Efficacy of interspinous device versus surgical decompression in the treatment of lumbar spinal stenosis: a modified network analysis.

Study designSystematic review using a modified network analysis.ObjectivesTo compare the effectiveness and morbidity of interspinous-device placement versus surgical decompression for the treatment of lumbar spinal stenosis.SummaryTraditionally, the most effective treatment for degenerative lumbar spinal stenosis is through surgical decompression. Recently, interspinous devices have been used in lieu of standard laminectomy.MethodsA review of the English-language literature was undertaken for articles published between 1970 and March 2010. Electronic databases and reference lists of key articles were searched to identify studies comparing surgical decompression with interspinous-device placement for the treatment of lumbar spinal stenosis. First, studies making the direct comparison (cohort or randomized trials) were searched. Second, randomized controlled trials (RCTs) comparing each treatment to conservative management were searched to allow for an indirect comparison through a modified network analysis approach. Comparison studies involving simultaneous decompression with placement of an interspinous device were not included. Studies that did not have a comparison group were not included since a treatment effect could not be calculated. Two independent reviewers assessed the strength of evidence using the GRADE criteria assessing quality, quantity, and consistency of results. The strengths of evidence for indirect comparisons were downgraded. Disagreements were resolved by consensus.ResultsWe identified five studies meeting our inclusion criteria. No RCTs or cohort studies were identified that made the direct comparison of interspinous-device placement with surgical decompression. For the indirect comparison, three RCTs compared surgical decompression to conservative management and two RCTs compared interspinous-device placement to conservative management. There was low evidence supporting greater treatment effects for interspinous-device placement compared to decompression for disability and pain outcomes at 12 months. There was low evidence demonstrating little to no difference in treatment effects between the groups for walking distance and complication rates.ConclusionThe indirect treatment effect for disability and pain favors the interspinous device compared to decompression. The low evidence suggests that any further research is very likely to have an important impact on the confidence in the estimate of effect and is likely to change the estimate. No significant treatment effect differences were observed for postoperative walking distance improvement or complication rates; however, findings should be considered with caution because of indirect comparisons and short follow-up periods

Dynamic stabilization versus fusion for treatment of degenerative spine conditions.

Study design Comparative effectiveness review.Study rationale Spinal fusion is believed to accelerate the degeneration of the vertebral segment above or below the fusion site, a condition called adjacent segment disease (ASD). The premise of dynamic stabilization is that motion preservation allows for less loading on the discs and facet joints at the adjacent, non-fused segments. In theory, this should decrease the rate of ASD. However, clinical evidence of this theoretical decrease in ASD is still lacking. We performed a systematic review to evaluate the evidence in the literature comparing dynamic stabilization with fusion.Clinical question In patients 18 years or older with degenerative disease of the cervical or lumbar spine, does dynamic stabilization lead to better outcomes and fewer complications, including ASD, than fusion in the short-term and the long-term?Methods A systematic search and review of the literature was undertaken to identify studies published through March 7, 2011. PubMed, Cochrane, and National Guideline Clearinghouse Databases as well as bibliographies of key articles were searched. Two individuals independently reviewed articles based on inclusion and exclusion criteria which were set a priori. Each article was evaluated using a predefined quality-rating scheme.Results No significant differences were identified between fusion and dynamic stabilization with regard to VAS, ODI, complications, and reoperations. There are no long-term data available to show whether dynamic stabilization decreases the rate of ASD.Conclusions There are no clinical data from comparative studies supporting the use of dynamic stabilization devices over standard fusion techniques

Outcomes after Surgery for Spinal Metastasis of Colorectal Origin: Case Series

Study DesignRetrospective study.PurposeThe aim of this study was to evaluate the clinical management and outcomes of patients who underwent surgical intervention for metastatic colorectal adenocarcinoma of the spine.Overview of LiteratureGastrointestinal (GI) cancer metastasis to the spine are relatively rare and represent later manifestations of the disease. Studies and reports on the outcomes of patients who undergo surgery for spinal metastasis of GI origin are scarce.MethodsA retrospective chart review of all patients who underwent surgery for spinal metastasis of colorectal origin was performed. Four patients were identified. Patient characteristics, outcomes, and survival were analyzed.ResultsTwo patients experienced improvement in pain or myelopathic symptoms. Although the mean survival was 15.3 months, this average included a patient still living at 57.1 months. The mean survival was just 1.3 months for the 3 patients who expired.ConclusionsIn certain cases, symptomatic improvement with prolonged survival is possible after surgery for metastatic spinal lesions of colorectal origin; however, survival is poor in the majority of cases

Magnetic-field dependence of electron spin relaxation in n-type semiconductors

We present a theoretical investigation of the magnetic field dependence of the longitudinal ($T_1$) and transverse ($T_2$) spin relaxation times of conduction band electrons in n-type III-V semiconductors. In particular, we find that the interplay between the Dyakonov-Perel process and an additional spin relaxation channel, which originates from the electron wave vector dependence of the electron $g$-factor, yields a maximal $T_2$ at a finite magnetic field. We compare our results with existing experimental data on n-type GaAs and make specific additional predictions for the magnetic field dependence of electron spin lifetimes.Comment: accepted for publication in PRB, minor changes to previous manuscrip

Clinical Validation of an Ultra High-Throughput Spiral Microfluidics for the Detection and Enrichment of Viable Circulating Tumor Cells

Background: Circulating tumor cells (CTCs) are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation. Methodology/Principal Findings: Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56) (Breast cancer samples: 12–1275 CTCs/ml; Lung cancer samples: 10–1535 CTCs/ml) rapidly from clinically relevant blood volumes (7.5 ml under 5 min). Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM), fluorescence in-situ hybridization (FISH) (EML4-ALK) or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA), and demonstrate concordance with the original tumor-biopsy samples. Conclusions/Significance: We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS) or proteomic analysis.Singapore-MIT Alliance for Research and Technolog

Rapid, Label-Free Detection of Brain Tumors with Stimulated Raman Scattering Microscopy

Surgery is an essential component in the treatment of brain tumors. However, delineating tumor from normal brain remains a major challenge. We describe the use of stimulated Raman scattering (SRS) microscopy for differentiating healthy human and mouse brain tissue from tumor-infiltrated brain based on histoarchitectural and biochemical differences. Unlike traditional histopathology, SRS is a label-free technique that can be rapidly performed in situ. SRS microscopy was able to differentiate tumor from nonneoplastic tissue in an infiltrative human glioblastoma xenograft mouse model based on their different Raman spectra. We further demonstrated a correlation between SRS and hematoxylin and eosin microscopy for detection of glioma infiltration (κ = 0.98). Finally, we applied SRS microscopy in vivo in mice during surgery to reveal tumor margins that were undetectable under standard operative conditions. By providing rapid intraoperative assessment of brain tissue, SRS microscopy may ultimately improve the safety and accuracy of surgeries where tumor boundaries are visually indistinct.Chemistry and Chemical Biolog

The impact of signal-to-noise ratio, diffusion-weighted directions and image resolution in cardiac diffusion tensor imaging - insights from the ex-vivo rat heart

Background: Cardiac diffusion tensor imaging (DTI) is limited by scan time and signal-to-noise (SNR) restrictions. This invariably leads to a trade-off between the number of averages, diffusion-weighted directions (ND), and image resolution. Systematic evaluation of these parameters is therefore important for adoption of cardiac DTI in clinical routine where time is a key constraint. Methods: High quality reference DTI data were acquired in five ex-vivo rat hearts. We then retrospectively set 2 ≤ SNR ≤ 97, 7 ≤ ND ≤ 61, varied the voxel volume by up to 192-fold and investigated the impact on the accuracy and precision of commonly derived parameters. Results: For maximal scan efficiency, the accuracy and precision of the mean diffusivity is optimised when SNR is maximised at the expense of ND. With typical parameter settings used clinically, we estimate that fractional anisotropy may be overestimated by up to 13% with an uncertainty of ±30%, while the precision of the sheetlet angles may be as poor as ±31°. Although the helix angle has better precision of ±14°, the transmural range of helix angles may be under-estimated by up to 30° in apical and basal slices, due to partial volume and tapering myocardial geometry. Conclusions: These findings inform a baseline of understanding upon which further issues inherent to in-vivo cardiac DTI, such as motion, strain and perfusion, can be considered. Furthermore, the reported bias and reproducibility provides a context in which to assess cardiac DTI biomarkers

Validation of diffusion tensor MRI measurements of cardiac microstructure with structure tensor synchrotron radiation imaging.

Background Diffusion tensor imaging (DTI) is widely used to assess tissue microstructure non-invasively. Cardiac DTI enables inference of cell and sheetlet orientations, which are altered under pathological conditions. However, DTI is affected by many factors, therefore robust validation is critical. Existing histological validation is intrinsically flawed, since it requires further tissue processing leading to sample distortion, is routinely limited in field-of-view and requires reconstruction of three-dimensional volumes from two-dimensional images. In contrast, synchrotron radiation imaging (SRI) data enables imaging of the heart in 3D without further preparation following DTI. The objective of the study was to validate DTI measurements based on structure tensor analysis of SRI data. Methods One isolated, fixed rat heart was imaged ex vivo with DTI and X-ray phase contrast SRI, and reconstructed at 100 μm and 3.6 μm isotropic resolution respectively. Structure tensors were determined from the SRI data and registered to the DTI data. Results Excellent agreement in helix angles (HA) and transverse angles (TA) was observed between the DTI and structure tensor synchrotron radiation imaging (STSRI) data, where HADTI-STSRI = −1.4° ± 23.2° and TADTI-STSRI = −1.4° ± 35.0° (mean ± 1.96 standard deviation across all voxels in the left ventricle). STSRI confirmed that the primary eigenvector of the diffusion tensor corresponds with the cardiomyocyte long-axis across the whole myocardium. Conclusions We have used STSRI as a novel and high-resolution gold standard for the validation of DTI, allowing like-with-like comparison of three-dimensional tissue structures in the same intact heart free of distortion. This represents a critical step forward in independently verifying the structural basis and informing the interpretation of cardiac DTI data, thereby supporting the further development and adoption of DTI in structure-based electro-mechanical modelling and routine clinical applications

Aortic stiffness in lone atrial fibrillation: A novel risk factor for arrhythmia recurrence

BACKGROUND Recent community-based research has linked aortic stiffness to the development of atrial fibrillation. We posit that aortic stiffness contributes to adverse atrial remodeling leading to the persistence of atrial fibrillation following catheter ablation in lone atrial fibrillation patients, despite the absence of apparent structural heart disease. Here, we aim to evaluate aortic stiffness in lone atrial fibrillation patients and determine its association with arrhythmia re currence following radio-frequency catheter ablation. METHODS We studied 68 consecutive lone atrial fibrillation patients who underwent catheter ablation procedure for atrial fibrillation and 50 healthy age- and sex-matched community controls. We performed radial artery applanation tonometry to obtain central measures of aortic stiffness: pulse pressure, augmentation pressure and augmentation index. Following ablation, arrhythmia recurrence was monitored at months 3, 6, 9, 12 and 6 monthly thereafter. RESULTS Compared to healthy controls, lone atrial fibrillation patients had significantly elevated peripheral pulse pressure, central pulse pressure, augmentation pressure and larger left atrial dimensions (all P<0.05). During a mean follow-up of 2.9±1.4 years, 38 of the 68 lone atrial fibrillation patients had atrial fibrillation recurrence after initial catheter ablation procedure. Neither blood pressure nor aortic stiffness indices differed between patients with and without atrial fibrillation recurrence. However, patients with highest levels (≥75th percentile) of peripheral pulse pressure, central pulse pressure and augmentation pressure had higher atrial fibrillation recurrence rates (all P<0.05). Only central aortic stiffness indices were associated with lower survival free from atrial fibrillation using Kaplan-Meier analysis. CONCLUSION Aortic stiffness is an important risk factor in patients with lone atrial fibrillation and contributes to higher atrial fibrillation recurrence following catheter ablation procedure.Dennis H. Lau, Melissa E. Middeldorp, Anthony G. Brooks, Anand N. Ganesan, Kurt C. Roberts-Thomson, Martin K. Stiles, Darryl P. Leong, Hany S. Abed, Han S. Lim, Christopher X. Wong, Scott R. Willoughby, Glenn D. Young, Jonathan M. Kalman, Walter P. Abhayaratna, Prashanthan Sander