Reconstruction of acetabular defects greater than Paprosky type 3B: the importance of functional imaging

BACKGROUND: 3D Surgical planning has become a key tool in complex hip revision surgery. The restoration of centre of rotation (CoR) of the hips and leg length (LL) are key factors in achieving good clinical outcome. Pelvic imaging is the gold standard for planning and assessment of LL. We aimed to better understand if 3D planning is effective at equalising LL when large acetabular defects are present. MATERIALS AND METHODS: This was a prospective case study of 25 patients. We report the analysis of pre-operative LL status and planned LL restoration measured on CT, in relation to the achieved LL measured post-operatively in functional, weight bearing position. Our primary objective was the assessment of restoration of CoR as well as the anatomical and functional LL using biplanar full-length standing low-dose radiographs; our secondary objective was to evaluate the clinical outcome. RESULTS: Pre-operative intra-pelvic discrepancy between right and left leg was a mean of 28 mm (SD 17.99, min = 3, max = 60 mm). Post-operatively, the difference between right and left vertical femoral offset (VFO), or CoR discrepancy, was of 7.4 mm on average, significantly different from the functional LL discrepancy (median = 15 mm), p = 0.0024. Anatomical LLD was a median of 15 mm. In one case there was transient foot drop, one dislocation occurred 6 months post-operatively and was treated by closed reduction, none of the patients had had revision surgery at the time of writing. Mean oxford hip score at latest follow up was 32.1/48. DISCUSSION: This is the first study to investigate limb length discrepancy in functional position after reconstruction of large acetabular defects. We observed that VFO is not an optimal surrogate for LL when there is significant bone loss leading to length inequality, fixed flexion of the knee and abduction deformity. CONCLUSIONS: Although challenging, LLD and gait abnormalities can be greatly improved with the aid of an accurate surgical planning. Surgeons and engineers should consider the integration of EOS imaging in surgical planning of reconstruction of large acetabular defects

Mechanical wear analysis helps understand a mechanism of failure in retrieved magnetically controlled growing rods: a retrieval study

BACKGROUND: To assess the relationship between mechanical wear and the failure of the internal lengthening mechanism in retrieved MAGnetic Expansion Control (MAGEC) growing rods. METHODS: This study included 34 MAGEC rods retrieved from 20 patients. The state of the internal mechanism and mechanical wear were assessed in all the rods using plain radiographs and visual inspection. Metrology was then performed to assess the topography and mechanical wear of the telescopic bars, using a Talyrond 365 (Taylor Hobson, Leicester, UK) roundness measuring machine. RESULTS: Plain radiographs showed evidence of a broken internal mechanism in 29% of retrieved rods. Single-side wear marks were found in 97% of retrieved rods. Material loss was found to significantly increase in rods with a damaged internal mechanism (p < 0.05) and rods with longer time in situ (r = 0.692, p < 0.05). CONCLUSIONS: We found an association between damage to the internal mechanism of the rods and (1) patterns of single-side longitudinal wear marks and (2) increased material loss. As the material loss was also found to increase over time of rod in situ, we emphasise the importance of early detection and revision of failed MAGEC rods in clinical practice

Understanding the implant performance of magnetically controlled growing spine rods: a review article

PURPOSE: Early-Onset Scoliosis (EOS) (defined as a curvature of the spine ≥ 10° with onset before 10 years of age) if not properly treated, can lead to increased morbidity and mortality. Traditionally Growing Rods (TGRs), implants fixated to the spine and extended every 6-8 months by surgery, are considered the gold standard, but Magnetically Controlled Growing Rods (MCGRs) avoid multiple surgeries. While the potential benefit of outpatient distraction procedure with MCGR is huge, concerns still remain about its risks, up to the release of a Medical Device Alert (MDA) by the Medicines and Healthcare Regulatory Agency (MHRA) advising not to implant MCGRs until further notice. The aim of this literature review is to (1) give an overview on the use of MCGRs and (2) identify what is currently understood about the surgical, implant and patient factors associated with the use of MCGRs. METHODS: Systematic literature review. RESULTS: Surgical factors such as use of single rod configuration or incorrect rod contouring might affect early failure of MCGRs. Patient's older age and higher BMI are correlated with rod slippage. Wear debris and distraction mechanism failure may result from implant design and iteration. CONCLUSION: Despite the complications reported, this technology still offers one of the best solutions to spine surgeons dealing with severe EOS. Lowering the complication rate by identifying risk factors for failure is possible and further studies in this direction are required. Once the risk factors are well described, some of these can be addressed enabling a safer use of MCGRs

Management of patients with magnetically controlled growth rods amidst the global COVID-19 pandemic

Introduction At the time of writing, we are all coping with the global COVID-19 pandemic. Amongst other things, this has had a significant impact on postponing virtually all routine clinic visits and elective surgeries. Concurrently, the Magnetic Expansion Control (MAGEC) rod has been issued with a number of field safety notices and UK regulator medical device alerts. Methods This document serves to provide an overview of the current situation regarding the use of MAGEC rods, primarily in the UK, and the impact that the pandemic has had on the management of patients with these rods. Results and Conclusion The care of each patient must of course be determined on an individual basis; however, the experience of the authors is that a short delay in scheduled distractions and clinic visits will not adversely impact patient treatment. The authors caution against a gap in distractions of longer than 6 months and emphasise the importance of continued remote patient monitoring to identify those who may need to be seen more urgently

Standardized volumetric 3D-analysis of SPECT/CT imaging in orthopaedics: overcoming the limitations of qualitative 2D analysis

<p>Abstract</p> <p>Background</p> <p>SPECT/CT combines high resolution anatomical 3D computerized tomography (CT) and single photon emission computerized tomography (SPECT) as functional imaging, which provides 3D information about biological processes into a single imaging modality. The clinical utility of SPECT/CT imaging has been recognized in a variety of medical fields and most recently in orthopaedics; however, clinical adoption has been limited due to shortcomings of analytical tools available. Specifically, SPECT analyses are mainly qualitative due to variation in overall metabolic uptake among patients. Furthermore, most analyses are done in 2D, although rich 3D data are available. Consequently, it is difficult to quantitatively compare the position, size, and intensity of SPECT uptake regions among patients, and therefore difficult to draw meaningful clinical conclusions.</p> <p>Methods</p> <p>We propose a method for normalizing orthopaedic SPECT/CT data that enables standardised 3D volumetric quantitative measurements and comparison among patients. Our method is based on 3D localisation using clinically relevant anatomical landmarks and frames of reference, along with intensity value normalisation using clinically relevant reference regions. Using the normalised data, we describe a thresholding technique to distinguish clinically relevant hot spots from background activity.</p> <p>Results</p> <p>Using an exemplar comparison of two patients, we demonstrate how the normalised, 3D-rendered data can provide a richer source of clinical information and allow quantitative comparison of SPECT/CT measurements across patients. Specifically, we demonstrate how non-normalized SPECT/CT analysis can lead to different clinical conclusions than the normalized SPECT/CT analysis, and that normalized quantitative analysis can be a more accurate indicator of pathology.</p> <p>Conclusions</p> <p>Conventional orthopaedic frames of reference, 3D volumetric data analysis and thresholding are used to distinguish clinically relevant hot spots from background activity. Our goal is to facilitate a standardised approach to quantitative data collection and comparison of clinical studies using SPECT/CT, enabling more widespread clinical use of this powerful imaging tool.</p

Human imprinted retrogenes exhibit non-canonical imprint chromatin signatures and reside in non-imprinted host genes

Imprinted retrotransposed genes share a common genomic organization including a promoter-associated differentially methylated region (DMR) and a position within the intron of a multi-exonic ‘host’ gene. In the mouse, at least one transcript of the host gene is also subject to genomic imprinting. Human retrogene orthologues are imprinted and we reveal that human host genes are not imprinted. This coincides with genomic rearrangements that occurred during primate evolution, which increase the separation between the retrogene DMRs and the host genes. To address the mechanisms governing imprinted retrogene expression, histone modifications were assayed at the DMRs. For the mouse retrogenes, the active mark H3K4me2 was associated with the unmethylated paternal allele, while the methylated maternal allele was enriched in repressive marks including H3K9me3 and H4K20me3. Two human retrogenes showed monoallelic enrichment of active, but not of repressive marks suggesting a partial uncoupling of the relationship between DNA methylation and repressive histone methylation, possibly due to the smaller size and lower CpG density of these DMRs. Finally, we show that the genes immediately flanking the host genes in mouse and human are biallelically expressed in a range of tissues, suggesting that these loci are distinct from large imprinted clusters

Characterization of Novel Paternal ncRNAs at the Plagl1 Locus, Including Hymai, Predicted to Interact with Regulators of Active Chromatin

Genomic imprinting is a complex epigenetic mechanism of transcriptional control that utilizes DNA methylation and histone modifications to bring about parent-of-origin specific monoallelic expression in mammals. Genes subject to imprinting are often organised in clusters associated with large non-coding RNAs (ncRNAs), some of which have cis-regulatory functions. Here we have undertaken a detailed allelic expression analysis of an imprinted domain on mouse proximal chromosome 10 comprising the paternally expressed Plagl1 gene. We identified three novel Plagl1 transcripts, only one of which contains protein-coding exons. In addition, we characterised two unspliced ncRNAs, Hymai, the mouse orthologue of HYMAI, and Plagl1it (Plagl1 intronic transcript), a transcript located in intron 5 of Plagl1. Imprinted expression of these novel ncRNAs requires DNMT3L-mediated maternal DNA methylation, which is also indispensable for establishing the correct chromatin profile at the Plagl1 DMR. Significantly, the two ncRNAs are retained in the nucleus, consistent with a potential regulatory function at the imprinted domain. Analysis with catRAPID, a protein-ncRNA association prediction algorithm, suggests that Hymai and Plagl1it RNAs both have potentially high affinity for Trithorax chromatin regulators. The two ncRNAs could therefore help to protect the paternal allele from DNA methylation by attracting Trithorax proteins that mediate H3 lysine-4 methylation

In-situ local phase-transitioned MoSe2 in La0.5Sr0.5CoO3-?? heterostructure and stable overall water electrolysis over 1000 hours

Developing efficient bifunctional catalysts for overall water splitting that are earth-abundant, cost-effective, and durable is of considerable importance from the practical perspective to mitigate the issues associated with precious metal-based catalysts. Herein, we introduce a heterostructure comprising perovskite oxides (La0.5Sr0.5CoO3?????) and molybdenum diselenide (MoSe2) as an electrochemical catalyst for overall water electrolysis. Interestingly, formation of the heterostructure of La0.5Sr0.5CoO3????? and MoSe2 induces a local phase transition in MoSe2, 2???H to 1???T phase, and more electrophilic La0.5Sr0.5CoO3????? with partial oxidation of the Co cation owing to electron transfer from Co to Mo. Together with these synergistic effects, the electrochemical activities are significantly improved for both hydrogen and oxygen evolution reactions. In the overall water splitting operation, the heterostructure showed excellent stability at the high current density of 100???mA???cm???2 over 1,000???h, which is exceptionally better than the stability of the state-of-the-art platinum and iridium oxide couple

Coordinated allele-specific histone acetylation at the differentially methylated regions of imprinted genes

Genomic imprinting is an epigenetic inheritance system characterized by parental allele-specific gene expression. Allele-specific DNA methylation and chromatin composition are two epigenetic modification systems that control imprinted gene expression. To get a general assessment of histone lysine acetylation at imprinted genes we measured allele-specific acetylation of a wide range of lysine residues, H3K4, H3K18, H3K27, H3K36, H3K79, H3K64, H4K5, H4K8, H4K12, H2AK5, H2BK12, H2BK16 and H2BK46 at 11 differentially methylated regions (DMRs) in reciprocal mouse crosses using multiplex chromatin immunoprecipitation SNuPE assays. Histone acetylation marks generally distinguished the methylation-free alleles from methylated alleles at DMRs in mouse embryo fibroblasts and embryos. Acetylated lysines that are typically found at transcription start sites exhibited stronger allelic bias than acetylated histone residues in general. Maternally methylated DMRs, that usually overlap with promoters exhibited higher levels of acetylation and a 10% stronger allele-specific bias than paternally methylated DMRs that reside in intergenic regions. Along the H19/Igf2 imprinted domain, allele-specific acetylation at each lysine residue depended on functional CTCF binding sites in the imprinting control region. Our results suggest that many different histone acetyltransferase and histone deacetylase enzymes must act in concert in setting up and maintaining reciprocal parental allelic histone acetylation at DMRs