Auto-Decompression - Preserved Neurological Function in Bilateral Cervical Facet Dislocations

Introduction Bilateral cervical facet dislocation (BCFD) is an uncommon injury with a high incidence of severe neurological impairment. We describe 4 cases of BCFD with preserved neurological function. Cases Case 1: A 78-year-old female who suffered two ground level falls (GLFs). Pre-operative American Spinal Injury Association (ASIA) Score was C5D. Imaging revealed a BCFD at C6/C7 and a C6 laminar fracture. Case 2: A 63-year-old male suffered a fall down 14 steps. Pre-operative ASIA score was E. Imaging demonstrated a BCFD at C7/T1, and a C6 laminar fracture. Case 3: A 46-year-old male collided with a tree while descending a hill on a bicycle. Pre-operative ASIA score was C6D. Imaging revealed a BCFD at C7/T1 and a C7 laminar fracture. Case 4: A 67-year-old male suffered a GLF while exiting a stationary car. Pre-operative ASIA score on admission was E. Imaging revealed a BCFD at C6/C7 with bilateral laminar fractures at C5 and C6. Outcome All cases underwent 2-stage surgical fixation. All cases maintained or had an improved ASIA score post-operatively. Conclusion In all cases, the presence of concurrent laminar fractures resulted in an auto-decompression of the spinal canal, preserving neurological function.

The Presence of a High Peak Feature Within Low-Average Shear Stimuli Induces Quiescence in Venous Endothelial Cells.

Wall shear stress (WSS) is an important stimulus in vascular remodelling and vascular lesion development. The current methods to assess and predict the risk associated with specific unsteady WSS consider the WSS mean values or the presence of reverse phases described by the oscillatory shear index. Recent evidence has shown that the accuracy of these methods is limited, especially with respect to the venous environment. Unsteady WSS are characterised by several features that may individually affect endothelial cells. Consequently, we assessed the effects of averaged WSS (TAWSS), temporal WSS gradient (TWSSG), maximum WSS (WSS peak) and reverse phase (OSI) by applying different WSS profiles to venous EC in-vitro, using a real-time controlled cone-and-plate cell-shearing device for 24 h. We found that TWSSG and WSS peak affect cell elongation and alignment respectively. We also found that the WSS waveforms with a peak of 1.5 Pa or higher significantly correlate with the induction of a protective phenotype. Cell phenotype induced by these high peak waveforms does not correlate to what is predicted by the hemodynamic indices currently used. The definition of reliable hemodynamic indices can be used to inform the computational models aimed at estimating the hemodynamic effects on vascular remodelling.

Degenerative tears of the posterior horn of the medial meniscus: correlation between MRI findings and outcome following intra-articular steroid/bupivacaine injection of the knee.

AIM: To evaluate the response of symptomatic degenerative tears of the posterior horn of the medial meniscus to guided intra-articular knee steroid/bupivacaine injection and to correlate clinical outcomes with preprocedural findings at magnetic resonance imaging (MRI). MATERIALS AND METHODS: Sixty patients who had clinical and MRI evidence of a symptomatic degenerative tear of the posterior horn of the medial meniscus, isolated or accompanied by additional features of degenerative arthritis, who had failed conservative approaches (physiotherapy, non-steroidal anti-inflammatories, and 3 months rest/knee bracing) were included in the study. Patients underwent intra-articular knee steroid/bupivacaine injection and were followed clinically for a minimum of 6 months. Preprocedural MRI findings were correlated with duration of symptoms, clinical response to injection (recorded as complete, partial or no response) and duration of response to injection. RESULTS: Forty-nine of 60 patients (82%) reported an improvement in symptoms following guided intra-articular knee steroid/bupivacaine injection (complete: 25 patients (42%), partial: 24 (40%) patients). Improvement was sustained in 32 of 60 patients (53%) at follow-up. Thirteen of 18 patients (72%) who had an isolated degenerative tear of the posterior horn of the medial meniscus recorded a complete resolution of symptoms. This was sustained at follow-up in 10 patients (56%). CONCLUSION: Intra-articular steroid/bupivacaine knee joint injection reduced pain symptoms in the majority of patients (81.7%) with degenerative tears of the posterior horn of the medial meniscus, usually with a sustained response. Preprocedural MRI appearances correlate with response to injection. Patients with isolated tears are more likely to have a favourable outcome.

Differing MRI appearances of symptomatic proximal hamstring tendinopathy with ageing: a comparison of appearances in patients below and above 45 years.

AIM: To compare magnetic resonance imaging (MRI) appearances of symptomatic proximal hamstring tendinopathy (PHT) in younger (<45 years) and older (>45 years) patients. MATERIALS AND METHODS: MRI of patients with symptomatic PHT were reviewed and compared to asymptomatic age- and sex-matched controls. Appearances recorded were as: type 0, normal tendon; type I, intra-substance signal abnormality; type II, ischial bone and soft-tissue oedema with/without type I findings; type III, curvilinear fluid signal tearing with/without type II findings; type IV, bony avulsion. Disease pattern was compared between age groups using Fisher's exact test. RESULTS: Thirty-one symptomatic patients (18 male, 13 female; mean age 42 years) were identified. Imaging findings of 16 patients >45 years, 15 patients <45 were as follows: type 0 n=8, type I n=7, type II n=6, type III n=10, type IV n=0. Those >45 years tended to have type III tendinopathy, no examples of type III disease were found in patients <45 years (p<0.001). No significant difference in disease pattern was seen between males and females (p=0.39). Seven of 31 controls >45 years had type III findings and four controls <45 years had type I findings. CONCLUSION: MRI appearances of symptomatic PHT differ with age. Differences may reflect mechanism, whereby overuse-related micro-tearing of healthy tendons occurs in young patients versus degenerative tendinopathy in older patients. Abnormal tendon appearances in patients >45 years may or may not be symptomatic. In contrast, abnormalities identified in younger patients are generally symptomatic. These described differences are important in the primary diagnosis and may impact upon patient response to therapy.

Protein and chemotherapy profiling of extracellular vesicles harvested from therapeutic induced senescent triple negative breast cancer cells.

Triple negative breast cancer (TNBC) is an aggressive subtype with relatively poor clinical outcomes and limited treatment options. Chemotherapy, while killing cancer cells, can result in the generation of highly chemoresistant therapeutic induced senescent (TIS) cells that potentially form stem cell niches resulting in metastases. Intriguingly, senescent cells release significantly more extracellular vesicles (EVs) than non-senescent cells. Our aim was to profile EVs harvested from TIS TNBC cells compared with control cells to identify a potential mechanism by which TIS TNBC cells maintain survival in the face of chemotherapy. TIS was induced and confirmed in Cal51 TNBC cells using the chemotherapeutic paclitaxel (PTX) (Taxol). Mass spectrometry (MS) analysis of EVs harvested from TIS compared with control Cal51 cells was performed using Ingenuity Pathway Analysis and InnateDB programs. We demonstrate that TIS Cal51 cells treated with 75 nM PTX for 7 days became senescent (senescence-associated ß-galactosidase (SA-ß-Gal) positive, Ki67-negative, increased p21 and p16, G2/M cell cycle arrest) and released significantly more EVs (P=0.0002) and exosomes (P=0.0007) than non-senescent control cells. Moreover, TIS cells displayed an increased expression of the multidrug resistance protein 1/p-glycoprotein. MS analysis demonstrated that EVs derived from senescent Cal51 cells contained 142 proteins with a significant increased fold change compared with control EVs. Key proteins included ATPases, annexins, tubulins, integrins, Rabs and insoluble senescence-associated secretory phenotype (SASP) factors. A fluorescent analogue of PTX (Flutax-2) allowed appreciation of the removal of chemotherapy in EVs from senescent cells. Treatment of TIS cells with the exosome biogenesis inhibitor GW4869 resulted in reduced SA-ß-Gal staining (P=0.04). In summary, this study demonstrates that TIS cells release significantly more EVs compared with control cells, containing chemotherapy and key proteins involved in cell proliferation, ATP depletion, apoptosis and the SASP. These findings may partially explain why cancer senescent cells remain viable despite chemotherapeutic challenge.

On the effect of computed tomography resolution to distinguish between abdominal aortic aneurysm wall tissue and calcification: A proof of concept.

PURPOSE: The purpose of this study is to determine the optimal target CT spatial resolution for accurately imaging abdominal aortic aneurysm (AAA) wall characteristics, distinguishing between tissue and calcification components, for an accurate assessment of rupture risk. MATERIALS AND METHODS: Ruptured and non-ruptured AAA-wall samples were acquired from eight patients undergoing open surgical aneurysm repair upon institutional review board approval and informed consent was obtained from all patients. Physical measurements of AAA-wall cross-section were made using scanning electron microscopy. Samples were scanned using high resolution micro-CT scanning. A resolution range of 15.5-155µm was used to quantify the influence of decreasing resolution on wall area measurements, in terms of tissue and calcification. A statistical comparison between the reference resolution (15.5µm) and multi-detector CT resolution (744µm) was also made. RESULTS: Electron microscopy examination of ruptured AAAs revealed extremely thin outer tissue structure <200µm in radial distribution which is supporting the aneurysm wall along with large areas of adjacent medial calcifications far greater in area than the tissue layer. The spatial resolution of 155µm is a significant predictor of the reference AAA-wall tissue and calcification area measurements (r=0.850; p<0.001; r=0.999; p<0.001 respectively). The tissue and calcification area at 155µm is correct within 8.8%±1.86 and 26.13%±9.40 respectively with sensitivity of 87.17% when compared to the reference. CONCLUSION: The inclusion of AAA-wall measurements, through the use of high resolution-CT will elucidate the variations in AAA-wall tissue and calcification distributions across the wall which may help to leverage an improved assessment of AAA rupture risk.

Calcification Volume Reduces Stretch Capability and Predisposes Plaque to Rupture in an in vitro Model of Carotid Artery Stenting.

OBJECTIVE/BACKGROUND: Carotid artery stenting (CAS) in calcified arteries carries a higher peri-operative risk. This study investigates the relationship between the stretching limits of carotid plaque samples and calcification in order to determine a stretch tolerance criterion for endovascular intervention. METHODS: Seventeen carotid plaque samples were acquired from standard endarterectomy procedures. The maximum stretch capability of the global plaque was determined by circumferentially extending the tissue to complete failure. Quantitative assessment of calcification was performed using high resolution computed tomography, including measures of percent calcification volume fraction (%CVF) and calcification configuration. Maximum stretch properties were then related to calcification measures in order to evaluate the predictive power of calcification for determining plaque stretching limits. RESULTS: A strong negative correlation was found between %CVF and stretch ratio with respect to specific calcification configuration types. All plaques with < 70% stenosis superseded the minimum required stretch threshold. Severe stenosis (> 70%) warrants a stretch of at least 2.33 during revascularisation and only plaques containing concentric calcifications with < 20% CVF successfully reached this minimum required stretch threshold. CONCLUSION: The addition of calcification measures to the stenosis classification may help in guiding endovascular intervention techniques to achieve a balance between an acceptable residual patency level while avoiding plaque rupture in calcified carotid plaques.

Improved Detection of Anterior Circulation Occlusions: The "Delayed Vessel Sign" on Multiphase CT Angiography.

BACKGROUND AND PURPOSE: Multiphase CTA, a technique to dynamically assess the vasculature in acute ischemic stroke, was primarily developed to evaluate collateral filling. We have observed that it is also useful in identifying distal anterior circulation occlusions due to delayed anterior circulation opacification on multiphase CTA, an observation we term the "delayed vessel sign." We aimed to determine the usefulness of this sign by comparing multiphase CTA with single-phase CTA. MATERIALS AND METHODS: All 23 distal anterior circulation occlusions during a 2-year period were included. Ten M1-segment occlusions and 10 cases without a vessel occlusion were also included. All patients had follow-up imaging confirming the diagnosis. Initially, the noncontrast CT and first phase of the multiphase CTA study for each patient were blindly evaluated (2 neuroradiologists, 2 radiology trainees) for an anterior circulation occlusion. Readers' confidence, speed, and sensitivity of detection were recorded. Readers were then educated on the "delayed vessel sign," and each multiphase CTA study was re-examined for a vessel occlusion after at least 14 days. RESULTS: There was significant improvement in the sensitivity of detection of distal anterior circulation vessel occlusions (P < .001), overall confidence (P < .001), and time taken to interpret (P < .001) with multiphase CTA compared with single-phase CTA. Readers preferred MIP images compared with source images in >90% of cases. CONCLUSIONS: The delayed vessel sign is a reliable indicator of anterior circulation vessel occlusion, particularly in cases involving distal branches. Assessment of the later phases of multiphase CTA for the delayed vessel sign leads to a significant improvement in the speed and confidence of interpretation, compared with single-phase CTA.

A role for susceptibility weighted imaging in progressive multifocal leukoencephalopathy.

We report a radiologic finding on magnetic resonance imaging (MRI) of the brain of two cases of progressive multifocal leukoencephalopathy (PML) of hypointense signal of subcortical U-fibres on susceptibility weighted (SW) sequence. The first case is a 50-year-old man recently treated with chemotherapy including rituximab for non-Hodgkin's lymphoma. The second case is a 64-year-old woman with human immunodeficiency virus (HIV) infection. Iron deposition is a likely causative factor. We propose that SWI may be especially useful in the assessment of indeterminate cases to reduce the likelihood of a missed diagnosis of PML.

Pre-Hospital Fast Positive Cases Identified by DFB Ambulance Paramedics: Final Clinical Diagnosis.

Ischaemic stroke clinical outcomes are improved by earlier treatment with intravenous thrombolysis. An existing pathway at the Mater University Hospital for assessment of suspected acute stroke in the Emergency Department was updated, aiming to shorten door-to-needle time. This study examines the final clinical diagnosis of Dublin Fire Brigade Ambulance Paramedic identified Face-Arm-Speech-Test (FAST) positive patients presenting to the Emergency Department over a 7 month period. A retrospective analysis was carried out of 177 consecutive FAST positive patients presenting between March and November 2014. The final clinical diagnosis was acute stroke in 57.1% (n=101) of patients. Of these, 76 were ischaemic strokes of whom 56.5% (n=43) were thrombolysed. In the pre-hospital setting Ambulance Paramedics can identify, with reasonable accuracy, acute stroke using the FAST test. Over half of the ischaemic stroke patients presenting via this pathway can be treated with intravenous thrombolysis.

Towards the characterisation of carotid plaque tissue toughness: Linking mechanical properties to plaque composition.

UNLABELLED: The morphological manifestation of calcification within an atherosclerotic plaque is diverse and the response to cutting balloon angioplasty remains an elusive target to predict in the presence of extensive calcification. This study examines the resistance of plaque tissue to blade penetration by characterising the underlying toughness properties and stratifying the upper and lower scale toughness limits based on the strong mechanical influence of calcification. Mechanical toughness properties of the common, bifurcation and internal carotid artery (n=62) were determined using guillotine-cutting tests measuring the energy required to pass a surgical blade through a unit length of plaque tissue. The corresponding structural composition of the dissected plaque segments was characterised using Fourier transform infrared analysis, electron microscopy and energy dispersive x-ray spectroscopy. Mechanical results reveal a clear distinction in toughness properties within each region of the carotid vessel with significantly tougher properties localised in the bifurcation (p=0.004) and internal region (p=0.0003) compared to the common. The severity of the intra-plaque variance is highest in plaques with high toughness localised in the bifurcation region (p<0.05). Structural examination reveals that the diverse mechanical influence of the level of calcification present is characteristic of specific regions within the carotid plaque. The energy required to overcome the calcific resistance and propagate a controlled cut in the calcified tissue at each region varies further with the degree of plaque progression. The identification of the localised calcification characteristics is a key determinant in achieving successful dissection of the severely toughened plaque segments during cutting balloon angioplasty. STATEMENT OF SIGNIFICANCE: Calcification plays a fundamental role in plaque tissue mechanics and demonstrates a diverse range of material moduli properties. This work addresses the characterisation of the toughness properties in human carotid plaque tissue using a fracture mechanics approach. Toughness determines the energy required to propagate a controlled cut in the plaque material. This parameter is crucial for predicting the cutting forces required during endovascular cutting balloon angioplasty intervention. Results demonstrate that a strong relationship exists between the structural calcification configurations, fracture mechanisms and associated toughness properties that are characteristic of specific regions within the carotid artery plaque. The identification of the morphological characteristics of localised calcification may serve as a valuable quantitative measure for cutting balloon angioplasty treatment.

Comparing the endothelialisation of extracellular matrix bioscaffolds with coated synthetic vascular graft materials.

INTRODUCTION: Existing synthetic vascular grafts have unacceptably high failure rates when replacing below knee arteries. In vitro endothelialisation is a technique, which has been shown to enhance the patency rates of below knee vascular grafts. Synthetic materials are however poor cellular substrates and must be combined with coatings to promote cellular growth and attachment. The most common coating clinically is fibrin-coated ePTFE. The aim of our study was to compare the endothelialisation of fibrin-coated ePTFE with novel extracellular matrix (ECM) biomaterials that we hypothesise will provide a superior substrate for cell growth. METHODS: Human endothelial cells were cultured on ECM scaffolds and fibrin-coated ePTFE. Uncoated Dacron and ePTFE acted as controls. The cells were examined for viability, phenotype, adhesion and proliferation. Cell morphology was accessed using scanning electron microscopy. RESULTS: Cells remained viable and produced von Willebrand factor on all substrates tested. ECM scaffolds and fibrin-modified ePTFE achieved statistically higher attachment efficiency when compared to both uncoated synthetic graft materials (p ≤ 0.001). At 90 min 80 ± 3.6% of cells had attached to the ECM scaffold compared to Dacron (30 ± 4.5%, n = 3) and ePTFE (33 ± 2.5%, n = 3). There was no difference in adhesion rates between ECM scaffolds and fibrin-coated ePTFE (p = 1.00). Endothelial cells proliferated fastest on ECM scaffolds when compared to all other materials tested (p < 0.001) and reached confluency on day seven. CONCLUSION: ECM bioscaffolds offer an improved substrate for promoting rapid endothelialisation compared to fibrin-coated ePTFE by combining firm cellular anchorage and superior cell expansion.

On the effect of calcification volume and configuration on the mechanical behaviour of carotid plaque tissue.

Vascular calcification is a complex molecular process that exhibits a number of relatively characteristic morphology patterns in atherosclerotic plaques. Treatment of arterial stenosis by endovascular intervention, involving forceful circumferential expansion of the plaque, can be unpredictable in calcified lesions. The aim of this study was to determine the mechanical stretching mechanisms and define the mechanical limits for circumferentially expanding carotid plaque lesions under the influence of distinct calcification patterns. Mechanical and structural characterisation was performed on 17 human carotid plaques acquired from patients undergoing endarterectomy procedures. The mechanical properties were determined using uniaxial extension tests that stretch the lesions to complete failure along their circumferential axis. Calcification morphology of mechanically ruptured plaque lesions was characterised using high resolution micro computed tomography imaging. Scanning electron microscopy was used to examine the mechanically induced failure sites and to identify the interface boundary conditions between calcified and non-calcified tissue. The mechanical tests produced four distinct trends in mechanical behaviour which corresponded to the calcification patterns that structurally defined each mechanical group. Each calcification pattern produced unique mechanical restraining effects on the plaque tissue stretching properties evidenced by the variation in degree of stretch to failure. Resistance to failure appears to rely on interactions between calcification and non-calcified tissue. Scanning electron microscopy examination revealed structural gradations at interface boundary conditions to facilitate the transfer of stress. This study emphasises the mechanical influence of distinct calcification configurations on plaque expansion properties and highlights the importance of pre-operative lesion characterisation to optimise treatment outcomes.

The influence of composition and location on the toughness of human atherosclerotic femoral plaque tissue.

The toughness of femoral atherosclerotic tissue is of pivotal importance to understanding the mechanism of luminal expansion during cutting balloon angioplasty (CBA) in the peripheral vessels. Furthermore, the ability to relate this parameter to plaque composition, pathological inclusions and location within the femoral vessels would allow for the improvement of existing CBA technology and for the stratification of patient treatment based on the predicted fracture response of the plaque tissue to CBA. Such information may lead to a reduction in clinically observed complications, an improvement in trial results and an increased adoption of the CBA technique to reduce vessel trauma and further endovascular treatment uptake. This study characterises the toughness of atherosclerotic plaque extracted from the femoral arteries of ten patients using a lubricated guillotine cutting test to determine the critical energy release rate. This information is related to the location that the plaque section was removed from within the femoral vessels and the composition of the plaque tissue, determined using Fourier Transform InfraRed spectroscopy, to establish the influence of location and composition on the toughness of the plaque tissue. Scanning electron microscopy (SEM) is employed to examine the fracture surfaces of the sections to determine the contribution of tissue morphology to toughness. Toughness results exhibit large inter and intra patient and location variance with values ranging far above and below the toughness of healthy porcine arterial tissue (Range: 1330-3035 for location and 140-4560J/m(2) for patients). No significant difference in mean toughness is observed between patients or location. However, the composition parameter representing the calcified tissue content of the plaque correlates significantly with sample toughness (r=0.949, p<0.001). SEM reveals the presence of large calcified regions in the toughest sections that are absent from the least tough sections. Regression analysis highlights the potential of employing the calcified tissue content of the plaque as a preoperative tool for predicting the fracture response of a target lesion to CBA (R(2)=0.885, p<0.001). STATEMENT OF SIGNIFICANCE: This study addresses a gap in current knowledge regarding the influence of plaque location, composition and morphology on the toughness of human femoral plaque tissue. Such information is of great importance to the continued improvement of endovascular treatments, particularly cutting balloon angioplasty (CBA), which require experimentally derived data as a framework for assessing clinical cases and advancing medical devices. This study identifies that femoral plaque tissue exhibits large inter and intra patient and location variance regarding tissue toughness. Increasing calcified plaque content is demonstrated to correlate significantly with increasing toughness. This highlights the potential for predicting target lesion toughness which may lead to an increased adoption of the CBA technique and also further the uptake of endovascular treatment.

A MultiCenter Pilot Randomized Controlled Trial of Remote Ischemic Preconditioning in Major Vascular Surgery.

A pilot randomized controlled trial that evaluated the effect of remote ischemic preconditioning (RIPC) on clinical outcomes following major vascular surgery was performed. Eligible patients were those scheduled to undergo open abdominal aortic aneurysm repair, endovascular aortic aneurysm repair, carotid endarterectomy, and lower limb revascularization procedures. Patients were randomized to RIPC or to control groups. The primary outcome was a composite clinical end point comprising any of cardiovascular death, myocardial infarction, new-onset arrhythmia, cardiac arrest, congestive cardiac failure, cerebrovascular accident, renal failure requiring renal replacement therapy, mesenteric ischemia, and urgent cardiac revascularization. Secondary outcomes were components of the primary outcome and myocardial injury as assessed by serum troponin values. The primary outcome occurred in 19 (19.2%) of 99 controls and 14 (14.1%) of 99 RIPC group patients (P = .446). There were no significant differences in secondary outcomes. Our trial generated data that will guide future trials. Further trials are urgently needed.