1.Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults (version 2024)
Qingde WANG ; Yuan HE ; Bohua CHEN ; Tongwei CHU ; Jinpeng DU ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Hua GUO ; Yong HAI ; Lijun HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Hongjian LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Hong XIA ; Guoyong YIN ; Jinglong YAN ; Wen YUAN ; Zhaoming YE ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Yingjie ZHOU ; Zhongmin ZHANG ; Wei MEI ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2024;40(2):97-106
Ankylosing spondylitis (AS) combined with lower cervical fracture is often categorized into unstable fracture, with a high incidence of neurological injury and a high rate of disability and morbidity. As factors such as shoulder occlusion may affect the accuracy of X-ray imaging diagnosis, it is often easily misdiagnosed at the primary diagnosis. Non-operative treatment has complications such as bone nonunion and the possibility of secondary neurological damage, while the timing, access and choice of surgical treatment are still controversial. Currently, there are no clinical practice guidelines for the treatment of AS combined with lower cervical fracture with or without dislocation. To this end, the Spinal Trauma Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate Clinical guidelines for the treatment of ankylosing spondylitis combined with lower cervical fracture in adults ( version 2024) in accordance with the principles of evidence-based medicine, scientificity and practicality, in which 11 recommendations were put forward in terms of the diagnosis, imaging evaluation, typing and treatment, etc, to provide guidance for the diagnosis and treatment of AS combined with lower cervical fracture.
2.Analysis of the current situation and development trend of bone age assessment of children in China based on questionnaires
Fengsen BAI ; Xinyu YUAN ; Yimin MA ; Yang YANG ; Yuchun YAN ; Haiyan XIN ; Xiaoguang CHENG
Chinese Journal of Radiology 2024;58(2):225-228
Objective:Based on the questionnaire, to analyze the current status of children′s bone age assessment in China, especially the application of artificial intelligence (AI)-assisted bone age assessment system in the clinic.Methods:This was a cross-sectional study. The questionnaire was adapted by ourselves through the literature method and expert interview method, and the whole volume included 22 questions, which were released in the form of WeChat applet questionnaire star to the physician groups of several associations and entrusted to the radiology and paediatricians with senior titles. The results of the different types of questions were summarised and analyzed, and the chi-square test was used to compare the count data.Results:A total of 450 valid questionnaires were collected from 162 medical institutions in 26 provinces and cities and autonomous regions, of which 232 (51.6%) were from 87 (53.7%) tertiary hospitals and 218 (48.4%) from 75 (46.3%) secondary hospitals. Of the respondents, 115 (25.6%) were senior, 137 (30.4%) middle and 198 (44.0%) junior. Child bone age measurement was performed at 75.9% (66/87) of tertiary care organizations and 26.7% (20/75) of secondary care organizations, and the difference was statistically significant ( χ2=39.10, P<0.001). Left wrist radiographs were predominantly used for bone age assessment (76.0%, 123/162), with 72.8% (118/162) of sites using the ATLAS method of assessment and 17.9% (29/162) using the scoring method. A total of 98.4% (443/450) of respondents agreed that AI technology should be used to assist in bone age assessment, but only 9.3% (15/162) of healthcare organizations used AI-assisted technology. Conclusion:At present, bone age assessment is widely used in medical institutions, but there are problems with non-standardized examination methods, inconsistent assessment standards, and imprecise assessment results. Expectations for AI technology-assisted diagnosis exist among a wide range of physicians, but there are fewer users.
3.Study on the mechanism of miRNA-20a in regulating lipopolysaccharide-induced pyroptosis and inflammation of A549 cells
Huixian TAO ; Muzi WANG ; Yan GUO ; Yunsu ZOU ; Zhitao LU ; Yifang DING ; Xiaoguang ZHOU ; Weidong XU
Chinese Journal of Neonatology 2023;38(2):107-114
Methods:Cultured human alveolar epithelial A549 cells were assigned into LPS group and blank control group. LPS group was stimulated with LPS and adenosine triphosphate to induce pyroptosis and inflammation. A549 cells were divided into 4 groups: miR-20a mimics group, mimics-negative control (NC) group, inhibitor group and inhibitor-NC group. MiRNA-20a mimics, mimics-NC, inhibitor, and inhibitor-NC were transfected respectively into A549 cells, and after 24 h, the cells were collected to verify transfection efficiency by qPCR. MiRNA-20a mimics and the constructed TLR4-3'UTR double luciferase reporter plasmid were co-transfected into A549 cells, and luciferase activity was analyzed. MiRNA-20a mimics/inhibitors were transfected into A549 cells, and then the cells were stimulated by LPS for 8 h followed by adenosine triphosphate for 30 min. QPCR, Western Blot and ELISA were used to detect the expression of GSDMD, inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and Signaling molecules (TLR4、NF-κB) in A549 cells at mRNA level and protein level. Immunofluorescence was used to detect the expression of TLR4 in the A549 cells and NF-κB in the nucleus of A549 cells after transfecting with miRNA-20a mimics/inhibitor.Results:The mRNA and protein expression of pyroptosis marker molecule (GSDMD) and inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) in A549 cells stimulated with LPS were significantly higher than those in the blank control group, and the differences were statistically significant ( P<0.05). The expression of miRNA-20 in the mimics group was significantly higher than that in the mimic-NC group ( P<0.05), while the expression of miRNA-20a in the inhibitor group was lower than that in the inhibitor-NC group ( P<0.01). The double luciferase reporter gene experiment showed that the relative fluorescence value of the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics was significantly lower than the co-transfection group for TLR4-3'UTR-WT and miRNA-20a mimics-NC ( P<0.05). The mRNA and protein levels of pyroptosis marker molecule (GSDMD) , inflammatory factors (ASC, NLRP3, Caspase-1, IL-1β) and signaling molecules (TLR4, NF-κB) were decreased in the mimics group compared to the mimics-NC group, and increased in inhibitor group compared to inhibitor-NC group. Conclusions:miRNA-20a may inhibit LPS-induced pyroptosis and inflammation of A549 cells via TLR4/NF-κB signal pathway.Objetive:To explore the potential role of miRNA-20a in lipopolysaccharide (LPS) induced pyroptosis and inflamation of human alveolar epithelial A549 cells and its regulation mechanisim.
4.Clinical guideline for diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture (version 2023)
Jianan ZHANG ; Bohua CHEN ; Tongwei CHU ; Yirui CHEN ; Jian DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Lijun HE ; Yuan HE ; Dianming JIANG ; Jianyuan JIANG ; Bin LIN ; Bin LIU ; Baoge LIU ; Dechun LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Wei MEI ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Honghui SUN ; Tiansheng SUN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Yongming XI ; Hong XIA ; Jinglong YAN ; Liang YAN ; Wen YUAN ; Gang ZHAO ; Jie ZHAO ; Jianguo ZHANG ; Xiaozhong ZHOU ; Yue ZHU ; Yingze ZHANG ; Dingjun HAO ; Baorong HE
Chinese Journal of Trauma 2023;39(3):204-213
Ankylosing spondylitis (AS) combined with spinal fractures with thoracic and lumbar fracture as the most common type shows characteristics of unstable fracture, high incidence of nerve injury, high mortality and high disability rate. The diagnosis may be missed because it is mostly caused by low-energy injury, when spinal rigidity and osteoporosis have a great impact on the accuracy of imaging examination. At the same time, the treatment choices are controversial, with no relevant specifications. Non-operative treatments can easily lead to bone nonunion, pseudoarthrosis and delayed nerve injury, while surgeries may be failed due to internal fixation failure. At present, there are no evidence-based guidelines for the diagnosis and treatment of AS combined with thoracic and lumbar fracture. In this context, the Spinal Trauma Academic Group of Orthopedics Branch of Chinese Medical Doctor Association organized experts to formulate the Clinical guideline for the diagnosis and treatment of adult ankylosing spondylitis combined with thoracolumbar fracture ( version 2023) by following the principles of evidence-based medicine and systematically review related literatures. Ten recommendations on the diagnosis, imaging evaluation, classification and treatment of AS combined with thoracic and lumbar fracture were put forward, aiming to standardize the clinical diagnosis and treatment of such disorder.
5.Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults (version 2023)
Yukun DU ; Dageng HUANG ; Wei TIAN ; Dingjun HAO ; Yongming XI ; Baorong HE ; Bohua CHEN ; Tongwei CHU ; Jian DONG ; Jun DONG ; Haoyu FENG ; Shunwu FAN ; Shiqing FENG ; Yanzheng GAO ; Zhong GUAN ; Yong HAI ; Lijun HE ; Yuan HE ; Dianming JIANG ; Jianyuan JIANG ; Weiqing KONG ; Bin LIN ; Bin LIU ; Baoge LIU ; Chunde LI ; Fang LI ; Feng LI ; Guohua LYU ; Li LI ; Qi LIAO ; Weishi LI ; Xiaoguang LIU ; Yong LIU ; Zhongjun LIU ; Shibao LU ; Fei LUO ; Jianyi LI ; Yong QIU ; Limin RONG ; Yong SHEN ; Huiyong SHEN ; Jun SHU ; Yueming SONG ; Tiansheng SUN ; Jiang SHAO ; Jiwei TIAN ; Yan WANG ; Zhe WANG ; Zheng WANG ; Xiangyang WANG ; Hong XIA ; Jinglong YAN ; Liang YAN ; Wen YUAN ; Jie ZHAO ; Jianguo ZHANG ; Yue ZHU ; Xuhui ZHOU ; Mingwei ZHAO
Chinese Journal of Trauma 2023;39(4):299-308
The acute combination fractures of the atlas and axis in adults have a higher rate of neurological injury and early death compared with atlas or axial fractures alone. Currently, the diagnosis and treatment choices of acute combination fractures of the atlas and axis in adults are controversial because of the lack of standards for implementation. Non-operative treatments have a high incidence of bone nonunion and complications, while surgeries may easily lead to the injury of the vertebral artery, spinal cord and nerve root. At present, there are no evidence-based Chinese guidelines for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults. To provide orthopedic surgeons with the most up-to-date and effective information in treating acute combination fractures of the atlas and axis in adults, the Spinal Trauma Group of Orthopedic Branch of Chinese Medical Doctor Association organized experts in the field of spinal trauma to develop the Evidence-based guideline for clinical diagnosis and treatment of acute combination fractures of the atlas and axis in adults ( version 2023) by referring to the "Management of acute combination fractures of the atlas and axis in adults" published by American Association of Neurological Surgeons (AANS)/Congress of Neurological Surgeons (CNS) in 2013 and the relevant Chinese and English literatures. Ten recommendations were made concerning the radiological diagnosis, stability judgment, treatment rules, treatment options and complications based on medical evidence, aiming to provide a reference for the diagnosis and treatment of acute combination fractures of the atlas and axis in adults.
6.Sampling study design and radiography protocol of a large-sample investigation on skeletal maturation in 3 to 18-year-old children in China
Kai LI ; Qian GAN ; Jian GENG ; Yimin MA ; Wenhai WANG ; Yandong LIU ; Qian ZHANG ; Zhenyu YANG ; Wenhua ZHAO ; Dong YAN ; Xiaoguang CHENG
Chinese Journal of Radiology 2023;57(4):348-352
Objective:To report the sampling study design and radiography protocol of a large-sample investigation on skeletal maturation of 3 to 18-year-old children in China.Methods:Multi-stage stratified random sampling was employed in this study. Two provinces, municipalities, or autonomous regions were randomly selected from each of the seven regions of China, including Northeast China, Northwest China, North China, Central China, East China, Southwest China, and South China. Then one rural and one urban investigation site were randomly selected from each province, municipality, or autonomous region. In total 28 sites were included. Among those sites, four residential districts were randomly selected from each urban site, and four townships from each rural site. For each residential district or township, 1-4 kindergartens, primary schools, and middle schools were chosen. Random cluster sampling was used to extract 3-<6-year-old children in kindergartens, and 6-18-year-old children in primary schools and middle schools. The investigation on skeletal maturation was sampled proportionate to the sampling of the whole study. The estimated simple size was 780 for each site, and 21 840 for all 28 sites in total. There were six groups of 3-<6-year-old children classified at 0.5-year intervals, and 12 groups of 6-18-year-old children classified at 1-year intervals. Posteroanterior position radiography of the left hand and wrist was achieved for all subjects.Results:The study was performed from August 26, 2019 to October 16, 2021. In total, 20 444 children received posteroanterior position radiography of the left hand and wrist, including 10 196 males and 10 248 females, 9 711 urban and 10 733 rural, respectively. The 3-<6-year-old group included 1 611 (male 819, female 792) subjects, and the 6 to 18-year-old group included 18 833 (male 9 377, female 9 456) subjects.Conclusion:This nationwide investigation on skeletal maturation of 3 to 18-year-old children in seven regions of China was successfully preformed. The results of this study can provide an important reference for establishing the current evaluation criteria of bone age in Chinese children and adolescents.
7.Applicability analysis of bone age assessment standards for children in rural areas of Beijing
Dong YAN ; Wenshuang ZHANG ; Qian ZHANG ; Jian GENG ; Wenhai WANG ; Pengju HUANG ; Wenhua ZHAO ; Xiaoguang CHENG
Chinese Journal of Radiology 2023;57(4):353-358
Objective:To evaluate the applicability of bone age (BA) assessment methods and to investigate the difference between BA and chronological age (CA) based on the data of children in rural areas of Beijing.Methods:A total of 412 healthy children (226 boys, 186 girls) with the age 8.6 (6.8, 10.3) years old were included in this study. The data of the prospective study were from a subgroup of the project "National Nutrition and Health Systematic Survey for 0-18 Years Old Children in China", which included children with age of 3-12 years old in Beijing rural areas. The non-dominant hand-wrist radiographs of all participants were obtained in April 2021. The Dr.Wise BA detection and analysis system was used to assess the BA according to the Tanner Whitehouse 3 (TW3) radius-ulna-short bone score (TW3-RUS), TW3 carpal bone score (TW3-Carpal), China-05 TW3-Chinese RUS (TW3-C RUS), China-05 TW3-Chinese carpal (TW3-C Carpal), and Greulich-Pyle (G-P) standards. The cases were stratified by the sex and different CA in the statistical analysis. The estimated BA obtained using different methods were compared with the CA using Wilcoxon signed ranks test.Results:The sex-stratified results showed that no significant difference was found between the estimated BA using G-P standards and CA in boys ( Z=-0.694, P=0.488), while all the other estimated BA results were statistically significantly higher than CA ( P<0.05). Stratified by both sex and CA, the estimated BA using G-P standards in 4-6 years old boy groups, as well as the estimated BA using TW3-Carpal and TW3-C Carpal standards in 11-12 years old girl groups were lower than CA, while in the other groups, the estimated BA were higher than CA. Conclusions:There were varying degrees of deviations in the BA estimations using TW3, China 05, and G-P methods for children in rural areas of Beijing. It is imperative to establish a new standard for the BA evaluation of the contemporary Chinese children.
8.Accuracy of bone age assessment system based on deep learning in children with abnormal growth and development
Sha CHANG ; Dong YAN ; Xia DU ; Yuqiao ZHANG ; Xiaoguang CHENG ; Jie YANG ; Lingling SONG ; Bo GAO ; Xian LUO
Chinese Journal of Radiology 2023;57(4):364-369
Objective:To explore the accuracy of artificial intelligence (AI) system based on deep learning in evaluating bone age of children with abnormal growth and development.Methods:The positive X-ray films of the left wrist of children with abnormal growth and development who were treated at the Affiliated Hospital of Guizhou Medical University from January 2020 to December 2021 were collected retrospectively. A total of 717 children were collected, including 266 males and 451 females, aged 2-18 (11±3) years. Based on Tanner Whitehouse 3 (TW 3)-RUS (radius, ulna, short bone) and TW3-Carpal (carpal bone) method, bone age was measured by 3 senior radiologists, and the mean value was taken as reference standard. The bone ages were independently evaluated by the AI system (Dr.Wise bone age prediction software) and two junior radiologists (physicians 1 and 2). The accuracy within 0.5 year, the accuracy within 1 year, the mean absolute error (MAE) and the root mean square error (RMSE) between the evaluation results and the reference standard were analyzed. Paired sample t-test was used to compare MAE between AI system and junior physicians. Intraclass correlation coefficient (ICC) was used to evaluate the consistency between AI system, junior physician and reference standard. The Bland-Altman diagram was drawn and the 95% consistency limit was calculated between AI system and reference standard. Results:For TW3-RUS bone age, compared with the reference standard, the accuracy within 0.5 year of AI system, physician 1 and physician 2 was 75.3% (540/717), 62.1% (445/717) and 66.2% (475/717), respectively. The accuracy within 1 year was 96.9% (695/717), 86.3% (619/717) and 89.1% (639/717), respectively. MAE was 0.360, 0.565 and 0.496 years, and RMSE was 0.469, 0.634 and 0.572 years, respectively. For TW3-Carpal bone age, compared with the reference standard, the accuracy within 0.5 year of AI system, physician 1 and physician 2 was 80.9% (580/717), 65.1% (467/717) and 71.7% (514/717), respectively. The accuracy within 1 year was 96.0% (688/717), 87.3% (626/717) and 90.4% (648/717), respectively. MAE was 0.330, 0.527 and 0.455 years, and RMSE was 0.458, 0.612, 0.538 years, respectively. Based on TW3-RUS and TW3-Carpal bone age, the MAE of AI system were lower than those of physician 1 and physician 2, and the differences were statistically significant ( P all<0.001). The evaluation results of AI, physician 1 and physician 2 were in good agreement with the reference standard (ICC all>0.950). The Bland-Altman analysis showed that the 95% agreement limits of AI system for assessing TW3-RUS and TW3-Carpal bone age were -0.75-1.02 years and-0.86-0.91 years, respectively. Conclusion:The accuracy of AI system in evaluating the bone age of children with abnormal growth and development is close to that of senior doctors, better than that of junior doctors, and in good agreement with senior doctors.
9.Value of dual-layer spectral detector CT in evaluating the intramedullary invasion of limb osteosarcoma
Huili ZHAN ; Zhanhua QIAN ; Yuan LI ; Rongjie BAI ; Xiaoguang CHENG ; Dong YAN ; Wei YE
Chinese Journal of Radiology 2023;57(8):844-848
Objective:To explore the optimal keV value of the virtual monoenergetic image (VMI) for displaying the osteosarcoma by using the dual-layer spectral detector CT and to evaluate its application value in determining the extent of intramedullary invasion of osteosarcoma.Methods:From August 2021 to August 2022, 57 patients with conventional osteosarcoma of long bone confirmed by biopsy in Beijing Jishuitan Hospital, Capital Medical University were retrospectively analyzed. All patients completed dual-layer spectral CT enhanced examination before limb salvage surgery, and tumor segment resection specimens were obtained after surgery. Conventional 120 kVp image and VMI of 40, 50, 60, 70 and 80 keV were obtained by spectral CT examination, and the CT values of tumors, image noise were measured and the signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) of the corresponding images were calculated. The objective evaluation among the six groups of images were assessed with the Friedman test, and then determined the optimal keV value. The maximum distance between the intramedullary boundary of osteosarcoma and the adjacent articular surfaces was measured on the best keV VMI and the tumor segment resection specimens. The Wilcoxon signed rank test was used to find the differences and the Spearman correlation analysis was used to evaluate the correlation between the distance measured from the best keV VMI and the specimens.Results:There were significant differences in CT value, image noise, SNR and CNR between 40-80 keV VMI and 120 kVp conventional CT images ( P<0.05). The CT value, SNR and CNR of 40 and 50 keV VMI were better than 120 kVp ( P<0.001). The 50 keV VMI was chosen as the best keV VMI to measure the intramedullary extent of osteosarcoma. The distance measured from 50 keV VMI was 103.9 (80.4, 131.4) mm, while the distance measured from specimens was 113.5 (94.0, 142.0) mm, and the difference was statistically significant ( Z=-5.76, P<0.001). The 50 keV VMI measurements in 51 patients were smaller than the gross specimens, which underestimated the tumor intramedullary extent, with the difference was 11.1 (6.6, 13.8) mm. The Spearman correlation analysis demonstrated a high positive correlation of distance measured on gross specimens with the 50 keV VMI ( r s=0.960, P<0.001). Conclusions:Dual-layer spectral detector CT with 50 keV VMI is the best image to show the limb osteosarcoma. Compared with gross specimens, the distance measured from CT underestimated the intramedullary invasion range of limb osteosarcoma about 10 mm, but the two show a good correlation.
10.Atrial septal defect and hydronephrosis associated with 2q13 microdeletion: a case report and literature review
Yan YU ; Yan YANG ; Xiaoguang LI ; Qi CHEN ; Yunpeng CHEN
Chinese Journal of Perinatal Medicine 2023;26(12):997-1001
Objective:To investigate the clinical and genetic features of 2q13 microdeletion.Methods:This study retrospectively analyzed the clinical and genetic features and prognosis of an infant who was admitted to the Fourth People's Hospital of Zhenjiang Affiliated to Jiangsu University and diagnosed with 2q13 microdeletion in October 2021. A literature review on the clinical and genetic characteristics of 2q13 microdeletion was conducted by searching CNKI, Wanfang database, Yiigle, VIP database, PubMed, Embase, and Cochrane Library databases up to March 2023, with "2q13 microdeletion" and "2q13" (both in Chinese and English) as the keywords.Results:(1) Case report: A fetus was found to have mild aortic arch stenosis and left hydronephrosis by prenatal ultrasound at 24 +2 gestational weeks. Fetal chromosomal microarray analysis following amniocentesis at 27 +6 weeks of gestation revealed a 2.23 Mb deletion at 2q13q14.1 chromosome, considered a possible pathogenic copy number variation. The newborn was delivered by cesarean section at 38 +5 weeks of gestation. Echocardiography indicated ostium secundum atrial septal defect and ultrasound showed left hydronephrosis. Other examinations detected no abnormalities. Results of imaging reexamination showed no significant changes when followed up by telephone at 13 months after birth, and a continued follow-up was recommended by the pediatrician. No other developmental abnormalities were found. (2) Literature review: There were 64 patients in 32 retrieved literature, and the one case in this report results in 65 cases. The 2q13 microdeletions can be de novo (15.6%, 10/64) or inherited from one of the parents with normal or abnormal phenotypes (35.9%, 23/64). The clinical manifestations include developmental delay (53.3%, 16/30), craniofacial abnormalities (56.8%, 21/37), and congenital heart diseases (35.0%, 14/40). In addition, some cases exhibited mental neurological symptoms with age, such as attention deficit hyperactivity disorder (48.0%, 12/25), autism spectrum disorders (35.7%, 10/28), etc. Conclusions:The 2q13 microdeletion is complex in its clinical characteristics and incomplete in penetrance. Chromosomal microarray analysis is recommended for confirming diagnosis when related phenotypes are identified prenatally. Some cases of 2q13 microdeletion will show neuropsychiatric symptoms with age, suggesting that long-term follow-up is necessary.

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