Opioid Use Prior to Adult Spine Deformity Correction Surgery is Associated With Worse Pre- and Postoperative Back Pain and Prolonged Opioid Demands.

STUDY DESIGN: Prospective multicenter database post-hoc analysis. OBJECTIVES: Opioids are frequently prescribed for painful spinal conditions to provide pain relief and to allow for functional improvement, both before and after spine surgery. Amidst a current opioid epidemic, it is important for providers to understand the impact of opioid use and its relationship with patient-reported outcomes. The purpose of this study was to evaluate pre-/postoperative opioid consumption surrounding ASD and assess patient-reported pain outcomes in older patients undergoing surgery for spinal deformity. METHODS: Patients ≥60 years of age from 12 international centers undergoing spinal fusion of at least 5 levels and a minimum 2-year follow-up were included. Patient-reported outcome scores were collected using the Numeric Rating Scale for back and leg pain (NRS-B; NRS-L) at baseline and at 2 years following surgery. Opioid use, defined based on a specific question on case report forms and question 11 from the SRS-22r questionnaire, was assessed at baseline and at 2-year follow-up. RESULT: Of the 219 patients who met inclusion criteria, 179 (81.7%) had 2-year data on opioid use. The percentages of patients reporting opioid use at baseline (n = 75, 34.2%) and 2 years after surgery (n = 55, 30.7%) were similar (P = .23). However, at last follow-up 39% of baseline opioid users (Opi) were no longer taking opioids, while 14% of initial non-users (No-Opi) reported opioid use. Regional pre- and postoperative opioid use was 5.8% and 7.7% in the Asian population, 58.3% and 53.1% in the European, and 50.5% and 40.2% in North American patients, respectively. Baseline opioid users reported more preoperative back pain than the No-Opi group (7.0 vs 5.7, P = .001), while NRS-Leg pain scores were comparable (4.8 vs 4, P = .159). Similarly, at last follow-up, patients in the Opi group had greater NRS-B scores than Non-Opi patients (3.2 vs 2.3, P = .012), but no differences in NRS-Leg pain scores (2.2 vs 2.4, P = .632) were observed. CONCLUSIONS: In this study, almost one-third of surgical ASD patients were consuming opioids both pre- and postoperatively world-wide. There were marked international variations, with patients from Asia having a much lower usage rate, suggesting a cultural influence. Despite both opioid users and nonusers benefitting from surgery, preoperative opioid use was strongly associated with significantly more back pain at baseline that persisted at 2-year follow up, as well as persistent postoperative opioid needs.

Governing cross-border healthcare in mainland China: a scoping review of national policies from 2002 to 2022.

This study reviews national-level policies regulating cross-border healthcare in mainland China after it acceded to the World Trade Organization (WTO). Policy documents from official websites of the State Council and 19 ministries were screened, from which 487 policy documents were analyzed. WTO's five modes of trade and WHO's six building blocks of healthcare system were used to guide the analysis of policymaking patterns, charting of policy evolution process, identification of key policy areas, differentiation of 29 detailed policy themes, and identification of major countries/regions involved in cross-border healthcare. The findings lead to four policy recommendations: (1) to establish a national-level committee to govern cross-border healthcare, (2) to build an information system to comprehensively integrate various information on cross-border healthcare consumption and provision, (3) to take more proactive policy actions in healthcare internationalization, and (4) to carry out reform experiments in key sub-national regions to fully explore various possibilities in developing and regulating cross-border healthcare.

Elasticity and cross-sectional thickness of paraspinal muscles in progressive adolescent idiopathic scoliosis.

Objectives: (1) Compare the cross-sectional thickness (CST) and shear wave speed (SWS) of paraspinal muscles (PSM) in adolescent idiopathic scoliosis (AIS) with and without curve progression; (2) investigate the relationship between CST/SWS and radiographic characteristics in AIS with curve progression; (3) compare the CST/SWS between AIS and non-scoliosis controls. Methods: This cross-sectional study analyzed the CST and SWS of PSM in 48 AIS with mild to moderate curvature and 24 non-scoliosis participants. Participants with scoliosis greater than 45° of Cobb angles were excluded. The Change of Cobb angles within the last 6-months was retrieved to allocate AIS into progression and non-progression groups. The SWS and CST of multifidus; longissimus and iliocostalis of the major curve were measured using B-mode ultrasound image with an elastography mode. Discrepancies of the SWS (SWS-ratio: SWS on the convex side divided by SWS on the concave side) and CST (CST-ratio: CST on the convex side divided by CST on the concave side) at the upper/lower end and apical vertebrae were studied. Results: A higher SWS at the apical vertebrae on the concave side of the major curve (multifidus: 3.9 ± 1.0 m/s vs. 3.1 ± 0.6 m/s; p < 0.01, longissimus: 3.3 ± 1.0 m/s vs. 3.0 ± 0.9 m/s; p < 0.01, iliocostalis: 2.8 ± 1.0 m/s vs. 2.5 ± 0.8 m/s; p < 0.01) was observed in AIS with curve progression. A lower SWS-ratio at apical vertebrae was detected with a greater vertebral rotation in participants with curve progression (multifidus [grade II]: 0.7 ± 0.1 vs. grade I: 0.9 ± 0.2; p = 0.03, longissimus [grade II]: 0.8 ± 0.2 vs. grade I: 1.1 ± 0.2; p < 0.01). CST was not different among the progressive, non-progressive AIS and non-scoliosis controls. Conclusions: Increased SWS of PSM without change of CST was observed on the concave side of the major curve in participants with progressive AIS.

Assessment of reliability and validity of a handheld surface spine scanner for measuring trunk rotation in adolescent idiopathic scoliosis.

PURPOSE: To assess the reliability and validity of a handheld scanner (SpineScan3D) for trunk rotation measurement in adolescent idiopathic scoliosis (AIS) subjects, as compared with Scoliometer. METHODS: This was a cross-sectional study with AIS subjects recruited. Biplanar spine radiographs were performed using an EOS imaging system with coronal Cobb angle (CCA) determined. The angle of trunk rotation (ATR) was measured using Scoliometer. SpineScan3D was employed to assess the axial rotation of subjects' back at forward bending, recorded as surface tilt angle (STA). Intra- and inter-examiner repeats were conducted to evaluate the reliability of SpineScan3D. RESULTS: 97 AIS patients were recruited. Intra- and inter-examiner reliability of STA measures were good to excellent in major thoracic and lumbar curves (p < 0.001). A strong correlation was found between STA and ATR measures in both curve types (p < 0.001) with a standard error of the ATR estimate of between 1 and 2 degrees from linear regression models (R squared: 0.8-0.9, p < 0.001). A similar correlation with CCA was found for STA and ATR measures (r: 0.5-0.6, p < 0.002), which also demonstrated a similar sensitivity (72%-74%) and specificity (62%-77%) for diagnosing moderate to severe curves. CONCLUSION: SpineScan3D is a handheld surface scanner with a potential of wide applications in subjects with AIS. The current study indicated that SpineScan3D is reliable and valid for measuring trunk rotation in AIS subjects, comparable to Scoliometer. Further studies are planned to investigate its measurements in coronal and sagittal planes and the potential of this device as a screening and monitoring tool. TRIAL REGISTRATION NUMBER (DATE OF REGISTRATION): HKUCTR-2288 (06 Dec 2017). LEVEL OF EVIDENCE: Level III.

A solitary osteolytic lesion with pathological fracture in the cervical spine - a case report.

BACKGROUND: Langerhans cell histiocytosis (LCH) is a rare disorder. The treatment options vary depending on how many organs are involved and how extensive the disease is. In this report, a case of LCH with isolated 6th cervical vertebra (C6) collapse was presented. This case was treated with anterior corpectomy and instrumented fusion, followed by local radiotherapy (RT), with a good clinical outcome up to postoperative six months. CASE PRESENTATION: This was a 47-year-old female patient with a complaint of neck pain and bilateral shoulder pain for two months before consultation. She was initially treated with analgesics, but the pain was persistent. Further radiological evaluations revealed an osteolytic lesion within the C6 vertebral body with a pathological fracture. Magnetic resonance imaging (MRI) with contrast of the cervical spine revealed diffused hypointense signal changes on the T1-weighted images and hyperintense signal changes on the T2-weighted images in the C6 vertebral body, with significant contrast-enhanced infiltration signals. Furthermore, in positron emission tomography-computed tomography (PET-CT), focal hypermetabolism and abnormal uptake signals were seen only in the C6 vertebral body. The patient underwent an anterior cervical corpectomy with instrumented fusion. The histopathological results confirmed the diagnosis of LCH. The patient reported significant pain relief on postoperative day one. Moreover, she was treated by local RT at postoperative one month. Good clinical outcomes were achieved in the form of no pain and recovery in neck mobility up to postoperative six months. No evidence of recurrence was observed at the final follow-up. CONCLUSIONS: This case report describes a treatment option for a solitary C6 collapse with LCH managed by anterior corpectomy and instrumented fusion, followed by local RT, with a good clinical outcome at postoperative six months. More studies are needed to elucidate whether such a treatment strategy is superior to surgery or RT alone.

Independent Prognostic Factors Associated With Improved Patient-Reported Outcomes in the Prospective Evaluation of Elderly Deformity Surgery (PEEDS) Study.

STUDY DESIGN: Prospective, multicenter, international, observational study. OBJECTIVE: Identify independent prognostic factors associated with achieving the minimal clinically important difference (MCID) in patient reported outcome measures (PROMs) among adult spinal deformity (ASD) patients ≥60 years of age undergoing primary reconstructive surgery. METHODS: Patients ≥60 years undergoing primary spinal deformity surgery having ≥5 levels fused were recruited for this study. Three approaches were used to assess MCID: (1) absolute change:0.5 point increase in the SRS-22r sub-total score/0.18 point increase in the EQ-5D index; (2) relative change: 15% increase in the SRS-22r sub-total/EQ-5D index; (3) relative change with a cut-off in the outcome at baseline: similar to the relative change with an imposed baseline score of ≤3.2/0.7 for the SRS-22r/EQ-5D, respectively. RESULTS: 171 patients completed the SRS-22r and 170 patients completed the EQ-5D at baseline and at 2 years postoperative. Patients who reached MCID in the SRS-22r self-reported more pain and worse health at baseline in both approaches (1) and (2). Lower baseline PROMs ((1) - OR: .01 [.00-.12]; (2)- OR: .00 [.00-.07]) and number of severe adverse events (AEs) ((1) - OR: .48 [.28-.82]; (2)- OR: .39 [.23-.69]) were the only identified risk factors. Patients who reached MCID in the EQ-5D demonstrated similar characteristics regarding pain and health at baseline as the SRS-22r using approaches (1) and (2). Higher baseline ODI ((1) - OR: 1.05 [1.02-1.07]) and number of severe AEs (OR: .58 [.38-.89]) were identified as predictive variables. Patients who reached MCID in the SRS22r experienced worse health at baseline using approach (3). The number of AEs (OR: .44 [.25-.77]) and baseline PROMs (OR: .01 [.00-.22] were the only identified predictive factors. Patients who reached MCID in the EQ-5D experienced less AEs and a lower number of actions taken due to the occurrence of AEs using approach (3). The number of actions taken due to AEs (OR: .50 [.35-.73]) was found to be the only predictive variable factor. No surgical, clinical, or radiographic variables were identified as risk factors using either of the aforementioned approaches. CONCLUSION: In this large multicenter prospective cohort of elderly patients undergoing primary reconstructive surgery for ASD, baseline health status, AEs, and severity of AEs were predictive of reaching MCID. No clinical, radiological, or surgical parameters were identified as factors that can be prognostic for reaching MCID.

Proprioception-related gene mutations in relation to the aetiopathogenesis of idiopathic scoliosis: A scoping review.

Since idiopathic scoliosis is a multifactorial disorder, the proprioceptive defect is considered one of its etiological factors. Genetic studies have separately revealed this relationship, yet it remains indeterminate which specific genes that related to proprioception contributed to the initiation, progression, pathology, and treatment outcomes of the curvature. A systematic search was conducted on four online databases, including PubMed, Web of Science, Embase, and Academic search complete. Studies were included if they involved human or animal subjects with idiopathic scoliosis and evaluated with proprioceptive genes. The search period was the inception of the database to February 21, 2023. Four genes (i.e., Ladybird homeobox 1 [LBX1], Piezo type mechanosensitive ion channel component 2 [PIEZO2], Runx family transcription factor 3 [RUNX3], and neurotrophin 3 [NTF3]) investigated in 19 studies were included. LBX1 has confirmed the correlation with the development of idiopathic scoliosis in 10 ethnicities, whereas PIEZO2 has shown a connection with clinical proprioceptive tests in subjects with idiopathic scoliosis. However, curve severity was less likely to be related to the proprioceptive genes. The potential pathology took place at the proprioceptive neurons. Evidence of proprioception-related gene mutations in association with idiopathic scoliosis was established. Nevertheless, the causation between the initiation, progression, and treatment outcomes with proprioceptive defect requires further investigation.

Inter-screw index as a novel diagnostic indicator of tether breakage.

PURPOSE: Tether breakage is the most common complication of Vertebral Body Tethering (VBT) occurring in up to 52% of Adolescent Idiopathic Scoliosis (AIS) patients and risks continued progression and revision. Radiographical diagnosis of tether breakage is commonly defined by a 5° increase in inter-screw angle and associates breakage with loss of correction. However, the sensitivity of this method was 56% only, suggesting that tethers can break without an increase in angulation, which was supported by other studies. To our knowledge, current literature lacks a method merely focusing on the diagnosis of tether breakage radiographically that does not associate the breakages with loss of correction. METHODS: This was a retrospective review of prospectively collected data of AIS patients who underwent VBT. The "inter-screw index" is defined as the percentage increase in inter-screw distance since post-op, with ≥ 13% increase defined as tether breakage as suggested by our mechanical tests. CTs were reviewed to identify the breakages and compared with inter-screw angle and inter-screw index. RESULTS: 94 segments from 13 CTs were reviewed, and 15 tether breakages were identified. Use of inter-screw index correctly identified 14 breakages (93%), whereas ≥ 5° increase in inter-screw angle only identified 12 breakages (80%). CONCLUSION: Use of inter-screw index is proven to be more sensitive than inter-screw angle in identifying tether breakages. Therefore, we propose the use of inter-screw index to diagnose tether breakages radiographically. Tether breakages were not necessarily accompanied by a loss of segmental correction leading to an increase in inter-screw angle, especially after skeletal maturity. LEVEL OF EVIDENCE: Level 3.

Ultrasound-triggered interfacial engineering-based microneedle for bacterial infection acne treatment.

Acne is an inflammatory skin disease mainly caused by Propionibacterium acnes, which can cause local inflammatory reactions and develop into chronic inflammatory diseases in severe cases. To avoid the use of antibiotics and to effectively treat the site of acne, we report a sodium hyaluronate microneedle patch that mediates the transdermal delivery of ultrasound-responsive nanoparticles for the effective treatment of acne. The patch contains nanoparticles formed by zinc porphyrin-based metal-organic framework and zinc oxide (ZnTCPP@ZnO). We demonstrated activated oxygen-mediated killing of P. acnes with an antibacterial efficiency of 99.73% under 15 min of ultrasound irradiation, resulting in a decrease in levels of acne-related factors, including tumor necrosis factor-α, interleukins, and matrix metalloproteinases. The zinc ions up-regulated DNA replication-related genes, promoting the proliferation of fibroblasts and, consequently, skin repair. This research leads to a highly effective strategy for acne treatment through the interface engineering of ultrasound response.

The Influence of Multilevel Spinal Deformity Surgery on the EuroQol 5 Dimensions' (EQ-5D) Questionnaire and Residential Status in the Elderly: A Prospective, Observational, Multicenter Study.

STUDY DESIGN: Multicenter, international prospective study. OBJECTIVE: This study investigated the clinical outcome up to 2 years after multi-level spinal deformity surgery in the elderly by reporting the minimal clinically important difference (MCID) of EuroQol 5-dimensions (EQ-5D), EQ-VAS, and residential status. METHODS: As an ancillary study of 219 patients ≥60 years with spinal deformity undergoing primary instrumented fusion surgery of ≥5 levels, this study focuses on EQ-5D (3-L) as the primary outcome and EQ-VAS and residential status as secondary outcomes. Data on EQ-5D were compared between pre-operatively and postoperatively at 10 weeks, 12 months, and 24 months. An anchor-based approach was used to calculate the MCID. RESULTS: The EQ-5D index and EQ-VAS, respectively, improved significantly at each time point compared to pre-operatively (from .53 (SD .21) and 55.6 (SD 23.0) pre-operatively to .64 (SD .18) and 65.8 (SD 18.7) at 10 weeks, .74 (SD .18) and 72.7 (SD 18.1) at 12 months, and .73 (SD .20) and 70.4 (SD 20.4) at 24 months). 217 (99.1%) patients lived at home pre-operatively, while 186 (88.6%), 184 (98.4%), and 172 (100%) did so at 10 weeks, 12 months, and 24 months, respectively. Our calculated MCID for the EQ-5D index at 1 year was .22 (95% CI .15-.29). CONCLUSIONS: The EQ-5D index significantly increased at each time point over 24 months after ≥5 level spinal deformity surgery in elderly patients. The MCID of the EQ-5D-3 L was .22. Patients living at home pre-operatively can expect to be able to live at home 2 years postoperatively.

Biomechanics of the tether breakage: tensile behaviour of a single-unit vertebral body tethering construct.

PURPOSE: Tether breakage was reported as the most common complication of vertebral body tethering. However, as the literature suggests the physiological loads do not have the potential to cause the failure of the tether. Currently, the biomechanical reason behind the tether breakage is unknown. The current study aims to elucidate the effects of the tension forces on the failure mechanisms of the VBT and provide mechanical justification for how it can be identified radiographically. METHODS: Tensile tests (20%/min strain rate) were performed on single-unit VBT samples. Failure modes and mechanical characteristics were reported. RESULTS: The failure took place prematurely due to the slippage of the tether at the screw-tether junction where the tether is damaged significantly by the locking cap. Slippage was initiated at 10-13% tensile strain level where the tensile stress and tension force were 50.4 ± 1.5 MPa and 582.2 ± 30.8 N, respectively. CONCLUSION: The failure occurs because of high-stress concentrations generated within the locking region which damages the tether surface and leads to the slippage of the tether. We observed that the loads leading to failure are within the physiological limits and may indicate the high likelihood of the tether breakage. The failure mode observed in our study is shown to be the dominant failure mode, and a design improvement on the gripping mechanism is suggested to avoid failure at the screw-tether junction. We observed that the tether elongates 10-13% prior to the breakage, which can be employed as a diagnostic criterion to screen for tether breakages radiographically.

Realizing Highly Efficient Sonodynamic Bactericidal Capability through the Phonon-Electron Coupling Effect Using Two-Dimensional Catalytic Planar Defects.

Conferring catalytic defects in sonosensitizers is of paramount importance in reinforcing sonodynamic therapy. However, the formation of such 0D defects is governed by the Schottky defect principle. Herein, 2D catalytic planar defects are designed within Ti3 C2  sheets to address this challenge. These specific planar slip dislocations with abundant Ti3+ species (Ti3 C2 -SD(Ti3+ )) can yield surface-bound O due to the effective activation of O2 , thus resulting in a substantial amount of 1 O2  generation and the 99.72% ± 0.03% bactericidal capability subject to ultrasound (US) stimulation. It is discovered that the 2D catalytic planar defects can intervene in electron transfer through the phonon drag effect-a coupling effect between surface electrons and US-triggered phonons-that simultaneously contributes to a dramatic decrease in O2  activation energy from 1.65 to 0.06 eV. This design has achieved a qualitative leap in which the US catalytic site has transformed from 0D to 2D. Moreover, it is revealed that the electron origin, electron transfer, and visible O2  activation pathway triggered by US can be attributed to the phonon-electron coupling effect. After coating with neutrophil membrane (NM) proteins, the NM-Ti3 C2 -SD(Ti3+ ) sheets further demonstrate a 6-log10  reduction in methicillin-resistant Staphylococcus aureus burden in the infected bony tissue.

Corrigendum to "Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone" [Bioact. Mater. 10C (April 2022) 32-47].

[This corrects the article DOI: 10.1016/j.bioactmat.2021.08.027.].

AO Spine Adult Spinal Deformity Patient Profile: A Paradigm Shift in Comprehensive Patient Evaluation in Order to Optimize Treatment and Improve Patient Care.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: Adult spinal deformity (ASD) is an increasingly recognized condition, comprising a spectrum of pathologies considerably impacting patients' health and functional status. Patients present with a combination of pain, disability, comorbidities and radiological deformity. The study aims to propose a systematic approach of gathering information on the factors that drive decision-making by developing a patient profile. METHODS: The present study comprises of 3 parts. Part 1: Development of prototype of patient profile: The data from the Core Outcome Study on SCOlisis (COSSCO) by Scoliosis Research Society (SRS) was categorized into a conceptual framework. Part 2: Modified Delphi study: Items reaching >70% agreement were included in a 4 round iterative process with 51 panellists across the globe. Part 3: Pilot testing-feasibility: Content validity and usability were evaluated quantitatively. RESULTS: The profile consisted of 4 domains. 1. General health with demographics and comorbidities, 2.Spine-specific health with spine related health and neurological status, 3. Imaging with radiographic and MRI parameters and 4. Deformity type. Each domain consisted of 1 or 2 components with various factors and their measuring instruments. Profile was found to have an excellent content validity (I-CVIr 0.78-1.00; Ave-CVI 0.92) appropriateness, relevance and usefulness. CONCLUSIONS: The present study, is first to provide a universally applicable multimodal ASD patient profile to methodically describe patients. Physicians are encouraged to assess ASD patients holistically using this profile and not just based on radiographic findings.

Quantitative physical performance tests can effectively detect Degenerative Cervical Myelopathy: A systematic review and meta-analysis.

PURPOSE: This review aimed to identify effective physical performance tests (PPT) as clinical outcome indicators for detecting and monitoring degenerative cervical myelopathy (DCM). METHODS: A comprehensive literature search was performed on seven electronic databases on the effectiveness in detection and monitoring of DCM by PPT. All included studies were reviewed and undergone quality assessments on the risk-of-bias by Newcastle-Ottawa Scale and were pooled by random-effect analysis with level of significance at 0.05. Homogeneity among studies was assessed by I2-statistics and effect of PPT was confirmed by Cohen's d effect size and confidence intervals. RESULTS: Totally, 3111 articles were retrieved, and 19 studies were included for review and meta-analysis. There were 13 studies investigating PPT regarding the upper limbs and 12 studies regarding the lower limbs. Performance in 10-second-Grip-and-Release Test (G&R) and 9-Hole-Peg Test (9HPT) was studied in 10 and 3 articles, respectively, while 10-second-Stepping Test (SST), 30-meter-Walking Test (30MWT) and Foot-Tapping Test (FTT) for lower limbs were studied in 5, 4, and 3 articles correspondingly. Only 1 study utilized the Triangle-Stepping Test. High-quality study with fair risk-of-bias was revealed from Newcastle-Ottawa scale. Large effect size facilitated detection and monitoring in DCM was unveiling for G&R, 9HPT, SST, and 30MWT. FTT, while also effective, was hindered by a high-degree heterogeneity in the meta-analysis. CONCLUSION: Effective PPT including G&R, 9HPT, SST, 30MWT, and FTT was identified for disease detection and monitoring in DCM.

Knowledge Gaps in Biophysical Changes After Powered Robotic Exoskeleton Walking by Individuals With Spinal Cord Injury-A Scoping Review.

In addition to helping individuals with spinal cord injury (SCI) regain the ability to ambulate, the rapidly evolving capabilities of robotic exoskeletons provide an array of secondary biophysical benefits which can reduce the complications resulting from prolonged immobilization. The proposed benefits of increased life-long over-ground walking capacity include improved upper body muscular fitness, improved circulatory response, improved bowel movement regularity, and reduced pain and spasticity. Beyond the positive changes related to physical and biological function, exoskeletons have been suggested to improve SCI individuals' quality of life (QOL) by allowing increased participation in day-to-day activities. Most of the currently available studies that have reported on the impact of exoskeletons on the QOL and prevention of secondary health complications on individuals with SCI, are of small scale and are heterogeneous in nature. Moreover, few meta-analyses and reviews have attempted to consolidate the dispersed data to reach more definitive conclusions of the effects of exoskeleton use. This scoping review seeks to provide an overview on the known effects of overground exoskeleton use, on the prevention of secondary health complications, changes to the QOL, and their effect on the independence of SCI individuals in the community settings. Moreover, the intent of the review is to identify gaps in the literature currently available, and to make recommendations on focus study areas and methods for future investigations.

SPINE20 recommendations 2021: spine care for people's health and prosperity.

PURPOSE: The focus of SPINE20 is to develop evidence-based policy recommendations for the G20 countries to work with governments to reduce the burden of spine disease, and disability. METHODS: On September 17-18, 2021, SPINE20 held its annual meeting in Rome, Italy. Prior to the meeting, the SPINE20 created six proposed recommendations. These recommendations were uploaded to the SPINE20 website 10 days before the meeting and opened to the public for comments. The recommendations were discussed at the meeting allowing the participants to object and provide comments. RESULTS: In total, 27 societies endorsed the following recommendations. SPINE20 calls upon the G20 countries: (1) to expand telehealth for the access to spine care, especially in light of the current situation with COVID-19. (2) To adopt value-based interprofessional spine care as an approach to improve patient outcomes and reduce disability. (3) To facilitate access and invest in the development of a competent rehabilitation workforce to reduce the burden of disability related to spine disorders. (4) To adopt a strategy to promote daily physical activity and exercises among the elderly population to maintain an active and independent life with a healthy spine, particularly after COVID-19 pandemic. (5) To engage in capacity building with emerging countries and underserved communities for the benefit of spine patients. (6) To promote strategies to transfer evidence-based advances into patient benefit through effective implementation processes. CONCLUSIONS: SPINE20's initiatives will make governments and decision makers aware of efforts to reduce needless suffering from disabling spine pain through education that can be instituted across the globe.

Divalent metal cations stimulate skeleton interoception for new bone formation in mouse injury models.

Bone formation induced by divalent metal cations has been widely reported; however, the underlying mechanism is unclear. Here we report that these cations stimulate skeleton interoception by promoting prostaglandin E2 secretion from macrophages. This immune response is accompanied by the sprouting and arborization of calcitonin gene-related polypeptide-α+ nerve fibers, which sense the inflammatory cue with PGE2 receptor 4 and convey the interoceptive signals to the central nervous system. Activating skeleton interoception downregulates sympathetic tone for new bone formation. Moreover, either macrophage depletion or knockout of cyclooxygenase-2 in the macrophage abolishes divalent cation-induced skeleton interoception. Furthermore, sensory denervation or knockout of EP4 in the sensory nerves eliminates the osteogenic effects of divalent cations. Thus, our study reveals that divalent cations promote bone formation through the skeleton interoceptive circuit, a finding which could prompt the development of novel biomaterials to elicit the therapeutic power of these divalent cations.

Slow twitch paraspinal muscle dysregulation in adolescent idiopathic scoliosis exhibiting HIF-2α misexpression.

Background: Adolescent idiopathic scoliosis (AIS) refers to a three-dimensional spinal deformity which has a typical onset during adolescence. In most cases, the cause of the deformity cannot be clearly identified. Unbalanced paraspinal muscle activity in AIS patients was reported and hypoxia was implicated to regulate myogenesis. This study aims to investigate the association between myogenesis/muscle toning and HIF-αs activity in the pathogenesis of AIS. Methods: HIF-αs expression was examined by enzyme-linked immunosorbent assay and western blot in paraspinal myoblasts isolated from 18 subjects who underwent deformity correction surgery. QPCR was conducted to measure the gene expression levels of perinatal muscle fiber markers MYH3, MYH8; slow twitch muscle fiber markers MHY7; fast twitch muscle fiber markers MYH4; and myogenic regulatory factors MYF5 and MYOG. Slow and fast twitch muscle fiber composition in concave/convex paraspinal musculature of AIS subjects was evaluated by immunostaining of myosin heavy chain type I (MyHC I) and myosin heavy chain type II (MyHC II). Results: Reduced HIF-2α induction under hypoxia was found in paraspinal myoblast culture of 33% AIS subjects. We detected a suppression of perinatal and slow twitch muscle fiber associated genes, but not fast twitch muscle fiber-associated genes and myogenic regulatory factors in HIF-2α misexpressed AIS myoblasts. Distinct reduction of slow twitch muscle fiber was evidenced in convex paraspinal musculature, suggesting an asymmetric expression of slow twitch muscle fiber in HIF-2α misexpressed AIS patients. Conclusions: This study indicates an association of abnormal HIF-2α expression in paraspinal myoblasts and a disproportionate slow twitch muscle fiber content in the convexity of the curvature in a subset of AIS subjects, suggesting HIF-2α dysregulation as a possible risk factor for AIS. The role of HIF-2α in paraspinal muscle function during spinal growth and its relevance in AIS prognosis warrants further investigation.

Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone.

Regardless of the advancement of synthetic bone substitutes, allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases. Nevertheless, the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure. Hence, improving osseointegration and transplantation efficiency remains important. The alteration of bone tissue microenvironment (TME) to facilitate osseointegration has been generally recognized. However, the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging. To address this concern, an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment. The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique. The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated. In the animal test, superior osseointegration between Mg-enriched graft and host bone was found, whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation. Furthermore, the bony in-growth appeared on magnesium-enriched allograft bone was significant higher. The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells. Lastly, our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.