Polyethylene glycol improves elution properties of polymethyl methacrylate bone cements.

BACKGROUND: Bone cements are used as adjuncts to fracture fixation methods and can also function as a local drug delivery system. The ability to elute drugs makes bone cement a promising and powerful chemotherapy treatment modality for osseous tumors. However, because of poor elution rates, the clinical application of this drug delivery mode remains challenging. Soluble fillers, such as sugars, salts, or biocompatible polymers, offer a solution to improve elution rates. This study quantified the effect of polyethylene glycol (PEG) on the elution properties of three commercially available bone cements. METHODS: Two grams of Vertebroplastic, Palacos, and Confidence bone cement powder containing three concentrations (0%, 20%, or 50%) of PEG filler were hand mixed with 10 mg of methotrexate. This powder mixture was then polymerized with 1.0 mL of the cement specific liquid monomer. The cylindrical elution samples were placed in saline solution and methotrexate elution was recorded for 720 h. RESULTS: The cumulative and daily elution rate increased as the concentration of PEG increased for each bone cement. However, the percent of increase depended on the bone cement used. Cumulative methotrexate elution increased by 40%-54% in case of the highest PEG filler concentration when compared with controls. CONCLUSIONS: PEG soluble filler offers a promising method for improving methotrexate drug elution in bone cement. Future studies need to optimize the PEG and bone cement ratio that produces the greatest drug elution profile without sacrificing the biomechanical properties of bone cement.

Stockinette application over a non-prepped foot risks proximal contamination.

This study sought to determine if there was an increased risk for surgical site contamination during stockinette application for a lower extremity surgery draping technique. Utilizing a simulated, sterile surgical field, stockinettes were applied over 10 cadaver lower extremities that were contaminated with non-pathogenic Escherichia coli on the foot. Of those, five specimens were then disinfected with Chloroprep and another 5 did not undergo any disinfection. All the specimens in which the stockinette was applied over a non-prepped foot showed proximal contamination. No contamination occurred in any of the specimens where the foot was disinfected. Stockinette can be a source of surgical site contamination when placed over a non-prepared foot.

Results of posterior spinal fusion after failed anterior vertebral body tethering.

PURPOSE: In patients with adolescent idiopathic scoliosis (AIS) undergoing anterior vertebral tethering (AVBT), some will subsequently require posterior spinal fusion (PSF). Limited data exist on clinical and radiographic outcomes of fusion after tether failure. METHODS: 490 patients who underwent AVBT were retrospectively analyzed. Twenty patients (4.1%) subsequently underwent conversion to PSF. A control group of patients with primary PSF (no previous AVBT) was matched for comparison. Data were compared using paired t-tests and Fisher Exact Tests. RESULTS: There was a significant increase in estimated blood loss (EBL) (p = 0.002), percent estimated blood volume (%EBV) (p = 0.013), operative time (p = 0.002), and increased amount of fluoroscopy (mGy) (p = 0.04) as well as number of levels fused (p = 0.02) in the AVBT conversion group compared to primary fusion. However, no difference was found in implant density (p = 0.37), blood transfusions (p = 0.11), or intraoperative neuromonitoring events (p > 0.99). Both groups attained similar thoracic and lumbar percent correction (major coronal curve angle) from pre-op to the latest follow-up (thoracic p = 0.507, lumbar p = 0.952). CONCLUSION: A subset of patients with AVBT will require conversion to PSF. Although technically more challenging, revision surgery can be safely performed with similar clinical and radiographic outcomes to primary PSF.

Creation of rabbit bone and soft tissue tumor using cultured VX2 cells.

BACKGROUND: To create rabbit VX2 bone tumors, it is surgically less demanding to implant VX2 cell suspensions than minced tumor fragments. A VX2 cell line that can be expanded using standard cell culture techniques might provide an unlimited supply of cells needed to create these bone tumors. Therefore, the aim of the present study was to establish a VX2 cell line and verify its tumorigenicity in an athymic mouse and rabbit animal model. MATERIALS AND METHODS: Minced VX2 tumor fragments were allowed to grow as a monolayer in 10 mL Dulbecco's modified Eagle medium/nutrient mixture F-12 (1:1) supplemented with 10% fetal calf serum and passaged multiple times. The tumorigenecity of the cultured VX2 cells were tested in athymic mice (intradermal tumor development) and in New Zealand white rabbits (bone and soft tissue tumor model). RESULTS: The VX2 cells proliferated rapidly in tissue culture flasks containing Dulbecco's modified Eagle medium/nutrient mixture F-12 medium supplemented with 10% fetal bovine serum. After reaching confluence, the VX2 cells can only be subcultured when plated at a greater density (e.g., at a dilution of 1:1). All 6 athymic mice developed tumors within 15 d of VX2 cell suspension implantation. In the rabbits, the VX2 cells were able to produce tumors in muscle tissue and in the distal femurs but not in the proximal tibia. CONCLUSIONS: VX2 cell lines can be successfully created from VX2 tumor fragments and passaged multiple times. In contrast to previous reports, the VX2 cells grown in vitro are capable of maintaining their tumorigenecity. However, successful tumor growth might depend on the initial number of cells implanted and the use of extracellular matrices for tumor proliferation.

Exosomal Lipid Biomarkers of Oligodendrocyte Pathology to Predict Scoliosis in Children with Cerebral Palsy.

Introduction: Cerebral Palsy (CP), the most common cause of disability in children, is phenotypically heterogeneous. Approximately 20% of cases develop severe scoliosis. A pathological hallmark of CP is periventricular leukomalacia (PVL), which is due to dysmyelination, suggesting the possibility of a lipidomic abnormality. Risk factors for CP include perinatal hypoxia, prematurity, multiple gestation, ischemia, infection, and maternal alcohol consumption. There is evidence for low serum levels of omega-3 (ω-3) fatty acids in CP patients, and separately in idiopathic scoliosis. Many effects of free fatty acids (FFAs) are mediated via specific G protein-coupled free fatty acid receptors (FFARs), which play essential roles as nutritional and signaling molecules. FFAs, including ω-3, and their receptors are involved in the development and metabolism of oligodendrocytes (OLs), and are critical to myelination. Thus, the cases of CP that will develop severe scoliosis might be those in which there is a deficiency of ω-3, FFARs, or other lipidomic abnormality that is detectable early in the plasma. If so, we might be able to predict scoliosis and prevent it with dietary supplementation. Methods: Blood samples were collected from four groups of patients at the Philadelphia Shriners Children's Hospital (SCH-P): 1) patients with CP; 2) severe scoliosis (>40o); 3) CP plus scoliosis; and 4) non-impaired controls stratified by age (2-18 yrs), gender, and race/ethnicity, under an IRB-approved protocol. Serum proteins and RNA were purified, and OL-derived exosomes (OL-Es) isolated, using myelin basic protein (MBP) as a late OL marker. Protein was used for the detection of MBP and FFAR by enzyme-linked immunosorbent assays (ELISAs), and by flow cytometry. RNA was assayed by digital droplet polymerase chain reaction (ddPCR) for OL markers and FFAR expression. Results: FFAR and MBP proteins were downregulated in each of the three patient groups compared to controls, and this difference was greatest in both patients with CP plus scoliosis. Conclusion: Altogether, MBP and FFAR levels were reduced in OL-Es from both children with CP plus scoliosis. The lipid abnormalities specific to CP with scoliosis were concentrated in OLs. Our data might i) suggest therapeutic targets to reduce dysmyelination and scoliosis in CP, ii) predict which children are at risk for developing scoliosis, iii) lead to therapeutic trials of fatty acids for CP and other dysmyelinating neurological disorders.

Atorvastatin activates heme oxygenase-1 at the stress response elements.

Statins are known to inhibit growth of a number of cancer cells, but their mechanism of action is not well established. In this study, human prostate adenocarcinoma PC-3 and breast adenocarcinoma MCF-7 cell lines were used as models to investigate the mechanism of action of atorvastatin, one of the statins. Atorvastatin was found to induce apoptosis in PC-3 cells at a concentration of 1 µM, and in MCF-7 cells at 50 µM. Initial survey of possible pathway using various pathway-specific luciferase reporter assays showed that atorvastatin-activated antioxidant response element (ARE), suggesting oxidative stress pathway may play a role in atorvastatin-induced apoptosis in both cell lines. Among the antioxidant response genes, heme oxygenase-1 (HO-1) was significantly up-regulated by atorvastatin. Pre-incubation of the cells with geranylgeranyl pyrophosphate blocked atorvastatin-induced apoptosis, but not up-regulation of HO-1, suggesting that atorvastatin-induced apoptosis is dependent on GTPase activity and up-regulation of HO-1 gene is not. Six ARE-like elements (designated StRE1 [stress response element] through StRE6) are present in the HO-1 promoter. Atorvastatin was able to activate all of the elements. Because these StRE sites are present in clusters in HO-1 promoter, up-regulation of HO-1 by atorvastatin may involve multiple StRE sites. The role of HO-1 in atorvastatin-induced apoptosis in PC-3 and MCF-7 remains to be studied.

Evaluation of elution and mechanical properties of two injectable chemotherapeutic bone cements.

Chemotherapeutic bone cements can both stabilize the bone fractures as well as deliver chemotherapy agents directly to the bone metastatic site and adjacent soft tissue tumors. This study evaluated the in vitro elution and flexural properties of Vertebroplastic™ and Confidence Ultra™ bone cements (Depuy Spine Inc., Raynham, Mass., USA) containing methotrexate. In vitro elution was measured by placing bone cement specimens containing 4 different methotrexate amounts in 20 ml saline, and the methotrexate elution was measured at regular intervals for 672 h. The flexural properties of bone cement containing 2 different initial methotrexate amounts after storage in physiological saline were measured using a 3-point bending test. The drug elution rate depended on the initial methotrexate amount added and the type of bone cement used. The relationship between the initial drug amount added and the drug elution rate was not linear. Methotrexate elution decreased the flexural modulus and strength of specimens; this decrease was not proportional to the initial amount of methotrexate added. The results show that bone cements are well suited for use with chemotherapy agents. However, the elution and mechanical properties of each bone cement-drug amount combination should be thoroughly quantified in vitro before using such a combination in a clinical setting.

Patient-Specific Coronary Artery Bypass Graft 3D Printing: Implications for Procedural Planning in Complex Percutaneous Coronary Interventions.

BACKGROUND: Three-dimensional (3D) printing technology has seen tremendous growth in augmenting didactics, research, and preprocedural planning with structural heart procedures. Limited investigative efforts have been made in other areas of the cardiovascular spectrum. 3D-printed models (PMs) of anatomically complex coronary artery bypass graft (CABG) patients from coronary computed tomography angiography (CCTA) have implications for adaptive learning and preprocedural planning. METHODS: Five patients with CCTA who underwent subsequent coronary angiography were 3D printed for retrospective comparisons. Standard slicer software was used to create a computer-aided image of the ascending aorta, native coronary arteries, bypass grafts, aortic arch, and great vessels and 3D printed using polylactic acid filament. The models were painted with acrylic paint to highlight anatomical features and comparison was made with coronary angiography and 3D-CTA images. RESULTS: All occluded vein grafts, left and right internal mammary artery (IMA) grafts, patent saphenous vein grafts, along with distal graft anastomotic sites, were accurately 3D printed. In cases with chronic total occlusions (CTOs), ambiguous ostial caps, mid or distal vessel chronic occlusions, and occlusions seen as CTOs on coronary angiography were 3D printed showing either distal vessel reconstitution via collaterals or complete arterial filling seen in a setting of calcification, microchannels, and collateral flow. Lastly, 3D printing of the aortic root and great vessels allowed for better appreciation of vessel tortuosity to aid in the cannulation of IMA grafts and optimizing engagement with diagnostic and guiding catheters. CONCLUSIONS: 3D printing of anatomically complex CABG patients has the potential to assist with preprocedural planning and operator understanding of complex coronary anatomy.

3D Printing of Carotid Artery and Aortic Arch Anatomy: Implications for Preprocedural Planning and Carotid Stenting.

BACKGROUND: Carotid artery stenting (CAS) has been associated with increased periprocedural stroke in comparison with carotid endarterectomy (CEA). Three-dimensional (3D) printing of aortic arch and carotid artery may aid with preprocedural planning and adaptive learning, possibly reducing procedure-related complications. METHODS: Five CAS cases with available computed tomography angiography (CTA) were retrospectively evaluated and 3D-printed models (3D-PMs) were made. One additional case that was 3D printed preprocedurally provided prospective analysis. Standard 3D printing software was used to create a computer-aided image from CTA series that were 3D printed. The models were painted with acrylic paint to highlight anatomical features. The type of aortic arch, common carotid artery (CCA) to internal carotid artery (ICA) angle, and ICA distal landing zone for embolic protection device (EPD) were analyzed. In addition, stent and EPD sizing was determined preprocedurally for the prospective case. Comparisons of 3D-PM were made with 3D-CTA reconstruction and carotid angiography. RESULTS: Of 6 cases, 2 had type III and 4 had type I aortic arches. One case, a failed endovascular approach from femoral artery access site requiring reattempt via right brachial artery, had a CCA to ICA angle >60° and a tortuous innominate artery and distal ICA for EPD. The remaining 5 cases had straight distal landing zones for EPD and <60° CCA to ICA angles with successful first endovascular attempt. Additionally, vessel-specific stent and EPD sizing was appropriately chosen for the 1 prospective case. CONCLUSIONS: 3D-PM for CAS offers added value compared with CTA by providing improved perceptual and visual understanding of 3D anatomy.

Dynamic cycling in atrial size and flow during obstructive apnoea.

OBJECTIVE: Obstructive sleep apnoea (OSA) is strongly associated with cardiovascular disease. However, acute cardiovascular effects of repetitive airway obstruction are poorly understood. While past research used a sustained Mueller manoeuver to simulate OSA we employed a series of gasping efforts to better simulate true obstructive apnoeas. This report describes acute changes in cardiac anatomy and flow related to sudden changes in intrathoracic pressure. METHODS AND RESULTS: 26 healthy, normal weight participants performed 5-6 gasping efforts (target intrathoracic pressure -40 mm Hg) while undergoing Doppler echocardiography. 14 participants had sufficient echocardiographic images to allow comparison of atrial areas during the manoeuver with baseline measurements. Mitral and tricuspid E-wave and A-wave velocities postmanoeuver were compared with baseline in all participants. Average atrial areas changed little during the manoeuver, but variance in both atrial areas was significantly greater than baseline. Further, an inverse relationship was noted with left atrial collapse and right atrial enlargement at onset of inspiratory effort. Significant inverse changes were noted in Doppler flow when comparing the first beat postmanoeuver (pMM1) with baseline. Mitral E-wave velocity increased 9.1 cm/s while tricuspid E-wave velocity decreased 7.0 cm/s; by the eighth beat postmanoeuver (pMM8) values were not different from baseline. Mitral and tricuspid A-wave velocities were not different from baseline at pMM1, but both were significantly higher by pMM8. CONCLUSIONS: Repetitive obstructive apnoeas produce dynamic, inverse changes in atrial size and Doppler flow across the atrioventricular valves. These observations have important implications for understanding the pathophysiology of OSA.

A Comparison of Three C-Arm Draping Techniques to Minimize Contamination of the Surgical Field.

The use of intraoperative fluoroscopy has become a routine and useful adjunct within orthopaedic surgery. However, the fluoroscopy machine may become an additional source of contamination in the operating room, particularly when maneuvering from the anterior-posterior position to the lateral position. Consequently, draping techniques were developed to maintain sterility of the operative field and surgeon. Despite a variety of methods, no studies exist to compare the sterility of these techniques specifically when the fluoroscopy machine is in the lateral imaging position. We evaluated the sterility of 3 c-arm draping techniques in a simulated operative environment. The 3 techniques consisted of a traditional 3-quarter sterile sheet attached to the side of the operative table, a modified clip-drape method, and a commercially available sterile pouch. Our study demonstrated that the traditional method poses a high risk for sterile field contamination, whereas the modified clip-drape method and commercially available sterile pouch kept floor contamination furthest from the surgical field. With the current data, we urge surgeons to use modified techniques rather than the traditional draping method.

Effect of atorvastatin on the cortical bones of corticosteroid treated rabbits.

Osteoporosis ("secondary" osteoporosis) and avascular necrosis (AVN) of the femoral head are well-known adverse effects of corticosteroid therapy. Statins have been reputed to increase bone strength and bone density. In this study, we evaluated the effect of atorvastatin calcium on the flexural properties (3-point bending strength and modulus) of corticosteroid (methylprednisolone acetate) treated rabbit femurs and tibias. Our study hypothesis was that the use of statins would counteract the loss of bone strength caused by corticosteroid treatment. The 40 rabbits were divided into 5 groups: control, corticosteroid alone and corticosteroid combined with oral doses of atorvastatin calcium (2, 10, or 20 mg/day). A daily oral dose of atorvastatin calcium treatment for 70 days weakened the long bones of methylprednisolone acetate treated rabbits irrespective of the dosage (2, 10, or 20 mg). Cortical bone strength was assessed using the 3-point bending test at the end of the study period. A daily oral dose of atorvastatin calcium did not attenuate the loss of cortical bone strength caused by corticosteroid treatment in rabbits. It appeared to decrease that bone strength. If these results hold true in humans, they would have wide applicability given the frequent combined use of corticosteroids and statins in many patients.