A porcine model of early-onset scoliosis combined with thoracic insufficiency syndrome: Construction and transcriptome analysis.

BACKGROUND: Early-onset scoliosis (EOS) is a scoliosis deformity caused by various reasons before the age of 10 years and is often combined with thoracic insufficiency syndrome (TIS) causing patients with difficulty in securing lung growth in the thoracic cage. Currently, there is a shortage of effective large animal models for evaluating EOS + TIS in therapeutic studies. Consequently, we propose to construct a porcine EOS + TIS model and evaluate its transcriptome changes by RNA sequencing. METHODS: Piglets were constructed using unilateral posterior spine-tethering and ipsilateral rib-tethering in the EOS + TIS model, and X-ray and computed tomography (CT) were performed to assess growth changes in the spine, thoracic cage and lungs. The H&E and Masson staining was performed for pathological analysis of lung tissue. After RNA sequencing of lung tissues, data were analyzed for differential expression of mRNA, functional enrichment analysis (GO, KEGG and GSEA) and protein-protein interaction (PPI) network construction, and differential expression of hub gene was verified by RT-qPCR. RESULTS: In the model group, growth (body weight and length) of piglets was significantly delayed; fusion of ribs occurred and cobb angle changes in the coronal and sagittal planes were significantly enlarged; total lung volume (TLV) was significantly reduced, especially at the T7-T10 level. Pathological analysis revealed that, in the model lung tissue, the alveolar wall of was poorly perfused, the alveolar space was enlarged, the number and size of alveoli were significantly reduced, and it was accompanied by collagen fiber deposition. Moreover, a total of 432 differentially expressed mRNAs (DE-mRNAs) were identified in model lung tissues, which contained 262 down-regulated and 170 up-regulated DE-mRNAs, and they were mainly involved in the regulation of immunity, inflammation, cell cycle and extracellular matrix. A PPI network containing 71 nodes and 158 edges was constructed based on all DE-mRNAs, and JUN, CCL2, EGR1, ATF3, BTG2, DUSP1 and THBS1 etc. were hub gene. CONCLUSIONS: Overall, we constructed a porcine model that was capable of replicating the common clinical features of EOS + TIS such as rib fusion, asymmetric thoracic cage, increased cobb angle, decreased TLV, and pulmonary hypoplasia. Also, we revealed transcriptomic changes in the EOS + TIS model that may cause pulmonary hypoplasia.

Factors Associated with Postoperative Respiratory Complications following Posterior Spinal Instrumentation in Children with Early-onset Scoliosis.

OBJECTIVE: To investigate the incidence and risk factors of postoperative respiratory complications (PRCs) in children with early-onset scoliosis (EOS) following posterior spine deformity surgery (PSDS) based on growth-friendly techniques, so as to help improve the safety of surgery. METHODS: A retrospective study of children with EOS admitted for PSDS based on growth-friendly techniques from October 2013 to October 2018 was reviewed at a single center. There were 73 children (30 boys, 43 girls) who fulfilled the criteria in this research. The mean age of the patients was 7 ± 6.2 years. Patients were divided into the groups with and without PRCs. Variables that might affect the PRCs during the perioperative period, including general factors, radiographic factors, laboratory factors and surgical factors, were analyzed using univariate analysis to evaluate the potential risk factors. The variables that were significantly different were further analyzed by binary logistic regression analysis to identify the independent factors of PRCs. RESULTS: All the 73 children included 42 idiopathic scoliosis (57.5%), 12 congenital scoliosis (16.4%), 10 syndromic scoliosis (13.7%) and nine neuromuscular scoliosis (12.3%). PRCs were detected in 16 children (21.9%) with nine different PRCs. The total frequency of detected PRCs was 54, including pleural effusion (25.9%), postoperative pneumonia (20.4%), hypoxemia (18.5%), atelectasis (14.8%), prolonged intubation with mechanical positive pressure ventilatory support (PIMPPVS) (7.4%), bronchospasm (3.7%), reintubation (3.7%), delayed extubation (3.7%) and pneumothorax (1.9%). Results of univariate testing demonstrated that the following six variables were statistically different (P < 0.05): nonidiopathic scoliosis, combined with pulmonary comorbidities, pretransferrin < 200 mg/dL, prealbumin < 3.5 g/dL, anesthesia time ≥ 300 min and blood loss to total blood volume ratio (BL/TBV) ≥ 15%. Binary logistic regression analysis confirmed that BL/TBV≥15% (odd ratio OR = 29.188, P = 0.010), combined with pulmonary comorbidities (OR = 19.216, P = 0.012), pretransferrin < 200 mg/dL (OR = 11.503, p = 0.024), and nonidiopathic scoliosis (OR = 7.632, P = 0.046) were positively linear correlated with PRCs in children with EOS following PSDS. CONCLUSION: PRCs has a higher incidence in children with EOS following PSDS. BL/TBV ≥15%, combined with pulmonary comorbidities, pre-transferrin < 200 mg/dL, and nonidiopathic scoliosis play an important role for the development of PRCs in this population.