Publications by authors named "Kenneth M C Cheung"

188 Publications

Regulation of macrophage polarization through surface topography design to facilitate implant-to-bone osteointegration.

Sci Adv 2021 Apr 2;7(14). Epub 2021 Apr 2.

Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong 999077, China.

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO structures were custom made on titanium (Ti) substrates to investigate cellular behaviors of RAW 264.7 macrophages and their immunomodulation on osteogenesis. We found that the reduced scale of honeycomb-like TiO structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, , and and released the highest amount of among other scales. Afterward, the resulting immune microenvironment favorably triggered osteogenic differentiation of murine mesenchymal stem cells in vitro and subsequent implant-to-bone osteointegration in vivo. Furthermore, transcriptomic analysis revealed that the minimal scale of TiO honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.
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http://dx.doi.org/10.1126/sciadv.abf6654DOI Listing
April 2021

The profile of the spinal column in subjects with lumbar developmental spinal stenosis.

Bone Joint J 2021 Apr;103-B(4):725-733

Department of Orthopaedics and Traumatology, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.

Aims: The aim of this study was to determine the differences in spinal imaging characteristics between subjects with or without lumbar developmental spinal stenosis (DSS) in a population-based cohort.

Methods: This was a radiological analysis of 2,387 participants who underwent L1-S1 MRI. Means and ranges were calculated for age, sex, BMI, and MRI measurements. Anteroposterior (AP) vertebral canal diameters were used to differentiate those with DSS from controls. Other imaging parameters included vertebral body dimensions, spinal canal dimensions, disc degeneration scores, and facet joint orientation. Mann-Whitney U and chi-squared tests were conducted to search for measurement differences between those with DSS and controls. In order to identify possible associations between DSS and MRI parameters, those who were statistically significant in the univariate binary logistic regression were included in a multivariate stepwise logistic regression after adjusting for demographics. Odds ratios (ORs) and 95% confidence intervals (CIs) were reported where appropriate.

Results: Axial AP vertebral canal diameter (p < 0.001), interpedicular distance (p < 0.001), AP dural sac diameter (p < 0.001), lamina angle (p < 0.001), and sagittal mid-vertebral body height (p < 0.001) were significantly different between those identified as having DSS and controls. Narrower interpedicular distance (OR 0.745 (95% CI 0.618 to 0.900); p = 0.002) and AP dural sac diameter (OR 0.506 (95% CI 0.400 to 0.641); p < 0.001) were associated with DSS. Lamina angle (OR 1.127 (95% CI 1.045 to 1.214); p = 0.002) and right facet joint angulation (OR 0.022 (95% CI 0.002 to 0.247); p = 0.002) were also associated with DSS. No association was observed between disc parameters and DSS.

Conclusion: From this large-scale cohort, the canal size is found to be independent of body stature. Other than spinal canal dimensions, abnormal orientations of lamina angle and facet joint angulation may also be a result of developmental variations, leading to increased likelihood of DSS. Other skeletal parameters are spared. There was no relationship between DSS and soft tissue changes of the spinal column, which suggests that DSS is a unique result of bony maldevelopment. These findings require validation in other ethnicities and populations. Level of Evidence: I (diagnostic study) Cite this article:  2021;103-B(4):725-733.
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http://dx.doi.org/10.1302/0301-620X.103B4.BJJ-2020-1792.R1DOI Listing
April 2021

Patient-Reported Outcomes After Complex Adult Spinal Deformity Surgery: 5-Year Results of the Scoli-Risk-1 Study.

Global Spine J 2021 Feb 9:2192568220988276. Epub 2021 Feb 9.

University of Virginia, Charlottesville, VA, USA.

Study Design: Prospective cohort.

Objective: To prospectively evaluate PROs up to 5-years after complex ASD surgery.

Methods: The Scoli-RISK-1 study enrolled 272 ASD patients undergoing surgery from 15 centers. Inclusion criteria was Cobb angle of >80°, corrective osteotomy for congenital or revision deformity, and/or 3-column osteotomy. The following PROs were measured prospectively at intervals up to 5-years postoperative: ODI, SF36-PCS/MCS, SRS-22, NRS back/leg. Among patients with 5-year follow-up, comparisons were made from both baseline and 2-years postoperative to 5-years postoperative. PROs were analyzed using mixed models for repeated measures.

Results: Seventy-seven patients (28.3%) had 5-year follow-up data. Comparing baseline to 5-year data among these 77 patients, significant improvement was seen in all PROs: ODI (45.2 vs. 29.3, < 0.001), SF36-PCS (31.5 vs. 38.8, < 0.001), SF36-MCS (44.9 vs. 49.1, = 0.009), SRS-22-total (2.78 vs. 3.61, < 0.001), NRS-back pain (5.70 vs. 2.95, < 0.001) and NRS leg pain (3.64 vs. 2.62, = 0.017). In the 2 to 5-year follow-up period, no significant changes were seen in any PROs. The percentage of patients achieving MCID from baseline to 5-years were: ODI (62.0%) and the SRS-22r domains of function (70.4%), pain (63.0%), mental health (37.5%), self-image (60.3%), and total (60.3%). Surprisingly, mean values ( > 0.05) and proportion achieving MCID did not differ significantly in patients with major surgery-related complications compared to those without.

Conclusions: After complex ASD surgery, significant improvement in PROs were seen at 5-years postoperative in ODI, SF36-PCS/MCS, SRS-22r, and NRS-back/leg pain. No significant changes in PROs occurred during the 2 to 5-year postoperative period. Those with major surgery-related complications had similar PROs and proportion of patients achieving MCID as those without these complications.
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http://dx.doi.org/10.1177/2192568220988276DOI Listing
February 2021

Regulation of extracellular bioactive cations in bone tissue microenvironment induces favorable osteoimmune conditions to accelerate bone regeneration.

Bioact Mater 2021 Aug 23;6(8):2315-2330. Epub 2021 Jan 23.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China.

The design of orthopedic biomaterials has gradually shifted from "immune-friendly" to "immunomodulatory," in which the biomaterials are able to modulate the inflammatory response via macrophage polarization in a local immune microenvironment that favors osteogenesis and implant-to-bone osseointegration. Despite the well-known effects of bioactive metallic ions on osteogenesis, how extracellular metallic ions manipulate immune cells in bone tissue microenvironments toward osteogenesis and subsequent bone formation has rarely been studied. Herein, we investigate the osteoimmunomodulatory effect of an extracellular bioactive cation (Mg) in the bone tissue microenvironment using custom-made poly lactic-co-glycolic acid (PLGA)/MgO-alendronate microspheres that endow controllable release of magnesium ions. The results suggest that the Mg-controlled tissue microenvironment can effectively induce macrophage polarization from the M0 to M2 phenotype via the enhancement of anti-inflammatory (IL-10) and pro-osteogenic (BMP-2 and TGF-β1) cytokines production. It also generates a favorable osteoimmune microenvironment that facilitates the proliferation and osteogenic differentiation of bone marrow mesenchymal stem cells. The results further verify that a large amount of bony tissue, with comparable bone mineral density and mechanical properties, has been generated at an early post-surgical stage in rat intramedullary bone defect models. This study demonstrates that the concept of immunomodulated osteogenesis can be realized in a controlled magnesium tissue microenvironment.
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http://dx.doi.org/10.1016/j.bioactmat.2021.01.018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7840811PMC
August 2021

Does curve pattern impact on the effects of physiotherapeutic scoliosis specific exercises on Cobb angles of participants with adolescent idiopathic scoliosis: A prospective clinical trial with two years follow-up.

PLoS One 2021 25;16(1):e0245829. Epub 2021 Jan 25.

Department of Orthopaedics, The University of Hong Kong - Shenzhen Hospital, Shenzhen, Guangdong Province, People's Republic of China.

Background: Current clinical evidence suggests that a well-planned physiotherapeutic scoliosis specific exercise (PSSE) program is effective for scoliosis regression.

Objectives: We investigated the effect of curve patterns on Cobb angles with PSSE.

Methods: This was a non-randomized prospective clinical trial that recruited participants with adolescent idiopathic scoliosis between January and June 2017. Participants were grouped by curve pattern into major thoracic and major lumbar groups. An outpatient-based PSSE program was conducted with the following schedule of intensive exercise: ≥ 1 session of supervised PSSE per month and > 30min of home exercise 5 days/week in the first 6 months, after which exercise frequency was reduced to 1 session of supervised PSSE every three months and > 30min of home exercise 5 days/week until 2 years after study initiation. Radiographic Cobb angle progressions were identified at the 1, 1.5 and 2-year follow-ups. A mixed model analysis of variance (ANOVA) was performed to examine the differences in Cobb angles between groups at four testing time points. The two-tailed significance level was set to 0.05.

Results: In total, 40 participants were recruited, including 22 with major thoracic curves (5 males and 17 females; mean age 13.5±1.8 years; Cobb angle 18-45 degrees) and 18 with major lumbar curves (7 males and 11 females; mean age 12.7±1.7 years; Cobb angle 15-48 degrees). Curve regressions, namely the reduction of Cobb angles between 7 to 10 degrees were noted in 9.1% of participants in the major thoracic group; reductions of 6 to 13 degrees were noted in 33.3% of participants in the major lumbar group at the 2-year follow-up. Repeated measurements revealed a significant time effect (F2.2,79.8 = 4.1, p = 0.02), but no group (F2.2,79.8 = 2.3, p = 0.1) or time × group (F1,37 = 0.97, p = 0.3) effects in reducing Cobb angles after 2 years of PSSE. A logistic regression analysis revealed that no correlation was observed between curve pattern and curve regression or stabilization (OR: 0.2, 95% CI: 0.31-1.1, p = 0.068) at the 2-year follow-up.

Conclusion: This was the first study to investigate the long-term effects of PSSE in reducing Cobb angles on the basis of major curve location. No significant differences in correction were observed between major thoracic and major lumbar curves. A regression effect and no curve deterioration were noted in both groups at the 2-year follow-up.

Trial Registration: ChiCTR1900028073.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0245829PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7833215PMC
January 2021

Impact of New Motor Deficit on HRQOL After Adult Spinal Deformity Surgery: Subanalysis From Scoli Risk 1 Prospective Study.

Spine (Phila Pa 1976) 2021 Apr;46(7):E450-E457

Department of Neurosurgery and Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA.

Study Design: International, multicenter, prospective, longitudinal observational cohort.

Objective: To assess how new motor deficits affect patient reported quality of life scores after adult deformity surgery.

Summary Of Background Data: Adult spinal deformity surgery is associated with high morbidity, including risk of new postoperative motor deficit. It is unclear what effect new motor deficit has on Health-related Quality of Life scores (HRQOL) scores.

Methods: Adult spinal deformity patients were enrolled prospectively at 15 sites worldwide. Other inclusion criteria included major Cobb more than 80°, C7-L2 curve apex, and any patient undergoing three column osteotomy. American Spinal Injury Association (ASIA) scores and standard HRQOL scores were recorded pre-op, 6 weeks, 6 months, and 2 years.

Results: Two hundred seventy two complex adult spinal deformity (ASD) patients enrolled. HRQOL scores were worse for patients with lower extremity motor score (LEMS). Mean HRQOL changes at 6 weeks and 2 years compared with pre-op for patients with motor worsening were: ODI (+12.4 at 6 weeks and -4.7 at 2 years), SF-36v2 physical (-4.5 at 6 weeks and +2.3 at 2 years), SRS-22r (0.0 at 6 weeks and +0.4 at 2 years). Mean HRQOL changes for motor-neutral patients were: ODI (+0.6 at 6 weeks and -12.1 at 2 years), SF-36v2 physical (-1.6 at 6 weeks and +5.9 at 2 years), and SRS-22r (+0.4 at 6 weeks and +0.7 at 2 years). For patients with LEMS improvement, mean HRQOL changes were: ODI (-0.6 at 6 weeks and -16.3 at 2 years), SF-36v2 physical (+1.0 at 6 weeks and +7.0 at 2 years), and SRS-22r (+0.5 at 6 weeks and +0.9 at 2 years).

Conclusion: In the subgroup of deformity patients who developed a new motor deficit, total HRQOLs and HRQOL changes were negatively impacted. Patients with more than 2 points of LEMS worsening had the worst changes, but still showed overall HRQOL improvement at 6 months and 2 years compared with pre-op baseline.Level of Evidence: 3.
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http://dx.doi.org/10.1097/BRS.0000000000003852DOI Listing
April 2021

Transformation of resident notochord-descendent nucleus pulposus cells in mouse injury-induced fibrotic intervertebral discs.

Aging Cell 2020 11 21;19(11):e13254. Epub 2020 Oct 21.

Centre for Reproduction, Development, and Growth, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, China.

Intervertebral disc degeneration (IDD), a major cause of low back pain, occurs with ageing. The core of the intervertebral disc, the nucleus pulposus (NP), embedded in a proteoglycan-rich and gelatinous matrix, is derived from the embryonic notochord. With IDD, the NP becomes fibrous, containing fewer cells, which are fibroblastic and of unknown origin. Here, we used a lineage tracing strategy to investigate the origin of cells in the NP in injury-induced mouse IDD. We established a Foxa2 notochord-specific enhancer-driven Cre transgenic mouse model (Foxa2mNE-Cre) that acts only in the embryonic to foetal period up to E14.5, to genetically label notochord cells with enhanced green fluorescent protein (EGFP). When this mouse is crossed to one carrying a Cre recombinase reporter, Z/EG, EGFP-labelled NP cells are present even at 2 years of age, consistent with their notochordal origin. We induced tail IDD in Foxa2mNE-Cre; Z/EG mice by annulus puncture and observed the degenerative changes for 12 weeks. Soon after puncture, EGFP-labelled NP cells showed strong Col2a1+ expression unlike uninjured control NP. Later, accompanying fibrotic changes, EGFP-positive NP cells expressed fibroblastic and myofibroblastic markers such as Col1a1, ASMA, FAPA and FSP-1. The number of EGFP+ cells co-expressing the fibroblastic markers increased with time after puncture. Our findings suggest resident NP cells initially upregulate Col2a1+ and later transform into fibroblast-like cells during injury-mediated disc degeneration and remodelling. This important discovery concerning the cellular origin of fibrotic pathology in injury-induced IDD has implications for management in disease and ageing.
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http://dx.doi.org/10.1111/acel.13254DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7681061PMC
November 2020

Stepwise 3D-spatio-temporal magnesium cationic niche: Nanocomposite scaffold mediated microenvironment for modulating intramembranous ossification.

Bioact Mater 2021 Feb 10;6(2):503-519. Epub 2020 Sep 10.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China.

The fate of cells and subsequent bone regeneration is highly correlated with temporospatial coordination of chemical, biological, or physical cues within a local tissue microenvironment. Deeper understanding of how mammalian cells react to local tissue microenvironment is paramount important when designing next generation of biomaterials for tissue engineering. This study aims to investigate that the regulation of magnesium cationic (Mg) tissue microenvironment is able to convince early-stage bone regeneration and its mechanism undergoes intramembranous ossification. It was discovered that moderate Mg content niche (~4.11 mM) led to superior bone regeneration, while Mg-free and strong Mg content (~16.44 mM) discouraged cell adhesion, proliferation and osteogenic differentiation, thereby bone formation was rarely found. When magnesium ions diffused into free Mg zone from concentrated zone in late time point, new bone formation on free Mg zone became significant through intramembranous ossification. This study successfully demonstrates that magnesium cationic microenvironment serves as an effective biochemical cue and is able to modulate the process of bony tissue regeneration. The knowledge of how a Mg cationic microenvironment intertwines with cells and subsequent bone formation gained from this study may provide a new insight to develop the next generation of tissue-repairing biomaterials.
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http://dx.doi.org/10.1016/j.bioactmat.2020.08.025DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7492774PMC
February 2021

Systematic investigation of metallosis associated with magnetically controlled growing rod implantation for early-onset scoliosis.

Bone Joint J 2020 Oct;102-B(10):1375-1383

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China.

Aims: To investigate metallosis in patients with magnetically controlled growing rods (MCGRs) and characterize the metal particle profile of the tissues surrounding the rod.

Methods: This was a prospective observational study of patients with early onset scoliosis (EOS) treated with MCGRs and undergoing rod exchange who were consecutively recruited between February 2019 and January 2020. Ten patients were recruited (mean age 12 years (SD 1.3); 2 M:8 F). The configurations of the MCGR were studied to reveal the distraction mechanisms, with crucial rod parts being the distractable piston rod and the magnetically driven rotor inside the barrel of the MCGR. Metal-on-metal contact in the form of ring-like wear marks on the piston was found on the distracted portion of the piston immediately outside the barrel opening (BO) through which the piston rod distracts. Biopsies of paraspinal muscles and control tissue samples were taken over and away from the wear marks, respectively. Spectral analyses of the rod alloy and biopsies were performed to reveal the metal constituents and concentrations. Histological analyses of the biopsies were performed with haematoxylin and eosin staining.

Results: Titanium (Ti), vanadium (V), and neodymium (Nd) concentrations in the biopsies taken near the wear marks were found to be significantly higher than those in the control tissue samples. Significantly increased Nd concentrations were also found in the tissues near the barrel of the MCGR. Chronic inflammation was revealed by the histological studies with fibrosis and macrophage infiltration. Black particles were present within the macrophages in the fibrotic tissues.

Conclusion: Ti and V were generated mainly at the BO due to metal-on-metal contact, whereas the Nd from the rotor of the MCGR is likely released from the BO during distraction sessions. Phagocytotic immune cells with black particles inside raise concern regarding the long-term implications of metallosis. Cite this article: 2020;102-B(10):1375-1383.
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http://dx.doi.org/10.1302/0301-620X.102B10.BJJ-2020-0842.R1DOI Listing
October 2020

In vitro and in vivo studies on ultrafine-grained biodegradable pure Mg, Mg-Ca alloy and Mg-Sr alloy processed by high-pressure torsion.

Biomater Sci 2020 Sep 19;8(18):5071-5087. Epub 2020 Aug 19.

Department of Materials Science and Engineering, College of Engineering, Peking University, Beijing 100871, China.

High-pressure torsion (HPT) can refine the microstructure and consequently modify the properties, such as mechanical and corrosion properties, of Mg and its alloys. Biodegradable magnesium materials alloyed with the essential elements of life, such as Ca and Sr, are a current research frontier. In this study, biodegradable ultrafine-grained pure Mg, Mg-Ca alloy, and Mg-Sr alloy were prepared using HPT processing. The microstructure, mechanical properties, biodegradable behaviors, and biocompatibility in vitro and in vivo of these materials were systematically investigated. Our results revealed that HPT pure Mg with a bimodal and ultrafine-grained microstructure showed higher mechanical strength, ductility, and degradation rate compared with the as-received materials. The good biocompatibility of HPT pure Mg was confirmed both in vitro and in vivo. The HPT Mg-Ca alloy and Mg-Sr alloy with homogeneous ultrafine-grained microstructures showed higher mechanical strength and lower degradation rate than their as-cast counterparts. The good biocompatibility of the HPT Mg-Ca alloy and Mg-Sr alloy was also revealed. All these findings indicate that HPT is an alternative avenue to fabricate biodegradable Mg-based materials.
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http://dx.doi.org/10.1039/d0bm00805bDOI Listing
September 2020

"Law of Temporary Diminishing Distraction Gains": The Phenomenon of Temporary Diminished Distraction Lengths With Magnetically Controlled Growing Rods That Is Reverted With Rod Exchange.

Global Spine J 2020 Aug 17:2192568220948475. Epub 2020 Aug 17.

25809The University of Hong Kong, Pokfulam, Hong Kong, SAR, China.

Study Design: Prospective study.

Objectives: To study the increasing divergence between targeted and achieved distractions observed with magnetically controlled growing rod (MCGR)lengthening, and the relationship of this reduced rate of achieved lengthening with remaining rod length.

Methods: Patients with early onset scoliosis (EOS) who underwent MCGRs with minimum 2-year follow-up were consecutively enrolled. Targeted and achieved lengths were compared. Correlation between percentage of lengthening achieved from targeted length was identified with the timing of rod exchanges.

Results: A total of 20 patients fulfilled the inclusion criteria. The mean age at index surgery was 9.5 years and mean postoperative follow-up was 68 ± 28 months. Of these, 8 patients had at least one rod exchange that occurred at 23 ± 4 months. A decrease in rate of achieved lengthening was observed when compared with targeted distractions. The achieved lengthening drops from 86% of targeted length at the first distraction to only 58.8% at the 21st distraction episode for the first set of rods. After rod exchange, the average achieved lengthening went back up to 81.3% of the targeted length but subsequently had a gradual reduction to 35% at the 19th distraction episode.

Conclusions: We propose a "law of temporary diminishing distraction gains" that MCGR users should be aware of when monitoring rod lengthening. Diminishing distraction length gains is observed as the rod is lengthened and is a phenomenon independent of patient factors. It is only temporary as the rates of achieved lengthening returns to baseline after rod exchange.
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http://dx.doi.org/10.1177/2192568220948475DOI Listing
August 2020

A tailored positively-charged hydrophobic surface reduces the risk of implant associated infections.

Acta Biomater 2020 09 22;114:421-430. Epub 2020 Jul 22.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong SAR, PR China; Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong Shenzhen Hospital, Shenzhen, PR China. Electronic address:

Implant-associated infections is one of the most challenging post-operative complications in bone-related implantations. To tackle this clinical issue, we developed a low-cost and durable surface coating for medical grade titanium implants that uses positively charged silane molecules. The in vitro antimicrobial tests revealed that the titanium surface coated with (3-aminopropyl) triethoxysilane, which has the appropriate length of hydrophobic alkyl chain and positive charged amino group, suppressed more than 90% of the initial bacterial adhesion of S. aureus, P. aeruginosa, and E. coli after 30 min of incubation. In terms of growth inhibitory rate, the treated surface was able to reduce 75.7% ± 11.9% of bacterial growth after a 24-hour culturing, thereby exhibiting superior anti-biofilm formation in the late stage. When implanted into the rat model infected by S. aureus, the treated surface eliminated the implant-associated infection through the mechanism of inhibition of bacterial adhesion on the implant surface. Additionally, the treated surface was highly compatible with mammalian cells. In general, our design demonstrated its potential for human clinical trials as a low-cost and effective antibacterial strategy to minimize post-operative implant-related bacterial infection.
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http://dx.doi.org/10.1016/j.actbio.2020.07.040DOI Listing
September 2020

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

Eur Spine J 2020 10 29;29(10):2409-2412. Epub 2020 Jun 29.

The Royal National Orthopaedic Hospital and Institute of Orthopaedics and Musculoskeletal Science, University College London, Brockley Hill, Stanmore, HA74LP, UK.

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.
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http://dx.doi.org/10.1007/s00586-020-06516-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7324002PMC
October 2020

A Radiographic Analysis of Lumbar Fusion Status and Instrumentation Failure After Complex Adult Spinal Deformity Surgery With Spinopelvic Fixation: Two-Year Follow-up From the Scoli-Risk-1 Prospective Database.

Clin Spine Surg 2020 Dec;33(10):E545-E552

Department of Neurological Surgery, University of Toronto, Toronto, ON, Canada.

Study Design: A retrospective review of prospectively collected data.

Objective: The objective of this study was to investigate the fusion status of the lumbar spine and lumbosacral junction at 2 years postoperatively after complex adult spinal deformity (ASD) surgery.

Summary Of Background Data: Achieving fusion is crucial for maintaining optimal alignment in ASD surgery. However, prospective data assessing fusion status using large patient populations are lacking in this patient population.

Materials And Methods: Postoperative radiographs of 162 patients from the Scoli-Risk-1 database, who underwent complex ASD surgery with fusion to the sacrum, were evaluated by 3 independent spine surgeons at 6-week, 6-month, and 2-year follow-up. The fusion rate of the lumbar spine segments at a 2-year follow-up was determined by using previously published radiographic grading criteria. We also assessed the prevalence of instrumentation failures.

Results: The interrater reliabilities for grading the fusion status were overall fair at each level evaluated (Fleiss κ, 0.337-0.439). Overall, 70.3% (114/162) demonstrated the solid fusion of the entire lumbar spine at a 2-year follow-up. The fusion rates of each segment were L1/L2: 87.0%, L2/L3: 82.0%, L3/L4: 83.9%, L4/L5: 89.5%, and L5/S1: 89.5%. Pedicle screw loosening was the most frequent implant failure throughout the observation period (9.2%, 11.6%, and 11.0% at 6-wk, 6-mo, and 2-y follow-up, respectively). No rod breakage was observed at 6 weeks, increasing to 9.8% at 2-year follow-up. The prevalence of postoperative proximal junctional kyphosis was 5.5% at 6 weeks, showing no difference at 2 years postoperative.

Conclusions: In this series of complex ASD surgeries often requiring 3-column osteotomies, 70.3% showed solid fusion of the entire lumbar spine, including the lumbosacral junction. The lumbosacral segments showed a relatively high fusion rate at a 2-year follow-up likely due to the frequent use of anterior column support and graft. The prevalence of rod breakage increased as follow-up proceeded to 9.8%, which was most commonly observed at the lumbosacral junction.

Level Of Evidence: Level IV.
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http://dx.doi.org/10.1097/BSD.0000000000001008DOI Listing
December 2020

Complications following surgery for adolescent idiopathic scoliosis over a 13-year period.

Bone Joint J 2020 Apr;102-B(4):519-523

Department of Orthopaedics and Traumatology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.

Aims: The purpose of this study was to evaluate the incidence and analyze the trends of surgeon-reported complications following surgery for adolescent idiopathic scoliosis (AIS) over a 13-year period from the Scoliosis Research Society (SRS) Morbidity and Mortality database.

Methods: All patients with AIS between ten and 18 years of age, entered into the SRS Morbidity and Mortality database between 2004 and 2016, were analyzed. All perioperative complications were evaluated for correlations with associated factors. Complication trends were analyzed by comparing the cohorts between 2004 to 2007 and 2013 to 2016.

Results: Between 2004 and 2016, a total of 84,320 patients were entered into the database. There were 1,268 patients associated with complications, giving an overall complication rate of 1.5%. Death occurred in 12 patients (0.014%). The three most commonly reported complications were surgical site infection (SSI) (441 patients; 0.52%), new neurological deficit (293; 0.35%), and implant-related complications (172; 0.20%). There was a statistically significant but weak correlation between the occurrence of a SSI and the magnitude of the primary curve ( = 0.227; p < 0.001), and blood loss in surgery ( = 0.111; p = 0.038), while the occurrence of a new neurological deficit was correlated statistically significantly but weakly with age at surgery ( = 0.147; p = 0.004) and magnitude of the primary curve ( = 0.258; p < 0.001). The overall complication rate decreased from 4.95% during 2004 to 2007 to 0.98% during 2013 to 2016 (p = 0.023).

Conclusion: An overall complication rate of 1.5% was found in our series after surgery for AIS, with a reduction of complication rates found in the second period of the analysis. Cite this article: 2020;102-B(4):519-523.
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http://dx.doi.org/10.1302/0301-620X.102B4.BJJ-2019-1371.R1DOI Listing
April 2020

Lumbar high-intensity zones on MRI: imaging biomarkers for severe, prolonged low back pain and sciatica in a population-based cohort.

Spine J 2020 07 3;20(7):1025-1034. Epub 2020 Mar 3.

Department of Orthopedic Surgery, Rush University Medical Center, Chicago, IL, USA; International Spine Research and Innovation Initiative, RUSH University Medical Center, Chicago, IL, USA. Electronic address:

Background Context: There is often discrepancy between clinical presentation and lumbar magnetic resonance imaging (MRI) findings.

Purpose: The purpose of this study was to assess the relationship of high-intensity zones (HIZs) on MRI with low back pain (LBP), sciatica, and back-related disability.

Study Design: Cross-sectional, population-based Southern Chinese cohort study.

Patient Sample: Of 1,414 possible participants, data from 1,214 participants (453 males, 761 females; mean age of 48.1±6.3 years) were included.

Outcome Measures: Presence of single-level, homogeneous multilevel (same type HIZs of morphology and topography) and heterogeneous multilevel (mixed type HIZs of morphology and topography) HIZs and other MRI phenotypes were assessed at each level with T2-weighted 3T sagittal MRI of L1-S1. Associations with LBP, sciatica and Oswestry Disability Index were correlated with HIZ profiles.

Results: In all, 718 individuals had HIZs (59.1%). Disc degeneration/displacement were more prevalent in HIZ individuals (p<.001). HIZ subjects experienced prolonged severe LBP more frequently (39.6% vs. 32.5%; p<.05) and had higher Oswestry Disability Index scores (10.7±13.7 vs. 8.9±11.3; p<.05). Posterior multilevel HIZ were significantly associated with prolonged severe LBP (OR: 2.18; 95% CI:1.42-3.37; p<.05) in comparison to anterior only, anterior/posterior or other patterns of HIZ. Multilevel homogeneous or heterogeneous HIZs were significantly associated with prolonged, severe LBP (OR: 1.53-1.57; p<.05). Individuals with homogeneous HIZs had a higher risk of sciatica (OR: 1.51, 95% CI: 1.01-2.27; p<.05).

Conclusions: This is the first large-scale study to note that lumbar HIZs, and specific patterns therein, are potentially clinically-relevant imaging biomarkers that are independently and significantly associated with prolonged/severe LBP and sciatica. HIZs, especially homogenous multilevel HIZ, should be noted in the global pain imaging phenotype assessment.
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http://dx.doi.org/10.1016/j.spinee.2020.02.015DOI Listing
July 2020

The effect of magnetically controlled growing rods on three-dimensional changes in deformity correction.

Spine Deform 2020 06 18;8(3):537-546. Epub 2020 Feb 18.

Department of Orthopaedics & Traumatology, The University of Hong Kong, Professorial Block, 5th Floor, 102 Pokfulam Road, Pokfulam, Hong Kong SAR, China.

Study Design: Prospective radiographic study.

Objectives: To determine the three-dimensional (3D) changes in deformity correction with magnetically controlled growing rod (MCGR) distractions. MCGRs can achieve similar coronal plane correction as traditional growing rods. The changes in the sagittal and axial planes are unknown and should be studied as these factors reflect potential for proximal junctional kyphosis and rotational deformity. Frequent MCGR distractions may potentially improve axial plane deformities to the same extent as coronal and sagittal plane deformities.

Methods: Early onset scoliosis (EOS) patients who underwent dual MCGRs with minimum 2-year follow-up were included in this study. 3D reconstructions of 6-monthly biplanar images were used to study changes in coronal, sagittal and axial planes. Changes in growth parameters (body height and arm span) were scaled to changes in coronal Cobb angles, sagittal profile (T1-12, T4-12, L1-L5, L1-S1), and rotational profile at the proximal thoracic, main thoracic and lumbar curves, and pelvic parameters (sagittal pelvic tilt, lateral pelvic tilt and pelvis rotation).

Results: A total of 10 EOS patients were studied. The mean age at index surgery was 8.2 ± 3.0 years and mean postoperative follow-up of 34.3 ± 9.5 months. Six patients had rod exchange at mean 29.5 ± 11.8 months after initial implantation. Despite consistent gains in body height and arm span, the main changes in coronal and rotational profiles only occurred at the initial rod implantation surgery with only small changes occurring with subsequent follow-ups. Patients with higher preoperative proximal junctional angles had flattening of the sagittal plane occurring at initial surgery with early rebound. No changes in pelvic parameters were observed.

Conclusions: The 3D changes with MCGR are mainly observed with initial rod implantation and no significant changes are observed with distractions. The MCGR can prevent deformity progression in the axial plane.

Level Of Evidence: IV.
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http://dx.doi.org/10.1007/s43390-020-00055-yDOI Listing
June 2020

Vanadium Dioxide Nanocoating Induces Tumor Cell Death through Mitochondrial Electron Transport Chain Interruption.

Glob Chall 2019 Mar 3;3(3):1800058. Epub 2018 Dec 3.

Department of Orthopaedics and Traumatology Li Ka Shing Faculty of Medicine The University of Hong Kong Pokfulam Hong Kong 999077 China.

A biomaterials surface enabling the induction of tumor cell death is particularly desirable for implantable biomedical devices that directly contact tumor tissues. However, this specific antitumor feature is rarely found. Consequently, an antitumor-cell nanocoating comprised of vanadium dioxide (VO) prepared by customized reactive magnetron sputtering has been proposed, and its antitumor-growth capability has been demonstrated using human cholangiocarcinoma cells. The results reveal that the VO nanocoating is able to interrupt the mitochondrial electron transport chain and then elevate the intracellular reactive oxygen species levels, leading to the collapse of the mitochondrial membrane potential and the destruction of cell redox homeostasis. Indeed, this chain reaction can effectively trigger oxidative damage in the cholangiocarcinoma cells. Additionally, this study has provided new insights into designing a tumor-cell-inhibited biomaterial surface, which is modulated by the mechanism of mitochondria-targeting tumor cell death.
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http://dx.doi.org/10.1002/gch2.201800058DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436600PMC
March 2019

A surface-engineered multifunctional TiO based nano-layer simultaneously elevates the corrosion resistance, osteoconductivity and antimicrobial property of a magnesium alloy.

Acta Biomater 2019 11 10;99:495-513. Epub 2019 Sep 10.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China; Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong Shenzhen Hospital, 1 Haiyuan 1st Road, Futian District, Shenzhen, China. Electronic address:

Magnesium biometals exhibit great potentials for orthopeadic applications owing to their biodegradability, bioactive effects and satisfactory mechanical properties. However, rapid corrosion of Mg implants in vivo combined with large amount of hydrogen gas evolution is harmful to bone healing process which seriously confines their clinical applications. Enlightened by the superior biocompatibility and corrosion resistance of passive titanium oxide layer automatically formed on titanium alloy, we employ the Ti and O dual plasma ion immersion implantation (PIII) technique to construct a multifunctional TiO based nano-layer on ZK60 magnesium substrates for enhanced corrosion resistance, osteoconductivity and antimicrobial activity. The constructed nano-layer (TiO/MgO) can effectively suppress degradation rate of ZK60 substrates in vitro and still maintain 94% implant volume after post-surgery eight weeks. In animal study, a large amount of bony tissue with increased bone mineral density and trabecular thickness is formed around the PIII treated group in post-operation eight weeks. Moreover, the newly formed bone in the PIII treated group is well mineralized and its mechanical property almost restores to the level of that of surrounding mature bone. Surprisingly, a remarkable killing ratio of 99.31% against S. aureus can be found on the PIII treated sample under ultra-violet (UV) irradiation which mainly attributes to the oxidative stress induced by the reactive oxygen species (ROS). We believe that this multifunctional TiO based nano-layer not only controls the degradation of magnesium implant, but also regulates its implant-to-bone integration effectively. STATEMENT OF SIGNIFICANCE: Rapid corrosion of magnesium implants is the major issue for orthopaedic applications. Inspired by the biocompatibility and corrosion resistance of passive titanium oxide layer automatically formed on titanium alloy, we construct a multifunctional TiO/MgO nanolayer on magnesium substrates to simultaneously achieve superior corrosion resistance, satisfactory osteoconductivity in rat intramedullary bone defect model and excellent antimicrobial activity against S. aureus under UV irradiation. The current findings suggest that the specific TiO/MgO nano-layer on magnesium surface can achieve the three objectives aforementioned and we believe this study can demonstrate the potential of biodegradable metals for future clinical applications.
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http://dx.doi.org/10.1016/j.actbio.2019.09.008DOI Listing
November 2019

Micro- and Nanohemispherical 3D Imprints Modulate the Osteogenic Differentiation and Mineralization Tendency of Bone Cells.

ACS Appl Mater Interfaces 2019 Oct 20;11(39):35513-35524. Epub 2019 Sep 20.

Department of Orthopaedics & Traumatology, Li Ka Shing Faculty of Medicine , The University of Hong Kong , Pokfulam, Hong Kong 999077 , China.

Surface topography has been reported to play a key role in modulating cell behaviors, yet the mechanism through which it modulates these behaviors is not fully understood, especially in the case of three-dimensional (3D) topographies. In this study, a series of novel hemispherical 3D imprints ranging from the nanoscale to the microscale were prepared on titanium (Ti) surfaces using a customized interfacial lithography method. Mouse embryo osteoblast precursor cells (MC3T3-E1) were selected to investigate the solitary effect of specific hemispherical 3D imprints on cellular behaviors. The results indicated that varied hemispherical 3D imprints can affect the formation of filopodia and the arrangement of the cytoskeleton in different ways. Specifically, they can alter the spreading morphologies of cells and lead to deformation of the nucleus, which eventually affects cell proliferation and osteogenic differentiation. Cells cultured on different hemispherical 3D imprints exhibited promoted proliferation and osteogenic differentiation to different degrees; for example, cells cultured on 90 and 500 nm hemispherical imprints formed abundant filopodia and exhibited the highest alkaline phosphatase activity and osteogenic gene expression, respectively. Four-week tibia implantation also confirmed that 90 nm hemispherical imprints improved the osteogenic ability compared with an unpatterned Ti substrate. In addition to promoted proliferation, colonization of more cells on the surface of implants and induction of rapid osteogenic differentiation can occur. Our work provides a rational way to balance cell proliferation and differentiation, which can accelerate bone integration of an implant and host tissue.
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http://dx.doi.org/10.1021/acsami.9b05521DOI Listing
October 2019

The Effect of Tobacco Smoking on Adverse Events Following Adult Complex Deformity Surgery: Analysis of 270 Patients From the Prospective, Multicenter Scoli-RISK-1 Study.

Spine (Phila Pa 1976) 2020 Jan;45(1):32-37

University of Toronto Spine Program and Toronto Western Hospital, Toronto, Ontario, Canada.

Study Design: Post-hoc analysis of a prospective, multicenter cohort study.

Objective: To analyze the impact of smoking on rates of postoperative adverse events (AEs) in patients undergoing high-risk adult spine deformity surgery.

Summary Of Background Data: Smoking is a known predictor of medical complications after adult deformity surgery, but the effect on complications, implant failure and other AEs has not been adequately described in prospective studies.

Methods: Twenty-six patients with a history of current smoking were identified out of the 272 patients enrolled in the SCOLI-RISK-1 study who underwent complex adult spinal deformity surgery at 15 centers, with 2-year follow-up. The outcomes and incidence of AEs in these patients were compared to the nonsmoking cohort (n = 244) using univariate analysis, with additional multivariate regression to adjust for the effect of patient demographics, complexity of surgery, and other confounders.

Results: The number of levels and complexity of surgery in both cohorts were comparable. In the univariate analysis, the rates of implant failure were almost double (odds ratio 2.28 [0.75-6.18]) in smoking group (n = 7; 26.9%)) that observed in the nonsmoking group (n = 34; 13.9%), but this was not statistically significant (P = 0.088). Surgery-related excessive bleeding (>4 L) was significantly higher in the smoking group (n = 5 vs. n = 9; 19.2% vs. 3.7%; OR 6.22[1.48 - 22.75]; P = 0.006). Wound infection rates and respiratory complications were similar in both groups. In the multivariate analysis, the smoking group demonstrated a higher incidence of any surgery-related AEs over 2 years (n = 13 vs. n = 95; 50.0% vs. 38.9%; OR 2.12 [0.88-5.09]) (P = 0.094).

Conclusion: In this secondary analysis of patients from the SCOLI-RISK-1 study, a history of smoking significantly increased the risk of excessive intraoperative bleeding and nonsignificantly increased the rate of implant failure or surgery-related AEs over 2 years. The authors therefore advocate a smoking cessation program in patients undergoing complex adult spine deformity surgery.

Level Of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000003200DOI Listing
January 2020

A functionalized TiO/MgTiO nano-layer on biodegradable magnesium implant enables superior bone-implant integration and bacterial disinfection.

Biomaterials 2019 10 25;219:119372. Epub 2019 Jul 25.

Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China; Shenzhen Key Laboratory for Innovative Technology in Orthopaedic Trauma, The University of Hong Kong Shenzhen Hospital, 1 Haiyuan 1st Road, Futian District, Shenzhen, China. Electronic address:

Rapid corrosion of biodegradable magnesium alloys under in vivo condition is a major concern for clinical applications. Inspired by the stability and biocompatibility of titanium oxide (TiO) passive layer, a functionalized TiO/MgTiO nano-layer has been constructed on the surface of WE43 magnesium implant by using plasma ion immersion implantation (PIII) technique. The customized nano-layer not only enhances corrosion resistance of Mg substrates significantly, but also elevates the osteoblastic differentiation capability in vitro due to the controlled release of magnesium ions. In the animal study, the increase of new bone formation adjacent to the PIII-treated magnesium substrate is 175% higher at post-operation 12 weeks, whereas the growth of new bone on titanium control and untreated magnesium substrate are only 97% and 29%, respectively. In addition, its Young's modulus can be restored to about 82% as compared with the surrounding matured bone. Furthermore, this specific TiO/MgTiO layer even exhibits photoactive bacteria disinfection capability when irradiated by ultraviolet light which is attributed to the intracellular reactive oxygen species (ROS) production. With all these constructive observations, it is believed that the TiO/MgTiO nano-layer on magnesium implants can significantly promote new bone formation and suppress bacterial infection, while the degradation behavior can be controlled simultaneously.
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http://dx.doi.org/10.1016/j.biomaterials.2019.119372DOI Listing
October 2019

Evolution and Advancement of Adult Spinal Deformity Research and Clinical Care: An Overview of the Scoli-RISK-1 Study.

Global Spine J 2019 May 8;9(1 Suppl):8S-14S. Epub 2019 May 8.

Norton Leatherman Spine Center, Louisville, KY, USA.

Study Design: Narrative review.

Objective: The prevalence of adult spinal deformity (ASD) has been cited anywhere between 2-32%, while the prevalence in the elderly population has been estimated at 68%. Neurologic complications following ASD surgery remains a concern. Previous literature reported incidence of neurologic complications varied between 1-10%, while non-neurologic complications reported were as high as 50%. To assess the incidence of neurologic deficits, complications, and outcomes following ASD surgery, an international group of spine deformity surgeons initiated a prospective, multicenter, international, observational study: Scoli-RISK-1.

Methods: Two hundred seventy-two patients were enrolled from 15 centers with ASD having primary or revision surgery with a major Cobb≥80°, revision including an osteotomy, and/or a complex 3-column osteotomy. Patients had lower extremity muscle strength (LEMS) exams performed preoperatively and at specific time points through 2-year follow-up.

Results: Preoperatively, 203 patients (74.9%) had no LEMS impairment (normal) and 68 (25.1%) had a LEMS of <50 (abnormal). Compared with baseline, 23.0% of all patients experienced a LEMS decline at discharge, with this rate decreasing to 17.1% at 6-weeks and to 9.9% at 6-months and remaining stable at 10.0% at 2-years.

Conclusion: This study revealed that a decline in LEMS after complex ASD surgery is common and more frequent than previously reported. We identified such a decline in 23.0% of patients at discharge, with neurologic function recovering over time to a decline of 10.0% at 2-years postoperatively. The Scoli-RISK-1 study revealed valuable information regarding the incidence, natural history, and prognosis of neurologic and non-neurologic complications following ASD surgery and provides useful information for patient counseling.
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http://dx.doi.org/10.1177/2192568219828729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512199PMC
May 2019

Responding to Intraoperative Neuromonitoring Changes During Pediatric Coronal Spinal Deformity Surgery.

Global Spine J 2019 May 8;9(1 Suppl):15S-21S. Epub 2019 May 8.

AOSpine Knowledge Forum Deformity, Davos, Switzerland.

Study Design: Retrospective case study on prospectively collected data.

Objectives: The purpose of this explorative study was: 1) to determine if patterns of spinal cord injury could be detected through intra-operative neuromonitoring (IONM) changes in pediatric patients undergoing spinal deformity corrections, 2) to identify if perfusion based or direct trauma causes of IONM changes could be distinguished, 3) to observe the effects of the interventions performed in response to these events, and 4) to attempt to identify different treatment algorithms for the different causes of IONM alerts.

Methods: Prospectively collected neuromonitoring data in pre-established forms on consecutive pediatric patients undergoing coronal spinal deformity surgery at a single center was reviewed. Real-time data was collected on IONM alerts with >50% loss in signal. Patients with alerts were divided into 2 groups: unilateral changes (direct cord trauma), and bilateral MEP changes (cord perfusion deficits).

Results: A total of 97 pediatric patients involving 71 females and 26 males with a mean age of 14.9 (11-18) years were included in this study. There were 39 alerts in 27 patients (27.8% overall incidence). All bilateral changes responded to a combination of transfusion, increasing blood pressure, and rod removal. Unilateral changes as a result of direct trauma, mainly during laminotomies for osteotomies, improved with removal of the causative agent. Following corrective actions in response to the alerts, all cases were completed as planned. Signal returned to near baseline in 20/27 patients at closure, with no new neurological deficits in this series.

Conclusion: A high incidence of alerts occurred in this series of cases. Dividing IONM changes into perfusion-based vs direct trauma directed treatment to the offending cause, allowing for safe corrections of the deformities. Patients did not need to recover IONM signal to baseline to have a normal neurological examination.
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http://dx.doi.org/10.1177/2192568219836993DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6512195PMC
May 2019

Genome-wide meta-analysis and replication studies in multiple ethnicities identify novel adolescent idiopathic scoliosis susceptibility loci.

Hum Mol Genet 2018 11;27(22):3986-3998

Sarah M. & Charles E. Seay Center for Musculoskeletal Research, Texas Scottish Rite Hospital for Children, Dallas, TX, USA.

Adolescent idiopathic scoliosis (AIS) is the most common musculoskeletal disorder of childhood development. The genetic architecture of AIS is complex, and the great majority of risk factors are undiscovered. To identify new AIS susceptibility loci, we conducted the first genome-wide meta-analysis of AIS genome-wide association studies, including 7956 cases and 88 459 controls from 3 ancestral groups. Three novel loci that surpassed genome-wide significance were uncovered in intragenic regions of the CDH13 (P-value_rs4513093 = 1.7E-15), ABO (P-value_ rs687621 = 7.3E-10) and SOX6 (P-value_rs1455114 = 2.98E-08) genes. Restricting the analysis to females improved the associations at multiple loci, most notably with variants within CDH13 despite the reduction in sample size. Genome-wide gene-functional enrichment analysis identified significant perturbation of pathways involving cartilage and connective tissue development. Expression of both SOX6 and CDH13 was detected in cartilage chondrocytes and chromatin immunoprecipitation sequencing experiments in that tissue revealed multiple HeK27ac-positive peaks overlapping associated loci. Our results further define the genetic architecture of AIS and highlight the importance of vertebral cartilage development in its pathogenesis.
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http://dx.doi.org/10.1093/hmg/ddy306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6488972PMC
November 2018

Contribution of the in situ release of endogenous cations from xenograft bone driven by fluoride incorporation toward enhanced bone regeneration.

Biomater Sci 2018 Nov 25;6(11):2951-2964. Epub 2018 Sep 25.

Department of Oral Implantology, Hospital of Stomatology, Guanghua School of Stomatology, Institute of Stomatological Research, Sun Yat-sen University, Guangzhou, P. R. China. and Guangdong Provincial Key Laboratory of Stomatology, Sun Yat-sen University, Guangzhou, P.R. China.

Xenograft, namely bone-derived biological apatite (BAp), is widely recognized as a favorable biomaterial in bone tissue engineering owing to its biodegradability, biocompatibility, and osteoconductive properties. Substitutions of endogenous trace ions are thought to improve the osteogenic capacity of xenograft compared with synthetic hydroxyapatite (HAp). In order to modify the physicochemical and biological properties of apatite, different approaches to induce trace ion incorporation have been widely considered. In this study, we demonstrated that the incorporation of fluoride ions into porcine bone-derived biological apatite (pBAp) contributes to altered crystal morphology of the apatite, the sustained release of fluoride, and the in situ release of endogenous trace ions (e.g., magnesium and calcium) into the peripheral tissue microenvironment. This ionic balanced perimaterial microenvironment not only led to superior proliferation and osteogenic differentiation of rat bone mesenchymal stem cells (rBMSCs), but also accelerated new bone formation of the calvarial defect on a rat model via the activation of Wnt/β-catenin signaling. These promising observations may be attributed to the controlled release of endogenous trace ions from the xenograft to the peripheral tissue microenvironment driven by fluoride ion incorporation. Lastly, this study may provide a new insight to strengthen the osteogenicity of xenografts for clinical applications in the future.
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http://dx.doi.org/10.1039/c8bm00910dDOI Listing
November 2018

Unilateral versus bilateral lower extremity motor deficit following complex adult spinal deformity surgery: is there a difference in recovery up to 2-year follow-up?

Spine J 2019 03 14;19(3):395-402. Epub 2018 Aug 14.

University of California San Francisco, 505 Parnassus Ave. San Francisco, CA 94143, United States.

Background Context: Scoli-RISK-1 is a multicenter prospective cohort designed to study neurologic outcomes following complex adult spinal deformity (ASD). The effect of unilateral versus bilateral postoperative motor deficits on the likelihood of long-term recovery has not been previously studied in this population.

Purpose: To evaluate whether bilateral postoperative neurologic deficits have a worse recovery than unilateral deficits.

Study Design: Secondary analysis of a prospective, multicenter, international cohort study.

Methods: In a cohort of 272 patients, neurologic decline was defined as deterioration of the American Spinal Injury Association Lower Extremity Motor Scores (LEMS) following surgery. Patients with lower extremity neurologic decline were grouped into unilateral and bilateral cohorts. Differences in demographics, surgical variables, and patient outcome measures between the two cohorts were analyzed.

Results: A total of 265 patients had LEMS completed at discharge. Unilateral decline was seen in 32 patients (12%), while 29 (11%) had bilateral symptoms. At 2 years, there was no significant difference in either median LEMS (unilateral 50.0, interquartile range [IQR] 47.5-50.0; bilateral 50.0, IQR 48.0-50.0, p=.939) or change in LEMS from baseline (unilateral 0.0, IQR -1.0 to 0.0; bilateral 0.0, IQR -1.0 to 0.0, p=.920). In both groups, approximately two-thirds of patients saw recovery to at least their preoperative baseline by 2 years postoperatively (unilateral n=15, 63%; bilateral n=14, 67%). The mean Scoliosis Research Society-22R (SRS-22R) score at 2 years was 3.7±0.6 versus 3.2±0.6 (p=.009) for unilateral and bilateral groups, respectively.

Conclusions: The prognosis for neurologic recovery of new motor deficits following complex adult spinal deformity is similar with both unilateral and bilateral weaknesses. Despite similar rates of neurologic recovery, patient reported outcomes for those with bilateral motor decline measured by SRS-22R are worse at 2 years after surgery.
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http://dx.doi.org/10.1016/j.spinee.2018.08.003DOI Listing
March 2019

Mean 6-Year Follow-up of Magnetically Controlled Growing Rod Patients With Early Onset Scoliosis: A Glimpse of What Happens to Graduates.

Neurosurgery 2019 05;84(5):1112-1123

Department of Orthopaedics and Tra-umatology, The University of Hong Kong, Pokfulam, Hong Kong, SAR, China.

Background: There is no agreement on frequency of distractions of magnetically controlled growing rods (MCGRs) but more frequent and smaller amounts of distractions mimic physiological spine growth. The mid- to long-term follow-up and management at skeletal maturity is unknown.

Objective: To analyze patients with mean 6 yr of follow-up and describe the fate of MCGR graduates.

Methods: Early onset scoliosis (EOS) patients treated with MCGRs with minimum 4 yr of follow-up and/or at graduation were studied. Parameters under study included Cobb angle, spine and instrumented lengths, and rod distraction gains. Relationship between timing of rod exchanges with changes in rate of lengthening was studied.

Results: Ten EOS patients with mean 6.1 yr of follow-up were studied. The greatest Cobb angle correction occurred at the initial implantation surgery and was stable thereafter. Consistent gains in T1-12, T1-S1, and instrumented segment were observed. Rate of lengthening reduced after the first year of use but improved back to initial rates after rod exchange. Seven of the ten patients experienced complications with reoperation rate of 40% for rod distraction failure and proximal foundation problems. Only mild further improvements in all radiological parameters were observed pre- and postfinal surgery. No clinically significant curve progression was observed for rod removal only. All postfinal surgery parameters remained similar at postoperative 2 yr.

Conclusion: This study provides an outlook of the end of MCGR treatment. Although this is a fusionless procedure, instrumented segments do experience stiffness limiting further correction and length gain during final surgery whether fusion or rod removal is performed.
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http://dx.doi.org/10.1093/neuros/nyy270DOI Listing
May 2019

Association of Modic changes with health-related quality of life among patients referred to spine surgery.

Scand J Pain 2014 Jan 1;5(1):36-40. Epub 2014 Jan 1.

Institute of Clinical Medicine, Department of Physical and Rehabilitation Medicine, University of Oulu, and Medical Research Center Oulu, Oulu, Finland.

Background and purpose Modic changes (MC) are bone marrow and vertebral endplate lesions seen in magnetic resonance imaging (MRI) which have been found to be associated with low back pain (LBP), but the association between MC and health-related quality of life (HRQoL) is poorly understood. The aim of this study was to assess the relationship between MC and HRQoL among patients referred to spine surgery. Methods The study population consisted of 181 patients referred to lumbar spine surgery in Northern and Eastern Finland between June 2007 and January 2011. HRQoL was assessed using RAND-36 health survey. Lumbar MC were evaluated and classified into 'No MC', 'Type I' (Type I or I/II), and 'Type II' (Type II, II/III or III). Results In total, 84 patients (46%) had MC. Of these, 37% had 'Type I' and 63% 'Type II'. Patients with MC were older, more likely females, had longer duration of LBP and a higher degree of disc degeneration than patients without MC. The total physical component or physical dimensions did not differ significantly between the groups. The total mental component of RAND-36 (P = 0.010), and dimensions of energy (P = 0.023), emotional well-being (P = 0.012) and emotional role functioning (P = 0.016) differed significantly between the groups after adjustments for age and gender. In the mental dimension scores, a statistically significant difference was found between 'No MC' and 'Type II'. Conclusions Among patients referred to spine surgery, MC were not associated with physical dimensions of HRQoL including dimension of pain. However, 'Type II' MC were associated with lower mental status of HRQoL. Implications Our study would suggest that Type II MC were associated with a worse mental status. This may affect the outcome of surgery as it is well recognized that patients with depression, for instance, have smaller improvements in HRQoL and disability. Thus the value of operative treatment for these patients should be recognized and taken into consideration in treatment. Our study shows that MC may affect outcome and thus clinicians and researchers should be cognizant of this and take this into account when comparing outcomes of surgical treatment in the future. A longitudinal study would be needed to properly address the relationship of MC with surgical outcome.
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http://dx.doi.org/10.1016/j.sjpain.2013.08.003DOI Listing
January 2014

An Analysis of the Incidence and Outcomes of Major Versus Minor Neurological Decline After Complex Adult Spinal Deformity Surgery: A Subanalysis of Scoli-RISK-1 Study.

Spine (Phila Pa 1976) 2018 07;43(13):905-912

University of California San Francisco, San Francisco, CA.

Study Design: A subanalysis from a prospective, multicenter, international cohort study in 15 sites (Scoli-RISK-1).

Objective: To report detailed information regarding the severity of neurological decline related to complex adult spine deformity (ASD) surgery and to examine outcomes based on severity.

Summary Of Background Data: Postoperative neurological decline after ASD surgeries can occur due to nerve root(s) or spinal cord dysfunction. The impact of decline and the pattern of recovery may be related to the anatomic location and the severity of the injury.

Methods: An investigation of 272 prospectively enrolled complex ASD surgical patients with neurological status measured by American Spinal Injury Association Lower Extremity Motor Scores (LEMS) was undertaken. Postoperative neurological decline was categorized into "major" (≥5 points loss) versus "minor" (<5 points loss) deficits. Timing and extent of recovery in LEMS were investigated for each group.

Results: Among the 265 patients with LEMS available at discharge, 61 patients (23%) had neurological decline, with 20 (33%) experiencing major decline. Of note, 90% of the patients with major decline had deficits in three or more myotomes. Full recovery was seen in 24% at 6 weeks and increased to 65% at 6 months. However, 34% continued to experience some neurological decline at 24 months, with 6% demonstrating no improvement. Of 41 patients (67%) with minor decline, 73% had deficits in one or two myotomes. Full recovery was seen in 49% at 6 weeks and increased to 70% at 6 months. Of note, 26% had persistence of some neurological deficit at 24 months, with 18% demonstrating no recovery.

Conclusion: In patients undergoing complex ASD correction, a rate of postoperative neurological decline of 23% was noted with 33% of these being "major." Although most patients showed substantial recovery by 6 months, approximately one-third continued to experience neurological dysfunction.

Level Of Evidence: 2.
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http://dx.doi.org/10.1097/BRS.0000000000002486DOI Listing
July 2018