The Whole-Exome Sequencing of a Cohort of 19 Families with Adolescent Idiopathic Scoliosis (AIS): Candidate Pathways.

A significant genetic involvement has been known for decades to exist in adolescent idiopathic scoliosis (AIS), a spine deformity affecting 1-3% of the world population. However, though biomechanical and endocrinological theories have emerged, no clear pathophysiological explanation has been found. Data from the whole-exome sequencing performed on 113 individuals in 19 multi-generational families with AIS have been filtered and analyzed via interaction pathways and functional category analysis (Varaft, Bingo and Panther). The subsequent list of 2566 variants has been compared to the variants already described in the literature, with an 18% match rate. The familial analysis in two families reveals mutations in the BICD2 gene, supporting the involvement of the muscular system in AIS etiology. The cellular component analysis revealed significant enrichment in myosin-related and neuronal activity-related categories. All together, these results reinforce the suspected role of the neuronal and muscular systems, highlighting the calmodulin pathway and suggesting a role of DNA-binding activities in AIS physiopathology.

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.

Quantifying Typical Progression of Adolescent Idiopathic Scoliosis: Longitudinal Three-Dimensional MRI Measures of Disk and Vertebral Deformities.

STUDY DESIGN: A prospective cohort study. OBJECTIVE: Detail typical three-dimensional segmental deformities and their rates of change that occur within developing adolescent idiopathic scoliosis (AIS) spines over multiple timepoints. SUMMARY OF BACKGROUND DATA: AIS is a potentially progressive deforming condition that occurs in three dimensions of the scoliotic spine during periods of growth. However, there remains a gap for multiple timepoint segmental deformity analysis in AIS cohorts during development. MATERIALS AND METHODS: Thirty-six female patients with Lenke 1 AIS curves underwent two to six sequential magnetic resonance images. Scans were reformatted to produce images in orthogonal dimensions. Wedging angles and rotatory values were measured for segmental elements within the major curve. Two-tailed, paired t tests compared morphologic differences between sequential scans. Rates of change were calculated for variables given the actual time between successive scans. Pearson correlation coefficients were determined for multidimensional deformity measurements. RESULTS: Vertebral bodies were typically coronally convexly wedged, locally lordotic, convexly axially rotated, and demonstrated evidence of local mechanical torsion. Between the first and final scans, apical measures of coronal wedging and axial rotation were all greater in both vertebral and intervertebral disk morphology than nonapical regions (all reaching differences where P <0.05). No measures of sagittal deformity demonstrated a statistically significant change between scans. Cross-planar correlations were predominantly apparent between coronal and axial planes, with sagittal plane parameters rarely correlating across dimensions. Rates of segmental deformity changes between earlier scans were characterized by coronal plane convex wedging and convexly directed axial rotation. The major locally lordotic deformity changes that did occur in the sagittal plane were static between scans. CONCLUSIONS: This novel investigation documented a three-dimensional characterization of segmental elements of the growing AIS spine and reported these changes across multiple timepoints. Segmental elements are typically deformed from initial presentation, and subsequent changes occur in separate orthogonal planes at unique times.

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.

Characteristics of paraspinal muscle degeneration in patients with adult degenerative scoliosis.

INTRODUCTION: Adult degenerative scoliosis (ADS) is a 3D deformity that greatly affects the quality of life of patients and is closely related to the quality of paraspinal muscles (PSMs), but the specific degenerative characteristics have not been described. METHODS: This study included ADS patients who were first diagnosed in our hospital from 2018 to 2022. Muscle volume (MV) and fat infiltration (FI) of PSM were measured by 3D reconstruction, and spinal parameters were assessed by X-ray. The values of convex side (CV) and concave side (CC) were compared. RESULTS: Fifty patients were enrolled with a mean age of 64.1 ± 5.8 years old. There were significant differences in MV, FI, and Cobb angle between male and female groups. The MV of MF and PS on the CC was significantly larger than that on the CV. In the apex and the segments above the apex, the FI of the MF on the CC is greater than the CV, and in the CV of the segment below the apex, the FI of the MF is greater than the CC. Besides, there was a significant positive correlation between the FI and Cobb angle in the MF of the CC-CV. CONCLUSION: There were significant differences in the MV and FI of PSM on both sides of the spine in ADS patients. It was determined that the PSM of ADS showed different degrees of degeneration in different levels of the lumbar spine and were positively correlated with Cobb angle.

Adolescent idiopathic scoliosis is associated with muscle area asymmetries in the lumbar spine.

PURPOSE: While the etiopathogenesis of adolescent idiopathic scoliosis (AIS) remains unclear, it is assumed that muscular asymmetries contribute to curve progression. As previous studies have found asymmetries of the thoracic paraspinal muscles in AIS patients, our study's aim was to analyze differences in the erector spinae, multifidus, quadratus lumborum, and psoas muscles of the lumbar spine depending on the curve's radiographic characteristics. METHODS: We retrospectively included all patients who received posterior reposition spondylodesis for AIS treatment at our institution. Patients were classified according to the Lenke classification. Muscle cross-sectional areas were obtained from magnetic resonance imaging of the lumbar spine. Data were analyzed with the Wilcoxon rank sum test, the Kruskal-Wallis test with post hoc testing, or the Spearman's correlation coefficient. RESULTS: Seventy-four (14 males and 60 females) AIS patients with a median age of 16 (IQR ± 4) years and a mean Cobb angle of 56.0° (± 18.0°) were included. In curve types Lenke 1 and 2 (n = 45), the erector spinae (p < 0.001) and multifidus (p < 0.001) muscles had a significantly larger cross-sectional area on the convex side, whereas the quadratus lumborum (p = 0.034) and psoas (p < 0.001) muscles each had a significantly larger cross-sectional area on the lumbar contralateral side. CONCLUSION: Our results show an asymmetry of the lumbar spine's muscles which depends on both the convexity and the extent of the scoliotic curve. While our results cannot prove whether these differences are the deformity's cause or effect, they may contribute to a better understanding of AIS pathogenesis and may allow for more specific preoperative physiotherapy.

Quantifying Muscle Size Asymmetry in Adolescent Idiopathic Scoliosis Using Three-dimensional Magnetic Resonance Imaging.

STUDY DESIGN: This is a case-control study of prospectively collected data. OBJECTIVE: To quantify paraspinal muscle size asymmetry in adolescent idiopathic scoliosis (AIS) and determine if this asymmetry is (i) greater than observed in adolescent controls with symmetrical spines; and (ii) positively associated with skeletal maturity using Risser grade, scoliosis severity using the Cobb angle, and chronological age in years. SUMMARY OF BACKGROUND DATA: AIS is a three-dimensional deformity of the spine which occurs in 2.5% to 3.7% of the Australian population. There is some evidence of asymmetry in paraspinal muscle activation and morphology in AIS. Asymmetric paraspinal muscle forces may facilitate asymmetric vertebral growth during adolescence. METHODS: An asymmetry index [Ln(concave/convex volume)] of deep and superficial paraspinal muscle volumes, at the level of the major curve apex (Thoracic 8-9 th vertebral level) and lower-end vertebrae ( LEV , Thoracic 10-12 th vertebral level), was determined from three-dimensional Magnetic Resonance Imaging of 25 adolescents with AIS (all right thoracic curves), and 22 healthy controls (convex=left); all female, 10 to 16 years. RESULTS: Asymmetry index of deep paraspinal muscle volumes was greater in AIS (0.16±0.20) than healthy spine controls (-0.06±0.13) at the level of the apex ( P <0.01, linear mixed-effects analysis) but not LEV ( P >0.05). Asymmetry index was positively correlated with Risser grade ( r =0.50, P <0.05) and scoliosis Cobb angle ( r =0.45, P <0.05), but not age ( r =0.34, P >0.05). There was no difference in the asymmetry index of superficial paraspinal muscle volumes between AIS and controls ( P >0.05). CONCLUSIONS: The asymmetry of deep apical paraspinal muscle volume in AIS at the scoliosis apex is greater than that observed at equivalent vertebral levels in controls and may play a role in the pathogenesis of AIS.

Early onset horizontal gaze palsy and progressive scoliosis due to a noncanonical splicing-site variant and a missense variant in the ROBO3 gene.

BACKGROUND: Homozygous or compound heterozygous ROBO3 gene mutations cause horizontal gaze palsy with progressive scoliosis (HGPPS). This is an autosomal recessive disorder that is characterized by congenital absence or severe restriction of horizontal gaze and progressive scoliosis. To date, almost 100 patients with HGPPS have been reported and 55 ROBO3 mutations have been identified. METHODS: We described an HGPPS patient and performed whole-exome sequencing (WES) to identify the causative gene. RESULTS: We identified a missense variant and a splice-site variant in the ROBO3 gene in the proband. Sanger sequencing of cDNA revealed the presence of an aberrant transcript with retention of 700 bp from intron 17, which was caused by a variation in the noncanonical splicing site. We identified five additional ROBO3 variants, which were likely pathogenic, and estimated the overall allele frequency in the southern Chinese population to be 9.44 × 10-4 , by a review of our in-house database. CONCLUSION: This study has broadened the mutation spectrum of the ROBO3 gene and has expanded our knowledge of variants in noncanonical splicing sites. The results could help to provide more accurate genetic counseling to affected families and prospective couples. We suggest that the ROBO3 gene should be included in the local screening strategy.

Bioinformatics analysis of paravertebral muscles atrophy in adult degenerative scoliosis.

Paravertebral muscles (PVM) act as one of the major dynamic factors to maintain human upright activities and play a remarkable role in maintaining the balance of the trunk. Adult degenerative scoliosis (ADS) has become one of the important causes of disability in the elderly population owing to the changes in spinal biomechanics, atrophy and degeneration of PVM, and imbalance of the spine. Previously, many studies focused on the physical evaluation of PVM degeneration. However, the molecular biological changes are still not completely known. In this study, we established a rat model of scoliosis and performed the proteomic analysis of the PVM of ADS. The results showed that the degree of atrophy, muscle fat deposition, and fibrosis of the PVM of rats positively correlated with the angle of scoliosis. The proteomic results showed that 177 differentially expressed proteins were present in the ADS group, which included 105 upregulated proteins and 72 downregulated proteins compared with the PVM in individuals without spinal deformities. Through the construction of a protein-protein interaction network, 18 core differentially expressed proteins were obtained, which included fibrinogen beta chain, apolipoprotein E, fibrinogen gamma chain, thrombospondin-1, integrin alpha-6, fibronectin-1, platelet factor 4, coagulation factor XIII A chain, ras-related protein Rap-1b, platelet endothelial cell adhesion molecule 1, complement C1q subcomponent subunit A, cathepsin G, myeloperoxidase, von Willebrand factor, integrin beta-1, integrin alpha-1, leukocyte surface antigen CD47, and complement C1q subcomponent subunit B. Further analysis of the Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) and immunofluorescence showed that the neutrophil extracellular traps (NETs) formation signaling pathway plays a major role in the pathogenesis of PVM degeneration in ADS. The results of the present study preliminarily laid the molecular biological foundation of PVM atrophy in ADS, which will provide a new therapeutic target for alleviating PVM atrophy and decreasing the occurrence of scoliosis.

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.

Ependymal polarity defects coupled with disorganized ciliary beating drive abnormal cerebrospinal fluid flow and spine curvature in zebrafish.

Idiopathic scoliosis (IS) is the most common spinal deformity diagnosed in childhood or early adolescence, while the underlying pathogenesis of this serious condition remains largely unknown. Here, we report zebrafish ccdc57 mutants exhibiting scoliosis during late development, similar to that observed in human adolescent idiopathic scoliosis (AIS). Zebrafish ccdc57 mutants developed hydrocephalus due to cerebrospinal fluid (CSF) flow defects caused by uncoordinated cilia beating in ependymal cells. Mechanistically, Ccdc57 localizes to ciliary basal bodies and controls the planar polarity of ependymal cells through regulating the organization of microtubule networks and proper positioning of basal bodies. Interestingly, ependymal cell polarity defects were first observed in ccdc57 mutants at approximately 17 days postfertilization, the same time when scoliosis became apparent and prior to multiciliated ependymal cell maturation. We further showed that mutant spinal cord exhibited altered expression pattern of the Urotensin neuropeptides, in consistent with the curvature of the spine. Strikingly, human IS patients also displayed abnormal Urotensin signaling in paraspinal muscles. Altogether, our data suggest that ependymal polarity defects are one of the earliest sign of scoliosis in zebrafish and disclose the essential and conserved roles of Urotensin signaling during scoliosis progression.

Compressive stress induces spinal vertebral growth plate chondrocytes apoptosis via Piezo1.

Many clinical studies have indicated an association between biomechanical factors and the incidence and pathological progression of adolescent idiopathic scoliosis (AIS). However, at present, the research on AIS is mainly focused on the etiology, and there are few studies reporting the causes of progressive aggravation of AIS. In the present study, we aim to investigate the role of Piezo1 in compressive stress-induced mouse spinal vertebral growth plate chondrocytes apoptosis. First, a scoliosis mouse model was established, and the expression of Piezo1 as well as the degree of apoptosis were investigated. We found that the expression of Piezo1 and the degree of apoptosis were significantly higher on the concave sides than that on the convex sides of the vertebral growth plate in mice with scoliosis. Spinal vertebral growth plate chondrocytes were further isolated and treated with Yoda1 to mimic Piezo1 overload. Excess Piezo1 significantly promoted apoptosis of spinal vertebral growth plate chondrocytes. Moreover, static gas compressive stress was used to simulate the increased concave compressive stress in the process of scoliosis with or without GsMTx4, a Piezo inhibitor. It was observed that with the increase of static compressive stress, the expression of Piezo1 increased, and the chondrocytes of vertebral growth plate treated with Piezo1 inhibitor GsMTx4 weakened the above phenomena. In conclusion, our results indicated that compressive stress is strongly associated with the different degrees of apoptosis on both sides on the convex and concave sides of the vertebral growth plate in scoliosis via inducing different expressions of Piezo1. Reducing the expression of Piezo1 in the concave side of the vertebral growth plate and inhibiting the apoptosis of chondrocytes in the bilateral vertebral growth plate caused by asymmetric stress on both sides of the concave vertebral body may be a promising treatment strategy for AIS.

Current models to understand the onset and progression of scoliotic deformities in adolescent idiopathic scoliosis: a systematic review.

PURPOSE: To create an updated and comprehensive overview of the modeling studies that have been done to understand the mechanics underlying deformities of adolescent idiopathic scoliosis (AIS), to predict the risk of curve progression and thereby substantiate etiopathogenetic theories. METHODS: In this systematic review, an online search in Scopus and PubMed together with an analysis in secondary references was done, which yielded 86 studies. The modeling types were extracted and the studies were categorized accordingly. RESULTS: Animal modeling, together with machine learning modeling, forms the category of black box models. This category is perceived as the most clinically relevant. While animal models provide a tangible idea of the biomechanical effects in scoliotic deformities, machine learning modeling was found to be the best curve-progression predictor. The second category, that of artificial models, has, just as animal modeling, a tangible model as a result, but focusses more on the biomechanical process of the scoliotic deformity. The third category is formed by computational models, which are very popular in etiopathogenetic parameter-based studies. They are also the best in calculating stresses and strains on vertebrae, intervertebral discs, and other surrounding tissues. CONCLUSION: This study presents a comprehensive overview of the current modeling techniques to understand the mechanics of the scoliotic deformities, predict the risk of curve progression in AIS and thereby substantiate etiopathogenetic theories. Although AIS remains to be seen as a complex and multifactorial problem, the progression of its deformity can be predicted with good accuracy. Modeling of AIS develops rapidly and may lead to the identification of risk factors and mitigation strategies in the near future. The overview presented provides a basis to follow this development.

The role of pineal gland volume in the development of scoliosis.

PURPOSE: Adolescent idiopathic scoliosis (AIS) is believed to be caused by genetic, neurological, osseous growth anomalies, histological variables including muscle fiber percentage and core structure changes, metabolic and hormonal dysfunction, vestibular dysfunction, and platelet microarchitecture. The objective of this study was to contribute to the determination of the cause of AIS by analyzing the changes in pineal gland volume in AIS cases. METHODS: Study (AIS) and control group were each comprised of 26 patients who met the inclusion requirements. Scoliosis radiograph and MRI of the pineal glands were used for radiological examinations. The distribution of age, gender, Risser grading for skeletal radiological development, and sexual maturation according to Tanner categorization were uniform and statistically insignificant between groups. RESULTS: When the pineal gland volumes of the cases were evaluated according to age, the AIS group was found to have significantly reduced pineal gland volumes in all age groups. The pineal gland volume was found to be 38.1% lower in the AIS group compared to the control group (p˂0.001). In the AIS group, patients aged 13 years had the lowest pineal gland volume (77.2 ± 13.86 mm3), while patients aged 15 years had the highest volume (97.9 ± 16.47 mm3). CONCLUSION: Changes in pineal gland volume support the role of the pineal gland in the etiopathogenesis of AIS.

Surface electromyography study on asymmetry in paravertebral muscle degeneration in patients with degenerative lumbar scoliosis.

The asymmetry of paravertebral muscle (PVM) degeneration in degenerative lumbar scoliosis (DLS) patients has been extensively studied by imaging and histological examination and has not yet been verified by surface electromyography (sEMG) techniques. To study the relationship between the surface electromyography (sEMG) and degenerative characteristics of paravertebral muscles (PVMs) in patients with degenerative lumbar scoliosis (DLS). In twenty DLS patients and fifteen healthy subjects, sEMG activity of the PVMs at the level of the upper end vertebra (UEV), apical vertebra (AV) and lower end vertebra (LEV) was measured during static standing and dynamic standing forward flexion and backward extension tasks. Action segmentation was achieved according to inertial measurement unit (IMU) data. The sEMG characteristics of the PVMs on the convex and concave sides were compared, and the relationship of these data with the Cobb angle and lumbar lordotic angle (LL) was analyzed. In the DLS group, there was no difference in sEMG activity between the convex and concave sides at the UEV or AV level, but in the motion and return phases of the standing forward flexion task (P = 0.000, P = 0.015) and the maintenance and return phases of the standing backward extension task (P = 0.001, P = 0.01), there was a significant difference in sEMG activity between the convex and concave sides at the LEV level. Asymmetrical sEMG activity at the LEV level was negatively correlated with the Cobb angle (F = 93.791, P < 0.001) and LL angle (F = 65.564, P < 0.001). In the DLS group, asymmetrical sEMG activity of the PVMs appeared at the LEV level, with the concave side being more active than the convex side. This sEMG characteristics were consistent with their imaging and histological degenerative features and correlated with bone structural parameters.

Conditional inactivation of the L-type amino acid transporter LAT1 in chondrocytes models idiopathic scoliosis in mice.

Scoliosis, usually diagnosed in childhood and early adolescence, is an abnormal lateral curvature of the spine. L-type amino acid transporter 1 (LAT1), encoded by solute carrier transporter 7a5 (Slc7a5), plays a crucial role in amino acid sensing and signaling in specific cell types. We previously demonstrated the pivotal role of LAT1 on bone homeostasis in mice, and the expression of LAT1/SLC7A5 in vertebral cartilage of pediatric scoliosis patients; however, its role in chondrocytes on spinal homeostasis and implications regarding the underlying mechanisms during the onset and progression of scoliosis, remain unknown. Here, we identified LAT1 in mouse chondrocytes as an important regulator of postnatal spinal homeostasis. Conditional inactivation of LAT1 in chondrocytes resulted in a postnatal-onset severe thoracic scoliosis at the early adolescent stage with normal embryonic spinal development. Histological analyses revealed that Slc7a5 deletion in chondrocytes led to general disorganization of chondrocytes in the vertebral growth plate, along with an increase in apoptosis and a decrease in cell proliferation. Furthermore, loss of Slc7a5 in chondrocytes activated the general amino acid control (GAAC) pathway but inactivated the mechanistic target of rapamycin complex 1 (mTORC1) pathway in the vertebrae. The spinal deformity in Slc7a5-deficient mice was corrected by genetic inactivation of the GAAC pathway, but not by genetic activation of the mTORC1 pathway. These findings suggest that the LAT1-GAAC pathway in chondrocytes plays a critical role in the maintenance of proper spinal homeostasis by modulating cell proliferation and survivability.

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.

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.

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.