiving thiazolidinediones have lower lung cancer rates which led to our double-blind, randomized, phase II placebo-controlled trial of oral pioglitazone in high-risk current or former smokers with sputum cytologic atypia or known endobronchial dysplasia. Bronchoscopy was performed at study entry and after completing 6 months of treatment.

Improving Physical Activity Through Adjunct Telerehabilitation Following Total Knee Arthroplasty: Randomized Controlled Trial Protocol.

Background: Physical activity remains low and nearly unchanged from preoperative levels following total knee arthroplasty (TKA), and this is thought to underlie long-term functional limitations, secondary health problems, and higher health care costs after TKA.

Objective: Our objective is to determine whether a telehealth-based intervention could improve physical activity and functional outcomes after TKA.

Design: The design is a 2-arm, parallel, assessor-blinded, randomized controlled trial with baseline, midintervention, postintervention, and 6-month follow-up assessments.

Effects of testosterone and progressive resistance exercise on vascular function in older men.

The cardiovascular effects of testosterone (T) are controversial. Low T has been associated with accelerated vascular aging, characterized by large elastic artery stiffening (decreased compliance), intimal-medial thickening (IMT), and endothelial dysfunction. Endurance exercise improves vascular function, but resistance training may increase arterial stiffness.

Final Report of a Phase I Trial of Olaparib with Cetuximab and Radiation for Heavy Smoker Patients with Locally Advanced Head and Neck Cancer.

Our goal was to evaluate the safety and toxicity of combining a PARP inhibitor, olaparib, with cetuximab and fractionated intensity-modulated radiotherapy for patients with locally advanced head and neck cancer and heavy smoking histories. Patients with ≥10 packs/year history of smoking were treated with olaparib at doses ranging from 25-200 mg orally twice daily beginning approximately 10 days prior to initiation of and with concurrent radiation (69.3 Gy in 33 fractions) using a time-to-event continual reassessment method model.

Cabozantinib Exhibits Potent Antitumor Activity in Colorectal Cancer Patient-Derived Tumor Xenograft Models via Autophagy and Signaling Mechanisms.

Antiangiogenic therapy used in treatment of metastatic colorectal cancer (mCRC) inevitably succumbs to treatment resistance. Upregulation of MET may play an essential role to acquired anti-VEGF resistance. We previously reported that cabozantinib (XL184), an inhibitor of receptor tyrosine kinases (RTK) including MET, AXL, and VEGFR2, had potent antitumor effects in mCRC patient-derived tumor explant models.

Vascular dysfunction across the stages of the menopausal transition is associated with menopausal symptoms and quality of life.

Objective: The menopausal transition is associated with somatic symptoms and increased rates of depression, which can impair quality of life (QOL) and increase cardiovascular disease (CVD) risk. This period is also associated with accelerated vascular aging (arterial stiffening and endothelial dysfunction), an antecedent to CVD. This secondary analysis sought to explore associations between depression, menopausal symptoms and QOL, and vascular aging across menopause stages.

The novel ATM inhibitor (AZ31) enhances antitumor activity in patient derived xenografts that are resistant to irinotecan monotherapy.

Irinotecan, a standard of care therapy for CRC, elicits cytotoxic effects by generating double strand breaks resulting in DNA damage. The activation of the ATM pathway plays a fundamental role in regulating the cellular response and repair to DNA damage. The objective of this preclinical study was to determine whether ATM inhibition would enhance sensitivity to irinotecan treatment.

High Symptom Burden and Low Functional Status in the Setting of Multimorbidity.

Objectives: To enhance understanding of the relationship between multimorbidity, symptom burden, and functional status in individuals with life-limiting illness.

Design: Secondary analysis of baseline data from a randomized clinical trial conducted in the Palliative Care Research Cooperative Group. Group differences were tested using a t-test; multivariate regression analysis was used to determine the effect of multiple variables on functional status and symptom burden.

Patterns of fractionation for patients with T2N0M0 glottic larynx cancer undergoing definitive radiotherapy in the United States.

Objectives: Among patients with T2N0M0 glottic larynx cancer undergoing definitive radiotherapy, recent retrospective and prospective data have suggested improved outcomes with altered fractionation over conventional fractionation (CFxn). We sought to characterize national fractionation patterns and to compare outcomes among them.

Materials And Methods: We queried the National Cancer Database for T2N0M0 squamous cell carcinomas of the glottis diagnosed from 2004-2014 and managed with definitive radiotherapy.