Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To investigate the clinical and radiologic characteristics of children with congenital pseudarthrosis of the tibia (CPT) in a single center.Methods:This is a retrospective case series study. According to inclusion and exclusion criteria, clinical data of 497 children(507 limbs) with CPT who were treated at Department of Orthopedics, the Children′s Hospital Affiliated to Xiangya School of Medicine, Central South University from January 2011 to December 2020 were collected. Baseline data included gender, age at initial visit, age at onset of symptoms, accompanying symptoms, domicile, whether first treated at our hospital, and treatment-related information such as surgical or conservative treatment, surgical complications, etc., were extracted and analyzed using the health information system. Imaging data of the children, including Crawford classification, bilateral leg lengths, presence of fibular pseudarthrosis, and location of pseudarthrosis along the tibia segment, were analyzed using the Picture Archiving and Communication System. Data were compared using independent sample t test or χ2 tests. Results:Among 497 children with CPT, there were 305 males (61.4%) and 192 females (38.6%). The age at initial visit was (3.6±3.2) years (range: 0.1 to 16.2 years). Neurofibromatosis type 1 (NF1) symptoms were positive in 340 children (68.4%), and negative in 157 children (31.6%). Among NF1-positive children, those with symptoms onset before 1 year of age were significantly more than NF1-negative children (74.1%(252/340) vs. 66.2%(104/157); χ2=9.24, P=0.001), and the proportion of fractures (92.9%,316/340) was significantly higher than that in the NF1-negative group (84.7%,133/157) ( χ2=8.33, P=0.004). According to imaging data, Crawford type Ⅳ was the most common type, with 321 limbs (63.3%), followed by type Ⅱ in 100 limbs (19.7%), type Ⅲ in 54 limbs (10.7%) and type Ⅰ in 32 limbs (6.3%). Pseudarthrosis occurred in the proximal third of the tibia in 14 limbs (2.8%), in the middle third in 185 limbs (36.5%), and in the distal third in 308 limbs (60.8%). Seventy-four children (14.9 %) had associated fibular pseudarthrosis. The lateral proximal tibial angle was 86.91°±5.21°(range: 72.17° to 102.08°), and the lateral distal tibial angle was 87.27°±10.73°(range: 51.07° to 128.17°). A total of 421 children (84.7%) underwent surgical treatment with (3.1±2.4) surgeries performed per child (range:0 to 12 surgeries); 76 children (15.3%) received conservative treatment. Postoperative complications mainly included ankle valgus (77 cases), leg length discrepancy (71 cases),refracture (48 cases), osteomyelitis (11 cases), and hardware failure (10 cases). NF1-positive children underwent more surgeries than NF1-negative children ((5.1±2.2)times vs.(2.1±1.8)times; t=14.93, P<0.01). Conclusions:Crawford type Ⅳ is the most common type of CPT in children in this study. CPT predominantly occurs in the middle or distal third of the tibia. The majority of children with CPT experienced symptoms and were seen at outpatient clinics before the age of 3 years. The main surgical complications currently associated with CPT treatment are ankle valgus and leg length discrepancy. Compared with CPT without NF1, children with NF1-positive CPT tend to have earlier symptom onset and may require more frequent treatments.

Objective:To explore the risk factors associated with tibia fractures in children with congenital anterolateral bowing of the tibia (ALBT).Methods:A retrospective analysis was conducted on data from 87 children diagnosed with ALBT at the Children's Hospital of Hunan Province from January 2012 to January 2020. The collected data included age at initial diagnosis, affected limb side, whether there was a concomitant type I neurofibromatosis, whether there was a concomitant fibular pseudoarthrosis, whether there was concomitant ankle joint deformity, whether there was bone cystic change in the region of tibial bowing deformity, location of the apex of the bowing deformity, diameter of the tibial bowing deformity on the affected side, diameter on the healthy side in the same plane as the tibial bowing deformity, angle of lateral bending deformity of the tibia, angle of anterior bending deformity of the tibia, occurrence of tibia fracture, history of trauma before fracture, location of fracture, and age at the time of fracture. The follow-up endpoint was January 2023. Receiver operating characteristic (ROC) curves were used to determine the optimal cutoff values for the angles of lateral and anterior bending deformity of the tibia and the ratio of cross-sectional areas. The correlation between the above factors and tibial fractures in children was analyzed by single factor survival analysis, and the indicators with statistical significance were included in multivariate Cox proportional risk regression analysis to determine the risk factors for tibial fractures in children with ALBT.Results:Of the 87 children diagnosed with ALBT, the median age at initial diagnosis was 14.0 months (range, 1-93 months), with 42 males and 45 females, 44 left-sided and 43 right-sided cases. The median follow-up time for non-fracture cases was 42.0 months (range, 1-124 months). At the last follow-up, 43 children had experienced fractures, while 44 had not. The average time to fracture-free survival was 70.3 months, the median fracture-free survival time was 55.0 months, and the median survival time without fractures was 42.0 months. The ROC curve results indicated a cutoff value of 25.55° for the lateral bending angle of the tibia and 32.63° for the anterior bending angle of the tibia, with no statistically significant significance for the cross-sectional area ratio [AUC=0.54, 95% CI (0.42, 0.66), P=0.530]. Single-factor analysis of fracture-free survival suggested that there were statistically significant differences in the intergroup fracture-free survival rates of four factors: lateral bending angle of the tibia (χ 2=7.06, P=0.008), anterior bending angle of the tibia (χ 2=8.96, P=0.003), history of trauma (χ 2=18.26, P<0.001), and tibial bone cystic change (χ 2=4.30, P=0.038). The results of the multivariate Cox proportional hazards regression analysis showed that a lateral bending angle of the tibia≥25.55° ( HR=2.73, P=0.007), tibial bone cystic change ( HR=2.35, P=0.018), and history of trauma ( HR=2.65, P=0.004) were all positively correlated with fractures. Conclusion:The main risk factors for tibia fractures in children with ALBT include trauma, tibial bowing deformity with concomitant bone cystic change, and lateral bending angle of the tibia≥25.55°.

Objective:To compare the genotypes and phenotypes between the monozygotic twins via whole genome sequencing to further clarify the autosomal dominant inherited neurofibromatosis type 1 (NF1) variants related to congenital pseudarthrosis (CP).Methods:According to the diagnostic criteria of congenital tibial pseudarthrosis and the clinical diagnostic criteria of NF1, two pairs of monozygotic twins with NF1 were included. Both were female and only one of each pair had congenital pseudarthrosis. The other did not have congenital pseudarthrosis. Whole genome sequencing was performed using the peripheral blood of the two pairs of monozygotic twins. Customized bioinformatics analysis was then performed to identify single nucleotide variants (SNVs), short insertion deletion variants (InDel), copy number variants (CNVs), and structural variants (SVs). Classified the variants according to the American College of Medical Genetics and Genomics (ACMG) and ClinGen criteria. The germline variants within the monozygotic twins were compared to identify the CP patients' unique variants. The shared pathogenic or likely pathogenic germline variants between the unique variants in the CP patients from the twins were also analyzed. Further, the identified disease-causing variants were validated by Sanger sequencing in the family of the twins and their parents. Finally, the genotypes and phenotypes regarding the pathogenic variants of the NF1 gene among the twins were characterized. Results:Both the two monozygotic twins were identified pathogenic variants in the NF1 gene. One with c.3047_3048del (p.Cys1016SerfsTer4), and the other with c.4267A>G (p.Lys1423Glu). By Sanger sequencing validation in family quads, the two CP patients and their siblings harbored de novo heterozygous variants of the NF1 gene. In addition to the NF1 gene, no other genes were identified pathogenic or likely pathogenic variants uniquely in the CP patients compared with their twin sisters, as well as SVs and CNVs. In addition, by analyzing the rare and damaging variants in the two CP patients from the two twins, they had no overlapping genes against the SNVs, InDels, SVs, or CNVs. Conclusion:Whole genome sequencing revealed that both the two monozygotic twins with NF1 were detected pathogenic variants of gene NF1. No other pathogenic variants specific to the CP patients among the twins were identified. The two CP patients shared no other common genes from the detected likely pathogenic variants.

Objective:To explore the family resilience resources in parents of children with congenital pseudarthrosis of the tibia (CPT) , so as to provide a reference for formulating nursing intervention to improve their family resilience.Methods:From December 2020 to January 2021, purposive sampling was used to select 13 father or mother of children with CPT in the Department of Orthopedics of Hunan Children's Hospital as the research object. Semi-structured interviews were conducted with parents of children with CPT using the phenomenological method in qualitative research. Colaizzi 7-step method was used to organize, summarize, analyze and refine the data.Results:The family resilience resources of parents of children with CPT were reflected in three aspects, namely, personal resources, family resources and social resources.Conclusions:Family resilience interventions should make full use of their own resources when implemented in parents of children with CPT. Individualized continuous intervention should be provided by taking into account the learning ability and psychological state of the children's parents and in combination with specific needs. The intervention target should include as many family members as possible, and strengthen the establishment of a diversified support system to help parents of children with a large number of social resources.

Objective:To identify the risk factors for premature proximal femur physeal closure (PPC) in children treated surgically for femoral neck fractures.Methods:Data of 106 children with an open triradiate cartilage who were treated surgically for a femoral neck fracture were retrospectively analyzed. Age, gender, laterality, mechanism of injury, the type of fracture, initial displacement, time to reduction, fixation method, whether the implant crossed the physeal plate, reduction method, reduction quality and development of femoral head avascular necrosis (AVN) were collected. PPC of the proximal femur was assessed through postoperative 6-12 months radiographs.Results:A total of 106 patients with an open triradiate cartilage were followed up, with an average duration of 20.4±13.3 months (range, 6-86 months). The overall rate of PPC following paediatric femoral neck fractures treated surgically was 36.8% (39/106). Among the 39 patients with PPC, 25 were males and 14 were females; the average age at the time of injury was 9.7±3.6 years (range, 3-15 years); 23 patients were involved in left hips and 16 were in right; the mechanisms of injury included motor vehicle accident in 5 fractures, falling injury in 21, sports-related injury in 12 and other causes in 1 fracture; two hips were Delbet type I, and 26 hips and 11 hips were Delbet type II and III, separately; type II and III of initial displacement were involved in 26 and 13 patients, separately; the mean duration from injury to surgery was 3.3±2.8 d (range, 1-14 d); 2 hips were treated with Kirschner wires, 35 hips with screw fixation, and the remaining 2 hips underwent screw and plate fixation; 2 hips had the hardware crossing the proximal femoral growth plate, and the remaining 37 hips didn’t; 15 hips were treated by closed reduction and internal fixation, and the other 24 hips underwent open reduction and internal fixation; anatomical reduction was achieved in 14 patients, acceptable reduction in 24 hips and unacceptable reduction in 1 hip; 24 hips developed AVN at the latest follow-up and the remaining 15 hips didn’t. Statistical analysis indicated that age ( t=3.875, P< 0.001), the severity of initial displacement ( Z=-2.118, P=0.034) and the rate of AVN ( χ2=42.280, P< 0.001) in patients with PPC were significantly higher than those in patients without; Logistic regression analysis confirmed age ( OR=1.288, P=0.011) and AVN ( OR=40.336, P< 0.001) as risk factors for PPC. ROC curve analysis indicated 10 years was the cut off age to significantly increase the rate of PPC. The rate of PPC in patients aged over 10 years (63.6%, 21/33) was significantly higher than that (24.7%, 18/73) in those aged less than 10 years ( χ2=14.848, P< 0.001). Conclusion:Age over 10 years and AVN are risk factors for PPC in children with femoral neck fractures treated surgically.

Objective:To identify and analyze different proteins expression in the periosteum of congenital pseudarthrosis of the tibia (CPT) using tandem mass tags (TMT) proteomics.Methods:The samples were divided into three groups, namely CPT with neurofibromatosis type 1 (NF1) group (NF1-CPT group), CPT without NF1 group (nonNF1-CPT group) and control group (patients with open tibial fracture). A fold change ≥1.5 or ≤0.66 and P-value <0.05 was regarded as the threshold to screen differentially expressed proteins (DEPs). Subsequently, bioinformatics resources such as online tools DAVID and STRING were used to conduct GO annotation, KEGG pathways enrichment and protein-protein interaction (PPI) network with DEPs. Results:A total of 347 proteins differentially expressed in NF1-CPT group, 212 of which were up-regulated and 135 down-regulated. We identified 467 DEPs in nonNF1-CPT group, including 281 up-regulated and 186 down-regulated. Among of them, NF1-CPT group and nonNF1-CPT group shared 231 DEPs, except for HLA-DRB1 which increased in NF1-CPT group but decreased in nonNF1-CPT group. The remaining 230 DEPs showed the same expression trend in the two positive groups, including 117 up-regulated and 113 down-regulated. In particular, a total of 116 proteins were altered only in NF1-CPT group, including 94 up-regulated and 22 down-regulated. However, there were 236 proteins altered only in nonNF1-CPT group, including 164 up-regulated and 72 down-regulated. The results indicated that the pathogenesis of NF1-CPT was similar as nonNF1-CPT largely with a few differences. Finally, compared with nonNF1-CPT, there were 47 proteins changed 1.5-fold and P-value <0.05 in NF1-CPT group. Conclusion:The proteins expression in the periosteum of CPT is different from that of normal tibia. The expression of periosteal protein is also different between NF1-CPT and nonNF1-CPT. The present study will deepen our understanding of the pathogenesis of CPT in the protein level.

Objective    To summarize the experience of treating adult recurrent pectus excavatum without plate turnover. Methods    Twenty-seven patients with recurrent pectus excavatum treated by thoracoscopy-assisted placement without plate turnover from 2010 to 2019 in our hospital were enrolled. There were 23 males and 4 females with the age of 3-29 (12.81±7.79) years at the first operation, and 18-29 (21.74±3.56) years at this operation. Incision of 2-3 cm at bilateral axillary midline of the deepest point of pectus excavatum was made, and an auxiliary incision under xiphoid process was adopted according to the intraoperative situation. Results    All patients underwent thoracoscopy-assisted correction of pectus excavatum without bar turnover, and subxiphoid incision was performed in 11 patients. Twenty-five patients had one bar placed, and two patients required two bars. The operation time was 28-45 (33.00±6.44) min. Postoperative Haller index (2.95±0.40) was improved compared with preoperation (4.63±1.03). The postoperative hospital stay was 4-6 (4.00±0.32) day. All patients were followed up for 1-8 years. Complications included poor wound healing in 1 patient, and steel wire fracture and displacement in 1 patient. There was no plate rotation or bar displacement. Fourteen patients removed the bar 29-84 (40.36±13.93) months after the placement. Haller index was improved to 2.43-3.61 (2.86±0.35) during removal of steel plate. Untill June 2020, there was no recurrence of pectus excavatum. Conclusion    The treatment of adult recurrent pectus excavatum without plate turnover is satisfactory, and the protection of intercostal muscle and firm fixation is the key to ensure the success of operation and long-term effects.

Objective To evaluate the diagnostic efficacy of mDIXON Quant for vertebral metastasis. Methods We retrospectively analyzed MRI images of 152 patients with clinically diagnosed malignant tumors and vertebral metastases. Scanning sequence included T1WI, STIR, mDIXON Quant and enhanced T1WI. We compared the diagnostic efficiency between T1WI and FF images for vertebral metastases. FF values between normal vertebral body and vertebral metastases were quantitatively compared, and the diagnostic efficacy of FF value was evaluated by ROC curve. Results The sensitivity, false positive rate, false negative rate, negative predictive value and accuracy of FF images in the diagnosis of vertebral metastases were all higher than those of T1WI images. The FF value of vertebral metastasis was significantly lower than that of normal vertebral body (Z=-21.792, P < 0.05), and the area under ROC curve was 0.987 and the cutoff value was 9.87%. The diagnostic sensitivity and specificity of vertebral metastasis were 99.6% and 92.0%. Conclusion mDIXON Quant can quantitatively determine the fat content of vertebral metastasis and has a high diagnostic efficiency for vertebral metastases.

Objective    To explore the surgical design and efficacy of novel modified Nuss procedure for pectus excavatum (PE). Methods    We retrospectively analyzed the clinical data of 903 patients with PE who were treated by the new kind of steel bar and the novel modified Nuss procedure. There were 716 males and 187 females at mean age of 2-45 (12.1±6.8) years. Preoperative chest CT scans Haller index (HI) was 3.1-15.2 (4.6±1.3), with 38 patients of mild PE (HI<3.2), 302 patients of moderate PE (HI 3.2-3.5), 521 patients of severe PE (HI 3.6-6.0), and 42 patients of extremely severe PE (HI>6.0). The operative time, operative blood loss, hospital stay time as well as postoperative complications were reviewed and analyzed. Results    All of the 903 patients successfully completed the surgery. The mean operative time was 20-45 (25.2±2.6) min for primary PE and that for special type of PE (including recurring PE, PE patients after heart disease operation and those corrected by 2 bars) was 48-150 (63.5±28.1) min. Blood loss was less than 10 mL for primary PE and 15-50 (23.5±5.5) mL for special type of PE. Postoperative hospital stay was 3-15 (4.5±1.6) d. A total of 845 patients (93.6%) required 1 steel bar insertion, 58 patients (6.4%) required 2 steel bars. Postoperative evaluation of the surgery outcomes revealed the following: excellent in 805 patients, good in 84 patients, fair in 14 patients and poor in 0. The good quality rate was 98.4%. Conclusion    Novel modified Nuss procedure can simplify and optimize the surgical design with good short and mid-term effects.