Publications by authors named "Keith Vandusen"

Purpose: This narrative review examines the current evidence on whether obstructive sleep apnea (OSA) is associated with postoperative delirium (POD) and postoperative cognitive dysfunction (POCD). The mechanisms that could predispose OSA patients to these disorders are also explored.

Source: Relevant literature was identified by searching for pertinent terms in Medline, Pubmed, Scopus, and Google scholar databases.

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Volumetric muscle loss (VML) is traumatic, degenerative, or surgical loss of skeletal muscle that exceeds the regenerative capacity of the remaining muscle, thus resulting in impaired muscle function. In humans, the loss of 30% or more mass of any one muscle will result in permanent structural and functional loss. Current VML repair treatments are limited by donor site morbidity and graft tissue availability, necessitating alternative muscle graft sources.

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Background: Postoperative cognitive dysfunction (POCD), a syndrome of cognitive deficits occurring 1-12 months after surgery primarily in older patients, is associated with poor postoperative outcomes. POCD is hypothesized to result from neuroinflammation; however, the pathways involved remain unclear. Unbiased proteomic analyses have been used to identify neuroinflammatory pathways in multiple neurologic diseases and syndromes but have not yet been applied to POCD.

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Background: APOE4 has been hypothesized to increase Alzheimer's disease risk by increasing neuroinflammation, though the specific neuroinflammatory pathways involved are unclear.

Objective: Characterize cerebrospinal fluid (CSF) proteomic changes related to APOE4 copy number.

Methods: We analyzed targeted proteomic data from ADNI CSF samples using a linear regression model adjusting for age, sex, and APOE4 copy number, and additional linear models also adjusting for AD clinical status or for CSF Aβ, tau, or p-tau levels.

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Background: Perioperative neurocognitive disorders (PND) are common complications in older adults associated with increased 1-year mortality and long-term cognitive decline. One risk factor for worsened long-term postoperative cognitive trajectory is the Alzheimer's disease (AD) genetic risk factor APOE4. APOE4 is thought to elevate AD risk partly by increasing neuroinflammation, which is also a theorized mechanism for PND.

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Skeletal muscle is the largest organ of human body with several important roles in everyday movement and metabolic homeostasis. The limited ability of small animal models of muscle disease to accurately predict drug efficacy and toxicity in humans has prompted the development in vitro models of human skeletal muscle that fatefully recapitulate cell and tissue level functions and drug responses. We first review methods for development of three-dimensional engineered muscle tissues and organ-on-a-chip microphysiological systems and discuss their potential utility in drug discovery research and development of new regenerative therapies.

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Volumetric muscle loss (VML) is a loss of skeletal muscle that results in a sustained impairment of function and is often accompanied by physical deformity. To address the need for more innovative repair options, our laboratory has developed scaffold-free, multiphasic tissue-engineered skeletal muscle units (SMUs) to treat VML injuries. In our previous work, using the concept of the "body as a bioreactor", we have shown that implantation promotes the maturation of our SMUs beyond what is possible Thus, in this study we sought to better understand the effect of implantation on the maturation of our SMUs, including the effects of implantation on SMU force production and cellular remodeling.

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Objective: The objective of this study was to evaluate the impact of the video-assisted thoracoscopic (VATS) approach on the outcomes of patients who underwent pneumonectomy.

Methods: The effect of the surgical approach on perioperative complications and survival in patients who underwent pneumonectomy for nonmetastatic non-small cell lung cancer across 3 institutions (2000-2016) was assessed using multivariable logistic regression, Cox proportional hazards analysis, and propensity-score matching. Completion pneumonectomies were excluded from this study, and an "intent-to-treat" analysis was performed.

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Background: A right-sided pneumonectomy after induction therapy for non-small cell lung cancer (NSCLC) has been shown to be associated with significant perioperative risk. We examined the effect of laterality on long-term survival after induction therapy and pneumonectomy using the National Cancer Data Base.

Methods: Perioperative and long-term outcomes of patients who underwent pneumonectomy after induction chemotherapy, with or without radiotherapy, from 2004 to 2014 in the National Cancer Data Base were evaluated using multivariable Cox proportional hazards modeling and propensity score-matched analysis.

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Purpose: To report the prevalence of ocular surface dysfunction in patients presenting for cataract surgery evaluation.

Setting: Duke University Eye Center and Weill Cornell Ophthalmology, single-physician practices.

Design: Prospective case series.

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Damage to peripheral nerve tissue may cause loss of function in both the nerve and the targeted muscles it innervates. This study compared the repair capability of engineered nerve conduit (ENC), engineered fibroblast conduit (EFC), and autograft in a 10-mm tibial nerve gap. ENCs were fabricated utilizing primary fibroblasts and the nerve cells of rats on embryonic day 15 (E15).

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Tissue-engineered skeletal muscle holds promise as a source of graft tissue for repair of volumetric muscle loss and as a model system for pharmaceutical testing. To reach this potential, engineered tissues must advance past the neonatal phenotype that characterizes the current state of the art. In this review, we describe native skeletal muscle development and identify important growth factors controlling this process.

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Anterior cruciate ligament (ACL) ruptures rank among the most prevalent and costly sports-related injuries. Current tendon grafts used for ACL reconstruction are limited by suboptimal biomechanical properties. We have addressed these issues by engineering multiphasic bone-ligament-bone (BLB) constructs that develop structural and mechanical properties similar to native ACL.

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Tissue engineered skeletal muscle has potential for application as a graft source for repairing soft tissue injuries, a model for testing pharmaceuticals, and a biomechanical actuator system for soft robots. However, engineered muscle to date has not produced forces comparable to native muscle, limiting its potential for repair and for use as an in vitro model for pharmaceutical testing. In this study, we examined the trophic effects of dexamethasone (DEX), a glucocorticoid that stimulates myoblast differentiation and fusion into myotubes, on our tissue engineered three-dimensional skeletal muscle units (SMUs).

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Volumetric muscle loss (VML) is the traumatic, degenerative, or surgical loss of muscle tissue, which may result in function loss and physical deformity. To date, clinical treatments for VML--the reflected muscle flap or transferred muscle graft--are limited by tissue availability and donor site morbidity. To address the need for more innovative skeletal muscle repair options, our laboratory has developed scaffoldless tissue-engineered skeletal muscle units (SMUs), multiphasic tissue constructs composed of engineered skeletal muscle with engineered bone-tendon ends, myotendinous junctions, and entheses, which in vitro can produce force both spontaneously and in response to electrical stimulation.

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Engineered skeletal muscle holds promise as a source of graft tissue for the repair of traumatic injuries such as volumetric muscle loss. The resident skeletal muscle stem cell, the satellite cell, has been identified as an ideal progenitor for tissue engineering due to its role as an essential player in the potent skeletal muscle regeneration mechanism. A significant challenge facing tissue engineers, however, is the isolation of sufficiently large satellite cell populations with high purity.

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