Low-grade chronic inflammation in regions of the normal mouse arterial intima predisposed to atherosclerosis

Atherosclerotic lesions develop in regions of arterial curvature and branch points, which are exposed to disturbed blood flow and have unique gene expression patterns. The cellular and molecular basis for atherosclerosis susceptibility in these regions is not completely understood. In the intima of atherosclerosis-predisposed regions of the wild-type C57BL/6 mouse aorta, we quantified increased expression of several proinflammatory genes that have been implicated in atherogenesis, including vascular cell adhesion molecule–1 (VCAM-1) and a relative abundance of dendritic cells, but only occasional T cells. In contrast, very few intimal leukocytes were detected in regions resistant to atherosclerosis; however, abundant macrophages, including T cells, were found throughout the adventitia (Adv). Considerably lower numbers of intimal CD68+ leukocytes were found in inbred atherosclerosis-resistant C3H and BALB/c mouse strains relative to C57BL/6 and 129; however, leukocyte distribution throughout the Adv of all strains was similar. The predominant mechanism for the accumulation of intimal CD68+ cells was continued recruitment of bone marrow–derived blood monocytes, suggestive of low-grade chronic inflammation. Local proliferation of intimal leukocytes was low. Intimal CD68+ leukocytes were reduced in VCAM-1–deficient mice, suggesting that mechanisms of leukocyte accumulation in the intima of normal aorta are analogous to those in atherosclerosis

Spinal cord stimulators and radiotherapy: First case report and practice guidelines

Spinal cord stimulators (SCS) are a well-recognised treatment modality in the management of a number of chronic neuropathic pain conditions, particularly failed back syndrome and radiculopathies. The implantable pulse generator (IPG) component of the SCS is designed and operates in a similar fashion to that of a cardiac pacemaker. The IPG consists of an electrical generator, lithium battery, transmitter/receiver and a minicomputer. When stimulated, it generates pulsed electrical signals which stimulate the dorsal columns of the spinal cord, thus alleviating pain. Analogous to a cardiac pacemaker, it can be potentially damaged by ionising radiation from a linear accelerator, in patients undergoing radiotherapy. Herein we report our clinical management of the first reported case of a patient requiring adjuvant breast radiotherapy who had a SCS in situ. We also provide useful practical recommendations on the management of this scenario within a radiation oncology department

Feasibility of Spinal Neuronavigation and Evaluation of Registration and Application Error Modalities Using Optical Topographic Imaging

Intra-operative navigation began with the localization of subsurface structures in cranial neurosurgery using frame-based stereotaxy. Advances in imaging and computing power have led to the development of modern frameless three-dimensional (3D) computer-assisted navigation (CAN), employed across multiple surgical disciplines. In spinal surgery, CAN may guide implant placement, bony decompression and soft-tissue resection. However, adoption of 3D CAN by spinal surgeons has been limited by cumbersome registration protocols, workflow disruption, high capital cost, and questionable quantitative and clinical utility. A novel technique for image-to-patient registration has recently been developed, based on optical topographic imaging (OTI). Whether OTI-based CAN is able to provide accurate intra-operative image-guidance for common spinal procedures, while addressing current limitations of CAN techniques, warrants study. First, we explored the current paradigms of reporting CAN accuracy in the context of spinal procedures, finding that quantitative application accuracy and radiographic screw placement do not correlate. We therefore proposed a combined quantitative and radiographic system of reporting CAN accuracy. Second, we examined the registration workflow and accuracy of OTI-CAN in open posterior thoracolumbar instrumentation, in pre-clinical swine and cadaveric models and subsequently in clinical in-vivo testing. We found that OTI-CAN is comparably accurate to but significantly faster than existing 3D CAN techniques. We subsequently found that OTI-CAN was similarly accurate, with maintained workflow improvements, in minimally-invasive (MIS) thoracolumbar and open cervical approaches. Finally, we explored mechanisms by which current CAN and specifically surface-based registration techniques, including OTI, may fail. We found that navigation error increases with greater working distance to the dynamic reference frame (DRF), and with greater geometric symmetry over the osseous posterior elements. Taken together, this body of work demonstrates that OTI is a feasible technique for spinal CAN, and may alleviate the primary issues plaguing current systems to allow increased adoption into settings where CAN may be most useful.Ph.D.2019-11-16 00:00:0

Chapter 8 - Intraoperative imaging and image guidance

This chapter is divided into four primary sections. The first (Evolution of computer-assisted navigation section) discusses the history and evolution of intraoperative computer-assisted navigation, beginning with a brief introduction of frame-based stereotaxis and subsequently exploring the development of frameless techniques and their extension to spinal applications. Section Evolution of computer-assisted navigation concludes by delineating the clinical rationale as well as limits to adoption of spinal navigation techniques. Section Registration, imaging, and actuation techniques in spinal computer-assisted navigation summarizes current imaging and registration techniques for contemporary navigation systems, including their relative merits and drawbacks. This section concludes with a description of instrument tracking and actuation techniques, including a comparison of freehand, freehand-navigated, and robotically actuated mechanisms

Neurosurgeon academic impact is associated with clinical outcomes after clipping of ruptured intracranial aneurysms.

Surgeon-dependent factors such as experience and volume are associated with patient outcomes. However, it is unknown whether a surgeon's research productivity could be related to outcomes. The main aim of this study is to investigate the association between the surgeon's academic productivity and clinical outcomes following neurosurgical clipping of ruptured aneurysms.We performed a post-hoc analysis of 3567 patients who underwent clipping of ruptured intracranial aneurysms in the randomized trials of tirilazad mesylate from 1990 to 1997. These trials included 162 centers and 156 surgeons from 21 countries. Primary and secondary outcomes were: Glasgow outcome scale score and mortality, respectively. Total publications, H-index, and graduate degrees were used as academic indicators for each surgeon. The association between outcomes and academic factors were assessed using a hierarchical logistic regression analysis, adjusting for patient covariates.Academic profiles were available for 147 surgeons, treating a total of 3307 patients. Most surgeons were from the USA (62, 42%), Canada (18, 12%), and Germany (15, 10%). On univariate analysis, the H-index correlated with better functional outcomes and lower mortality rates. In the multivariate model, patients under the care of surgeons with higher H-indices demonstrated improved neurological outcomes (p = 0.01) compared to surgeons with lower H-indices, without any significant difference in mortality. None of the other academic indicators were significantly associated with outcomes.Although prognostication following surgery for ruptured intracranial aneurysms primarily depends on clinical and radiological factors, the academic impact of the operating neurosurgeon may explain some heterogeneity in surgical outcomes

Quantification of computational geometric congruence in surface-based registration for spinal intra-operative three-dimensional navigation.

Background contextComputer-assisted navigation (CAN) may guide spinal instrumentation, and requires alignment of patient anatomy to imaging. Iterative closest-point (ICP) algorithms register anatomical and imaging surface datasets, which may fail in the presence of geometric symmetry (congruence), leading to failed registration or inaccurate navigation. Here we computationally quantify geometric congruence in posterior spinal exposures, and identify predictors of potential navigation inaccuracy.MethodsMidline posterior exposures were performed from C1-S1 in four human cadavers. An optically-based CAN generated surface maps of the posterior elements at each level. Maps were reconstructed to include bilateral hemilamina, or unilateral hemilamina with/without the base of the spinous process. Maps were fitted to symmetrical geometries (cylindrical/spherical/planar) using computational modelling, and the degree of model fit quantified based on the ratio of model inliers to total points. Geometric congruence was subsequently assessed clinically in 11 patients undergoing midline exposures in the cervical/thoracic/lumbar spine for posterior instrumented fusion.ResultsIn cadaveric testing, increased cylindrical/spherical/planar symmetry was seen in the high-cervical and subaxial cervical spine relative to the thoracolumbar spine (pConclusionsGeometric congruence is most evident at C1 and the subaxial cervical spine, warranting greater vigilance in navigation accuracy verification. At all levels, inclusion of the base of the spinous process in unilateral registration decreases the likelihood of geometric symmetry and navigation error. This work is important to allow the extension of line-of-sight based registration techniques to minimally-invasive unilateral approaches

Fixed-effects analysis of the association of patient- and surgeons' H-index on mortality.

<p>Fixed-effects analysis of the association of patient- and surgeons' H-index on mortality.</p

Bar chart of patient outcomes in percentages and divided into two groups as per the mean of time-adjusted H-index = 1.77.

<p>Higher rates of poor outcomes and mortality by surgeons with a time-adjusted H-index below the mean.</p

Heterogeneity in empty model intercept.

<p>Heterogeneity by surgeons in Glasgow Outcome Scale (GOS) (<i>top plot</i>), and mortality (<i>bottom plot</i>).</p