Mitochondrial-Targeted Metal-Phenolic Nanoparticles to Attenuate Intervertebral Disc Degeneration: Alleviating Oxidative Stress and Mitochondrial Dysfunction.

As intervertebral disc degeneration (IVDD) proceeds, the dysfunctional mitochondria disrupt the viability of nucleus pulposus cells, initiating the degradation of the extracellular matrix. To date, there is a lack of effective therapies targeting the mitochondria of nucleus pulposus cells. Here, we synthesized polygallic acid-manganese (PGA-Mn) nanoparticles via self-assembly polymerization of gallic acid in an aqueous medium and introduced a mitochondrial targeting peptide (TP04) onto the nanoparticles using a Schiff base linkage, resulting in PGA-Mn-TP04 nanoparticles. With a size smaller than 50 nm, PGA-Mn-TP04 possesses pH-buffering capacity, avoiding lysosomal confinement and selectively accumulating within mitochondria through electrostatic interactions. The rapid electron exchange between manganese ions and gallic acid enhances the redox capability of PGA-Mn-TP04, effectively reducing mitochondrial damage caused by mitochondrial reactive oxygen species. Moreover, PGA-Mn-TP04 restores mitochondrial function by facilitating the fusion of mitochondria and minimizing their fission, thereby sustaining the vitality of nucleus pulposus cells. In the rat IVDD model, PGA-Mn-TP04 maintained intervertebral disc height and nucleus pulposus tissue hydration. It offers a nonoperative treatment approach for IVDD and other skeletal muscle diseases resulting from mitochondrial dysfunction, presenting an alternative to traditional surgical interventions.

Treatment of Symptomatic Spinal Muscular Atrophy with Nusinersen: A Prospective Longitudinal Study on Scoliosis Progression.

Background: Nusinersen treatment has demonstrated efficacy in improving clinical outcomes for spinal muscular atrophy (SMA), yet its impact on scoliosis progression remains unclear. Objective: This study aimed to assess the progression of scoliosis in pediatric patients with SMA undergoing nusinersen treatment. Methods: In this prospective study, data were systematically collected from Hong Kong pediatric SMA patients receiving nusinersen between 2018 and 2023. All patients had longitudinal radiographic studies pre-nusinersen, and at half-yearly or yearly intervals during treatment based on the scoliosis severity. Motor function evaluations were conducted pre-nusinersen, and after starting treatment at 6- and 12-month intervals. Results: Twenty-three patients ((SMA type 1 (SMA1) = 8, SMA type 2 (SMA2) = 7, SMA type 3 (SMA3) = 8)) with a median age of 5.8 years (range: 0.4-17.5 years) at nusinersen initiation, and median follow-up duration of 3.4 years (range: 1.1-5.2 years) were included. During the study period, motor scores remained stable or improved in 83% of patients. However, scoliosis progressed across all subtypes, with mean annual progression rates of 5.2, 11.9, and 3.6 degrees in SMA1, SMA2, and SMA3 respectively. Patients initiating nusinersen between ages 5 and 11 years exhibited the most rapid progression, with rates of 11.8, 16.5, and 7.3 degrees per year in SMA1, SMA2, and SMA3 respectively. Positive correlations were observed between the difference in CHOP-INTEND score post-nusinersen and scoliosis progression in SMA1 (rs = 0.741, p = 0.041). Conversely, negative correlations were found between the difference in HFMSE score post-nusinersen and scoliosis progression in SMA2 (rs =-0.890, p = 0.012) and SMA3 (rs =-0.777, p = 0.028). Conclusions: This study reveals that nusinersen treatment in symptomatic pediatric SMA patients with motor improvement is linked to increased scoliosis progression in SMA1, whereas it is associated with decreased progression in SMA2 and SMA3. Age, baseline Cobb angle, and motor milestone improvement are influential factors in scoliosis progression.

Incidence of back pain from initial presentation to 3 years of follow-up in subjects with untreated adolescent idiopathic scoliosis.

BACKGROUND: Although back pain may be present in subjects with adolescent idiopathic scoliosis (AIS), its natural history is unknown. Therefore, this study evaluated the incidence of back pain in scoliotic adolescents longitudinally. METHODS: This retrospective analysis examined prospectively collected pain subscale data of the Scoliosis Research Society questionnaire between the initial presentation and up to 3 years of follow-up. Consecutive subjects with AIS aged 10-18 at baseline managed by observation within the study period were included. Study subjects with at least one time point of follow-up data were considered. Alternatively, a group with physiotherapy-treated was also included for comparison. RESULTS: We enrolled 428 subjects under observation. The incidence of back pain among study subjects was 14.7%, 18.8%, and 19.0% for the first year, second year, and third year of follow-up, respectively. Most experienced mild pain (1 out of 5 points) throughout the study. Neither incidence nor intensity of pain significantly differed between subjects under observation and received physiotherapy. Additionally, study subjects with a new onset of back pain had poorer function, self-image, and mental health scores than those without pain. CONCLUSION: We investigated the incidence of back pain longitudinally in subjects suffering from AIS. Further validation of the current results is warranted.

Impact of mental health components on the development of back pain in young adults with adolescent idiopathic scoliosis.

BACKGROUND: Back pain occurs commonly in adults and is multifactorial in nature. This study aimed to assess the prevalence and intensity of back pain during young adulthood in subjects with adolescent idiopathic scoliosis (AIS), as well as factors that may be associated with its prognosis. METHODS: Subjects with AIS aged 20-39 treated conservatively were included in this study. Patient-reported outcome measures in adulthood involved episodes of back pain, and scales of self-image, depression, anxiety, and stress. Additionally, pain, self-image, and mental health scores were retrieved at the first clinic consultation. Occurrence of back pain was defined as a numeric pain rating scale ≥ 6. RESULTS: 101 participants were enrolled. The prevalence of back pain in the lifetime, past 12 months, past 6 months, past 1 month, past 7 days, and past 24 h were 37%, 35%, 31%, 27%, 23%, and 20%, respectively. Male, self-image, and depression were significant associated factors for the development of back pain at all time points. Furthermore, the analyses of the initial presentation of participants have shown that participants with back pain in adulthood were characterised by poor self-image and mental health during their adolescence. CONCLUSION: The present study addressed the natural history of back pain in young adults with conservatively treated AIS. Psychological makeup has been shown to constitute the development of back pain and is strongly hinted as an early sign of having back pain in adulthood among subjects with AIS.

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.

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.

Does Diabetes Affect the Surgical Outcomes in Cases With Cervical Ossification of the Posterior Longitudinal Ligament? A Multicenter Study From Asia Pacific Spine Study Group.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To evaluate the surgical outcomes of cervical ossification of the posterior longitudinal ligament (OPLL) in diabetes mellitus (DM) patients. METHODS: Approximately 253 cervical OPLL patients who underwent surgical decompression with or without fixation were registered at 4 institutions in 3 Asian countries. They were followed up for at least 2 years. Demographics, imaging, and surgical information were collected, and cervical Japanese Orthopaedic Association (JOA) scores and the visual analog scale (VAS) for the neck were used for evaluation. RESULTS: Forty-seven patients had DM, showing higher hypertension and cardiovascular disease prevalence. Although they presented worse preoperative JOA scores than non-DM patients (10.5 ± 3.1 vs. 11.8 ± 3.2; P = 0.01), the former showed comparable neurologic recovery at the final follow-up (13.9 ± 2.9 vs. 14.2 ± 2.6; P = 0.41). No correlation was noted between the hemoglobin A1c level in the DM group and the pre- and postoperative JOA scores. No significant difference was noted in VAS scores between the groups at pre- and postsurgery. Regarding perioperative complications, DM patients presented a higher C5 palsy frequency (14.9% vs. 5.8%; P = 0.04). A similar trend was observed when surgical procedure was limited to laminoplasty. CONCLUSIONS: This is the first multicenter Asian study to evaluate the impact of DM on cervical OPLL patients. Surgical results were favorable even in DM cases, regardless of preoperative hemoglobin A1c levels or operative procedures. However, caution is warranted for the occurrence of C5 palsy after surgery.

Prevention of Surgical Site Infections in Spine Surgery: An International Survey of Clinical Practices Among Expert Spine Surgeons.

STUDY DESIGN: Questionnaire-based survey. OBJECTIVES: Surgical site infection (SSI) is a common complication in spine surgery but universal guidelines for SSI prevention are lacking. The objectives of this study are to depict a global status quo on implemented prevention strategies in spine surgery, common themes of practice and determine key areas for future research. METHODS: An 80-item survey was distributed among spine surgeons worldwide via email. The questionnaire was designed and approved by an International Consensus Group on spine SSI. Consensus was defined as more than 60% of participants agreeing to a specific prevention strategy. RESULTS: Four hundred seventy-two surgeons participated in the survey. Screening for Staphylococcus aureus (SA) is not common, whereas preoperative decolonization is performed in almost half of all hospitals. Body mass index (BMI) was not important for surgery planning. In contrast, elevated HbA1c level and hypoalbuminemia were often considered as reasons to postpone surgery. Cefazoline is the common drug for antimicrobial prophylaxis. Alcohol-based chlorhexidine is mainly used for skin disinfection. Double-gloving, wound irrigation, and tissue-conserving surgical techniques are routine in the operating room (OR). Local antibiotic administration is not common. Wound closure techniques and postoperative wound dressing routines vary greatly between the participating institutions. CONCLUSIONS: With this study we provide an international overview on the heterogeneity of SSI prevention strategies in spine surgery. We demonstrated a large heterogeneity for pre-, peri- and postoperative measures to prevent SSI. Our data illustrated the need for developing universal guidelines and for testing areas of controversy in prospective clinical trials.

An international survey of the structure and process of care for traumatic spinal cord injury in acute and rehabilitation facilities: lessons learned from a pilot study.

BACKGROUND: To describe the key findings and lessons learned from an international pilot study that surveyed spinal cord injury programs in acute and rehabilitation facilities to understand the status of spinal cord injury care. METHODS: An online survey with two questionnaires, a 74-item for acute care and a 51-item for rehabilitation, was used. A subset of survey items relevant to the themes of specialized care, timeliness, patient-centeredness, and evidence-based care were operationalized as structure or process indicators. Percentages of facilities reporting the structure or process to be present, and percentages of indicators met by each facility were calculated and reported separately for facilities from high-income countries (HIC) and from low and middle-income countries (LMIC) to identify "hard to meet" indicators defined as those met by less than two-thirds of facilities and to describe performance level. RESULTS: A total of 26 acute and 26 rehabilitation facilities from 25 countries participated in the study. The comparison of the facilities based on the country income level revealed three general observations: 1) some indicators were met equally well by both HIC and LMIC, such as 24-hour access to CT scanners in acute care and out-patient services at rehabilitation facilities; 2) some indicators were hard to meet for LMIC but not for HIC, such as having a multidisciplinary team for both acute and rehabilitation settings; and 3) some indicators were hard to meet by both HIC and LMIC, including having peer counselling programs. Variability was also observed for the same indicator between acute and rehabilitation facilities, and a wide range in the total number of indicators met among HIC facilities (acute 59-100%; rehabilitation 36-100%) and among LMIC facilities (acute: 41-82%; rehabilitation: 36-93%) was reported. CONCLUSIONS: Results from this international pilot study found that the participating acute and rehabilitation facilities on average adhered to 74% of the selected indicators, suggesting that the structure and processes to provide ideal traumatic spinal cord injury care were broadly available. Recruiting a representative sample of SCI facilities and incorporating regional attributes in future surveys will be helpful to examine factors affecting adherence to indicators.

Are clinical outcomes affected by laminoplasty method and K-line in patients with cervical ossification of posterior longitudinal ligament? A multicenter study.

BACKGROUND: Open-door laminoplasty (ODL) and French-door laminoplasty (FDL) are the main laminoplasty techniques used to treat cervical ossification of the posterior longitudinal ligament (C-OPLL). However, few studies have compared the outcomes of ODL and modified FDL (mFDL) for C-OPLL. We explored the differences in outcomes between ODL and mFDL for C-OPLL and analyzed the technical efficacy of each procedure in patients with K-line (+) or (-) C-OPLL. METHODS: From January 2010 to December 2015, 202 patients with K-line (+) or (-) C-OPLL were retrospectively recruited from 4 institutions. Clinical outcomes were evaluated using the Japanese Orthopaedic Association (JOA) score, JOA score recovery rate, operative time, blood loss, and complications. Univariate analysis and binary logistic regression models were adjusted for confounding factors. RESULTS: Two hundred patients (mFDL, n = 69; ODL, n = 131) with a median follow-up of 42 months (range 36-54 months) were included. The postoperative JOA score significantly improved in both groups (P < 0.05). After adjusting for confounding factors, there was a statistically significant difference in blood loss (≥ 300 mL) between the two groups (P = 0.005), but there was no significant difference in the postoperative JOA score (≥ 14) (P = 0.062), JOA score recovery rate (≥ 0.82) (P = 0.187), or operative time (≥ 90 min) (P = 0.925). C5 palsy tended to occur more often in the mFDL group, although the difference was not significant (P > 0.05). The stratified analysis of the K-line status showed more blood loss in K-line (+) patients who underwent mFDL, but there was no significant difference in the postoperative JOA score, JOA score recovery rate, or operative time between the ODL and mFDL groups. Additionally, there was no significant difference in blood loss, postoperative JOA score, JOA score recovery rate, or operative time among all patients with K-line (+) or (-) C-OPLL in both groups. CONCLUSIONS: Both ODL and mFDL are effective for patients with C-OPLL. However, more blood loss tends to occur during mFDL. This study showed no significant difference in the operative time or incidence of complications between the two techniques. The efficacy of ODL and mFDL was not affected by the K-line status (+ or -) in patients with C-OPLL.

Reliability of a three-dimensional spinal proprioception assessment for patients with adolescent idiopathic scoliosis.

PURPOSE: Although it is evident that some patients with adolescent idiopathic scoliosis (AIS) have proprioceptive deficit in peripheral joints, knowledge on the proprioceptive function of the deformed spine is limited. Nonetheless, spinal proprioception in AIS may be affected three-dimensionally, prior studies only focussed on evaluating peripheral proprioception in single plane. Therefore, this study aimed to develop a novel spinal proprioception assessment using three-dimensional motion analysis in patients with AIS. METHODS: Participants were included if they had a primary diagnosis of AIS who did not receive or failed conservative treatments. Three trunk repositioning tests involving flexion-extension, lateral-flexion, and axial-rotation were conducted. A three-dimensional kinematics of the trunk was used as the outcome measures. The proprioceptive acuity was quantified by the repositioning error. The intra-examiner and test-retest reliability were analysed by the intraclass correlation coefficient (ICC). RESULTS: Fifty-nine patients with AIS were recruited. Regarding the trunk flexion-extension test, the single measure ICC showed moderate reliability (0.46) and the average measures ICC demonstrated good reliability (0.72). As for the trunk lateral-flexion test, the reliability of single measure and average measures ICC was moderate (0.44) and good (0.70) reliability, respectively. For the trunk axial-rotation test, the single measure ICC indicated fair reliability (0.32), while the average measures ICC showed moderate reliability (0.59). CONCLUSION: This is the first study to evaluate the reliability of novel three-dimensional spinal proprioception assessments in patients with AIS. The trunk flexion-extension repositioning test may be preferable clinical test given its highest reliability.

Timely Revisit of Proprioceptive Deficits in Adolescent Idiopathic Scoliosis: A Systematic Review and Meta-Analysis.

STUDY DESIGN: Systematic review and meta-analysis. OBJECTIVES: The present review aimed to summarize the evidence regarding differences in proprioception between children with and without adolescent idiopathic scoliosis (AIS). METHODS: Seven electronic databases were searched from their inception to April 10, 2021. Articles were included if they involved: (1) AIS patients aged between 10 and 18 years, (2) measurements of proprioceptive abilities, and (3) comparisons with non-AIS controls. Animal studies, case reports, commentaries, conference proceedings, research protocols, and reviews were excluded. Two reviewers independently conducted literature screening, data extraction, risks of bias assessments, and quality of evidence evaluations. Relevant information was pooled for meta-analyses. RESULTS: From 432 identified citations, 11 case-control studies comprising 1121 participants were included. The meta-analyses showed that AIS participants displayed proprioceptive deficits as compared to non-AIS controls. Moderate evidence supported that AIS participants showed significantly larger repositioning errors than healthy controls (pooled mean difference = 1.27 degrees, P < .01). Low evidence substantiated that AIS participants had significantly greater motion detection threshold (pooled mean difference = 1.60 degrees, P < .01) and abnormal somatosensory evoked potentials (pooled mean difference = .36 milliseconds, P = .01) than non-AIS counterparts. CONCLUSIONS: Consistent findings revealed that proprioceptive deficits occurred in AIS patients. Further investigations on the causal relationship between AIS and proprioception, and the identification of the subgroup of AIS patients with proprioceptive deficit are needed.

Dynamic Radiographs in Assessing Stability of Cervical Spine Fractures: A Multicentre Study.

BACKGROUND: In the management of a trauma patient with cervical spine injury, the need for accurate diagnostic imaging is key to ensure correct management. Different classification systems have been developed including the Subaxial Injury Classification (SLIC) system and AO cervical spine fracture classification. Through a multicentre study, we have identified a group of cases where the use of CT alone to classify fractures by either SLIC or AO score may be deficient and the use of dynamic cervical spine radiographs could help identify instability. METHODS: Three level 1 trauma centers retrospectively reviewed patients with cervical spine injuries. Cervical spine radiographs (AP and lateral) were undertaken in collar, in all patients with suspected cervical spine injury within 2 weeks, followed by reanalysis of scoring systems. RESULTS: Eleven cases were identified in total, and 72% were male with a mean age of 65 years, with approximately 54% being older than 70 years. All patients reported their pain as severe using the Visual Analogue Scale scale. The predynamic radiograph mean SLIC score was 0.73, which is in contrast to the postdynamic radiograph mean SLIC score of 6. The statistical significance (P = 0.004) was found using the Wilcoxon signed-rank test. CONCLUSION: Supine imaging eliminates the gravitational loads normally exerted on the c-spine. The cases show assumed cervical stability based on CT, but dynamic c-spine radiographs subsequently demonstrated instability. Therefore, we suggest a combination of SLIC and AO classification using radiologic imaging to classify fracture and correlate clinical symptoms with persistent neck pain, which warrants a Miami-J collar and dynamic c-spine radiograph to assess stability with re-evaluation of scoring.

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.

Biomimicking Bone-Implant Interface Facilitates the Bioadaption of a New Degradable Magnesium Alloy to the Bone Tissue Microenvironment.

The most critical factor determining the success of biodegradable bone implants is the host tissue response, which greatly depends on their degradation behaviors. Here, a new magnesium-based implant, namely magnesium-silicon-calcium (Mg-0.2Si-1.0Ca) alloy, that coordinates its biodegradation along with the bone regenerative process via a self-assembled, multilayered bone-implant interface is designed. At first, its rapid biocorrosion contributes to a burst release of Mg2+ , leading to a pro-osteogenic immune microenvironment in bone. Meanwhile, with the simultaneous intervention of Ca and Si in the secondary phases of the new alloy, a hierarchical layered calcified matrix is rapidly formed at the degrading interface that favored the subsequent bone mineralization. In contrast, pure Mg or Mg-0.2Si alloy without the development of this interface at the beginning will unavoidably induce detrimental bone loss. Hence, it is believed this biomimicking interface justifies its bioadaptability in which it can modulate its degradation in vivo and accelerate bone mineralization.

Development and validation of the scoliosis misconception scale (SMS) for assessing level of misconception of patients with adolescent idiopathic scoliosis.

BACKGROUND: Little is known about patients' understanding of adolescent idiopathic scoliosis (AIS). This paper aims to develop and validate the Scoliosis Misconception Scale (SMS) and to explore patients' level of misconception about AIS. METHODS: A total of 195 patients who were newly referred with newly diagnosed AIS were recruited to assess their levels of misconception and psychological distress before and after their first consultation with a specialist. The 17-item SMS was administered to assess patients' level of misconception about AIS and the Kessler Psychological Distress Scale (K10) was used to measure their level of distress. RESULTS: According to the Item Response Theory, all items were within the acceptable range from -3.69 to 2.39 for difficulty parameters, which determined the difficulty of the scale, while most of the items were within the acceptable range from 0.11 to 1.54 for the discrimination parameters, which determined the rate at which the probability of endorsing a correct item changes given ability levels. Internal consistency by marginal reliability was 0.66. One-sample t test revealed that participants on average scored 6.79 (SD = 2.12) before the first clinic session and 6.45 (SD = 2.51) after the first clinic session, both significantly higher than 0 [t(75) = 27.86, p < .001; t(75) = 22.43, p < .001]. CONCLUSIONS: Despite a longstanding clinical model that functions well to treat AIS, most patients still have significant misconceptions about the condition. This highlights the necessity to assess patients' knowledge level of a medical condition and potential generalisability of misconception-distress link to the forefront across other illnesses.

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

Proper immune responses are critical for successful biomaterial implantation. Here, four scales of honeycomb-like TiO2 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 TiO2 structures could significantly activate the anti-inflammatory macrophage phenotype (M2), in which the 90-nanometer sample induced the highest expression level of CD206, interleukin-4, and interleukin-10 and released the highest amount of bone morphogenetic protein-2 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 TiO2 honeycomb-like structure (90 nanometers) facilitated macrophage filopodia formation and up-regulated the Rho family of guanosine triphosphatases (RhoA, Rac1, and CDC42), which reinforced the polarization of macrophages through the activation of the RhoA/Rho-associated protein kinase signaling pathway.

Predictors of neurologic outcome after surgery for cervical ossification of the posterior longitudinal ligament differ based on myelopathy severity: a multicenter study.

OBJECTIVE: The purpose of this retrospective multicenter study was to compare prognostic factors for neurological recovery in patients undergoing surgery for cervical ossification of the posterior longitudinal ligament (OPLL) based on their presenting mild, moderate, or severe myelopathy. METHODS: The study included 372 consecutive patients with OPLL who underwent surgery for cervical myelopathy between 2006 and 2016 in East Asian countries with a high OPLL prevalence. Baseline and postoperative clinical outcomes were assessed using the Japanese Orthopaedic Association (JOA) myelopathy score and recovery ratio. Radiographic assessment included occupying ratio, cervical range of motion, and sagittal alignment parameters. Patient myelopathy was classified as mild, moderate, or severe based on the preoperative JOA score. Linear and multivariate regression analyses were performed to identify patient and surgical factors associated with neurological recovery stratified by baseline myelopathy severity. RESULTS: The mean follow-up period was 45.4 months (range 25-140 months). The mean preoperative and postoperative JOA scores and recovery ratios for the total cohort were 11.7 ± 3.0, 14.5 ± 2.7, and 55.2% ± 39.3%, respectively. In patients with mild myelopathy, only age and diabetes correlated with recovery. In patients with moderate to severe myelopathy, older age and preoperative increased signal intensity on T2-weighted imaging were significantly correlated with a lower likelihood of recovery, while female sex and anterior decompression with fusion (ADF) were associated with better recovery. CONCLUSIONS: Various patient and surgical factors are correlated with likelihood of neurological recovery after surgical treatment for cervical OPLL, depending on the severity of presenting myelopathy. Older age, male sex, intramedullary high signal intensity, and posterior decompression are associated with less myelopathy improvement in patients with worse baseline function. Therefore, myelopathy-specific preoperative counseling regarding prognosis for postoperative long-term neurological improvement should include consideration of these individual and surgical factors.