Cellular responses to flow diverters in a tissue-engineered aneurysm model.

BACKGROUND: Notwithstanding the widespread implementation of flow diverters (FDs) in the treatment of intracranial aneurysms, the exact mechanism of action of these devices remains elusive. We aimed to advance the understanding of cellular responses to FD implantation using a 3D tissue-engineered in vitro aneurysm model. METHODS: Aneurysm-like blood vessel mimics (aBVMs) were constructed by electrospinning polycaprolactone nanofibers onto desired aneurysm-like geometries. aBVMs were seeded with human aortic smooth muscle cells (SMCs) followed by human aortic endothelial cells (ECs). FDs were then deployed in the parent vessel of aBVMs covering the aneurysm neck and were cultivated for 7, 14, or 28 days (n=3 for each time point). The EC and SMC coverage in the neck was measured semi-quantitatively. RESULTS: At day 7, the device segment in contact with the parent vessel was partially endothelialized. Also, the majority of device struts, but not pores, at the parent vessel and neck interface were partially covered with ECs and SMCs, while device struts in the middle of the neck lacked cell coverage. At 14 days, histology verified a neointimal-like lining had formed, partially covering both the struts and pores in the center of the neck. At 28 days, the majority of the neck was covered with a translucent neointimal-like layer. A higher degree of cellular coverage was seen on the struts and pores at the neck at 28 days compared with both 7 and 14 days. CONCLUSION: aBVMs can be a valuable alternative tool for evaluating the healing mechanisms of endovascular aneurysm devices.

Tissue-engineered aneurysm models for in vitro assessment of neurovascular devices.

PURPOSE: Preclinical testing of neurovascular devices is crucial for successful device design and is commonly performed using in vivo organisms such as the rabbit elastase-induced aneurysm model; however, simple in vitro models may help further refine this testing paradigm. The purpose of the current work was to evaluate, and further develop, tissue-engineered blood vessel mimics (BVMs) as simple, early-stage models to assess neurovascular devices in vitro prior to animal or clinical use. METHODS: The first part of this work used standard straight-vessel BVMs to evaluate flow diverters at 1, 3, and 5 days post-deployment. The second part developed custom aneurysm-shaped scaffolds to create aneurysm BVMs. Aneurysm scaffolds were characterized based on overall dimensions and microstructural features and then used for cell deposition and vessel cultivation. RESULTS: It was feasible to deploy flow diverters within standard BVMs and cellular linings could withstand and respond to implanted devices, with increasing cell coverage over time. This provided the motivation and foundation for the second phase of work, where methods were successfully developed to create saccular, fusiform, and blister aneurysm scaffolds using a wax molding process. Results demonstrated appropriate fiber morphology within different aneurysm shapes, consistent cell deposition, and successful cultivation of aneurysm BVMs. CONCLUSION: It is feasible to use tissue-engineered BVMs for assessing cellular responses to flow diverters, and to create custom aneurysm BVMs. This supports future use of these models for simple, early-stage in vitro testing of flow diverters and other neurovascular devices.

Appropriateness of the treatment of fatigued patients with stage IV cancer.

BACKGROUND: Fatigue among patients with cancer is prevalent, disabling, and treatable. While fatigue management guidelines have been in place for a decade, their use remains unclear. METHODS: We surveyed 160 patients with stage IV lung (40), breast (40), colon (40), and prostate (40) cancer who reported moderate to severe fatigue (i.e., >5 of 10 on an 11-point numerical rating scale). Participants were queried about receipt of treatments in fatigue management domains emphasized in the National Comprehensive Cancer Network guidelines: general management strategies, activity enhancement, psychosocial strategies, and pharmaceuticals. RESULTS: The cohort was half male, had a mean age of 67, and reported an average fatigue rating of 6.4. Participants reported treatment or receipt of specific guidance in the fatigue management domains as follows: general management strategies 16.8 %, activity enhancement 11.9 %, psychosocial strategies 9.9 %, and pharmaceuticals 37.3 %. Fatigue >7 of 10 increased the likelihood of instruction in activity enhancement but no other domain. CONCLUSION: The low rates of guideline-congruent treatment reported here are concerning, particularly as better validated behavioral treatments were the least prescribed.

A home-based exercise program to improve function, fatigue, and sleep quality in patients with Stage IV lung and colorectal cancer: a randomized controlled trial.

CONTEXT: Exercise benefits patients with cancer, but studies of home-based approaches, particularly among those with Stage IV disease, remain small and exploratory. OBJECTIVES: To conduct an adequately powered trial of a home-based exercise intervention that can be facilely integrated into established delivery and reimbursement structures. METHODS: Sixty-six adults with Stage IV lung or colorectal cancer were randomized, in an eight-week trial, to usual care or incremental walking and home-based strength training. The exercising participants were instructed during a single physiotherapy visit and subsequently exercised four days or more per week; training and step-count goals were advanced during bimonthly telephone calls. The primary outcome measure was mobility assessed with the Ambulatory Post Acute Care Basic Mobility Short Form. Secondary outcomes included ratings of pain and sleep quality as well as the ability to perform daily activities (Ambulatory Post Acute Care Daily Activities Short Form), quality of life (Functional Assessment of Cancer Therapy-General), and fatigue (Functional Assessment of Cancer Therapy-Fatigue). RESULTS: Three participants dropped out and seven died (five in the intervention and two in the control group, P=0.28). At Week 8, the intervention group reported improved mobility (P=0.01), fatigue (P=0.02), and sleep quality (P=0.05) compared with the usual care group, but did not differ on the other measures. CONCLUSION: A home-based exercise program seems capable of improving the mobility, fatigue, and sleep quality of patients with Stage IV lung and colorectal cancer.