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.

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.

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.

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.

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.

Perioperative chemotherapy in the treatment of osteosarcoma: a 26-year single institution review.

BACKGROUND: Chemotherapy in the multimodality treatment of osteosarcoma has improved survival. Reported outcomes on adult patients are limited. Poor necrosis rates post neoadjuvant chemotherapy (NAC) is considered an adverse prognostic factor and attempts have been made to improve survival in this group. PATIENTS AND METHODS: Adult and young adult patients diagnosed with osteosarcoma between January 1986 and August 2012 were retrospectively reviewed. Patients identified were stratified according to stage (localised or metastatic) and age (≤40 and >40 years). Event free survival (EFS) and overall survival (OS) outcomes were determined. In patients with localised disease ≤40 years, survival was assessed according to necrosis rates post NAC (<90 and ≥90%). NAC consisted of two cycles of methotrexate alternating with doxorubicin/cisplatin (MAP) followed by definitive surgery. Those with ≥90% tumour necrosis continued on MAP. Patients with <90% necrosis received ifosfamide and etoposide (IE) post operatively. RESULTS: A total of 108 patients were reviewed and 97 were included. Median age was 23 years (range 16-75) and 70% of patients were male. Five year EFS and OS across all groups was 57% and 63% respectively. Of the patients with localised disease (N = 81), 5-year overall survival (OS), with a median follow up of 7 years (2-26) was 70% (p < 0.0001). Patients aged 16-40 (N = 68) with localised osteosarcoma had a significantly improved 5-year OS (74%) compared to those >40 years (N = 13) (42%) (p = 0.004). Of the 68 patients with localised osteosarcoma ≤40 years, 62 were evaluated according to necrosis rates post MAP. In 33 patients who achieved ≥90% necrosis and continued MAP, 5-year OS was 82%. In 29 patients who had <90% tumour necrosis and received adjuvant IE, 5-year OS was 68% (p = 0.15). Multivariate analysis confirmed age and stage as prognostic factors but not poor necrosis rates in our treated population. CONCLUSIONS: Long-term survival outcomes in a predominantly adult Irish population are similar to large reported trials. Age and stage at diagnosis are prognostic. Postoperative ifosfamide/etoposide alone in patients with poor necrosis rates is a feasible regimen, but its role in the adjuvant setting remains uncertain.

Spinal dysraphisms in the parturient: implications for perioperative anaesthetic care and labour analgesia.

Anaesthetists may encounter parturients with a spectrum of anatomical and functional abnormalities secondary to spinal dysraphisms, which are among the most common neurodevelopmental anomalies. These range from surgically corrected open dysraphisms to previously undiagnosed closed dysraphisms. Both bony and neural structures may be abnormal. In true bony spina bifida, which occurs in up to 50% of the population, failure of fusion of the vertebral arch is seen and neural structures are normal. Ninety percent of such cases are confined to the sacrum. In open dysraphisms, sensory preservation is variable and may be present even in those with grossly impaired motor function. Both epidural and spinal blockade have been described for labour analgesia and operative anaesthesia in selected cases but higher failure and complication rates are reported. Clinical assessment should be performed on an outpatient basis to assess neurological function, evaluate central nervous system shunts and determine latex allergy status. Magnetic resonance imagining is recommended to clarify anatomical abnormalities and to identify levels at which neuraxial techniques can be performed. Of particular concern when performing neuraxial blockade is the possibility of a low-lying spinal cord or conus medullaris and spinal cord tethering. Previous corrective de-tethering surgery frequently does not result in ascent of the conus and re-tethering may be asymptomatic. Ultrasound is not sufficiently validated at the point of care to reliably detect low-lying cords. Epidurals should be performed at anatomically normal levels but spread of local anaesthetic may be impaired by previous surgery.

Comparison of four chondral repair techniques in the hip joint: a biomechanical study using a physiological human cadaveric model.

OBJECTIVE: The objective of this study was to assess the biomechanical stability of three types of chondral flap repair techniques as well as a hydrogel scaffold implantation on the acetabular articular surface using a physiological human cadaveric model. METHODS: Chondral flaps were created in the antero-superior zone of the acetabulum in a series of human cadaveric hip joints. The chondral flap was repaired by fibrin glue, cyanoacrylate, suture technique and an agarose hydrogel scaffold sealed with fibrin glue using six hips in each case. After each repair, the specimens were mounted in a validated jig and tested for 1500 gait cycles. In order to determine the stability of the repair, specimens were evaluated arthroscopically at specific intervals. RESULTS: The fibrin glue and cyanoacrylate techniques were technically the easiest to perform arthroscopically, all flaps repaired with fibrin were detached at 50 cycles while those repaired with cyanoacrylate lasted for an average of 635 cycles. On the other hand, both the suture repair and scaffold implantation techniques were more technically challenging but were both stable till the endpoint of 1500 cycles. CONCLUSION: Fibrin glue on its own does not provide sufficient fixation to repair chondral flaps on the acetabular surface. Cyanoacrylate repairs universally failed midway through the testing protocol employed here, raising doubts as to the effectiveness of that technique. The suture and hydrogel scaffold technique were the most reliable for chondral repair at any given cycle. The results of this biomechanical study demonstrate the relative effectiveness of chondral repair and fixation techniques.

The role of venous diameter in predicting arteriovenous fistula maturation: when not to expect an AVF to mature according to pre-operative vein diameter measurements? A best evidence topic.

This best evidence topic was investigated according to a described protocol. We asked the question: what is the minimal vein diameter that can successfully predict maturation of an arteriovenous fistula (AVF) in patients undergoing dialysis. Using the reported search 804 papers were found, of which five represented the best evidence to answer the clinical question. All studies assessed the association between successful AVF maturation and the size of vein used. The strongest evidence came from a nonrandomised controlled follow-up study in which 76% of fistulas created using >2 mm cephalic vein successfully matured compared to 16% when the vein measured ≤2 mm. Another prospective, multicentre study showed 65% successful maturation using veins >4 mm compared to 45% with veins <3 mm. Vein diameter was found to be an independent predictor of maturation in multivariate regression analysis in two retrospective observational studies. Another retrospective observational study found that using venous measurements of ≥2.5 mm following tourniquet application resulted in more fistulas been created that would have otherwise been denied based on venous ultrasound mapping. A large multicentre randomised clinical trial assessing the use of different vein sizes both with and without tourniquet application using proper statistical tools - such as receiver operating characteristic - is required to make a final recommendation. Until then, a vein diameter of <2.5 mm should be considered inadequate for formation of an AVF, particularly if those measurements remain unchanged following the use of tourniquet.

Nerve growth factor-mediated inhibition of apoptosis post-caspase activation is due to removal of active caspase-3 in a lysosome-dependent manner.

Nerve growth factor (NGF) is well characterised as an important pro-survival factor in neuronal cells that can inhibit apoptotic cell death upstream of mitochondrial outer membrane permeabilisation. Here we addressed the question of whether NGF can also protect against apoptosis downstream of caspase activation. NGF treatment promoted a rapid reduction in the level of the p17 subunit of active caspase-3 in PC12 cells that had been induced to undergo apoptosis by various cytotoxins. The mechanism involved TrkA-dependent activation of extracellular signal-regulated kinase (ERK1/2) but not phosphatidylinositol 3-kinase (PI3K)/Akt, and de novo protein synthesis. Involvement of inhibitor of apoptosis proteins (IAPs) and proteasomal degradation were ruled out. In contrast, inhibition of lysosome function using chloroquine and concanamycin A reversed NGF-induced removal of p17. Moreover, in NGF-treated cells, active caspases were found to be localised to lysosomes. The involvement of macroautophagy and chaperone-mediated autophagy were ruled out. Taken together, these findings suggest an anti-apoptotic mechanism by which NGF induces removal of active caspase-3 in a lysosome-dependent manner.

Appendicitis in De Garengeot's Hernia Presenting as a Nontender Inguinal Mass: Case Report and Review of the Literature.

Introduction. De Garengeot first described a femoral hernia containing the appendix in 1731. Appendicitis occurring in this rare clinical setting represents a challenge in diagnosis and management. Case Presentation. We present the case of a 71-year-old male with a three-day history of a nontender inguinal mass. Computed tomography (CT) suggested a femoral hernia. Intraoperatively, the hernia sac was noted to contain a perforated appendix. Discussion. This is an infrequently reported clinical scenario and only the 14th reported case in peer-reviewed literature which includes preoperative CT images. Our case adds to previously reported low sensitivity of CT for diagnosing De Garengeot's hernia. Furthermore, unlike our case the vast majority of previous reports noted a painful inguinal swelling. Conclusion. Perforated appendicitis in a femoral hernia is an extremely uncommon presentation. However, consideration should be given to De Garengeot's hernia in patients with a groin mass, even if nontender.

Assessing the quality of online information for patients with carotid disease.

INTRODUCTION: Controversy exists relating to carotid endarterectomy (CEA) versus carotid artery stenting (CAS). We aimed to assess the quality of online patient information relating to both. METHODS: The Google search engine was searched for "carotid endarterectomy" and "carotid stenting". The first 50 webpages returned were assessed. The Gunning Fog Index (GFI) and Flesch Reading Ease Score (FRES) were calculated to assess readability. The LIDA tool (Minervation Ltd., Oxford, U.K.) was used to assess accessibility, usability and reliability. RESULTS: 20% (n = 10) of the webpages returned for CEA were from peer reviewed sources with 34% (n = 17) posted by hospitals or health services. Comparatively, for CAS, 40% (n = 20) were peer reviewed with 16% (n = 8) posted by hospitals or health services. GFI and FRES scores indicated webpages for both CEA and CAS had poor general readability. Webpages for CEA were easier to read than those for CAS (mean FRES difference of 6.7 (95% CI 0.51 to 12.93, p = 0.03). Median LIDA scores demonstrated acceptable reliability, accessibility and usability of information for both CEA and CAS webpages. The more readable webpages were not associated with higher LIDA scores for either CEA or CAS webpages. CONCLUSION: Webpages providing information on carotid disease management must be made more readable. Online information currently available to patients regarding CAS is more difficult to read and comprehend than CEA.

Multifocal giant cell tumor of the tendon sheath: case report and literature review.

In this study, we present the rare case of a patient with a multifocal giant cell tumor of the tendon sheath occurring at three different localizations along the same tendon. We review radiographic, ultrasonographic, and magnetic resonance imaging findings, and discuss previously reported cases.