Abstract: Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. Questions/purposes To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier’s ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier’s ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? Methods Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier’s ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10] , 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10] ; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10] , 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10] ); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson’s trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 μm × 300 μm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss’κ coefficient. P values 〈 0.05 were considered statistically significant. Results There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15] ; χ 2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12] ; χ 2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 μm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. Conclusion Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. Clinical Relevance We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.

Abstract: A retrospective multicenter study. Objective. To determine the surgical site infection (SSI) rate, associated risk factors, and causative pathogens in pediatric patients with spinal deformity. Summary of Background Data. There have been no extensive investigations of the risk factors for SSI in Japan. Methods. Demographic data, radiographic findings, and the incidence of SSI were retrospectively analyzed in 1449 pediatric patients who underwent primary definitive fusion surgery for spinal deformity at any of 15 institutions from 2015 to 2017. SSI was defined according to the US Centers for Disease Control and Prevention guideline. Results. The incidence of all SSIs was 1.4% and that of deep SSIs was 0.76%. The most common pathogenic microbes were methicillin-resistant staphylococci (n = 5) followed by gram-negative rods (n = 4), methicillin-sensitive staphylococci (n = 1), and others (n = 10). In univariate analysis, younger age, male sex, a diagnosis of kyphosis, type of scoliosis, American Society of Anesthesiologists (ASA) class ≥3, mental retardation urinary incontinence, combined anterior-posterior fusion, greater magnitude of kyphosis, three-column osteotomy, use of blood transfusion, and number of antibiotic administration were associated with the likelihood of SSI (all P   〈  0.05). Multivariate logistic regression analysis identified the following independent risk factors for SSI: syndromic scoliosis etiology ( vs. idiopathic scoliosis; adjusted odds ratio [OR] 16.106; 95% confidence interval [CI] 2.225–116.602), neuromuscular scoliosis etiology ( vs. idiopathic scoliosis; adjusted OR 11.814; 95% CI 1.109–125.805), ASA class 3 ( vs. class 2; adjusted OR 15.231; 95% CI 1.201–193.178), and administration of antibiotic therapy twice daily ( vs. three times daily; adjusted OR 6.121; 95% CI 1.261–29.718). Conclusion. The overall infection rate was low. The most common causative bacteria were methicillin-resistant followed by gram-negative rods. Independent risk factors for SSI in pediatric patients undergoing spinal deformity surgery were scoliosis etiology, ASA class 3, and administration of antibiotic therapy twice daily. Level of Evidence: 3

Abstract: Tearing and insufficiency of the ulnar collateral ligament (UCL) of the elbow result in valgus instability, which can lead to pain while throwing and decline in performance in overhead athletes. Purpose: To assess the clinical results of a modified UCL reconstruction technique using 1 bone hole in the ulna and 1 bone tunnel in the humerus in baseball players. Study Design: Case series; Level of evidence, 4. Methods: The inclusion criteria were medial elbow pain preventing effective playing, clinically medial elbow laxity, and magnetic resonance imaging results consistent with UCL injury. Patients who were engaged in other sports and in other positions in baseball except pitchers were excluded from this study. Our modified Tommy John procedure was performed via a muscle-splitting approach and an original single-bone-tunnel technique, using a suture anchor. After a minimum of 24 months, patients were evaluated using the Conway scale and the Timmerman-Andrews score. Results: Of 31 patients, 20 baseball pitchers (20 male: 5 high school, 5 collegiate, 8 nonprofessional, and 2 professional pitchers) were reviewed. The mean patient age at the time of operation was 21.9 years, and the mean postoperative follow-up period was 35.1 months (range, 24-66 months). The mean Timmerman-Andrews subjective score improved significantly from pre- to postoperatively (from 68.3 to 98.3; P 〈 .05); the objective score also improved significantly (from 81.1 to 96.4; P = .01). No complications were detected at the latest follow-up. Overall, 19 patients were able to return to their preinjury level of sports or higher. Conclusion: UCL reconstruction with 1 bone hole in the ulna and 1 bone tunnel in the humerus demonstrated satisfactory results in baseball pitchers. Our modified technique was safe and achieved satisfactory clinical results, with a 95% rate of return to sports.

Abstract: Thoracic outlet syndrome is more common in overhead athletes. The anterior and middle scalene muscles have been associated with thoracic outlet syndrome; however, the relationship between the elastic moduli of the scalene muscles and the overhead-throwing position has not been evaluated. Purpose: To investigate the elastic moduli of the anterior and middle scalene muscles in simulated throwing positions using shear wave elastography. Study Design: Descriptive laboratory study. Methods: We enrolled collegiate baseball players who underwent preseason medical checkups in January and February 2020. The anterior and middle scalene muscles were visualized in the short-axis view using ultrasound. In this view, the elastic moduli of the anterior and middle scalene muscles were measured using shear wave elastography in the following arm and neck positions: (1) adduction and neutral rotation of the shoulder (neutral), (2) 90° of abduction and external rotation of the shoulder (ABER), and (3) ABER with neck rotation toward the nonthrowing side (ABER+NR). Repeated-measures analysis of variance and a paired t test were used to compare the elastic modulus values among the 3 positions and between the 2 muscles, respectively. Results: Overall, 30 baseball players were included. In both scalene muscles, the elastic moduli were significantly greater in the ABER versus neutral position (anterior scalene: 14.4 ± 3.8 vs 9.4 ± 2.0 kPa, respectively [ P 〈 .001]; middle scalene: 15.8 ± 5.0 vs 10.9 ± 3.4 kPa, respectively [ P 〈 .001]). In the neutral position, the elastic modulus was significantly greater in the middle scalene than the anterior scalene (10.9 ± 3.4 vs 9.4 ± 2.0 kPa, respectively; P = .03). In the ABER+NR position, the elastic modulus was significantly greater in the anterior scalene than the middle scalene (18.1 ± 4.6 vs 15.8 ± 2.6 kPa, respectively; P = .03). Conclusion: Because the ABER position was a simulation of the throwing position, these results indicate that this position could be associated with high elastic moduli of the scalene muscles, and both the anterior and middle scalene muscles may be involved.

Abstract: Retrospective case series. Objective. The aim of this study was to investigate the clinical outcomes 〉 10 years following laminoplasty and pedicle screw fixation for cervical myelopathy associated with athetoid cerebral palsy (CP). Summary of Background Data. Surgery for cervical myelopathy associated with CP remains a challenge because of perioperative instrumentation failure and adjacent segment problems due to patients’ repetitive involuntary neck movements with deformity of the cervical spine. Methods. A single-center series of 14 patients were reviewed. The patients comprised seven women and seven men with a mean age of 52 years at the time of surgery. The mean follow-up period was 12.5 years. The Barthel index (BI), which shows independence in activities of daily life, and Japanese Orthopaedic Association (JOA) score were assessed. Radiographic evaluation included changes of the C2–C7 angle in the sagittal plane, fusion rate, adjacent segment degeneration, and instrument failure. Results. The 10-year BI and JOA score significantly improved at 36% and 31%, respectively. The preoperative Cobb angle of the sagittal plane from C2–C7 measured 11.9° of kyphosis, which improved to 0.8° of lordosis. In the radiographic analysis, 35% (proximal) and 21% (distal) of the adjacent segment showed progression in degeneration of more than one grade after 10 years. More than 90% of the patients who underwent magnetic resonance imaging showed progressive disc degeneration on either side after 10 years. Autofusion inside the disc or anterior vertebral bony bridging was observed in 86% of intervertebral levels without anterior procedures. Conclusion. The procedure showed favorable initial stability and maintained favorable clinical outcomes in patients with CP. More than 90% of the patients showed disc degeneration on either side. The rate of proximal adjacent segment degeneration was higher than that of distal segments with or without symptoms at the 〉 10-year follow-up. Level of Evidence: 4

Abstract: A retrospective multicenter cohort study. Objective. The aim of this study was to identify the incidence and risk factors for UPROR within minimum 2-year follow-up in primary definitive fusion for pediatric spinal deformity. Summary of Background Data. Several previous reports have elucidated the incidence of complications after pediatric scoliosis surgery; however, there has been no study that described the incidence and risk factors for unplanned return to the operating room (UPROR) with long-term follow-up in surgery for pediatric scoliosis with every etiology. Methods. We retrospectively extracted data of patients aged 〈 19 years, from 14 institutes in Japan, who underwent primary definitive fusion surgery for spinal deformity between January 1, 2015 and December 31, 2017. The primary outcomes were the incidence of UPROR within the minimum 2-year follow-up period for any reason. Univariate and multivariate logistical analyses were conducted to identify potential risk factors associated with UPROR. Results. We identified 1417 eligible patients (287 males and 1130 females) with a mean age of 13.9 years. UPROR for any reason within minimum 2-year follow-up was identified in 68 patients (4.8%). The most frequent cause for UPROR was implant failure found in 29 patients, followed by surgical site infection in 14 patients, junctional problems in 10 patients, and neurological complications in six patients. The multivariate logistic regression analysis revealed that a diagnosis of kyphosis (odds ratio [OR], 2.65; 95% confidence interval [CI] 1.16–6.04), etiology of congenital or structural type (OR 2.21; 95% CI 1.08–4.53), etiology of syndromic type (OR 2.67; 95% CI 1.27–5.64), and increased operation time of ≥300 minutes (OR 1.81; 95% CI 1.07–3.07) were the risk factors for the incidence of UPROR. Conclusion. The present multicenter study identified for the first time the incidence and risk factors for UPROR with minimum 2-year follow-up after primary definitive fusion surgery for pediatric spinal deformity with every etiology. Level of Evidence: 3

Abstract:  Less-invasive early diagnosis of lung cancer is essential for improving patient survival rates. The purpose of this study is to demonstrate that serum comprehensive miRNA profile is high sensitive biomarker to early-stage lung cancer in direct comparison to the conventional blood biomarker using next-generation sequencing (NGS) technology combined with automated machine learning (AutoML). Methods We first evaluated the reproducibility of our measurement system using Pearson’s correlation coefficients between samples derived from a single pooled RNA sample. To generate comprehensive miRNA profile, we performed NGS analysis of miRNAs in 262 serum samples. Among the discovery set (57 patients with lung cancer and 57 healthy controls), 1123 miRNA-based diagnostic models for lung cancer detection were constructed and screened using AutoML technology. The diagnostic faculty of the best performance model was evaluated by inspecting the validation samples (74 patients with lung cancer and 74 healthy controls). Results The Pearson’s correlation coefficients between samples derived from the pooled RNA sample ≥ 0.98. In the validation analysis, the best model showed a high AUC score (0.98) and a high sensitivity for early stage lung cancer (85.7%, n  = 28). Furthermore, in comparison to carcinoembryonic antigen (CEA), a conventional blood biomarker for adenocarcinoma, the miRNA-based model showed higher sensitivity for early-stage lung adenocarcinoma (CEA, 27.8%, n  = 18; miRNA-based model, 77.8%, n  = 18). Conclusion The miRNA-based diagnostic model showed a high sensitivity for lung cancer, including early-stage disease. Our study provides the experimental evidence that serum comprehensive miRNA profile can be a highly sensitive blood biomarker for early-stage lung cancer.