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Study Design: Retrospective cohort study. Objective: To determine risk factors that may affect the rate of pedicle screws loosening in patients with degenerative diseases of the lumbar spine. Methods: A total of 250 patients with a low-grade spondylolisthesis and lumbar instability associated with degenerative diseases were enrolled. Preoperatively patients underwent computed tomography (CT) and cancellous bone radiodensity of a vertebral body was measured in Hounsfield units (HU). Pedicle screw fixation was used to treat patients either with a posterior fusion only or in combination with transforaminal lumbar interbody fusion (TLIF), anterior lumbar interbody fusion (ALIF), and direct lateral interbody fusion (D-LIF). Minimal follow-up period accounted for 18 months. Cases with screw loosening were registered assessing association with risk factors using logistic regression. Results: The rate of screw loosening was in positive correlation with the number fused levels and decreasing bone radiodensity. Fusion with a greater load-bearing surface cage was associated with the decrease in rate of pedicle screws loosening. Incomplete reduction in case of spondylolisthesis, bilateral facet joints removal, and laminectomy performed without anterior support favored pedicle screws loosening development. The estimated model classifies correctly 79% of cases with the specificity and sensitivity accounting for 87% and 66% respectively. Conclusions: The decreasing bone radiodensity in Hounsfield units has a considerable correlation with the rate of pedicle screws loosening. On the other hand, the length of fixation and applied surgical technique including fusion type also have a significant impact on complication rate. Spinal instrumentations should be planned by taking into account all potential risk factors and not characteristics relevant to bone quality assessment alone.

TASK-1 is a two-pore K + leak channel. The name, TASK-1, stands for TWIK-related acid-sensitive potassium channel 1, and this channel is encoded by the KCNK3 gene. TASK-1 channels are expressed in humans and modulate cell excitability in excitable cells such as neurons, cardiomyocytes, and vascular smooth muscle cells. TASK-1 inhibition is a mechanism of action for some respiratory stimulants, such as doxapram. TASK-1 channels have also been suggested to play a role in circumventing cell apoptosis in a population of non-small-cell lung cancer cells. We propose that the inner vestibule of the TASK-1 channel, a known binding site of known TASK-1 inhibitors, BAY10000493 and BAY2341237, can be exploited via virtual screening to find other novel TASK-1 inhibitors. Our results show that by targeting the inner vestibule site, we found an active TASK-1 inhibitor. We suspect that this region of interest can be further exploited to discover additional TASK-1 inhibitors. Our initial success lends validity to our virtual screening methodology and parameters. In this study, we identified a novel TASK-1 inhibitor, KU124, which we verified using an in vitro assay.

To study the possible effects of various diagnostic strategies and the relative contribution of various structures in order to determine the optimal diagnostic strategy in treating patients with noncompressive pain syndromes. Prospective, nonrandomized cohort study of 83 consecutive patients with noncompressive pain syndromes resistant to repeated courses of conservative treatment. The follow-up period was 18 months. Nucleoplasty was effective in cases of discogenic pain; the consequences related to false positive results of the discography were significant. The most specific criterion was 80% pain relief after facet joint blocks, whereas 50% pain relief and any subjective pain relief were not associated with a significant increase in the success rate. A considerable rate of false negative results was associated with 80% pain relief, whereas 50% pain relief after facet joint blocks showed the optimal ratio of sensitivity and specificity. Facet joint pain was detected in 50.6% of cases (95% confidence interval 44.1%-66.3%), discogenic pain in 16.9% cases (95% confidence interval 9.5%-26.7%), and sacroiliac joint pain in 7.2% cases (95% confidence interval 2.7%-15%). It was impossible to differentiate the main source of pain in 25.3% of cases. It is rational to adjust the diagnostic algorithm to the probability of detecting a particular pain source and, in doing so, reduce the number of invasive diagnostic measures to evaluate a pain source. False positive results of diagnostic measures can negatively affect the overall efficacy of a particular technology; therefore, all reasons for the failure should be studied in order to reach an unbiased conclusion. In choosing diagnostic criteria, not only should the success rate of a particular technology be taken into consideration but also the rate of false negative results. Acceptable diagnostic criteria should be based on a rational balance of sensitivity and specificity.

Background: Bone cement leakage during vertebroplasty is a frequently reported complication with the potential for neural injury. Objective: To assess risk factors for epidural cement leakage during vertebroplasty. Setting: Neurosurgical department of a scientific research institute. Study Design: This is a prospective cross-sectional randomized trial. Methods: Seventy-five patients with intractable pain due to low energy vertebral compression fractures between T11 and L5 were treated with vertebroplasty at 150 vertebral levels. Preoperative computed tomography (CT) scans were utilized to characterize vertebral parameters including the type of nutrient foramena in the posterior vertebral cortex. Following vertebroplasty, distance from the needle tracts to the midline and the presence and type of any epidural cement leakage were determined. Using logistic regression analysis, significant risk factors for cement leakage were determined. Results: A smaller distance between the tip of the needle and the midline and a magistral type of venobasillar system were found to be significant risk factors for epidural cement leakage (P < 0.0001). Use of a bipedicular vs. monopedicular technique did not significantly affect the rate of epidural cement leakage (P = 0.3869). Limitations: This study is limited because of the relatively small number of patients and the lack of any patients who had clinical consequences as a result of extensive epidural cement leakage. Conclusion: The type of venobasillar system should be taken into account when planning a vertebroplasty procedure as a magistral type of venobasillar system is associated with the increased rate of epidural cement leakage. It is important to try and achieve a large distance between the needle tip and the midline, especially when a magistral type of venobasillar system is present, to reduce the risk of epidural cement leakage. Key words: Vertebroplasty, intracanal cement leakage, low energy vertebra fracture

Background: Despite the evident progress in treating vertebral column degenerative diseases, the rate of a so-called “failed back surgery syndrome” associated with pain and disability remains relatively high. However, this term has an imprecise definition and includes several different morbid conditions following spinal surgery, not all of which directly illustrate the efficacy of the applied technology; furthermore, some of them could even be irrelevant. Objective: To evaluate and systematize the reasons for persistent pain syndromes following surgical nerve root decompression. Study Design: Prospective, nonrandomized, cohort study of 138 consecutive patients with radicular pain syndromes, associated with nerve root compression caused by lumbar disc herniation, and resistant to conservative therapy for at least one month. The minimal period of follow-up was 18 months. Setting: Hospital outpatient department, Russian Federation Methods: Pre-operatively, patients were examined clinically, applying the visual analog scale (VAS), Oswestry Disability Index (ODI), magnetic resonance imaging (MRI), discography and computed tomography (CT). According to the disc herniation morphology and applied type of surgery, all participants were divided into the following groups: for those with disc extrusion or sequester, microdiscectomy was applied (n = 65); for those with disc protrusion, nucleoplasty was applied (n = 46); for those with disc extrusion, nucleoplasty was applied (n = 27). After surgery, participants were examined clinically and the VAS and ODI were applied. All those with permanent or temporary pain syndromes were examined applying MRI imaging, functional roentgenograms, and, to validate the cause of pain syndromes, different types of blocks were applied (facet joint blocks, paravertebral muscular blocks, transforaminal and caudal epidural blocks). Results: Group 1 showed a considerable rate of pain syndromes related to tissue damage during the intervention; the rates of radicular pain caused by epidural scar and myofascial pain were 12.3% and 26.1% respectively. Facet joint pain was found in 23.1% of the cases. Group 2 showed a significant rate of facet joint pain (16.9%) despite the minimally invasive intervention. The specificity of Group 3 was the very high rate of unresolved or recurred nerve root compression (63.0%); in other words, in the majority of cases, the aim of the intervention was not achieved. The results of the applied intervention were considered clinically significant if 50% pain relief on the VAS and a 40% decrease in the ODI were achieved. Limitations: This study is limited because of the loss of participants to follow-up and because it is nonrandomized; also it could be criticized because the dynamics of numeric scores were not provided. Conclusion: The results of our study show that an analysis of the reasons for failures and partial effects of applied interventions for nerve root decompression may help to understand better the efficacy of the interventions and could be helpful in improving surgical strategies, otherwise the validity of the conclusion could be limited because not all sources of residual pain illustrate the applied technology efficacy. In the majority of cases, the cause of the residual or recurrent pain can be identified, and this may open new possibilities to improve the condition of patients presenting with failed back surgery syndrome. Key words: microdiscectomy, nucleoplasty, epidural scar, facet joint pain, recurrent herniation, myofascial pain

Several options were designed to provide higher stability of pedicle screws in patients with poor bone quality, the most frequently used are bone augmentation with cement and expandable screws.3 Potential hazards associated with bone cement application for augmentation are frequently discussed in literature; those are intracanal cement leakage, pulmonary embolism, cytotoxicity and poor feasibility for revision surgery.3-6 For those reasons, some authors consider the application of expandable screws safer than augmentation of pedicle screws with cement, although the anchorage strength of the former is lower.3-5 The aim of our study is to report rarely discussed implant related complications in patients which are operated on using expandable pedicle screws and to propose revision options in case of implant failure. In other two cases, only core and proximal non-expandable segment of a ruptured screw were extracted. Because of a strong anchorage in the bone, all attempts to remove the remaining fragments with expanded screw segment failed. The number of surgeries performed annually is still on the rise because of the aging population and growing number of spinal injuries including low energy trauma.7 It has been proven that poor bone healing with pseudoarthrosis formation and poor bone quality in elderly patients may cause a considerable increase in implant failure rate including pedicle screw breakage and screw loosening.3,8,9 To prevent those complications, pedicle screw augmentation with bone cement and expandable screws were introduced into a clinical practice and it has been reported that expandable screws can provide a 25-50 per cent increase tolerance towards pull out forces applied to pedicle screws.4,5,10,11 An additional benefit is that the application of expandable screws seems to be safer because this technology provides the opportunity to get rid of challenges associated with liquid cement injection.10 In a study with a sample of 331 patient it has been shown that implant related complications rate is low if expandable screws are used as far as no screw loosening was detected, while implant breakage accounts for only 2.8 per cent.11 According to the results of our study the complication rate was relatively higher forming 7 per cent, however, the design of screws differed from that used in the study by Cook et al. According to our experience it is supposed that the weakest part of screws used in this study is a junction of expandable and proximal nonexpendable screw segments.

This chapter discusses alternative methods for drug delivery. Specifically, we focused on the use of mesenchymal stem cells (MSCs) and to show how these stem cells can be available as off-the-shelf cells. The advantages of MSCs are their unique immune properties and the ability of these cells to migrate to areas of inflammation such as tumors. In addition, MSCs are easy to harvest with several fold expansion, as well as little to no ethical concern. Although MSCs are similar by phenotype, the effectiveness from each source needs to be compared for homing to the desired organ/tissue, intercellular communication and the delivery of non-coding RNA through secreted exosomes. A major advantage of MSCs is the ease by which they can become available as off-the-shelf cells containing the drugs or RNA for immediate transplant to patients. There is little concern that MSCs will linger for a prolonged period because the clinical and experimental evidence indicate that allogeneic MSCs (off-the-shelf) can be readily cleared by the immune system. The chapter discusses why there is an immediate need for cellular delivery of drugs, given the cumbersome regulation and confounds of current single drug trials.

The blood brain barrier (BBB) poses a problem to deliver drugs for brain malignancies and neurodegenerative disorders. Stem cells such as neural stem cells (NSCs) and mesenchymal stem cells (MSCs) can be used to delivery drugs or RNA to the brain. This use of methods to bypass the hurdles of delivering drugs across the BBB is particularly important for diseases with poor prognosis such as glioblastoma multiforme (GBM). Stem cell treatment to deliver drugs to neural tumors is currently in clinical trial. This method, albeit in the early phase, could be an advantage because stem cells can cross the BBB into the brain. MSCs are particularly interesting because to date, the experimental and clinical evidence showed ‘no alarm signal’ with regards to safety. Additionally, MSCs do not form tumors as other more primitive stem cells such as embryonic stem cells. More importantly, MSCs showed pathotropism by migrating to sites of tissue insult. Due to the ability of MSCs to be transplanted across allogeneic barrier, drug-engineered MSCs can be available as off-the-shelf cells for rapid transplantation. This review discusses the advantages and disadvantages of stem cells to deliver prodrugs, genes and RNA to treat neural disorders.

This paper provides a study of two bone substitutes: a hybrid porous polymer and an osteoplastic matrix based on a bovine-derived xenograft. Both materials are porous, but their pore characteristics are different. The osteoplastic matrix has pores of 300–600 µm and the hybrid polymer has smaller pores, generally of 6–20 µm, but with some pores up to 100 µm across. SEM data confirmed the porometry results and demonstrated the different structures of the materials. Therefore, both materials were characterized by an interconnected porous structure and provided conditions for the adhesion and vital activity of human ASCs in vitro. In an experimental model of rabbit shin bone defect, it was shown that, during the 6-month observation period, neither of the materials caused negative reactions in the experimental animals. By the end of the observation period, restoration of the defects in animals in both groups was completed, and elements of both materials were preserved in the defect areas. Data from morphological examinations and CT data demonstrated that the rate of rabbit bone tissue regeneration with the hybrid polymer was comparable to that with the osteoplastic matrix. Therefore, the hybrid polymer has good potential for use in further research and improvement in biomedical applications.