Regulatory T Cell Migration Is Dependent on Glucokinase-Mediated Glycolysis.

Migration of activated regulatory T (Treg) cells to inflamed tissue is crucial for their immune-modulatory function. While metabolic reprogramming during Treg cell differentiation has been extensively studied, the bioenergetics of Treg cell trafficking remains undefined. We have investigated the metabolic demands of migrating Treg cells in vitro and in vivo. We show that glycolysis was instrumental for their migration and was initiated by pro-migratory stimuli via a PI3K-mTORC2-mediated pathway culminating in induction of the enzyme glucokinase (GCK). Subsequently, GCK promoted cytoskeletal rearrangements by associating with actin. Treg cells lacking this pathway were functionally suppressive but failed to migrate to skin allografts and inhibit rejection. Similarly, human carriers of a loss-of-function GCK regulatory protein gene-leading to increased GCK activity-had reduced numbers of circulating Treg cells. These cells displayed enhanced migratory activity but similar suppressive function, while conventional T cells were unaffected. Thus, GCK-dependent glycolysis regulates Treg cell migration.

Bile acid-activated receptors in innate and adaptive immunity: targeted drugs and biological agents.

Bile acid-activated receptors (BARs) such as a G-protein bile acid receptor 1 and the farnesol X receptor are activated by bile acids (BAs) and have been implicated in the regulation of microbiota-host immunity in the intestine. The mechanistic roles of these receptors in immune signaling suggest that they may also influence the development of metabolic disorders. In this perspective, we provide a summary of recent literature describing the main regulatory pathways and mechanisms of BARs and how they affect both innate and adaptive immune system, cell proliferation, and signaling in the context of inflammatory diseases. We also discuss new approaches for therapy and summarize clinical projects on BAs for the treatment of diseases. In parallel, some drugs that are classically used for other therapeutic purposes and BAR activity have recently been proposed as regulators of immune cells phenotype. Another strategy consists of using specific strains of gut bacteria to regulate BA production in the intestine.

CD31 orchestrates metabolic regulation in autophagy pathways of rheumatoid arthritis.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

A unique AtSar1D-AtRabD2a nexus modulates autophagosome biogenesis in Arabidopsis thaliana.

In eukaryotes, secretory proteins traffic from the endoplasmic reticulum (ER) to the Golgi apparatus via coat protein complex II (COPII) vesicles. Intriguingly, during nutrient starvation, the COPII machinery acts constructively as a membrane source for autophagosomes during autophagy to maintain cellular homeostasis by recycling intermediate metabolites. In higher plants, essential roles of autophagy have been implicated in plant development and stress responses. Nonetheless, the membrane sources of autophagosomes, especially the participation of the COPII machinery in the autophagic pathway and autophagosome biogenesis, remains elusive in plants. Here, we provided evidence in support of a novel role of a specific Sar1 homolog AtSar1d in plant autophagy in concert with a unique Rab1/Ypt1 homolog AtRabD2a. First, proteomic analysis of the plant ATG (autophagy-related gene) interactome uncovered the mechanistic connections between ATG machinery and specific COPII components including AtSar1d and Sec23s, while a dominant negative mutant of AtSar1d exhibited distinct inhibition on YFP-ATG8 vacuolar degradation upon autophagic induction. Second, a transfer DNA insertion mutant of AtSar1d displayed starvation-related phenotypes. Third, AtSar1d regulated autophagosome progression through specific recognition of ATG8e by a noncanonical motif. Fourth, we demonstrated that a plant-unique Rab1/Ypt1 homolog AtRabD2a coordinates with AtSar1d to function as the molecular switch in mediating the COPII functions in the autophagy pathway. AtRabD2a appears to be essential for bridging the specific AtSar1d-positive COPII vesicles to the autophagy initiation complex and therefore contributes to autophagosome formation in plants. Taken together, we identified a plant-specific nexus of AtSar1d-AtRabD2a in regulating autophagosome biogenesis.

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.

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.

Systematic prediction of autophagy-related proteins using Arabidopsis thaliana interactome data.

Autophagy is a self-degradative process that is crucial for maintaining cellular homeostasis by removing damaged cytoplasmic components and recycling nutrients. Such an evolutionary conserved proteolysis process is regulated by the autophagy-related (Atg) proteins. The incomplete understanding of plant autophagy proteome and the importance of a proteome-wide understanding of the autophagy pathway prompted us to predict Atg proteins and regulators in Arabidopsis. Here, we developed a systems-level algorithm to identify autophagy-related modules (ARMs) based on protein subcellular localization, protein-protein interactions, and known Atg proteins. This generates a detailed landscape of the autophagic modules in Arabidopsis. We found that the newly identified genes in each ARM tend to be upregulated and coexpressed during the senescence stage of Arabidopsis. We also demonstrated that the Golgi apparatus ARM, ARM13, functions in the autophagy process by module clustering and functional analysis. To verify the in silico analysis, the Atg candidates in ARM13 that are functionally similar to the core Atg proteins were selected for experimental validation. Interestingly, two of the previously uncharacterized proteins identified from the ARM analysis, AGD1 and Sec14, exhibited bona fide association with the autophagy protein complex in plant cells, which provides evidence for a cross-talk between intracellular pathways and autophagy. Thus, the computational framework has facilitated the identification and characterization of plant-specific autophagy-related proteins and novel autophagy proteins/regulators in higher eukaryotes.

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.

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.

Learning-based fully automated prediction of lumbar disc degeneration progression with specified clinical parameters and preliminary validation.

BACKGROUND: Lumbar disc degeneration (LDD) may be related to aging, biomechanical and genetic factors. Despite the extensive work on understanding its etiology, there is currently no automated tool for accurate prediction of its progression. PURPOSE: We aim to establish a novel deep learning-based pipeline to predict the progression of LDD-related findings using lumbar MRIs. MATERIALS AND METHODS: We utilized our dataset with MRIs acquired from 1,343 individual participants (taken at the baseline and the 5-year follow-up timepoint), and progression assessments (the Schneiderman score, disc bulging, and Pfirrmann grading) that were labelled by spine specialists with over ten years clinical experience. Our new pipeline was realized by integrating the MRI-SegFlow and the Visual Geometry Group-Medium (VGG-M) for automated disc region detection and LDD progression prediction correspondingly. The LDD progression was quantified by comparing the Schneiderman score, disc bulging and Pfirrmann grading at the baseline and at follow-up. A fivefold cross-validation was conducted to assess the predictive performance of the new pipeline. RESULTS: Our pipeline achieved very good performances on the LDD progression prediction, with high progression prediction accuracy of the Schneiderman score (Accuracy: 90.2 ± 0.9%), disc bulging (Accuracy: 90.4% ± 1.1%), and Pfirrmann grading (Accuracy: 89.9% ± 2.1%). CONCLUSION: This is the first attempt of using deep learning to predict LDD progression on a large dataset with 5-year follow-up. Requiring no human interference, our pipeline can potentially achieve similar predictive performances in new settings with minimal efforts.

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.

Current Perspectives on Nucleus Pulposus Fibrosis in Disc Degeneration and Repair.

A growing body of evidence in humans and animal models indicates an association between intervertebral disc degeneration (IDD) and increased fibrotic elements in the nucleus pulposus (NP). These include enhanced matrix turnover along with the abnormal deposition of collagens and other fibrous matrices, the emergence of fibrosis effector cells, such as macrophages and active fibroblasts, and the upregulation of the fibroinflammatory factors TGF-ß1 and IL-1/-13. Studies have suggested a role for NP cells in fibroblastic differentiation through the TGF-ßR1-Smad2/3 pathway, inflammatory activation and mechanosensing machineries. Moreover, NP fibrosis is linked to abnormal MMP activity, consistent with the role of matrix proteases in regulating tissue fibrosis. MMP-2 and MMP-12 are the two main profibrogenic markers of myofibroblastic NP cells. This review revisits studies in the literature relevant to NP fibrosis in an attempt to stratify its biochemical features and the molecular identity of fibroblastic cells in the context of IDD. Given the role of fibrosis in tissue healing and diseases, the perspective may provide new insights into the pathomechanism of IDD and its management.

The Scoli-RISK 1 results of lower extremity motor function 5 years after complex adult spinal deformity surgery.

INTRODUCTION: Neurologic complications after complex adult spinal deformity (ASD) surgery are important, yet outcomes are heterogeneously reported, and long-term follow-up of actual lower extremity motor function is unknown. OBJECTIVE: To prospectively evaluate lower extremity motor function scores (LEMS) before and at 5 years after surgical correction of complex ASD. DESIGN: Retrospective analysis of a prospective, multicenter, international observational study. METHODS: The Scoli-RISK-1 study enrolled 272 ASD patients undergoing surgery from 15 centers around the world. Inclusion criteria were Cobb angle of > 80°, corrective osteotomy for congenital or revision deformity and/or 3-column osteotomy. Among patients with 5-year follow-up, comparisons of LEMS to baseline and within each follow-up period were made via documented neurologic exams on each patient. RESULTS: Seventy-seven (28.3%) patients had 5-year follow-up. Among these 77 patients with 5-year follow-up, rates of postoperative LEMS deterioration were: 14.3% hospital discharge, 10.7% at 6 weeks, 6.5% at 6 months, 9.5% at 2 years and 9.3% at 5 years postoperative. During the 2-5 year window, while mean LEMS did not change significantly (-0.5, p = 0.442), eight (11.1%) patients deteriorated (of which 3 were ≥ 4 motor points), and six (8.3%) patients improved (of which 2 were ≥ 4 points). Of the 14 neurologic complications, four (28.6%) were surgery-related, three of which required reoperation. While mean LEMS were not impacted in patients with a major surgery-related complication, mean LEMS were significantly lower in patients with neurologic surgery-related complications at discharge (p = 0.041) and 6 months (p = 0.008) between the two groups as well as the change from baseline to 5 years (p = 0.041). CONCLUSIONS: In 77 patients undergoing complex ASD surgery with 5-year follow-up, while mean LEMS did not change from 2 to 5 years, subtle neurologic changes occurred in approximately 1 in 5 patients (11.1% deteriorated; 8.3% improved). Major surgery-related complication did not result in decreased LEMS; however, those with neurologic surgery-related complications continued to have decreased lower extremity motor function at 5 years postoperative. These results underscore the importance of long-term follow-up to 5 years, using individual motor scores rather than group averages, and comparing outcomes to both baseline and last follow-up.

Are Higher Global Alignment and Proportion Scores Associated With Increased Risks of Mechanical Complications After Adult Spinal Deformity Surgery? An External Validation.

BACKGROUND: The Global Alignment and Proportion (GAP) score, based on pelvic incidence-based proportional parameters, was recently developed to predict mechanical complications after surgery for spinal deformities in adults. However, this score has not been validated in an independent external dataset. QUESTIONS/PURPOSES: After adult spinal deformity surgery, is a higher GAP score associated with (1) an increased risk of mechanical complications, defined as rod fractures, implant-related complications, proximal or distal junctional kyphosis or failure; (2) a higher likelihood of undergoing revision surgery to treat a mechanical complication; and (3) is a lower (more proportioned) GAP score category associated with better validated outcomes scores using the Oswestry Disability Index (ODI), Scoliosis Research Society-22 (SRS-22) and the Short Form-36 questionnaires? METHODS: A total of 272 patients who had undergone corrective surgeries for complex spinal deformities were enrolled in the Scoli-RISK-1 prospective trial. Patients were included in this secondary analysis if they fulfilled the original inclusion criteria by Yilgor et al. From the original 272 patients, 14% (39) did not satisfy the radiographic inclusion criteria, the GAP score could not be calculated in 14% (37), and 24% (64) did not have radiographic assessment at postoperative 2 years, leaving 59% (159) for analysis in this review of data from the original trial. A total of 159 patients were included in this study,with a mean age of 58 ± 14 years at the time of surgery. Most patients were female (72%, 115 of 159), the mean number of levels involved in surgery was 12 ± 4, and three-column osteotomy was performed in 76% (120 of 159) of patients. The GAP score was calculated using parameters from early postoperative radiographs (between 3 and 12 weeks) including pelvic incidence, sacral slope, lumbar lordosis, lower arc lordosis and global tilt, which were independently obtained from a computer software based on centralized patient radiographs. The GAP score was categorized as proportional (scores of 0 to 2), moderately disproportional (scores of 3 to 6), or severely disproportional (scores higher than 7 to 13). Receiver operating characteristic area under curve (AUC) was used to assess associations between GAP score and risk of mechanical complications and risk of revision surgery. An AUC of 0.5 to 0.7 was classified as "no or low associative power", 0.7 to 0.9 as "moderate" and greater than 0.9 as "high". We analyzed differences in validated outcome scores between the GAP categories using Wilcoxon rank sum test. RESULTS: At a minimum of 2 years' follow-up, a higher GAP score was not associated with increased risks of mechanical complications (AUC = 0.60 [95% CI 0.50 to 0.70]). A higher GAP score was not associated with a higher likelihood of undergoing a revision surgery to treat a mechanical complication (AUC = 0.66 [95% 0.53 to 0.78]). However, a moderately disproportioned GAP score category was associated with better SF-36 physical component summary score (36 ± 10 versus 40 ± 11; p = 0.047), better SF-36 mental component summary score (46 ± 13 versus 51 ± 12; p = 0.01), better SRS-22 total score (3.4 ± 0.8 versus 3.7 ± 0.7, p = 0.02) and better ODI score (35 ± 21 versus 25 ± 20; p = 0.003) than severely disproportioned GAP score category. CONCLUSION: Based on the findings of this external validation study, we found that alignment targets based on the GAP score alone were not associated with increased risks of mechanical complications and mechanical revisions in patients with complex adult spinal disorders. Parameters not included in the original GAP score needed to be considered to reduce the likelihood of mechanical complications. LEVEL OF EVIDENCE: Level III, diagnostic study.

The first magnetically controlled growing rod (MCGR) in the world - lessons learned and how the identified complications helped to develop the implant in the past decade: case report.

BACKGROUND: The first magnetically controlled growing rod (MCGR) was implanted in 2009. Since then multiple complications have been identified that have helped drive the development of the MCGR and its surgery. The aim of this report is to illustrate how identified complications in the first MCGR helped with developments in the past decade and to report a unique failure mechanism with stud fracture close to the barrel opening. CASE PRESENTATION: A 5-year old girl with a scoliosis of 58.5 degrees at T1-9 and 72.8 degrees at T9-L4 had a single MCGR inserted and anchored at T3-4 and L3-4. At postoperative 13 months the MCGR was noted to have lost of distraction between lengthening episodes due to unrestricted turning of the internal magnet. To prevent further loss of distraction, an external magnet was placed outside the skin to prevent the magnet from turning back. The overall balance was suboptimal and after the rod was fully distracted, proximal junctional kyphosis occurred. Subsequently, the MCGR was modified with an internal keeper plate to prevent loss of distraction and a dual set of these rods were implanted when the patient was 9 years old. Extension proximally to C7-T1 was done to manage the proximal junctional kyphosis. Her spinal balance improved and distractions continued. She subsequently developed add-on below and the piston rod was not aligned with the actuator. The lumbar spine was also observed to have autofusion. She subsequently had final fusion surgery performed at the age of 15 from C7-L4 leaving a residual tilt below to avoid fusion to the pelvis. The final extracted rod on the left side indicated the "crooked rod sign" on X-ray and rod dissections revealed a new failure mechanism of stud fracture close to the barrel opening. Body fluids and tissue may infiltrate the rod despite no obvious deformation or fractures resulting in hastened wearing of the threads. CONCLUSIONS: There are various complications associated with MCGRs that are related to rod design and surgical inexperience. Repeated rod stalling is not recommended with potential stud fracture and "crooked rod sign". Rotor stalling and thread wearing which indicates rod failure still require solutions.

Multidisciplinary programme for rehabilitation of chronic low back pain - factors predicting successful return to work.

BACKGROUND: There are no clear indicators for predicting return to work for patients with chronic low back pain (LBP). We aim to report the outcomes of a 14-week multidisciplinary programme targeting patients with chronic LBP who failed conventional physiotherapy to provide functional rehabilitation. Also, this study will identify factors predicting successful return to work (RTW). METHODS: A collected cohort of patients with chronic LBP was consecutively enrolled into the programme from 1996 to 2014. All recruited patients failed to RTW despite at least 3 months of conservative treatment. Patient underwent weekly multidisciplinary sessions with physiotherapists, occupational therapists and clinical psychologists. Patient perceived function was considered the primary outcome of the programme. Patients were assessed for their sitting, standing and walking tolerance. Oswestry Disability Index (ODI) and Spinal Function Sort Score (SFSS) were used to assess patient perceived disability. RESULTS: One hundred and fifty-eight patients were recruited. After the programme, statistically significant improvement was found in ODI (47.5 to 45.0, p = 0.01) and SFSS (98.0 to 109.5, p <  0.001). There was statistically significant improvement (p <  0.01) in sitting, standing, walking tolerance and straight leg raise tests. 47.4% of the patients were able to meet their work demand. Multivariate logistic regression model (R2 = 59.5%, χ2 (9) = 85.640, p <  0.001) demonstrated that lower initial job demand level and higher patient-perceived back function correlated with greater likelihood of returning to work. CONCLUSION: The results of this study may support the use of this multidisciplinary programme to improve patient function and return to work.

Magnetically controlled growing rods in early onset scoliosis: radiological results, outcome, and complications in a series of 22 patients.

INTRODUCTION: Magnetically controlled growing rods (MCGR) for the surgical treatment of early onset scoliosis (EOS) allow non-invasive outpatient based distractions during spinal growth. The purpose of this study is to present the results of a single center case series of 22 patients, evaluate the effect of MCGR treatment on the development of spino-pelvic parameters during growth, and report initial outcomes after end of treatment. MATERIALS AND METHODS: Prospectively collected data of 22 EOS patients with MCGR treatment has been analyzed. The following radiological parameters were measured before index surgery, after index surgery, 1 year after index surgery, and at last follow-up: Cobb angle of the major curves, thoracic kyphosis (TK), lumbar lordosis (LL), sagittal vertical axis (SVA), pelvic incidence (PI), pelvic tilt (PT), and sacral slope (SS). Mean age at index surgery was 9.5 years (range: 4-14 years). Mean length of follow-up was 47.6 months (range: 25-121 months). Etiology of diagnosis was idiopathic in 14 patients, associated with neurofibromatosis in 2 patients, and neuromuscular or syndromic in 6 patients. RESULTS: Mean Cobb angle of the major curve was 57° preoperatively and 29° at last follow-up (p < 0.0005). Mean TK was 20.1° preoperatively and 20° at last follow-up (p > 0.05). Mean LL was 52.8° preoperatively and 53.2° at last follow-up (p > 0.05). Mean PI was 43.2° preoperatively and 46.3° at last follow-up (p > 0.05). Mean PT was 4.1° preoperatively and 5.8° at last follow-up (p > 0.05). Mean SS was 39.2° preoperatively and 41.7° at last follow-up (p > 0.05). 14 patients finished treatment: nine received final fusion and five received rod removal without fusion. Twelve complications occurred: one deep wound infection, six patients developed proximal junctional kyphosis (PJK), one rod fracture, two rods failed to distract, one deformity progressed after rod removal and required spinal fusion, and one patient developed autofusion of the spine prior to end of treatment. CONCLUSION: MCGR treatment is able to control deformity progression. Complication rate was 54.5%. Sagittal balance was not altered and treatment does not seem to have a negative impact on the development of spino-pelvic parameters during growth. Optimal end of treatment for the individual patient still has to be defined.

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

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.

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

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