Ruptured Abdominal Aortic Aneurysm: Does Trauma Center Designation Affect Outcome?

Ruptured abdominal aortic aneurysm (RAAA) continues to be a major cause of mortality in the United States. Rapid diagnosis and uncomplicated surgical repair remain paramount to improving survival in this population. We proposed that the addition of an organized trauma service and subsequent improved management of critically ill patients who present with RAAA would positively impact overall mortality. A retrospective analysis was performed on all patients treated for RAAA at Santa Barbara Cottage Hospital for the years 1985-2004. Patients treated before level II trauma center designation (1985-1999) were compared to those treated after the trauma center was instituted. A total of 76 patients were included in this analysis. The two groups were similar with regard to demographics. However, significant decreases in transport time from the emergency department to the operating room and overall 30-day mortality were seen in patients after the trauma center designation. This designation also led to an increase in the number of cases performed per year, centralizing the treatment for these critically ill patients. Institution of a well-prepared and organized service, such as trauma, improved the outcome for patients treated with RAAA, with a particular benefit in the unstable patient.     

Engineered mesenchymal stem cells for cartilage repair

Healthy cartilage is a highly robust tissue, and is resilient against the stringent mechanical and biological constraints imposed upon it. Cartilage defects are common features of joint diseases, but current treatments can rarely restore the full function of native cartilage. Recent studies have provided new perspectives for cartilage engineering using mesenchymal stem cells (MSCs). However, the sequential events occurring during chondrogenesis must be fully understood before we are able to reproduce faithfully the complex molecular events that lead to MSC differentiation and long-term maintenance of cartilage characteristics. Here, we focus on the potential of MSCs to repair cartilage with an emphasis on the factors that are known to be required in inducing chondrogenesis.     

Betel-derived alkaloid up-regulates keratinocyte alphavbeta6 integrin expression and promotes oral submucous fibrosis

Oral submucous fibrosis (OSF) is a premalignant, fibrosing disorder of the mouth, pharynx, and oesophagus, with a malignant transformation rate of 7-13%. OSF is strongly associated with areca (betel) nut chewing and worldwide, over 5 million people are affected. As αvβ6 integrin is capable of promoting both tissue fibrosis and carcinoma invasion, we examined its expression in fibroepithelial hyperplasia and OSF. αvβ6 was markedly up-regulated in OSF, with high expression detected in 22 of 41 cases (p < 0.001). We investigated the functional role of αvβ6 using oral keratinocyte-derived cells genetically modified to express high αvβ6 (VB6), and also NTERT-immortalized oral keratinocytes, which express low αvβ6 (OKF6/TERT-1). VB6 cells showed significant αvβ6-dependent activation of TGF-β1, which induced transdifferentiation of oral fibroblasts into myofibroblasts and resulted in up-regulation of genes associated with tissue fibrosis. These experimental in vitro findings were confirmed using human clinical samples, where we showed that the stroma of OSF contained myofibroblasts and that TGF-β1-dependent Smad signalling was detectable both in keratinocytes and in myofibroblasts. We also found that arecoline, the major alkaloid of areca nuts, up-regulated keratinocyte αvβ6 expression. This was modulated through the M(4) muscarinic acetylcholine receptor and was suppressed by the M(4) antagonist, tropicamide. Arecoline-dependent αvβ6 up-regulation promoted keratinocyte migration and induced invasion, raising the possibility that this mechanism may support malignant transformation. Over 80% of OSF-related oral cancers examined had moderate/high αvβ6 expression. These data suggest that the pathogenesis of OSF may be epithelial-driven and involve arecoline-dependent up-regulation of αvβ6 integrin.     

Three-dimensional reconstruction of the scoliotic spine and pelvis from uncalibrated biplanar x-ray images

Current three-dimensional (3D) reconstruction methods based on explicit or implicit calibration procedure require a calibration object to generate calibrated x-rays for the 3D reconstruction of the human spine and the pelvis. However, to conduct retrospective studies where no 3D technology is available, 3D reconstruction must be performed from x-ray images where no calibration object was used. The current state of the art offers a variety of methods to obtain a personalized 3D model of a patient's spine, however, none have presented a clinically proven method which allows a 3D reconstruction using uncalibrated x-rays. The main objective of this study was to propose a self-calibration method using only the anatomic content of the x-ray images and evaluate its clinical feasibility on uncalibrated x-ray images for the 3D reconstruction of the scoliotic spine and pelvis. The rationale for proposing a 3D reconstruction method from uncalibrated x-rays is to allow access to 3D evaluation of spinal deformities in any standard clinical setup and to enable the conduct of retrospective studies of any kind. To assess the validity of the 3D reconstructions yielded by the proposed algorithm, a clinical study using 60 pairs of digitized x-rays of children was conducted. The mean age for this group of 60 patients was of 14+/-3 (range 8 to 18) years old. All the children in the study group had scoliosis, with an average Cobb angle on the frontal plane of 25 degrees (range 3 to 70 degrees). For each case, a 3D reconstruction of the spine and pelvis was obtained using both explicit and self-calibration methods, from calibrated and uncalibrated x-rays, respectively. Results show that 3D reconstructions obtained with the proposed method from uncalibrated x-ray images yield- geometrical models that exhibit insignificant differences for 2D and 3D clinical indices commonly used in the evaluation of spinal deformities. This allows a 3D clinical assessment of scoliotic deformities from standard x-rays without the need for calibration, and providing access to this technology in any clinical setup and allowing to perform retrospective studies, which were previously impossible.     

Nocardia nova as the causative agent in spondylodiscitis and psoas abscess

We describe here the first case of Nocardia nova spondylodiscitis accompanied by a psoas abscess due to spreading from pulmonary nocardiosis. Nocardia was cultured from all affected sites. After 1 year of an appropriate antimicrobial therapy and a surgical drainage of the abscess that was required, the patient's clinical condition had improved.     

Estrogen's effects on central and circulating immune cells vary with reproductive age

Previous work from this lab has shown that estrogen attenuates inflammatory cytokine production following brain lesions in young adult female rats, but not in older, reproductive senescent females. The present study was designed to elucidate whether these effects result from estrogen's actions on brain-resident immune cells (microglia) or on circulating immune cells recruited to the brain from blood. Microglia, harvested from the olfactory bulbs of ovariectomized young adult and reproductive senescent animals, were pretreated with 17beta-estradiol and subsequently with the bacterial endotoxin LPS. LPS treatment significantly increased the pro-inflammatory cytokine IL-1beta in microglial cultures harvested from young and senescent females, but estrogen treatment had no effect on cytokine expression in either group. In young adult-derived microglia, LPS treatment also increased nitric oxide (NO), which was attenuated by estrogen, and MMP-9, which was not affected by estrogen. Reproductive senescent-derived microglia cultures had higher basal expression of NO and MMP-9 activity as compared to those from young adult microglial cultures, although LPS did not further stimulate these inflammatory markers. In blood cultures, LPS stimulated a dose-dependent increase in the inflammatory cytokine TNF-alpha expression in both young adult and reproductive senescent animals. Estrogen replacement significantly attenuated TNF-alpha induction by LPS in blood cultures derived from young adult females. Paradoxically, estrogen replacement increased LPS-induced TNF-alpha expression in blood cultures derived from reproductive senescent animals as compared to age-matched controls. The age and estrogen dependent effects on circulating immune cells found in whole blood cultures closely mimic the effects of estrogen on cytokine expression in the young and senescent animals that we reported in vivo, supporting the hypothesis that the immunosuppressive actions of estrogen replacement on neural injury may result from hormone-action on circulating immune cells.     

Diffusion kurtosis imaging and log‐normal distribution function imaging enhance the visualisation of lesions in animal stroke models

In this work, we report a case study of a stroke model in animals using two methods of quantification of the deviations from Gaussian behaviour: diffusion kurtosis imaging (DKI) and log‐normal distribution function imaging (LNDFI). The affected regions were predominantly in grey rather than in white matter. The parameter maps were constructed for metrics quantifying the apparent diffusivity (evaluated from conventional diffusion tensor imaging, DKI and LNDFI) and for those quantifying the degree of deviations (mean kurtosis and a parameter σ characterising the width of the distribution). We showed that both DKI and LNDFI were able to dramatically enhance the visualisation of ischaemic lesions in comparison with conventional methods. The largest relative change in the affected versus healthy regions was observed in the mean kurtosis values. The average changes in the mean kurtosis and σ values in the lesions were a factor of two to three larger than the relative changes observed in the mean diffusivity. In conclusion, the applied methods promise valuable perspectives in the assessment of stroke. Copyright © 2012 John Wiley & Sons, Ltd.     

Quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images

Background

For some scoliotic patients the spinal instrumentation is inevitable. Among these patients, those with stiff curvature will need thoracoscopic disk resection. The removal of the intervertebral disk with only thoracoscopic images is a tedious and challenging task for the surgeon. With computer aided surgery and 3D visualisation of the interverterbral disk during surgery, surgeons will have access to additional information such as the remaining disk tissue or the distance of surgical tools from critical anatomical structures like the aorta or spinal canal. We hypothesized that automatically extracting 3D information of the intervertebral disk from MR images would aid the surgeons to evaluate the remaining disk and would add a security factor to the patient during thoracoscopic disk resection.

Methods

This paper presents a quantitative evaluation of an automatic segmentation method for 3D reconstruction of intervertebral scoliotic disks from MR images. The automatic segmentation method is based on the watershed technique and morphological operators. The 3D Dice Similarity Coefficient (DSC) is the main statistical metric used to validate the automatically detected preoperative disk volumes. The automatic detections of intervertebral disks of real clinical MR images are compared to manual segmentation done by clinicians.

Results

Results show that depending on the type of MR acquisition sequence, the 3D DSC can be as high as 0.79 (±0.04). These 3D results are also supported by a 2D quantitative evaluation as well as by robustness and variability evaluations. The mean discrepancy (in 2D) between the manual and automatic segmentations for regions around the spinal canal is of 1.8 (±0.8) mm. The robustness study shows that among the five factors evaluated, only the type of MRI acquisition sequence can affect the segmentation results. Finally, the variability of the automatic segmentation method is lower than the variability associated with manual segmentation performed by different physicians.

Conclusions

This comprehensive evaluation of the automatic segmentation and 3D reconstruction of intervertebral disks shows that the proposed technique used with specific MRI acquisition protocol can detect intervertebral disk of scoliotic patient. The newly developed technique is promising for clinical context and can eventually help surgeons during thoracoscopic intervertebral disk resection.