Scoliosis and kyphosis in blue-spotted and marbled flathead fish associated with a Myxobolus acanthogobii-like parasite.

Spinal deformities in finfish have the potential to impact aquaculture industries and wild populations by increasing morbidity, mortality, and reducing growth rates. Myxobolus acanthogobii has been implicated in causing scoliosis and lordosis in various aquatic species in Japan. We investigated 4 cases of spinal deformity in 2 flathead (Platycephalus) species that were submitted to the Elizabeth Macarthur Agricultural Institute (EMAI) in New South Wales (NSW), Australia, between 2015 and 2021. Flathead are commercially significant species that are popular among Australian consumers, and are also sought-after species targeted by recreational fishers. Gross deformities are concerning to the community and may impact the quality and quantity of specimens available for consumption. Three blue-spotted flathead (P. caeruleopunctatus) and one marbled flathead (P. marmoratus) were submitted, all with marked scoliosis and kyphosis; 1-2-mm cysts were present on the dorsum of the brain, most often over the optic lobe or cerebellum. Cytology and differential interference microscopy of cyst material revealed numerous oval spores, x̄ 14 ± SD 0.75 µm × x̄ 11.5 ± SD 0.70 µm, with 2 pyriform polar capsules, the morphology of which is consistent with a Myxobolus sp. PCR assay and 18S rDNA sequencing of the cyst material identified a Myxobolus sp. with 96% identity to M. acanthogobii. The identification of this Myxobolus sp. confirms the presence of parasites with the potential to cause spinal deformity in significant aquatic species in NSW waterways.

BMP6 participates in the pathogenesis of adolescent idiopathic scoliosis by regulating osteopenia.

Adolescent idiopathic scoliosis (AIS) is a complex disease characterized by three-dimensional structural deformities of the spine. Its pathogenesis is associated with osteopenia. Bone-marrow-derived mesenchymal stem cells (BMSCs) play an important role in bone metabolism. We detected 1919 differentially expressed mRNAs and 744 differentially expressed lncRNAs in BMSCs from seven patients with AIS and five patients without AIS via high-throughput sequencing. Multiple analyses identified bone morphogenetic protein-6 (BMP6) as a hub gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS. BMP6 expression was found to be decreased in AIS and its knockdown in human BMSCs significantly altered the degree of osteogenic differentiation. Additionally, CAP1-217 has been shown to be a potential upstream regulatory molecule of BMP6. We showed that CAP1-217 knockdown downregulated the expression of BMP6 and the osteogenic differentiation of BMSCs. Simultaneously, knockout of BMP6 in zebrafish embryos significantly increased the deformity rate. The findings of this study suggest that BMP6 is a key gene that regulates the abnormal osteogenic differentiation of BMSCs in AIS via the CAP1-217/BMP6/RUNX2 axis.

Reduced volume and altered composition of paraspinal muscles in Marfan syndrome: A retrospective cohort study.

Retrospective cohort study. Spinal deformities in patients with Marfan syndrome (MFS) are distinct from those in patients with idiopathic scoliosis (IS). It is more prone to progression and more likely to present with sagittal malalignment than IS. However, the etiology of this characteristic spinal deformity in MFS remains unclear. This study aimed to determine the spinal musculature characteristics in patients with MFS on the hypothesis that the paraspinal muscles of patients with MFS would be qualitatively or quantitatively different from those of patients with IS. Seventeen consecutive patients with MFS aged 25 years or younger undergoing surgery for scoliosis in our hospital were compared with age- and sex-matched patients with IS undergoing surgery for scoliosis. The body size-adjusted relative cross-sectional area (rCSA), fatty infiltration ratio (FI%), and relative functional cross-sectional area (rFCSA) of the psoas muscles (PM) and paravertebral muscles (PVM) at L3/4 and L4/5 were measured using preoperative T2-weighted magnetic resonance imaging. Functional CSA was defined as total CSA minus the fatty infiltration area of each muscle and rFCSA was calculated as the body size-adjusted functional CSA. The rCSA of the PM at L3/4 and L4/5 was significantly smaller in the MFS group than in the IS group (L3/4, P = .021; L4/5, P = .002). The FI% of the PM at L4/5 was significantly higher in the MFS group (P = .044). Consequently, the rFCSA of the PM at L3/4 and L4/5 and the rFCSA of the PVM at L3/4 in the MFS group were significantly smaller than those in the IS group (PM at L3/4, P = .021; PM at L4/5, P = .001; PVM at L3/4, P = .025). Compared with patients with IS, patients with MFS exhibited significantly decreased body-size-adjusted CSA of the PM and reduced body-size-adjusted functional CSA of the PVM and PM. These findings may partially explain the characteristics of distinctive spinal deformities in patients with MFS.

Effects of spinal deformities on lung development in children: a review.

Scoliosis before the age of 5 years is referred to as early-onset scoliosis (EOS). While causes may vary, EOS can potentially affect respiratory function and lung development as children grow. Moreover, scoliosis can lead to thoracic insufficiency syndrome when aggravated or left untreated. Therefore, spinal thoracic deformities often require intervention in early childhood, and solving these problems requires new methods that include the means for both deformity correction and growth maintenance. Therapeutic strategies for preserving the growing spine and thorax include growth rods, vertically expandable titanium artificial ribs, MAGEC rods, braces and casts. The goals of any growth-promoting surgical strategy are to alter the natural history of cardiorespiratory development, limit the progression of underlying spondylarthrosis deformities and minimize negative changes in spondylothorax biomechanics due to the instrumental action of the implant. This review further elucidates EOS in terms of its aetiology, pathogenesis, pathology and treatment.

Drug-induced Fanconi syndrome in patients with kidney allograft transplantation.

Background: Patients after kidney transplantation need to take long-term immunosuppressive and other drugs. Some of these drug side effects are easily confused with the symptoms of Fanconi syndrome, resulting in misdiagnosis and missed diagnosis, and causing serious consequences to patients. Therefore, improving awareness, early diagnosis and treatment of Fanconi syndrome after kidney transplantation is critical. Methods: This retrospective study analyzed 1728 cases of allogeneic kidney transplant patients admitted to the Second Xiangya Hospital of Central South University from July 2016 to January 2021. Two patients with Fanconi syndrome secondary to drugs, adefovir dipivoxil (ADV) and tacrolimus, were screened. We summarized the diagnostic process, clinical data, and prognosis. Results: The onset of Fanconi syndrome secondary to ADV after renal transplantation was insidious, and the condition developed after long-term medication (>10 years). It mainly manifested as bone pain, osteomalacia, and scoliosis in the late stage and was accompanied by obvious proximal renal tubular damage (severe hypophosphatemia, hypokalemia, hypocalcemia, hypouricemia, glycosuria, protein urine, acidosis, etc.) and renal function damage (increased creatinine and azotemia). The pathological findings included mitochondrial swelling and deformity in renal tubular epithelial cells. The above symptoms and signs were relieved after drug withdrawal, but the scoliosis was difficult to rectify. Fanconi syndrome secondary to tacrolimus has a single manifestation, increased creatinine, which can be easily confused with tacrolimus nephrotoxicity. However, it is often ineffective to reduce the dose of tacrolomus, and proximal renal failure can be found in the later stage of disease development. There was no abnormality in the bone metabolism index and imageological examination findings. The creatinine level decreased rapidly, the proximal renal tubule function returned to normal, and no severe electrolyte imbalance or urinary component loss occurred when the immunosuppression was changed from tacrolimus to cyclosporine A. Conclusions: For the first time, drug-induced Fanconi syndrome after kidney transplantation was reported. These results confirmed that the long-term use of ADV or tacrolimus after kidney transplantation may have serious consequences, some of which are irreversible. Greater understanding of Fanconi syndrome after kidney transplantation is necessary in order to avoid incorrect and missed diagnosis.

Comparison of multifidus degeneration between scoliosis and lumbar disc herniation.

OBJECTIVE: To assess and compare the pathological and radiological outcomes of multifidus degeneration in scoliosis and lumbar disc herniation patients. METHODS: We performed a retrospective review on 24 patients with scoliosis and 26 patients with lumbar disc herniation (LDH) in the Third Hospital of Hebei Medical University from January 2017 to March2021. The patients were divided into scoliosis group and LDH group according to the treatment. The MRI fatty infiltration rate (FIR) of multifidus and strength of back muscle were calculated to evaluate muscle condition. Multifidus biopsy samples were obtained during surgery in the affected side at L4 or L5 segment in LDH group and on the concavity side of apical vertebrae in scoliosis group. The biopsy fatty infiltration degree (FID) and FIR in two groups, the FIR of affected and unaffected side in LDH group, and the FIR of concavity and convexity side in scoliosis group were compared. The correlation between concavity-convexity FIR difference and cobb angle in scoliosis group, back muscle strength and FIR in LDH group, FID and FIR in both groups was calculated respectively. RESULTS: The FIR was higher in scoliosis group than in LDH group, higher in concavity side than convexity side in scoliosis group (both P < 0.05). The FID was higher in scoliosis group than in LDH group (P < 0.05). No significant difference was found between affected and unaffected side in LDH group (P > 0.05). There was a positive correlation between concavity-convexity FIR difference and cobb angle, FIR and FID (both P < 0.01). There was a negative correlation between back muscle strength and FIR (P < 0.01). The biopsy staining results showed that both two groups were found the existence of rimmed vacuoles, nuclear aggregation, and abnormal enzyme activity, indicating that the scoliosis and LDH may be associated with myogenic diseases. CONCLUSION: The scoliosis patients showed more serious fatty infiltration than LDH patients and rare pathological findings were found in both diseases.

Osteoid osteoma: A pathology that is confused with ankylosing spondylitis.

Osteoid osteoma is a small and benign osteoblastic tumor seen typically in males aged below 25 years. Although it is rarely seen in the vertebrae, it should be considered in the differential diagnosis of spondyloarthropathies, especially for those which occur in young people, along with back and lumbar pain, which increases during the night. Early diagnosis is essential to alle-viate symptoms and prevent the risk of structural spinal deformities, such as scoliosis. Here, we describe the case of a 28-year-old man with vertebral osteoid osteoma that was misdiagnosed as ankylosing spondylitis and provide a detailed account of the radiological investigations.

Using deep transfer learning to detect scoliosis and spondylolisthesis from x-ray images.

Recent years have witnessed wider prevalence of vertebral column pathologies due to lifestyle changes, sedentary behaviors, or injuries. Spondylolisthesis and scoliosis are two of the most common ailments with an incidence of 5% and 3% in the United States population, respectively. Both of these abnormalities can affect children at a young age and, if left untreated, can progress into severe pain. Moreover, severe scoliosis can even lead to lung and heart problems. Thus, early diagnosis can make it easier to apply remedies/interventions and prevent further disease progression. Current diagnosis methods are based on visual inspection by physicians of radiographs and/or calculation of certain angles (e.g., Cobb angle). Traditional artificial intelligence-based diagnosis systems utilized these parameters to perform automated classification, which enabled fast and easy diagnosis supporting tools. However, they still require the specialists to perform error-prone tedious measurements. To this end, automated measurement tools were proposed based on processing techniques of X-ray images. In this paper, we utilize advances in deep transfer learning to diagnose spondylolisthesis and scoliosis from X-ray images without the need for any measurements. We collected raw data from real X-ray images of 338 subjects (i.e., 188 scoliosis, 79 spondylolisthesis, and 71 healthy). Deep transfer learning models were developed to perform three-class classification as well as pair-wise binary classifications among the three classes. The highest mean accuracy and maximum accuracy for three-class classification was 96.73% and 98.02%, respectively. Regarding pair-wise binary classification, high accuracy values were achieved for most of the models (i.e., > 98%). These results and other performance metrics reflect a robust ability to diagnose the subjects' vertebral column disorders from standard X-ray images. The current study provides a supporting tool that can reasonably help the physicians make the correct early diagnosis with less effort and errors, and reduce the need for surgical interventions.

Scoliosis: an unusual clinical presentation of paraspinal ganglioneuroma.

PURPOSE: To comprehensively present the clinical characteristics and treatment strategies in patients with scoliosis secondary to ganglioneuroma (S-GN). METHODS: Six patients with S-GN treated surgically at a median age of 12 years were retrospectively reviewed and the median follow-up period was 6 years (4-14 years). The radiological features of GN and the associated scoliosis were evaluated. The surgical strategies and the corresponding outcomes were investigated. RESULTS: All patients had a delayed diagnosis age of GN than scoliosis (12 vs. 9 years). GN was located at the posterior mediastinum in four patients (66.7%) and at retroperitoneum in two, respectively. Tumor occupancies were frequently detected on the X-ray films for four patients (66.7%), being uniformly on the convexity of the main curve. All patients complained of rapid progressive deformities during the growth period. Five patients (83.3%) received total tumor resections, one accepted partial resection. Deformity correction was implemented for all patients with an average rate of 66.4% on the main curve. No recurrence of the GN was detected for all totally tumor-resected patients at the latest follow-up. CONCLUSION: S-GN is often misdiagnosed clinically. Paravertebral mass neighboring the apex of scoliosis can be meticulously detected from the X-ray films. Total tumor resection should be aggressively performed if possible. The deformity correction could be satisfactorily obtained and the risk of recurrence of the GN was relatively low.

Altered mechanotransduction in adolescent idiopathic scoliosis osteoblasts: an exploratory in vitro study.

Adolescent idiopathic scoliosis (AIS) is the most prevalent pediatric spinal deformity. We previously demonstrated elongated cilia and an altered molecular mechanosensory response in AIS osteoblasts. The purpose of this exploratory study was to characterize the mechanosensory defect occurring in AIS osteoblasts. We found that cilia length dynamics in response to flow significantly differ in AIS osteoblasts compared to control cells. In addition, strain-induced rearrangement of actin filaments was compromised resulting in a failure of AIS osteoblasts to position or elongate in function of the bidirectional-applied flow. Contrary to control osteoblasts, fluid flow had an inhibitory effect on AIS cell migration. Moreover, flow induced an increase in secreted VEGF-A and PGE2 in control but not AIS cells. Collectively our data demonstrated that in addition to the observed primary cilium defects, there are cytoskeletal abnormalities correlated to impaired mechanotransduction in AIS. Thus, we propose that the AIS etiology could be a result of generalized defects in cellular mechanotransduction given that an adolescent growing spine is under constant stimulation for growth and bone remodeling in response to applied mechanical forces. Recognition of an altered mechanotransduction as part of the AIS pathomechanism must be considered in the conception and development of more effective bracing treatments.

Extended phenotypes of PIEZO1-related lymphatic dysplasia caused by two novel compound heterozygous variants.

Defects in the PIEZO1 gene cause lymphatic dysplasia in an autosomal recessive manner, mostly by loss-of-function variants. Moreover, since 2019, the role of PIEZO1 in bone formation has been established, but there have been no PIEZO1-related cases presenting definite skeletal involvement to date. A 21-year-old male with primary lymphatic dysplasia had some other distinctive clinical features, including multiple fracture history during infancy, thoracolumbar scoliosis, short stature, and left-sided facial bone hypoplasia. We analyzed the whole exome of the patient and found two novel pathogenic variants of PIEZO1 in trans: a 93.7 kb heterozygous deletion (chr16:88,782,477-88,876,207; exon 1-50) and c.2858G>A (p.Arg953His). Sanger sequencing validated the deletion with breakpoints, and each variant was inherited from a different parent. This study presented an extremely rare case of a patient with lymphatic dysplasia caused by compound heterozygous variants of PIEZO1, along with additional clinical manifestations including several skeletal phenotypes.

The Clinical and Genotypic Spectrum of Scoliosis in Multiple Pterygium Syndrome: A Case Series on 12 Children.

BACKGROUND: Multiple pterygium syndrome (MPS) is a genetically heterogeneous rare form of arthrogryposis multiplex congenita characterized by joint contractures and webbing or pterygia, as well as distinctive facial features related to diminished fetal movement. It is divided into prenatally lethal (LMPS, MIM253290) and nonlethal (Escobar variant MPS, MIM 265000) types. Developmental spine deformities are common, may present early and progress rapidly, requiring regular fo llow-up and orthopedic management. METHODS: Retrospective chart review and prospective data collection were conducted at three hospital centers. Molecular diagnosis was confirmed with whole exome or whole genome sequencing. RESULTS: This case series describes the clinical features and scoliosis treatment on 12 patients from 11 unrelated families. A molecular diagnosis was confirmed in seven; two with MYH3 variants and five with CHRNG. Scoliosis was present in all but our youngest patient. The remaining 11 patients spanned the spectrum between mild (curve ≤ 25°) and malignant scoliosis (≥50° curve before 4 years of age); the two patients with MYH3 mutations presented with malignant scoliosis. Bracing and serial spine casting appear to be beneficial for a few years; non-fusion spinal instrumentation may be needed to modulate more severe curves during growth and spontaneous spine fusions may occur in those cases. CONCLUSIONS: Molecular diagnosis and careful monitoring of the spine is needed in children with MPS.

Risk factors for screw loosening in patients with adult degenerative scoliosis: the importance of paraspinal muscle degeneration.

BACKGROUND: Paraspinal muscle is an important component to maintain spinal stability. But the relationship between the degeneration of paraspinal muscle and postoperative screw loosening in patients with adult degenerative scoliosis has not been studied. The objective of this study was to investigate risk factors for screw loosening in patients with adult degenerative scoliosis, including paraspinal muscle degeneration. METHODS: We investigated 93 patients with adult degenerative scoliosis who underwent spinal interbody fusion and pedicle screw fixation surgery. The lateral curvature was located in the lumbar spine and the follow-up time was ≥ 2 years. The patients were divided into loosening and non-loosening groups. Screw loosening was defined as a 1-mm or wider circumferential radiolucent line around the pedicle screw. We checked the cross-sectional area of paraspinal muscles, spinopelvic parameters, bone mineral density, number of fusion segment, and other factors. The potential risk factors for screw loosening were investigated by using binary logistical regression analysis. RESULTS: Fifty-seven patients showed screw loosening, which is 63.4% of total. Compared with patients in the non-loosening group, the cross-sectional area of erector spinae and psoas major muscle at L5 level were significantly smaller in patients with screw loosening (P < 0.05). Among these factors, the number of fused segments and relative erector spinae total cross-sectional area were independent risk factors for screw loosening. CONCLUSIONS: The degeneration of paraspinal muscle and the increase of fusion segment were independent factors for screw loosening in patients with adult degenerative scoliosis.

Transiency of postoperative cervical kyphosis seen after surgical correction of sagittal malalignment in adult spinal deformity patients.

OBJECTIVE: In this study, we evaluated factors affecting changes in cervical lordosis after deformity correction and during follow-up period in adult spinal deformity (ASD) patients with severe sagittal imbalance. METHODS: Seventy-nine patients, with an average age of 71.6 years, who underwent long-segment fixation from T10 to S1 with sacropelvic fixation were included. We performed a comparative analysis of the radiographic parameters after surgery (Post) and at the last follow-up (Last). We calculated the Pearson's correlation coefficient and performed multilinear regression analysis to predict independent parameters for Post and Last cervical lordosis (CL), T1 slope (T1S), and thoracic kyphosis (TK). RESULTS: Hyperlordotic changes of -23.3° in CL before surgery was reduced to -7° after surgery, and Last CL had increased to -15.3°. T1S was reduced from 27° before surgery to 14.4° after surgery and had increased to 18.8° at the last follow-up. Through multilinear regression analysis, we found that Post CL and T1S were more significantly affected by the amount of LL correction (p = .045 and .049). The effect of Last T1S was significantly associated with the Last CL; the effect of Last TK, with the Last T1S; and the effect of Post PI-LL, with the Last TK (p < .05). CONCLUSION: The postoperative kyphotic change in CL in ASD patients with preoperative cervical hyperlordosis is not permanent and is affected by drastic LL correction and SVA restoration. To achieve spinopelvic harmony proportional to the difference in LL relative to PI, TK becomes modified over time to increase T1S and CL, in an effort to achieve optimal spine curvature.

Methylation of Estrogen Receptor 1 Gene in the Paraspinal Muscles of Girls with Idiopathic Scoliosis and Its Association with Disease Severity.

Idiopathic scoliosis (IS) is a multifactorial disease with epigenetic modifications. Tissue dependent and differentially methylated regions (T-DMRs) may regulate tissue-specific expression of the estrogen receptor 1 gene (ESR1). This study aimed to analyze methylation levels within T-DMR1 and T-DMR2 and its concatenation with ESR1 expression of IS patients. The study involved 87 tissue samples (deep paravertebral muscles, both on the convex and the concave side of the curve, and from back superficial muscles) from 29 girls who underwent an operation due to IS. Patient subgroups were analyzed according to Cobb angle ≤70° vs. >70°. Methylation was significantly higher in the superficial muscles than in deep paravertebral muscles in half of the T-DMR1 CpGs and all T-DMR2 CpGs. The methylation level correlated with ESR1 expression level on the concave, but not convex, side of the curvature in a majority of the T-DMR2 CpGs. The T-DMR2 methylation level in the deep paravertebral muscles on the curvature's concave side was significantly lower in patients with a Cobb angle ≤70° in four CpGs. DNA methylation of the T-DMRs is specific to muscle tissue location and may be related to ESR1 expression regulation. Additionally, the difference in T-DMR2 methylation may be associated with IS severity.

Scoliosis in Friedreich's ataxia: longitudinal characterization in a large heterogeneous cohort.

OBJECTIVE: The objective of this study was to characterize the incidence and progression of scoliosis in the natural history of Friedreich's ataxia (FRDA) and document the factors leading to the requirement for corrective surgery. METHODS: Data on the prevalence of scoliosis and scoliosis surgery from up to 17 years of follow-up collected during a large natural history study in FRDA (1116 patients at 4928 visits) were summarized descriptively and subjected to time to event analyses. RESULTS: Well over 90% of early or typical FRDA patients (as determined by age of onset) developed intermediate to severe scoliosis, while patients with a later onset (>14 years) had no or much lower prevalence of scoliosis. Diagnosis of scoliosis occurs during the onset of ataxia and in rare cases even prior to that. Major progression follows throughout the growth phase and puberty, leading to the need for surgical intervention in more than 50% of individuals in the most severe subgroup. The youngest patients appear to delay surgery until the end of the growth period, leading to further progression before surgical intervention. Age of onset of FRDA before or after reaching 15 years sharply separated severe and relatively mild incidence and progression of scoliosis. INTERPRETATION: Scoliosis is an important comorbidity of FRDA. Our comprehensive documentation of scoliosis progression in this natural history study provides a baseline for comparison as novel treatments become available.

The Clinical and Radiologic Outcomes of Patients With Different 3-Dimensional Hemivertebra Morphologies Undergoing Posterior-Only Hemivertebra Resection and Fusion.

OBJECTIVE: To compare the clinical and radiologic outcomes of patients with different 3-dimensional (3D) hemivertebra morphologies undergoing posterior-only hemivertebra resection and fusion. METHODS: The files of patients with congenital scoliosis (CS) due to single hemivertebra undergoing posterior-only hemivertebra resection and fusion from January 2010 to January 2018 were reviewed. After evaluating the 3D computed tomography images, CS patients were divided into a unison hemivertebra group and a discordant hemivertebra group. Clinical outcomes, radiologic outcomes, and incidence of complications were compared. RESULTS: A total of 42 consecutive patients with CS patients due to a single hemivertebra undergoing posterior-only hemivertebra resection and fusion were included in this study. The Cobb angle of the segmental curve was significantly improved postoperatively and at the last follow-up in both groups (all P < 0.05). At both postoperation and the last follow-up, no significant differences were found in the incidence of complications, Cobb angle of the segmental curve, correction rate of the segmental curve, or other radiologic outcomes between the unison hemivertebra group and discordant hemivertebra group (all P > 0.05). Compared with the unison hemivertebra group, increased operation time (P = 0.006) and intraoperative blood loss (P = 0.037) were found in the discordant hemivertebra group. CONCLUSIONS: For CS patients with unison hemivertebra or discordant hemivertebra, satisfactory radiologic results were obtained by posterior-only hemivertebra resection and fusion. In terms of surgery, the radiologic outcomes of discordant hemivertebra patients were similar to those of unison hemivertebra patients, but discordant hemivertebrae could easily result in longer operation time and more intraoperative blood loss.

Influence of curve morphology and location on the efficacy of rigid conservative treatment in patients with adolescent idiopathic scoliosis.

AIMS: The aim of the present study was to answer the question whether curve morphology and location have an influence on rigid conservative treatment in patients with adolescent idiopathic scoliosis (AIS). METHODS: We retrospectively analyzed AIS in 127 patients with single and double curves who had been treated with a Chêneau brace and physiotherapeutic specific exercises (B-PSE). The inclusion criteria were the presence of structural major curves ≥ 20° and < 50° (Risser stage 0 to 2) at the time when B-PSE was initiated. The patients were divided into two groups according to the outcome of treatment: failure (curve progression to ≥ 45° or surgery) and success (curve progression < 45° and no surgery). The main curve type (MCT), curve magnitude, and length (overall, above and below the apex), apical rotation, initial curve correction, flexibility, and derotation by the brace were compared between the two groups. RESULTS: In univariate analysis treatment failure depended significantly on: 1) MCT (p = 0.008); 2) the apical rotation of the major curve before (p = 0.007) and during brace treatment (p < 0.001); 3) the initial and in-brace Cobb angles of the major (p = 0.001 and p < 0.001, respectively) and minor curves (p = 0.015 and p = 0.002); 4) major curve flexibility (p = 0.005) and the in-brace curve correction rates (major p = 0.008, minor p = 0.034); and 5) the length of the major curve (LoC) above (p < 0.001) and below (p = 0.002) the apex. Furthermore, MCT (p = 0.043, p = 0.129, and p = 0.017 in MCT comparisons), LoC (upper length p = 0.003, lower length p = 0.005), and in-brace Cobb angles (major p = 0.002, minor p = 0.027) were significant in binary logistic regression analysis. CONCLUSION: Curve size, location, and morphology were found to influence the outcome of rigid conservative treatment of AIS. These findings may improve future brace design and patient selection for conservative treatment. Cite this article: Bone Joint J 2021;103-B(2):373-381.

Targeting miR-10a-5p/IL-6R axis for reducing IL-6-induced cartilage cell ferroptosis.

BACKGROUND: Intervertebral disc degeneration (IDD) causes lower back pain, and is often accompanied with robust inflammation. However, whether inflammation plays a role in IDD remains controversial, and the mechanism is ill-elucidated. METHODS: Cartilage specimens from patients with scoliosis (control) and IDD were examined for IL-6 and its receptor expression by qPCR and western blot. Primary human articular chondrocyte was employed as a model for in vitro assessment of IL-6 effects in cell viability, cellular oxidative stress and iron homeostasis by MTT, MDA, ROS and Iron Colorimetric assays. The underlying mechanism was explored by qPCR, western blot, RIP in combination with bioinformatics analysis. RESULTS: We found in this study that IL-6 and its receptor were aberrantly expressed in cartilage tissues of IDD patients. IL-6 down-regulated miR-10a-5p, which subsequently derepressed IL-6R expression. IL-6 exposure caused cartilage cell ferroptosis by inducing cellular oxidative stress and disturbing iron homeostasis. Overexpressing miR-10a-5p suppressed IL-6R expression, and partially abolished IL-6-induced ferroptosis. CONCLUSION: Results from current study suggests that inflammatory cytokine IL-6 appeared in IVD aggravates its degeneration by inducing cartilage cell ferroptosis. This is caused partially by inhibiting miR-10a-5p and subsequently derepressing IL-6R signaling pathway. Our study provides a novel mechanism explaining inflammatory cytokine-caused cartilage cell death in degenerative IVD, and makes IL-6/miR-10a-5p/IL-6R axis a potential therapeutic target for intervention of IDD.

A novel homozygous frameshift mutation in the DCC gene in a Pakistani family with autosomal recessive horizontal gaze palsy with progressive scoliosis-2 with impaired intellectual development.

Horizontal Gaze Palsy with Progressive Scoliosis-2 with Impaired Intellectual Development (HGPPS2) is a rare congenital disorder characterized by absence of conjugate horizontal eye movements, and progressive scoliosis developing in childhood and adolescence. We report three new patients with HGPPS2 in a consanguineous Pakistani family, presenting varying degrees of progressive scoliosis, developmental delays, horizontal gaze palsy, agenesis of corpus callosum, and absence of cerebral commissures. Analysis of genotyping data identified shared loss of heterozygosity (LOH) region on chromosomes 5p15.33-15.31, 6q11.2-12, and 18q21.1-21.3. A hypothesis-free, unbiased exome data analysis detected an insertion of nucleotide A (c.2399dupA) in exon 16 of the DCC gene. The insertion is predicted to cause frameshift p.(Asn800Lysfs*11). Interestingly, DCC gene is present in the LOH region on chromosome 18. Variant (c.2399dupA) in the DCC gene is considered as the most probable candidate variant for HGPPS2 based on the presence of DCC in the LOH region, previously reported role of DCC in HGPPS2, perfect segregation of candidate variant with the disease, prediction of variant pathogenicity, and absence of variant in variation databases. Sanger Sequencing confirmed the presence of the novel homozygous mutation in all three patients; the parents were heterozygous carriers of the mutation, in accordance with an autosomal recessive inheritance pattern. DCC encodes a netrin-1 receptor protein; its role in the development of the CNS has recently been established. Biallelic DCC mutations have previously been shown to cause HGPPS2. A novel homozygous variant in patients of the reported family extend the genotypic and phenotypic spectrum of HGPPS2.