Few programs exist to address persistent impairment in functional status, quality of life, and mental health in lung cancer survivors. We aimed to determine whether a 12-wk multimodal survivorship ...program imparts clinical benefit.
Any patient at the Durham Veterans Affairs Medical Center with lung cancer and a Karnofsky score of ≥60 could participate. Chronic obstructive pulmonary disease medications were optimized at the enrollment visit. Participants with a Hospital Anxiety and Depression Scale (HADS) score of >8 were offered pharmacotherapy and mental health referral. Participants did home-based exercise with a goal of 1 hr/d, 5 d/wk. They were called weekly to assess exercise progress and review depression/anxiety symptoms. Participants were offered pharmacotherapy for smoking cessation.
Twenty-three (50%) of the first 46 enrollees completed the full 12-wk program. Paired changes from enrollment to completion (mean ± SD) were observed in 6-min walk test (73.6 ± 96.9 m, P = .002), BODE (Body mass index, airflow Obstruction, Dyspnea, and Exercise) index (-1.45 ± 1.64 points, P < .001), Duke Activity Status Index (3.84 ± 7.12 points, P = .02), Fried Frailty Index (-0.588 ± 0.939 points, P = .02), modified Medical Research Council dyspnea scale (-0.619 ± 1.284 points, P = .04), Functional Assessment of Cancer Therapy-Lung Emotional subscale score (1.52 ± 2.96 points, P = .03), HADS total score (-2.63 ± 4.34 points, P = .02), and HADS Anxiety subscale score (-1.47 ± 2.29 points, P = .01).
A comprehensive Lung Cancer Survivorship Program provides clinically meaningful improvements in functional status, quality of life, and mental health.
Background and Purpose
Mapping the topology of the visual system is critical for understanding how complex cognitive processes like reading can occur. We aim to describe the connectivity of the ...visual system to understand how the cerebrum accesses visual information in the lateral occipital lobe.
Methods
Using meta‐analytic software focused on task‐based functional MRI studies, an activation likelihood estimation (ALE) of the visual network was created. Regions of interest corresponding to the cortical parcellation scheme previously published under the Human Connectome Project were co‐registered onto the ALE to identify the hub‐like regions of the visual network. Diffusion Spectrum Imaging‐based fiber tractography was performed to determine the structural connectivity of these regions with extraoccipital cortices.
Results
The fundus of the superior temporal sulcus (FST) and parietal area H (PH) were identified as hub‐like regions for the visual network. FST and PH demonstrated several areas of coactivation beyond the occipital lobe and visual network. Furthermore, these parcellations were highly interconnected with other cortical regions throughout extraoccipital cortices related to their nonvisual functional roles. A cortical model demonstrating connections to these hub‐like areas was created.
Conclusions
FST and PH are two hub‐like areas that demonstrate extensive functional coactivation and structural connections to nonvisual cerebrum. Their structural interconnectedness with language cortices along with the abnormal activation of areas commonly located in the temporo‐occipital region in dyslexic individuals suggests possible important roles of FST and PH in the integration of information related to language and reading. Future studies should refine our model by examining the functional roles of these hub areas and their clinical significance.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
The salience network (SN) is a transitory mediator between active and passive states of mind. Multiple cortical areas, including the opercular, insular, and cingulate cortices have been ...linked in this processing, though knowledge of network connectivity has been devoid of structural specificity.
Objective
The current study sought to create an anatomically specific connectivity model of the neural substrates involved in the salience network.
Methods
A literature search of PubMed and BrainMap Sleuth was conducted for resting‐state and task‐based fMRI studies relevant to the salience network according to PRISMA guidelines. Publicly available meta‐analytic software was utilized to extract relevant fMRI data for the creation of an activation likelihood estimation (ALE) map and relevant parcellations from the human connectome project overlapping with the ALE data were identified for inclusion in our SN model. DSI‐based fiber tractography was then performed on publicaly available data from healthy subjects to determine the structural connections between cortical parcellations comprising the network.
Results
Nine cortical regions were found to comprise the salience network: areas AVI (anterior ventral insula), MI (middle insula), FOP4 (frontal operculum 4), FOP5 (frontal operculum 5), a24pr (anterior 24 prime), a32pr (anterior 32 prime), p32pr (posterior 32 prime), and SCEF (supplementary and cingulate eye field), and 46. The frontal aslant tract was found to connect the opercular‐insular cluster to the middle cingulate clusters of the network, while mostly short U‐fibers connected adjacent nodes of the network.
Conclusion
Here we provide an anatomically specific connectivity model of the neural substrates involved in the salience network. These results may serve as an empiric basis for clinical translation in this region and for future study which seeks to expand our understanding of how specific neural substrates are involved in salience processing and guide subsequent human behavior.
This study provides a detailed model of the salience network (SN) based on its structural and functional connectivity within an anatomically specific parcellation scheme. A coordinate‐based meta‐analysis of the literature and subsequent tractographic analysis on identified regions demonstrate that the SN comprises three clusters of interconnected cortical regions that are extensively connected with both frontal aslant tract fibers and short local association fibers, generally forming a large cingulate and insular‐opercular system. These results may serve as an empirical basis for clinical translation in this region and for future studies that seek to expand our understanding of how specific neural substrates are involved in salience processing and guide subsequent human behavior.
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FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
ABSTRACT
In this supplement, we build on work previously published under the Human Connectome Project. Specifically, we seek to show a comprehensive anatomic atlas of the human cerebrum demonstrating ...all 180 distinct regions comprising the cerebral cortex. The location, functional connectivity, and structural connectivity of these regions are outlined, and where possible a discussion is included of the functional significance of these areas. In part 9, we specifically address regions relevant to the occipital lobe and the visual system.
Aneurysm pathophysiology remains poorly understood, in part from the disparity of murine models with human physiology and the requirement for invasive aortic exposure to apply agents used to create ...aneurysm models. A retrievable drug infusion stent graft (RDIS) was developed to isolate the aortic wall intraluminally for drug exposure. We hypothesized that an RDIS could deliver aneurysm-promoting enzymes to create a porcine model of thoracic aneurysms without major surgical exposure.
Retrievable nitinol stent graft frames were designed with an isolated drug delivery chamber, covered with polytetrafluoroethylene, and connected to a delivery wire with a drug infusion catheter installed to the outer chamber. Institutional Animal Care and Use Committee-approved Yorkshire pigs (n = 5) underwent percutaneous access of the femoral artery, baseline aortogram and stent placement in the thoracic aorta followed by 30-minute exposure to a cocktail of elastase, collagenase, and trypsin. After aspiration of excess drug, stent retrieval, and femoral artery repair, animals were recovered, with angiograms at 1 and 4 weeks followed by explant. Histological analysis, in situ zymography, and multiplex cytokine assays were performed.
The RDIS isolated a segment of anterior aorta angiographically, while the center lumen preserved distal perfusion during drug treatment (baseline femoral mean arterial pressure, 70 ± 14 mm Hg; after RDIS, 75 ± 12; P = .55). Endovascular induction of thoracic aneurysms did not require prior mechanical injury and animals revealed no evidence of toxicity. Within 1 week, significant aneurysmal growth was observed in all five animals (1.4 ± 0.1 cm baseline to 2.9 ± 0.7 cm; P = .002) and only within the treated region of the aorta. Aneurysms persisted out to 4 weeks. Aneurysm histology demonstrated loss of elastin and collagen that was otherwise preserved in untreated aorta. Proinflammatory cytokines and increased matrix metalloproteinase activity were increased significantly within the aneurysm.
An RDIS achieves isolated drug delivery while preserving distal perfusion to achieve an endovascular porcine model of thoracic aneurysms without major surgery. This model may have value for surgical training, device testing, and to better understand aneurysm pathogenesis. Most important, although the RDIS was used to simulate aortic pathology, this tool offers intriguing horizons for focused therapeutic drug delivery directly to aneurysms and, more broadly, focused locoregional drug delivery to vessels and vascular beds.
The pathology behind aortic aneurysms remains poorly understood owing to limitations of current animal models. A novel drug infusion stent graft was developed to create endovascular aneurysms in a porcine model without open surgery. Aortic dilation, loss of both smooth muscle cells and elastin, as well as pro-inflammatory cytokines mirror findings in human aneurysms. The additional finding of endogenous enzyme activity suggests that this may underscore the self sustaining pathology of aneurysms. This model offers a platform to understand the biology of aneurysms and the retrievable drug infusion stent offers an important tool to potentially deliver therapies to potentially treat aneurysms.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract only Introduction: Half of vascular interventions will fail in under 5 years due to restenosis. While drug coated balloons (DCB) are used to minimize restenosis, there are several ...disadvantages: 1) Limitations of the amount of drug that can be adhered to a balloon, 2) Significant drug is washed off the balloon by the circulation and 3) There are limits on the time of balloon inflation due to ischemia concerns. We developed a dumbbell shaped, retrievable drug delivery stentgraft (RDDS) that isolates a segment of artery with an outer chamber ( OC ) (Fig 1A). The center lumen of the stent maintains distal perfusion to allow longer drug exposure and this stent is removed after use. Methods: A RDDS stentgraft was fashioned from laser cut nitinol scaffold, covered in polymer and an infusion cannula was installed (Fig B). In a porcine model, bilateral common iliac arteries were dilated by plain balloon angioplasty to simulate endovascular intervention. Next a commercial DCB with paclitaxel (PXL) was used to treat one iliac, while an RDDS infused a similar dose of PXL to treat the contralateral iliac. Vessels and serum had PXL quantitation by liquid chromatography-mass spectrophotometry. Results: Angiographically, the RDDS maintained distal flow while the OC isolated the arterial wall for PXL delivery (Fig C, D). Blood samples distal to the treated areas demonstrated lower concentrations of PXL during treatment with the RDDS compared to DCB (10.50 ± 0.77 vs. 2310.07 ± 471.69 ng/mL, p < 0.0001). There was equivalent drug delivery to target vessel wall between the two approaches (33.85 ± 8.78 vs. 41.45 ± 12.51 ng/mg, p = 0.251, RDDS vs. DCB). Conclusions: The RDDS angiographically isolated a segment of artery, while maintaining distal perfusion. Moreover, compared to a DCB, the RDDS was able to prevent loss of drug to the circulation and effectively deliver paclitaxel to the vessel wall. This this study concludes that chambered retrievable stentgrafts may have a role in locoregional drug delivery.
Abstract only Objectives: Murine models present limitations for the study of aortic aneurysm due to disparate hemodynamics from humans, small size and the necessity for open surgery and aortic ...clamping to apply otherwise toxic aneurysmogenic enzymes. We have developed a retrievable chambered stentgraft that can isolate aortic wall and more importantly restrict enzyme to only the anterior aorta. Figure 1 shows a posterior central lumen (CL) that preserves distal perfusion while excluding posterior spinal cord branches, and an outer chamber (OC) delivers drug to anterior aortic wall. We hypothesized that a Retrievable Aortic Drug Delivery Stentgraft (RADDS) could deliver enzymes directly to the aortic wall to create a porcine model of thoracic aortic aneurysms (TAA). Methods: The RADDS stentgraft scaffold was laser cut from nitinol, shapeset, and covered in polymer. A permanent delivery wire was affixed distally, and a perfusion cannula to the OC. The stent was delivered from percutaneous femoral access to the thoracic aorta in a porcine model (n=6). Following angiography, an enzyme cocktail (elastase/collagenase) was infused to the OC then aspirated and the stent retrieved via sheath advancement. Results: The RADDS achieved angiographic isolation of the anterior aortic wall from both the circulation and spinal cord. Distal perfusion was preserved through the CL and femoral arterial pressures were unchanged after stent placement (p = 0.88). Spinal paresis was not observed. All animals developed acute aortic degeneration ranging from 1 hour to 6 weeks post-treatment with H&E histology reflecting deteriorated aortic media with specific disruption of elastic lamina. Conclusions: The RADDS allowed endovascular delivery of systemically toxic agents directly to the aortic wall for creation of TAA. These findings herald a novel approach to isolate potentially toxic therapies to the aortic wall and may offer future opportunities to instead deliver aneurysm treating therapies.
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