Complications of Posterior Column Osteotomies in the Pediatric Spinal Deformity Patient.

BACKGROUND: In spinal deformity surgery, posterior column osteotomies (PCOs) are used to increase spinal flexibility and permit greater deformity correction, while avoiding the morbidity of anterior column surgery. Complications related to use of PCOs have been well characterized in adults; however, there is a paucity of information in the pediatric population. METHODS: A single-surgeon retrospective analysis was completed of 484 PCOs in 142 patients (average age: 14.5 years) undergoing spinal deformity surgery. All surgeries were completed by a standard posterior approach using a midline incision and dual-rod, pedicle screw constructs. PCO-related complications were recorded (intraoperative monitoring alerts, postoperative neurologic deficit, dural tear/violations, cerebrospinal fluid [CSF] leak, pseudarthrosis, etc.) and analyzed by diagnosis (idiopathic, congenital, neuromuscular, syndromic). RESULTS: The diagnoses for the 142 patients were idiopathic (103 patients), neuromuscular (23 patients), syndromic (14 patients), and congenital (2 patients). In a subset of 87 patients with 2-year radiographic follow-up, the preoperative major coronal Cobb measurement was 75.5° ± 17.6°, which corrected to 34.9° ± 17.5° postoperatively and 37.8° ± 17.9° at last follow-up (p < .0001, p < .0001). Complications evaluated were postoperative neurologic deficit (0% of patients, 0/142), dural tears/violations at site of PCO (0.4% of PCOs, 2/484), CSF leak (0% of patients, 0/142), and pseudoarthrosis at site of PCO (0% of PCOs, 0/290). CONCLUSION: The overall frequency of complications related to PCOs was 0.4% (0.4% dural tears/violations) with 0% postoperative neurologic deficit, CSF leak, or pseudarthrosis. Based on these data, PCOs appear to be a safe technique in pediatric spine deformity surgery, with a low rate of technique-related complications. STUDY DESIGN: Retrospective case series. OBJECTIVES: To report the frequency of posterior column osteotomy complications (neurologic deficit, dural tear, cerebrospinal fluid leak, and pseudarthrosis) in pediatric patients undergoing spinal deformity surgery. LEVEL OF EVIDENCE: Level IV.

Optimization of an endovascular magnetic filter for maximized capture of magnetic nanoparticles.

To computationally optimize the design of an endovascular magnetic filtration device that binds iron oxide nanoparticles and to validate simulations with experimental results of prototype devices in physiologic flow testing. Three-dimensional computational models of different endovascular magnetic filter devices assessed magnetic particle capture. We simulated a series of cylindrical neodymium N52 magnets and capture of 1500 iron oxide nanoparticles infused in a simulated 14 mm-diameter vessel. Device parameters varied included: magnetization orientation (across the diameter, "D", along the length, "L", of the filter), magnet outer diameter (3, 4, 5 mm), magnet length (5, 10 mm), and spacing between magnets (1, 3 mm). Top designs were tested in vitro using 89Zr-radiolabeled iron oxide nanoparticles and gamma counting both in continuous and multiple pass flow model. Computationally, "D" magnetized devices had greater capture than "L" magnetized devices. Increasing outer diameter of magnets increased particle capture as follows: "D" designs, 3 mm: 12.8-13.6 %, 4 mm: 16.6-17.6 %, 5 mm: 21.8-24.6 %; "L" designs, 3 mm: 5.6-10 %, 4 mm: 9.4-15.8 %, 5 mm: 14.8-21.2 %. In vitro, while there was significant capture by all device designs, with most capturing 87-93 % within the first two minutes, compared to control non-magnetic devices, there was no significant difference in particle capture with the parameters varied. The computational study predicts that endovascular magnetic filters demonstrate maximum particle capture with "D" magnetization. In vitro flow testing demonstrated no difference in capture with varied parameters. Clinically, "D" magnetized devices would be most practical, sized as large as possible without causing intravascular flow obstruction.

In vitro clearance of doxorubicin with a DNA-based filtration device designed for intravascular use with intra-arterial chemotherapy.

To report a novel method using immobilized DNA within mesh to sequester drugs that have intrinsic DNA binding characteristics directly from flowing blood. DNA binding experiments were carried out in vitro with doxorubicin in saline (PBS solution), porcine serum, and porcine blood. Genomic DNA was used to identify the concentration of DNA that shows optimum binding clearance of doxorubicin from solution. Doxorubicin binding kinetics by DNA enclosed within porous mesh bags was evaluated. Flow model simulating blood flow in the inferior vena cava was used to determine in vitro binding kinetics between doxorubicin and DNA. The kinetics of doxorubicin binding to free DNA is dose-dependent and rapid, with 82-96 % decrease in drug concentration from physiologic solutions within 1 min of reaction time. DNA demonstrates faster binding kinetics by doxorubicin as compared to polystyrene resins that use an ion exchange mechanism. DNA contained within mesh yields an approximately 70 % decrease in doxorubicin concentration from solution within 5 min. In the IVC flow model, there is a 70 % drop in doxorubicin concentration at 60 min. A DNA-containing ChemoFilter device can rapidly clear clinical doses of doxorubicin from a flow model in simple and complex physiological solutions, thereby suggesting a novel approach to reduce the toxicity of DNA-binding drugs.

In Vitro Capture of Small Ferrous Particles with a Magnetic Filtration Device Designed for Intravascular Use with Intraarterial Chemotherapy: Proof-of-Concept Study.

PURPOSE: To establish that a magnetic device designed for intravascular use can bind small iron particles in physiologic flow models. MATERIALS AND METHODS: Uncoated iron oxide particles 50-100 nm and 1-5 µm in size were tested in a water flow chamber over a period of 10 minutes without a magnet (ie, control) and with large and small prototype magnets. These same particles and 1-µm carboxylic acid-coated iron oxide beads were likewise tested in a serum flow chamber model without a magnet (ie, control) and with the small prototype magnet. RESULTS: Particles were successfully captured from solution. Particle concentrations in solution decreased in all experiments (P < .05 vs matched control runs). At 10 minutes, concentrations were 98% (50-100-nm particles in water with a large magnet), 97% (50-100-nm particles in water with a small magnet), 99% (1-5-µm particles in water with a large magnet), 99% (1-5-µm particles in water with a small magnet), 95% (50-100-nm particles in serum with a small magnet), 92% (1-5-µm particles in serum with a small magnet), and 75% (1-µm coated beads in serum with a small magnet) lower compared with matched control runs. CONCLUSIONS: This study demonstrates the concept of magnetic capture of small iron oxide particles in physiologic flow models by using a small wire-mounted magnetic filter designed for intravascular use.

Image analysis algorithms for immunohistochemical assessment of cell death.

Light microscopy allows for the inexpensive and fast detection of neuronal /glial cell demise and estimation of infarct and traumatic lesion volumes; the direct correlates of cell death. Quantitative assessment of brain tissue damage following stroke, traumatic brain injury (TBI ) or neurodegenerative diseases, and recovery after therapeutic intervention has been facilitated by recent developments in computer-assisted image analysis technologies that enable more objective and accurate morphometric quantification of cell injury in whole brain sections. In this chapter, the proposed workflow describes what tasks need to be fulfilled to visualize and gauge cell death characterization by histological stains and immunohistochemical markers.

Neuronal deletion of caspase 8 protects against brain injury in mouse models of controlled cortical impact and kainic acid-induced excitotoxicity.

BACKGROUND: Acute brain injury is an important health problem. Given the critical position of caspase 8 at the crossroads of cell death pathways, we generated a new viable mouse line (Ncasp8(-/-)), in which the gene encoding caspase 8 was selectively deleted in neurons by cre-lox system. METHODOLOGY/PRINCIPAL FINDINGS: Caspase 8 deletion reduced rates of neuronal cell death in primary neuronal cultures and in whole brain organotypic coronal slice cultures prepared from 4 and 8 month old mice and cultivated up to 14 days in vitro. Treatments of cultures with recombinant murine TNFα (100 ng/ml) or TRAIL (250 ng/mL) plus cyclohexamide significantly protected neurons against cell death induced by these apoptosis-inducing ligands. A protective role of caspase 8 deletion in vivo was also demonstrated using a controlled cortical impact (CCI) model of traumatic brain injury (TBI) and seizure-induced brain injury caused by kainic acid (KA). Morphometric analyses were performed using digital imaging in conjunction with image analysis algorithms. By employing virtual images of hundreds of brain sections, we were able to perform quantitative morphometry of histological and immunohistochemical staining data in an unbiased manner. In the TBI model, homozygous deletion of caspase 8 resulted in reduced lesion volumes, improved post-injury motor performance, superior learning and memory retention, decreased apoptosis, diminished proteolytic processing of caspases and caspase substrates, and less neuronal degeneration, compared to wild type, homozygous cre, and caspase 8-floxed control mice. In the KA model, Ncasp8(-/-) mice demonstrated superior survival, reduced seizure severity, less apoptosis, and reduced caspase 3 processing. Uninjured aged knockout mice showed improved learning and memory, implicating a possible role for caspase 8 in cognitive decline with aging. CONCLUSIONS: Neuron-specific deletion of caspase 8 reduces brain damage and improves post-traumatic functional outcomes, suggesting an important role for this caspase in pathophysiology of acute brain trauma.