Critical Review of the State-of-the-Art on Lumbar Percutaneous Cement Discoplasty

Interbody fusion is the gold standard surgery to treat lumbar disc degeneration disease but can be a high-risk procedure in elderly and polymorbid patients. Percutaneous Cement Discoplasty (PCD) is a minimally invasive technique developed to treat advanced stage of disc degeneration exhibiting a vacuum phenomenon. A patient-specificstand-alone spacer is created by filling the disc with polymethylmethacrylate cement, allowing to recover the disc height and improve the patient’s conditions. As it has recently been introduced in the lumbar spine, this review aims to present a transversal state-of-the-art of the surgery from its clinical practice and outcome to biomechanical and engineering topics. The literature was searched across multiple databases using predefined keywords over no limited period of time. Papers about vertebroplasty were excluded. Among 466 identified papers, the relevant ones included twelve clinical papers reporting the variations of the surgical technique, follow-up and complications, four papers reporting biomechanical ex vivo and numerical tests, and four letters related to published clinical papers. Papers presenting the operative practice are reported, as well as follow-ups up to four years. The papers found, consistently reported that PCD significantly improved the clinical status of the patients and maintained it after two years. Spine alignment was impacted by PCD: the sacral slope was significantly reduced, and disc height increased. The foramen opening correlated to the volume of injected cement. Substitutes to the acrylic cement exhibited better osteointegration and mechanical properties closer to bone tissue. Finally, limitations and risks of the surgery are discussed as well as potential improvements such as the development of new filling materials with better mechanical properties and biological integration or the investigation of the inner disc

Intervertebral disc classification by its degree of degeneration from T2-weighted magnetic resonance images

Purpose: The primary goal of this article is to achieve an automatic and objective method to compute the Pfirrmann’s degeneration grade of intervertebral discs (IVD) from MRI. This grading system is used in the diagnosis and management of patients with low back pain (LBP). In addition, biomechanical models, which are employed to assess the treatment on patients with LBP, require this grading value to compute proper material properties. Materials and methods: T2-weighted MR images of 48 patients were employed in this work. The 240 lumbar IVDs were divided into a training set (140) and a testing set (100). Three experts manually classified the whole set of IVDs using the Pfirrmann’s grading system and the ground truth was selected as the most voted value among them. The developed method employs active contour models to delineate the boundaries of the IVD. Subsequently, the classification is achieved using a trained Neural Network (NN) with eight designed features that contain shape and intensity information of the IVDs. Results: The classification method was evaluated using the testing set, resulting in a mean specificity (95.5 %) and sensitivity (87.3 %) comparable to those of every expert with respect to the ground truth. Conclusions: Our results show that the automatic method and humans perform equally well in terms of the classification accuracy. However, human annotations have inherent inter- and intra-observer variabilities, which lead to inconsistent assessments. In contrast, the proposed automatic method is objective, being only dependent on the input MRI

Biomechanical assessment of vertebrae with lytic metastases with subject-specific finite element models

The assessment of risk of vertebral fracture in patients with lytic metastases is challenging, due to the complexity in modelling the mechanical properties of this heterogeneous material. Currently clinical assessment of patients at high risk of fracture is based on the Spinal Instability Neoplastic Score (SINS), which however in many cases does not provide clear guidelines. The goal of this study was to develop a computational approach to provide a comparative biomechanical assessment of vertebrae with lytic lesions with respect to the adjacent controls and highlight the critical vertebrae. The computed tomography images of the thoracolumbar spine of eight patients suffering of vertebral lytic metastases with SINS between 7 and 12 (indeterminate unstable) were analysed. For each patient one or two vertebrae with lytic lesions were modelled and the closest vertebrae without lesions were considered as control. Metastatic vertebrae (N = 12) and controls (N = 18) were converted to subject-specific, heterogeneous, isotropic, nonlinear finite element models for simulating uniaxial compression. Densitometric and mechanical properties were computed for each vertebra. In average, similar mechanical properties were found for vertebrae with lytic lesions and controls (e.g. ultimate force equal to 6.2 ± 2.7 kN for vertebrae with lytic lesions and to 6.2 ± 3.0 kN for control vertebrae). Only in three patients the vertebrae with lytic lesions were found to be mechanically weaker (−19% to −75% difference for ultimate stress) than the controls. In conclusion, in this study we presented an approach to estimate the mechanical competence of vertebrae with lytic metastases. It remains to be investigated in a clinical study if this method, together with the SINS, can better classify patients with vertebrae with lytic lesions at high risk of fracture

Accurate Segmentation of Vertebral Bodies and Processes Using Statistical Shape Decomposition and Conditional Models

Detailed segmentation of the vertebrae is an important pre-requisite in various applications of image-based spine assessment, surgery and biomechanical modeling. In particular, accurate segmentation of the processes is required for image-guided interventions, for example for optimal placement of bone grafts between the transverse processes. Furthermore, the geometry of the processes is now required in musculoskeletal models due to their interaction with the muscles and ligaments. In this paper, we present a new method for detailed segmentation of both the vertebral bodies and processes based on statistical shape decomposition and conditional models. The proposed technique is specifically developed with the aim to handle the complex geometry of the processes and the large variability between individuals. The key technical novelty in this work is the introduction of a part-based statistical decomposition of the vertebrae, such that the complexity of the subparts is effectively reduced, and model specificity is increased. Subsequently, in order to maintain the statistical and anatomic coherence of the ensemble, conditional models are used to model the statistical inter-relationships between the different subparts. For shape reconstruction and segmentation, a robust model fitting procedure is used to exclude improbable inter-part relationships in the estimation of the shape parameters. Segmentation results based on a dataset of 30 healthy CT scans and a dataset of 10 pathological scans show a point-to-surface error improvement of 20% and 17% respectively, and the potential of the proposed technique for detailed vertebral modeling

Development of a computer-aided design and finite element analysis combined method for affordable spine surgical navigation with 3D-printed customized template

Introduction: Revision surgery of a previous lumbosacral non-union is highly challenging, especially in case of complications, such as a broken screw at the first sacral level (S1). Here, we propose the implementation of a new method based on the CT scan of a clinical case using 3D reconstruction, combined with finite element analysis (FEA), computer-assisted design (CAD), and 3D-printing technology to provide accurate surgical navigation to aid the surgeon in performing the optimal surgical technique by inserting a pedicle screw at the S1 level. Materials and Methods: A step-by-step approach was developed and performed as follows: (1) Quantitative CT based patient-specific FE model of the sacrum was created. (2) The CAD model of the pedicle screw was inserted into the sacrum model in a bicortical convergent and a monocortical divergent position, by overcoming the geometrical difficulty caused by the broken screw. (3) Static FEAs (Abaqus, Dassault Systemes) were performed using 500 N tensile load applied to the screw head. (4) A template with two screw guiding structures for the sacrum was designed and manufactured using CAD design and 3D-printing technologies, and investment casting. (5) The proposed surgical technique was performed on the patient-specific physical model created with the FDM printing technology. The patient-specific model was CT scanned and a comparison with the virtual plan was performed to evaluate the template accuracy Results: FEA results proved that the modified bicortical convergent insertion is stiffer (6,617.23 N/mm) compared to monocortical divergent placement (2,989.07 N/mm). The final template was created via investment casting from cobalt-chrome. The template design concept was shown to be accurate (grade A, Gertzbein-Robbins scale) based on the comparison of the simulated surgery using the patient-specific physical model and the 3D virtual surgical plan. Conclusion: Compared to the conventional surgical navigation techniques, the presented method allows the consideration of the patient-specific biomechanical parameters; is more affordable, and the intraoperative X-ray exposure can be reduced. This new patient- and condition-specific approach may be widely used in revision spine surgeries or in challenging primary cases after its further clinical validation

A novel three-dimensional computational method to assess rod contour deformation and to map bony fusion in a lumbopelvic reconstruction after en-bloc sacrectomy.

Introduction: En-bloc resection of a primary malignant sacral tumor with wide oncological margins impacts the biomechanics of the spinopelvic complex, deteriorating postoperative function. The closed-loop technique (CLT) for spinopelvic fixation (SPF) uses a single U-shaped rod to restore the spinopelvic biomechanical integrity. The CLT method was designed to provide a non-rigid fixation, however this hypothesis has not been previously tested. Here, we establish a computational method to measure the deformation of the implant and characterize the bony fusion process based on the 6-year follow-up (FU) data. Materials and Methods: Post-operative CT scans were collected of a male patient who underwent total sacrectomy at the age of 42 due to a chordoma. CLT was used to reconstruct the spinopelvic junction. We defined the 3D geometry of the implant construct. Using rigid registration algorithms, a common coordinate system was created for the CLT to measure and visualize the deformation of the construct during the FU. In order to demonstrate the cyclical loading of the construct, the patient underwent gait analysis at the 6th year FU. First, a region of interest (ROI) was selected at the proximal level of the construct, then the deformation was determined during the follow-up period. In order to investigate the fusion process, a single axial slice-based voxel finite element (FE) mesh was created. The Hounsfield values (HU) were determined, then using an empirical linear equation, bone mineral density (BMD) values were assigned for every mesh element, out of 10 color-coded categories (1st category = 0 g/cm3, 10th category 1.12 g/cm3). Results: Significant correlation was found between the number of days postoperatively and deformation in the sagittal plane, resulting in a forward bending tendency of the construct. Volume distributions were determined and visualized over time for the different BMD categories and it was found that the total volume of the elements in the highest BMD category in the first postoperative CT was 0.04 cm3, at the 2nd year, FU was 0.98 cm3, and after 6 years, it was 2.30 cm3. Conclusion: The CLT provides a non-rigid fixation. The quantification of implant deformation and bony fusion may help understate the complex lumbopelvic biomechanics after sacrectomy

Variability in the Effect of 5-HTTLPR on Depression in a Large European Population: The Role of Age, Symptom Profile, Type and Intensity of Life Stressors.

BACKGROUND: Although 5-HTTLPR has been shown to influence the risk of life stress-induced depression in the majority of studies, others have produced contradictory results, possibly due to weak effects and/or sample heterogeneity. METHODS: In the present study we investigated how age, type and intensity of life-stressors modulate the effect of 5-HTTLPR on depression and anxiety in a European population cohort of over 2300 subjects. Recent negative life events (RLE), childhood adversity (CHA), lifetime depression, Brief Symptoms Inventory (BSI) depression and anxiety scores were determined in each subject. Besides traditional statistical analysis we calculated Bayesian effect strength and relevance of 5-HTTLPR genotypes in specified models. RESULTS: The short (s) low expressing allele showed association with increased risk of depression related phenotypes, but all nominally significant effects would turn to non-significant after correction for multiple testing in the traditional analysis. Bayesian effect strength and relevance analysis, however, confirmed the role of 5-HTTLPR. Regarding current (BSI) and lifetime depression 5-HTTLPR-by-RLE interactions were confirmed. Main effect, with other words direct association, was supported with BSI anxiety. With more frequent RLE the prevalence or symptoms of depression increased in ss carriers. Although CHA failed to show an interaction with 5-HTTLPR, in young subjects CHA sensitized towards the depression promoting effect of even mild RLE. Furthermore, the direct association of anxiety with the s allele was driven by young (</=30) individuals. LIMITATIONS: Our study is cross-sectional and applies self-report questionnaires. CONCLUSIONS: Albeit 5-HTTLPR has only weak/moderate effects, the s allele is directly associated with anxiety and modulates development of depression in homogeneous subgroups

In Vivo Characterization of the Homing Endonuclease within the polB Gene in the Halophilic Archaeon Haloferax volcanii

Inteins are parasitic genetic elements, analogous to introns that excise themselves at the protein level by self-splicing, allowing the formation of functional non-disrupted proteins. Many inteins contain a homing endonuclease (HEN) gene, and rely on its activity for horizontal propagation. In the halophilic archaeon, Haloferax volcanii, the gene encoding DNA polymerase B (polB) contains an intein with an annotated but uncharacterized HEN. Here we examine the activity of the polB HEN in vivo, within its natural archaeal host. We show that this HEN is highly active, and able to insert the intein into both a chromosomal target and an extra-chromosomal plasmid target, by gene conversion. We also demonstrate that the frequency of its incorporation depends on the length of the flanking homologous sequences around the target site, reflecting its dependence on the homologous recombination machinery. Although several evolutionary models predict that the presence of an intein involves a change in the fitness of the host organism, our results show that a strain deleted for the intein sequence shows no significant changes in growth rate compared to the wild type

Maternal bonding styles in smokers and non-smokers: a comparative study

BACKGROUND: Parental bonding has been implicated in smoking behavior, and the quality of maternal bonding (MB) has been associated with poor mental health and substance use. However, little is known about the association of MB and the smoking of the offspring. METHODS: In our study, 129 smokers and 610 non-smoker medical students completed the parental bonding instrument, which measures MB along two dimensions: care and overprotection. Four categories can be created by high and low scores on care and overprotection: optimal parenting (OP; high care/low overprotection); affectionless control (ALC; low care/high overprotection); affectionate constraint (AC; high care/high overprotection), and neglectful parenting (NP; low care/low overprotection). Nicotine dependence was assessed by the Fagerstrom Nicotine Dependence Test, exhaled CO level, and daily cigarette consumption (CPD). RESULTS: Higher CPD was significantly associated with lower overprotection (p = 0.016) and higher care (p = 0.023) scores. The odds for being a smoker were significantly higher in the neglectful maternal bonding style compared to the other rearing styles (p = 0.022). Besides, smokers showed significantly higher care and lower overprotection scores with the Mann-Whitney U-test than non-smokers, although these associations did not remain significant in multiple regression models. CONCLUSION: Our results indicate that focusing on early life relationship between patient and mother can be important in psychotherapeutic interventions for smoking. Registration trials retrospectively registered

Financial difficulties but not other types of recent negative life events show strong interactions with 5-HTTLPR genotype in the development of depressive symptoms

Several studies indicate that 5-HTTLPR mediates the effect of childhood adversity in the development of depression, while results are contradictory for recent negative life events. For childhood adversity the interaction with genotype is strongest for sexual abuse, but not for other types of childhood maltreatment; however, possible interactions with specific recent life events have not been investigated separately. The aim of our study was to investigate the effect of four distinct types of recent life events in the development of depressive symptoms in a large community sample. Interaction between different types of recent life events measured by the List of Threatening Experiences and the 5-HTTLPR genotype on current depression measured by the depression subscale and additional items of the Brief Symptom Inventory was investigated in 2588 subjects in Manchester and Budapest. Only a nominal interaction was found between life events overall and 5-HTTLPR on depression, which failed to survive correction for multiple testing. However, subcategorising life events into four categories showed a robust interaction between financial difficulties and the 5-HTTLPR genotype, and a weaker interaction in the case of illness/injury. No interaction effect for the other two life event categories was present. We investigated a general non-representative sample in a cross-sectional approach. Depressive symptoms and life event evaluations were self-reported. The 5-HTTLPR polymorphism showed a differential interaction pattern with different types of recent life events, with the strongest interaction effects of financial difficulties on depressive symptoms. This specificity of interaction with only particular types of life events may help to explain previous contradictory findings