Is Stand-Alone Anterior Lumbar Interbody Fusion a Safe and Efficacious Treatment for Isthmic Spondylolisthesis of L5-S1?

STUDY DESIGN: A systematic review. OBJECTIVE: The objective of this study was to determine the safety and efficacy of stand-alone anterior lumbar interbody fusion (sa-ALIF) for the treatment of symptomatic isthmic spondylolisthesis of L5-S1 by assessing the level of available clinical and radiographic evidence. METHODS: A systematic review utilizing Medline, Embase, and Scopus online databases was undertaken. Clinical, radiographic, and adverse outcome data were extracted for the relevant isthmic spondylolisthesis cases with the intention of undertaking a meta-analysis. RESULTS: The database search between January 1980 and December 2015 yielded 23 articles that concerned sa-ALIF for isthmic spondylolisthesis of L5-S1. Only in 9 of the 23 articles data could be extracted specific to sa-ALIF for isthmic spondylolisthesis of L5-S1. There was considerable inconsistency in the standards for reporting outcomes of the surgery due to which meta-analysis could not be undertaken, and hence each article was reviewed. CONCLUSIONS: There was insufficient evidence to support the safety and efficacy of sa-ALIF for the treatment of isthmic spondylolisthesis of L5-S1. Although sa-ALIF is widely documented in the literature, there was insufficient evidence to support its use in treating this specific pathology. The unique pathological and anatomical situation that isthmic spondylolisthesis of L5-S1 presents must be recognized and its treatment with sa-ALIF should be well thought out

The Role of Sacral Slope in the Progression of a Bilateral Spondylolytic Defect at L5 to Spondylolisthesis: A Biomechanical Investigation Using Finite Element Analysis

© The Author(s) 2017. Study Design: A biomechanical study using finite element analysis. Objectives: The main objective of this study was to investigate the role of sacral slope in the progression of a L5 bilateral spondylolytic defect to spondylolisthesis. Methods: A 3-dimensional model of lumbosacral spine was built using computed tomography (CT) data procured from an anonymized healthy male subject. The segmented CT data was manipulated to generate 3 more models representing L5 bilateral spondylolytic defect with normal sacral slope (SS), sacral slope increased by 10° (SS+10), and sacral slope decreased by 10° (SS-10). The 3D models were imported into finite element modelling software Strand7 for preprocessing, running nonlinear static solves, and postprocessing of the results. Results: Directional biomechanical instabilities were induced in the lumbosacral spine as a result of changes in the L5-S1 disc shape secondary to the changes in sacral slope. Compared with the normal L5 lytic model, wedging of the L5-S1 disc (SS+10) resulted in a significantly greater range of motion in flexion (18% ↑) but extension motion characteristics were similar. Conversely, flattening of the L5-S1 disc (SS-10) resulted in a significantly greater range of motion in extension (16% ↑) but flexion motion characteristics were similar to that of the normal L5 lytic model. Conclusions: Variations in sacral slope while preserving the L5-S1 mid-disc height and orientation of the L5 vertebra resulted in variations in the L5-S1 disc shape. The results suggest that for such extremities in the L5-S1 disc shape different pathomechanisms exist for the progression of the L5 lytic defect to spondylolisthesis

Mild (not severe) disc degeneration is implicated in the progression of bilateral L5 spondylolysis to spondylolisthesis

© 2018 The Author(s). Background: Spondylolytic (or lytic) spondylolisthesis is often associated with disc degeneration at the index-level; however, it is not clear if disc degeneration is the cause or the consequence of lytic spondylolisthesis. The main objective of this computed tomography based finite element modelling study was to examine the role of different grades of disc degeneration in the progression of a bilateral L5-lytic defect to spondylolisthesis. Methods: High-resolution computed tomography data of the lumbosacral spine from an anonymised healthy male subject (26 years old) were segmented to build a 3D-computational model of an INTACT L1-S1 spine. The INTACT model was manipulated to generate four more models representing a bilateral L5-lytic defect and the following states of the L5-S1 disc: nil degeneration (NOR LYTIC), mild degeneration (M-DEG LYTIC), mild degeneration with 50% disc height collapse (M-DEG-COL LYTIC), and severe degeneration with 50% disc height collapse(S-COL LYTIC). The models were imported into a finite element modelling software for pre-processing, running nonlinear-static solves, and post-processing of the results. Results: Compared with the baseline INTACT model, M-DEG LYTIC model experienced the greatest increase in kinematics (Fx range of motion: 73% ↑, Fx intervertebral translation: 53%↑), shear stresses in the annulus (Fx anteroposterior: 163%↑, Fx posteroanterior: 31%↑), and strain in the iliolumbar ligament (Fx: 90%↑). The S-COL LYTIC model experienced a decrease in mobility (Fx range of motion: 48%↓, Fx intervertebral translation: 69%↓) and an increase in normal stresses in the annulus (Fx Tensile: 170%↑; Fx Compressive: 397%↑). No significant difference in results was noted between M-DEG-COL LYTIC and S-COL LYTIC models. Conclusions: In the presence of a bilateral L5 spondylolytic defect, a mildly degenerate index-level disc experienced greater intervertebral motions and shear stresses compared with a severely degenerate index-level disc in flexion and extension bending motions. Disc height collapse, with or without degenerative changes in the stiffness properties of the disc, is one of the plausible re-stabilisation mechanisms available to the L5-S1 motion segment to mitigate increased intervertebral motions and shear stresses due to a bilateral L5 lytic defect

Disrupted hippocampal sharp-wave ripple-associated spike dynamics in a transgenic mouse model of dementia.

This is the peer reviewed version of the article, which has been published in final form at DOI: 10.1113/jphysiol.2014.282889. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.Neurons within the CA1 region of the hippocampus are co-activated during high frequency (100-250 Hz) sharp wave ripple (SWR) activity in a manner that likely drives synaptic plasticity and promotes memory consolidation. In this study we have used a transgenic mouse model of dementia (rTg4510 mice) which overexpresses a mutant form of tau protein, to examine the effects of tauopathy on hippocampal SWRs and associated neuronal firing. Tetrodes were used to record simultaneous extracellular action potentials and local field potentials from the dorsal CA1 pyramidal cell layer of 7-8 month old wild-type and rTg4510 mice at rest in their home cage. At this age point these mice exhibit neurofibrillary tangles, neurodegeneration and cognitive deficits. Epochs of sleep or quiet restfulness were characterised by minimal locomotor activity and a low theta/delta ratio in the local field potential power spectrum. SWRs detected off-line were significantly lower in amplitude and had an altered temporal structure in rTg4510 mice. Nevertheless, the average frequency profile and duration of the SWRs were relatively unaltered. Putative interneurons displayed significantly less temporal and phase locking to SWRs in rTg4510 mice, whilst putative pyramidal neurons showed increased temporal and phase locking to SWRs. These findings indicate there is reduced inhibitory control of hippocampal network events and points to a novel mechanism which may contribute to impairments in memory consolidation in this model of dementia. This article is protected by copyright. All rights reserved.Alzheimer’s Research UKMedical Research Counci

A novel magnetic resonance imaging postprocessing technique for the assessment of intervertebral disc degeneration-Correlation with histological grading in a rabbit disc degeneration model.

Introduction: Estimation of intervertebral disc degeneration on magnetic resonance imaging (MRI) is challenging. Qualitative schemes used in clinical practice correlate poorly with pain and quantitative techniques have not entered widespread clinical use. Methods: As part of a prior study, 25 New Zealand white rabbits underwent annular puncture to induce disc degeneration in 50 noncontiguous lumbar discs. At 16 weeks, the animals underwent multi-echo T2 MRI scanning and were euthanized. The discs were stained and examined histologically. Quantitative T2 relaxation maps were prepared using the nonlinear least squares method. Decay Variance maps were created using a novel technique of aggregating the deviation in the intensity of each echo signal from the expected intensity based on the previous rate of decay. Results: Decay Variance maps showed a clear and well demarcated nucleus pulposus with a consistent rate of decay (low Decay Variance) in healthy discs that showed progressively more variable decay (higher Decay Variance) with increasing degeneration. Decay Variance maps required significantly less time to generate (1.0 ± 0.0 second) compared with traditional T2 relaxometry maps (5 (±0.9) to 1788.9 (±116) seconds). Histology scores correlated strongly with Decay Variance scores (r = 0.82, P < .01) and weakly with T2 signal intensity (r = 0.32, P < .01) and quantitative T2 relaxometry (r = 0.39, P < .01). Decay Variance had superior sensitivity and specificity for the detection of degenerate discs when compared to T2 signal intensity or Quantitative T2 mapping. Conclusion: Our results show that using a multi-echo T2 MRI sequence, Decay Variance can quantitatively assess disc degeneration more accurately and with less image-processing time than quantitative T2 relaxometry in a rabbit disc puncture model. The technique is a viable candidate for quantitative assessment of disc degeneration on MRI scans. Further validation on human subjects is needed

Theoretical Uncertainties in Electroweak Boson Production Cross Sections at 7, 10, and 14 TeV at the LHC

We present an updated study of the systematic errors in the measurements of the electroweak boson cross-sections at the LHC for various experimental cuts for a center of mass energy of 7, 10 and 14 TeV. The size of both electroweak and NNLO QCD contributions are estimated, together with the systematic error from the parton distributions. The effects of new versions of the MSTW, CTEQ, and NNPDF PDFs are considered.Comment: PDFLatex with JHEP3.cls. 22 pages, 43 figures. Version 2 adds the CT10W PDF set to analysis and updates the final systematic error table and conclusions, plus several citations and minor wording changes. Version 3 adds some references on electroweak and mixed QED/QCD corrections. Version 4 adds more references and acknowledgement

Depletion of T cells via Inducible Caspase 9 Increases Safety of Adoptive T-Cell Therapy Against Chronic Hepatitis B

T-cell therapy with T cells that are re-directed to hepatitis B virus (HBV)-infected cells by virus-specific receptors is a promising therapeutic approach for treatment of chronic hepatitis B and HBV-associated cancer. Due to the high number of target cells, however, side effects such as cytokine release syndrome or hepatotoxicity may limit safety. A safeguard mechanism, which allows depletion of transferred T cells on demand, would thus be an interesting means to increase confidence in this approach. In this study, T cells were generated by retroviral transduction to express either an HBV-specific chimeric antigen receptor (S-CAR) or T-cell receptor (TCR), and in addition either inducible caspase 9 (iC9) or herpes simplex virus thymidine kinase (HSV-TK) as a safety switch. Real-time cytotoxicity assays using HBV-replicating hepatoma cells as targets revealed that activation of both safety switches stopped cytotoxicity of S-CAR- or TCR-transduced T cells within less than one hour. In vivo, induction of iC9 led to a strong and rapid reduction of transferred S-CAR T cells adoptively transferred into AAV-HBV-infected immune incompetent mice. One to six hours after injection of the iC9 dimerizer, over 90% reduction of S-CAR T cells in the blood and the spleen and of over 99% in the liver was observed, thereby limiting hepatotoxicity and stopping cytokine secretion. Simultaneously, however, the antiviral effect of S-CAR T cells was diminished because remaining S-CAR T cells were mostly non-functional and could not be restimulated with HBsAg. A second induction of iC9 was only able to deplete T cells in the liver. In conclusion, T cells co-expressing iC9 and HBV-specific receptors efficiently recognize and kill HBV-replicating cells. Induction of T-cell death via iC9 proved to be an efficient means to deplete transferred T cells in vitro and in vivo containing unwanted hepatotoxicity

Limited value of pulse wave analysis in assessing arterial wave reflection and stiffness in the pulmonary artery

We explored the use of the augmentation index (AI) based on pulse wave analysis (PWA) in the pulmonary circulation as a measure of wave reflection and arterial stiffness in individuals with and without pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH). Right heart catheterization was performed using a pressure and Doppler flow sensor–tipped catheter to obtain simultaneous pressure and flow velocity measurements in the pulmonary artery in 10 controls, 11 PAH patients, and 11 CTEPH patients. PWA was applied to the measured pressure, while wave intensity analysis (WIA) and wave separation analysis (WSA) were performed using both the pressure and velocity to determine the magnitudes and timings of reflected waves. Type C (AI 12%) waveform dominated in PAH patients, while there was a mixture of types A, B, and C among CTEPH patients. AI was greater and the inflection time shorter in CTEPH compared to PAH patients. There was a poor correlation between AI and arterial wave speed as well as measures of wave reflection derived from WIA and WSA. The infection point did not match the timing of the backward compression wave in ~50% of the cases. In patients with type C waveforms, the inflection time correlated well to the timing of the late systolic forward decompression wave caused by ventricular relaxation. In conclusion quantifying pulmonary arterial wave reflection and stiffness using AI based on PWA may be inaccurate and should therefore be discouraged

Molecular evidence for Anaplasma phagocytophilum in Israel

Sequences from the Anaplasma phagocytophilum 16S rRNA gene were detected in 5 ticks representing 3 species (Hyalomma marginatum, Rhipicephalus turanicus, and Boophilus kohlsi) collected from roe deer (Capreolus capreolus) in Mount Carmel, Israel. The sequences were all identical to those of Ap-variant 1 strain