Variations in vertebral venous vasculature

INTRODUCTION Cadaveric studies have previously documented typical patterns of venous drainage within vertebral bodies (VBs) [1,2,3], comprised primarily of the basivertebral vein, a planar tree like structure at the mid-height of the VB. These studies, however, are limited in the number of samples available, and so have not examined any potential differences in this anatomy in conditions such as scoliosis. MRI is able to create 3D images of soft tissue structures in the spine, including the basivertebral vein without the use of contrast. As a non-invasive imaging technique this opens up the possibility of examining the venous network in multiple VBs within the same subject, in healthy controls as well as in subjects with abnormal anatomy such as adolescent idiopathic scoliosis (AIS). CONCLUSIONS High resolution MRI scans allow in vivo quantification of the vertebral venous system at multiple levels on healthy and scoliotic populations for the first time. The length of the basivertebral vein was seen to have a significant bias to the right hand side of the VB in both healthy and AIS adolescents. The spatial pattern of this vein showed large variations in branching both within and across individuals

Discovery of novel GPVI receptor antagonists by structure-based repurposing.

Inappropriate platelet aggregation creates a cardiovascular risk that is largely managed with thienopyridines and aspirin. Although effective, these drugs carry risks of increased bleeding and drug 'resistance', underpinning a drive for new antiplatelet agents. To discover such drugs, one strategy is to identify a suitable druggable target and then find small molecules that modulate it. A good and unexploited target is the platelet collagen receptor, GPVI, which promotes thrombus formation. To identify inhibitors of GPVI that are safe and bioavailable, we docked a FDA-approved drug library into the GPVI collagen-binding site in silico. We now report that losartan and cinanserin inhibit GPVI-mediated platelet activation in a selective, competitive and dose-dependent manner. This mechanism of action likely underpins the cardioprotective effects of losartan that could not be ascribed to its antihypertensive effects. We have, therefore, identified small molecule inhibitors of GPVI-mediated platelet activation, and also demonstrated the utility of structure-based repurposing

The Fukushima Daiichi Accident

The Fukushima Daiichi Accident consists of a Report by the IAEA Director General and five technical volumes. It is the result of an extensive international collaborative effort involving five working groups with about 180 experts from 42 Member States with and without nuclear power programmes and several international bodies. It provides a description of the accident and its causes, evolution and consequences, based on the evaluation of data and information from a large number of sources available at the time of writing. The set contains six printed parts and five supplementary CD-ROMs. Contents: Report by the Director General; Technical Volume 1/5, Description and Context of the Accident; Technical Volume 2/5, Safety Assessment; Technical Volume 3/5, Emergency Preparedness and Response; Technical Volume 4/5, Radiological Consequences; Technical Volume 5/5, Post-accident Recovery; Annexes. The JRC contributed to volumes 1,2 and 3, which are attached.JRC.F.5-Nuclear Reactor Safety Assessmen

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Growing rod analysis for the fusionless correction of early onset scoliosis (EOS)

Managing spinal deformities in young children is challenging, particularly early onset scoliosis (EOS). Surgical intervention is often required if EOS has been unresponsive to conservative treatment particularly with rapidly progressive curves. An emerging treatment option for EOS is fusionless scoliosis surgery. Similar to bracing, this surgical option potentially harnesses growth, motion and function of the spine along with correcting spinal deformity. Dual growing rods are one such fusionless treatment, which aims to modulate growth of the vertebrae. The aim of this study was to ascertain the extent to which semi-constrained growing rods (Medtronic Sofamor Danek Memphis, TN, USA) with a telescopic sleeve component, reduce rotational constraint on the spine compared with standard rigid rods and hence potentially provide a more physiological mechanical environment for the growing spine. This study found that semi-constrained growing rods would be expected to allow growth via the telescopic rod components while maintaining the axial flexibility of the spine and the improved capacity for final correction

Inexpensive and readily available fiducial marker options for use with magnetic resonance imaging

A fiducial marker is an object placed in the field of view of an image to provide as a point of reference. For example, a ruler placed next to an object in a photograph to demonstrate the size of the object is a commonly seen fiducial. Fiducial markers used in the context of medicine may be implanted within the body part of interest or placed externally on the surface. Non-implantable fiducial markers are used in clinical imaging for a variety of applications. They are placed in the field of view of the scanner or attached externally to the anatomy, and they display as distinct regions of high intensity. As such, they assist in pinpointing specific anatomical landmarks or pathologies on the acquired clinical images as well as allowing images of the same subject produced with different imaging systems to be correlated or registered against each other. While commercially available fiducial markers are easily identifiable and clearly visualised in magnetic resonance images (MRI), they are expensive and typically single use, making the cost of research studies where multiple markers are required for numerous subjects prohibitive. For this reason, the current study sought to assess the validity of various ‘everyday’ items, which could be easily and economically sourced, to provide a reliable alternative to the comparatively expensive commercial fiducial markers

Finding an inexpensive fiducial surface marker for use in magnetic resonance imaging in both the clinical and research settings

A fiducial marker displays on an image as a distinct high intensity region to pinpoint specific landmarks and pathologies as well as allowing images from different sources to be registered against each other. While commercial markers are clearly visualised in magnetic resonance images (MRI), they are expensive and typically single use, making the cost of research requiring multiple markers prohibitive. We assessed various ‘everyday’ items, to find a reliable alternative to commercial surface fiducial markers. Depending on the MRI sequence required, four alternative cheap and easily sourced markers were determined. The fish oil capsule is already commonly used in clinical MRI departments but the capsule is too large for some applications and is a rupture risk under body weight. Ultimately, the Vitamin D capsule provided an excellent balance between availability, size, cost, usability and quality of visualisation for all the common MRI sequences analysed

The vertebral venous system in healthy and scoliotic adolescent spines - a 3D MRI investigation

Introduction. The venous drainage system within vertebral bodies (VBs) has been well documented previously in cadaveric specimens. Advances in 3D imaging and image processing now allow for in vivo quantification of larger venous vessels, such as the basivertebral vein. Differences between healthy and scoliotic VB veins can therefore be investigated. Methods. 20 healthy adolescent controls and 21 AIS patients were recruited (with ethics approval) to undergo 3D MRI, using a 3 Tesla, T1-weighted 3D gradient echo sequence, resulting in 512 slices across the thoraco-lumbar spine, with a voxel size of 0.5x0.5x0.5mm. Using Amira Filament Editor, five transverse slices through the VB were examined simultaneously and the resulting observable vascular network traced. Each VB was assessed, and a vascular network recorded when observable. A local coordinate system was created in the centre of each VB and the vascular networks aligned to this. The length of the vascular network on the left and right sides (with a small central region) of the VB was calculated, and the spatial patterning of the networks assessed level-by-level within each subject. Results. An average of 6 (range 4-10) vascular networks, consistent with descriptions of the basivertebral vein, were identifiable within each subject, most commonly between T10-L1. Differences were seen in the left/right distribution of vessels in the control and AIS subjects. Healthy controls saw a percentage distribution of 29:18:53 across the left:centre:right regions respectively, whereas the AIS subjects had a slightly shifted distribution of 33:25:42. The control group showed consistent spatial patterning of the vascular networks across most levels, but this was not seen in the AIS group. Conclusion. Observation and quantification of the basivertebral vein in vivo is possible using 3D MRI. The AIS group lacked the spatial pattern repetition seen in the control group and minor differences were seen in the left/right distribution of vessels

Use of 3D printing in complex spinal surgery: historical perspectives, current usage and future directions

Three-dimensional (3D) printing has been used in complex spinal surgical planning since the 1990s and is now increasingly utilized to produce surgical guides, templates, and more recently customized implants. Surgeons report beneficial impacts using 3D-printed biomodels as a preoperative planning aid as it generally provides for a better representation of the patient's anatomy than on-screen viewing of computed tomography or magnetic resonance imaging. Furthermore, it has proven to be very beneficial in surgical training, and in explaining complex deformity and surgical plans to patients/parents. This paper reviews the historical perspective, current use, and future directions in using 3D printing in complex spinal surgery cases. This review reflects the authors' opinion of where the field is moving in light of the current literature. Despite the reported benefits of 3D printing for surgical planning in the recent years, it remains a highly niche market. This review raises the question as to why the use of this technology has not progressed more rapidly despite the reported advantages-decreased operating time, decreased radiation exposure to patients intraoperatively, improved overall surgical outcomes, preoperative implant selection, as well as being an excellent communication aid for all medical and surgical team members. Increasingly, the greatest benefits of 3D-printing technology in spinal surgery are custom designed drill guides, templates for pedicle screw placement, and customized patient-specific implants. With applications such as these, 3D-printing technology could potentially revolutionize health care in the near future

Change in lung volume after thoracoscopic anterior spinal fusion surgery for adolescent idiopathic scoliosis: A three dimensional computed tomography study

Retrospective analysis of volumetric lung reconstructions from low dose CT scans of adolescent idiopathic scoliosis (AIS) patients treated with thoracoscopic anterior spinal fusion (TASF). Scans were analysed to determine the change in lung volume after surgical correction. Deformity correction surgery resulted in an improvement in the symmetry of the thoracic architecture in addition to postural balance and trunk appearance. Furthermore, change in lung volume was significantly correlated with changes in Cobb angle, hemithoracic asymmetry, and increased patient height, which are major consequences of deformity correction surgery