Interleukin-7 expression by CAR-T cells improves CAR-T cell survival and efficacy in chordoma.

Chordoma is a rare bone tumor that frequently recurs after surgery, and the prognosis is poor with current treatments. This study aimed to identify potential novel immunotherapeutic targets for chordomas by identifying target proteins in clinical samples as well as tumor microenvironmental factors to enhance efficacy. Fourteen chordoma samples were analyzed by single-cell RNA sequencing, and B7-H3 and IL-7 were identified as potential targets and potentiators, respectively. B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized and their anti-tumor activity evaluated in vitro, including in primary chordoma organoid models. The B7-H3 CAR-T/IL-7 therapy showed enhanced cytotoxicity and prolonged duration of action against tumor cells. Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.

Modified Thoracoplasty for Rib Hump Deformity in Scoliosis Patients: A Case-Control Study.

BACKGROUND: Razorback deformity with stiff thoracic scoliosis creates a complex three-dimensional deformity. Posterior spinal fusion (PSF) and thoracoplasty can correct rib hump deformity and improve patient satisfaction. However, conventional thoracoplasty may impair pulmonary function and increase complications. We present a modified thoracoplasty (MTP) technique for addressing rib hump deformity in stiff thoracic scoliosis patients, emphasizing its clinical efficacy and safety. METHODS: This study included 44 patients with stiff thoracic scoliosis and razorback deformity who underwent surgery between January 2010 and May 2021. Patients were divided into PSF + MTP (n = 27) and PSF (n = 17) groups. Surgical parameters, complications, radiographic improvements, pulmonary function, and Scoliosis Research Society-22 scores were evaluated preoperatively and at 3 months and 2 years postoperatively. RESULTS: There were no significant differences in baseline characteristics between the 2 groups, except for the rib hump height, which was higher in the PSF + MTP group. The PSF + MTP group showed superior correction of the thoracic curve and rib hump height compared to the PSF group, with significant improvements in self-image scores. No significant differences were observed in pulmonary function between the groups. The operative time was longer in the PSF + MTP group, but there were no significant differences in intraoperative blood loss, hospitalization costs, or major complications. Regression analysis indicated that the type of surgery, thoracic Cobb angle, and preoperative self-image scores were significant predictors of postoperative self-image scores. CONCLUSIONS: MTP provides enhanced correction of thoracic curve and rib hump deformity without significantly increasing pulmonary function impairment or complication rates. It also improves patients' self-image, making it a valuable addition to PSF in treating stiff thoracic scoliosis with rib hump deformity.

Analysis of Failed Atlantoaxial Reduction: Causes of Failure and Strategies for Revision.

OBJECTIVE: The craniovertebral junction (CVJ) presents intricate anatomical challenges. In severe or irreducible malformations, complications such as reduction loss and fixation failure may occur, necessitating revision surgery. The posterior facet joint distraction and fusion (PFDF) technique, offers a solely posterior approach for revisions. Hence, we delineate varied revision scenarios, proposing surgical strategies and technical details to enhance outcomes and mitigate risks, thereby enriching the neurosurgical community's repertoire. METHODS: This was a retrospective cohort study, analyzed patient data from Xuanwu Hospital, between 2017 to 2023. All patients had a history of surgical treatment for CVJ malformations, and experienced failure or loss of reduction. The distance from the odontoid process tip to the Chamberlain's line (DCL), the atlantodental interval (ADI), clivus-canal angle, cervicomedullary angle, width of subarachnoid space, CVJ area, and width of syrinx were used for radiographic assessment. Japanese Orthopaedic Association (JOA) scores and SF-12 scores were used for clinical assessment. Independent sample t-tests were employed. A significance level of p < 0.05 indicates statistically significant differences. RESULTS: We analyzed data from 35 patients. For patients who underwent PFDF, the postoperative DCL, ADI, and clivus-canal angle significantly improved. For all patients, the postoperative cervicomedullary angle, width of subarachnoid space, CVJ area, and width of syrinx all demonstrated significant improvement, indicating the relief of neural compression. All patients showed significant improvement in both symptoms and clinical assessments. CONCLUSION: Severe atlantoaxial joint locking or ligament contracting are the fundamental cause of reduction and fixation failure. Anterior odontoidectomy is indicated for patients with robust bony fusion of the atlantoaxial joint in an unreduced position. The PFDF technique is safe and effective for patients with incomplete atlantoaxial bony fusion. Preoperative assessment of surgical feasibility and vertebral artery status ensures surgical safety and efficacy.

The pons as an optimal background reference region for spinal 18F-FET PET/MRI evaluation.

BACKGROUND: This study aims to evaluate the effect of various background reference regions on spinal 18F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results. RESULTS: A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2-C7, and T1-T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p < 0.001) compared to the other three regions. However, its coefficient of variation (CV) was significantly lower than that of the C2-C7 (p < 0.0001) and T1-T3 segments (p < 0.05). The SUVRmax values, calculated using the regions of pons, C2-C7 and T1-T3, were found to significantly differentiate between tumors and myelitis (p < 0.05). However, only the pons-based SUVRmean was able to significantly distinguish between the two groups (p < 0.05). Additionally, the pons-based SUVRmax (r = 0.63, p = 0.013) and SUVRmean (r = 0.67, p = 0.007) demonstrated a significant positive correlation with the Ki-67 index. CONCLUSIONS: This study suggests that the pons may be considered a suitable reference region for spinal 18F-FET PET imaging, which can improve the differentiation between spinal tumors and myelitis. The significant correlation between pons-based SUVR values and the Ki-67 index further highlights the potential of this approach in assessing tumor cell proliferation.

FET PET provides adjunctive value to FDG PET in distinction of spinal cord tumors.

Objective: This study aimed to compare the diagnostic efficacy of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET and 2-deoxy-2-[18F]fluoro-d-deoxyglucose (18F-FDG) PET for spinal cord lesions. Materials and methods: Paired preoperative 18F-FDG PET/MRI and 18F-FET PET/MRI scans were conducted on patients with suspected spinal cord tumors. Clinical manifestations and PET performance, including SUVmean, SUVmax, TBRmean, TBRmax, metabolic tumor volume (MTV), and total lesion metabolism (TLM), and tumor volume, were compared using group analysis and receiver operating characteristic (ROC) curves. Results: Thirty-five patients were categorized into three groups based on their pathological diagnosis: high-grade tumors (HGTs, n = 6), low-grade tumors (LGTs, n = 19), and non-tumor diseases (NTDs, n = 10). The background SUVmean of 18F-FET PET was significantly lower than that of 18F-FDG PET (p < 0.0001), while the delineated tumor volumes showed no significant difference (p > 0.05). The mass SUVmean, SUVmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET were statistically different between HGTs and LGTs (p < 0.05). Similarly, the mass SUVmax, TBRmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET, as well as the mass SUVmean of 18F-FET PET, exhibited statistical differences between HGTs and NTDs (p < 0.05). But none were able to distinguish LGTs and NTDs (p > 0.05). Notably, 18F-FET PET provided valuable supporting diagnostic evidence in 1 case of mixed neuronal-glial tumor (MNGT) and 2 cases of intramedullary inflammatory lesions. Optimal cut-off values of all measured parameters for distinguishing tumors and NTDs were determined through ROC analysis. Conclusion: 18F-FET PET presented comparable diagnostic performance to 18F-FDG PET in differentiating HGTs, LGTs, and NTDs, but exhibited particular utility in MNGT and inflammatory lesions.

Bismuth oxychloride nanosheets anchored aramid separator with sponge-like structure for improved lithium-ion battery performance.

Functional modification of inorganic particles is an effective approach to tackle the issue of Li+ transport and the lithium dendrites formation in lithium-ion batteries (LIBs). In this study, PMIA/BiOCl composite separators are prepared by nonsolvent induce phase separation (NIPS) method using P-type semiconductor bismuth oxychloride (BiOCl) functionalized poly (m-phenylene isophthalamide) (PMIA) separators. Compared with the polypropylene (PP) separator, PMIA has superior thermal stability and the addition of BiOCl further enhances its flame retardancy. And the prepared PMIA/BiOCl separator presents improved porosity (66.47 %), enhanced electrolyte uptake rate (863 %) and higher ionic conductivity (0.49 mS∙cm-1). Besides, the incorporation of BiOCl can anchor PF6- to the three-dimensional network skeleton of the PMIA/BiOCl separators, enabling the desolvation of Li+ and selectively facilitating Li+ transport (the Li+ transfer number is 0.79). Moreover, the uniform porous structure of the PMIA/BiOCl separators and the efficient transport of Li+ uniformly deposite Li+, and minimize the growth of lithium dendrites. Batteries assembled with PMIA/BiOCl separators have a discharge specific capacity of 124.4 mAh∙g-1 and capacity retention of 96.7 % after 200 cycles at 0.2C. Therefore, this work provides an effective route in the design strategy of separators for LIBs.

Diffusion Tensor Imaging Identifies Cervical Spondylosis, Myelitis, and Spinal Cord Tumors.

BACKGROUND: Diffusion tensor imaging (DTI) has been increasingly recognized for its capability to study microstructural changes in the neuropathology of brain diseases. However, the optimal DTI metric and its diagnostic utility for a variety of spinal cord diseases are still under investigation. PURPOSE: To evaluate the diagnostic efficacy of DTI metrics for differentiating between cervical spondylosis, myelitis, and spinal tumors. METHODS: This retrospective study analyzed DTI scans from 68 patients (22 with cervical spondylosis, 23 with myelitis, and 23 with spinal tumors). DTI indicators, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated. The Kruskal-Wallis test was used to compare these indicators, followed by Receiver Operating Characteristic (ROC) curve analysis, to evaluate the diagnostic efficacy of each indicator across disease pairs. Additionally, we explored the correlations of DTI indicators with specific clinical measurements. RESULTS: FA values were significantly lower in tumor patients compared to those with cervical spondylosis (p < 0.0001) and myelitis (p < 0.05). Additionally, tumor patients exhibited significantly elevated MD and RD values relative to the spondylosis and myelitis groups. ROC curve analysis underscored FA's superior discriminative performance, with an area under the curve (AUC) of 0.902 for differentiating tumors from cervical spondylosis, and an AUC of 0.748 for distinguishing cervical myelitis from spondylosis. Furthermore, a significant negative correlation was observed between FA values and Expanded Disability Status Scores (EDSSs) in myelitis patients (r = -0.62, p = 0.002), as well as between FA values and Ki-67 scores in tumor patients (r = -0.71, p = 0.0002). CONCLUSION: DTI indicators, especially FA, have the potential in distinguishing spondylosis, myelitis, and spinal cord tumors. The significant correlation between FA values and clinical indicators highlights the value of FA in the clinical assessment and prognosis of spinal diseases and may be applied in diagnostic protocols in the future.

Spinal neurenteric cysts: experience with 9 cases via an anterior cervical approach.

OBJECTIVE: Intraspinal cysts are uncommon, and the success rate of complete resection is still low for spinal neurenteric cysts (NCs). The aim of this study was to evaluate the efficacies of an anterior microscopic surgical approach in the treatment of ventral and ventrolateral subaxial cervical NCs (SCNCs). METHODS: Between 2019 and 2022, 9 patients with NCs of the subaxial spine underwent an anterior microsurgical approach. Their clinical presentations, radiological features, operative findings, and follow-up data were retrospectively reviewed and analyzed. RESULTS: All spinal cysts were intradural and extramedullary in origin. Five patients were first-time cases while 4 patients with recurrence underwent revision surgery. The most common clinical manifestation was pain (77.78%). One patient was found to have a concomitant disorder of Klippel-Feil syndrome. Microscopically confirmed gross-total resection was achieved in 8 patients (88.89%) based on clinical comparisons between pre- and postoperative MRI and intraoperative video. One patient had symptom recurrence 1 year after subtotal resection, while there was no evidence of recurrence during follow-up for the other patients. Dense adhesions within the spinal cord were observed in 8 patients (88.89%) intraoperatively. Most importantly, the surgical outcome was significantly improved in all patients, and the mean (± SE) Japanese Orthopaedic Association score increased from 11.33 ± 0.91 preoperatively to 16.22 ± 0.32 postoperatively (p = 0.008). CONCLUSIONS: An anterior surgical approach was proven to be both safe and effective in treating the ventral or ventrolateral SCNCs. The authors believe that an anterior microsurgical approach should be considered as a useful approach especially in patients with ventral recurrent SCNCs. Its clinical efficacy compared with a posterior approach in ventral spinal cyst may be better as most of the neurenteric cysts are ventrally or ventrolaterally located.

A novel computed tomography scoring system for evaluating the risk of dural defects in anterior surgery for cervical ossification of the posterior longitudinal ligament.

OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.

Single-cell sequencing reveals VEGFR as a potential target for CAR-T cell therapy in chordoma.

BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.

Posterior intra-articular distraction technique to treat pediatric atlantoaxial instability.

PURPOSE: Surgical treatment for atlantoaxial instability in pediatric patients is challenging. We report our experience with posterior intra-articular distraction technique in treating this disorder. METHODS: This is a retrospective descriptive study which included 15 patients of atlantoaxial instability whose age was less than 16 years at the time of clinical presentation. All patients underwent anterior soft tissue released through a posterior-only approach, followed by intra-facet cage implantation, cantilever correction, and instrumentation. Clinical results were measured using the Japanese Orthopedic Association (JOA) scale and radiographic measurements including the atlantodental interval (ADI), posterior atlantodental interval (pADI), the distance of odontoid tip above Chamberlain's line, clivuscanal angle (CCA), and triangular area (TA) of craniovertebral junction. RESULTS: The follow-up period ranged from 18 to 72 months, with an average of 41.2 ± 15.2 months. The JOA score increased from 13.6 ± 2.3 to 16.6 ± 0.8. ADI decreased from 4.31 ± 2.37 to 1.85 ± 1.09 mm, and TA decreased from 261.96 ± 107.99 to 197.12 ± 72.37 mm2. pADI increased from 12.89 ± 3.52 to 18.25 ± 3.89 mm, and CCA improved from 132.19 ± 16.34 to 144.35 ± 13.91°. All changes in measurements showed statistically significant. There were no evidence of surgery-related complications or iatrogenic secondary cervical deformity during follow-up. Radiological evaluation showed satisfactory corrections and bony fusions of C1-2 facet joint in all cases. CONCLUSION: Posterior intra-articular distraction followed by cage implantation and cantilever correction can be one of the safe and effective ways to solve atlantoaxial instability in pediatric patients.

TREM1 promotes cancer associated malignant phenotype through activated MAPK signaling pathway and predicts poor prognosis in gastric cancer.

Background: CD molecules plays a vital role in gastric cancer (GC). We used bioinformatics analysis methods to develop prognosis related CD molecules risk signature; On the other hand, we used the experiments to further explore the function and mechanism of differentially expressed prognostic CD molecules (TREM1) in GC. Methods: Kaplan-Meier survival and univariate Cox regression analysis were used to evaluate the overall survival of CD molecule genes in gastric cancer. ROC curve and Kaplan-Meier curves were used to analyze the predictive value of CD molecule related genes risk signature by "survival and timeROC" R packages. GSEA, and Cibersortx software were used to analyze the functional enrichment. Finally, we verified the function and mechanism of TREM1 in GC by gene silencing and MAPK inhibitor (SB203580) in vitro and vivo. Results: A total of 41 prognosis related risk factors in gastric cancer were identified based on CD molecules, including TREM1 and ect. The high-risk patients had higher risk score and shorter survival time. ROC curves revealed that this risk signature accurately predicted survival times of gastric cancer patients at the 1-, 2-, 3-, 4- and 5-year. The frequency of T cells follicular helper and NK cells activated were added in low-risk group. Next, differentially expressed prognostic CD molecules analysis revealed that TREM1 was identified as key genes in GC progression based on TCGA and GES158662 and GSE15459 datasets of GC. In vitro experiments, TREM1 silencing significantly inhibited GC cell proliferation and migration, induced cell apoptosis. GSEA revealed that TREM1 activated cancer related signaling pathway, including MAPK signaling pathway and ect. High expression of TREM1 was related Macrophages M2 and Mast cells resting in GC tissues. Moreover, knockdown of TREM1 inhibited tumor growth through downregulated MAPK signaling pathway in vivo. Conclusion: These results identified that CD molecule related genes as a novel prognostic and diagnostic biomarker in gastric cancer. TREM1 acts as an oncogene role in GC by activated MAPK signaling pathway.

Sliding transformer with uncertainty estimation for vestibular schwannoma automatic segmentation.

Objective.Automated segmentation of vestibular schwannoma (VS) using magnetic resonance imaging (MRI) can enhance clinical efficiency. Though many advanced methods exist for automated VS segmentation, the accuracy is hindered by ambivalent tumor borders and cystic regions in some patients. In addition, these methods provide results that do not indicate segmentation uncertainty, making their translation into clinical workflows difficult due to potential errors. Providing a definitive segmentation result along with segmentation uncertainty or self-confidence is crucial for the conversion of automated segmentation programs to clinical aid diagnostic tools.Approach.To address these issues, we propose a U-shaped cascade transformer structure with a sliding window that utilizes multiple sliding samples, a segmentation head, and an uncertainty head to obtain both the segmentation mask and uncertainty map. We collected multimodal MRI data from 60 clinical patients with VS from Xuanwu Hospital. Each patient case includes T1-weighted images, contrast-enhanced T1-weighted images, T2-weighted images, and a tumor mask. The images exhibit an in-plane resolution ranging from 0.70 × 0.70 to 0.76 × 0.76 mm, an in-plane matrix spanning from 216 × 256 to 284 × 256, a slice thickness varying between 0.50 and 0.80 mm, and a range of slice numbers from 72 to 120.Main results.Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods. On our collected multimodal MRI dataset of clinical VS, our method achieved the dice similarity coefficient (DSC) of 96.08% ± 1.30. On a publicly available VS dataset, our method achieved the mean DSC of 94.23% ± 2.53.Significance.The method efficiently solves the VS segmentation task while providing an uncertainty map of the segmentation results, which helps clinical experts review the segmentation results more efficiently and helps to transform the automated segmentation program into a clinical aid diagnostic tool.

Role of Preoperative Albumin Quotient in Surgical Planning for Posttraumatic Syringomyelia: A Comparative Cohort Study.

OBJECTIVE: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. METHODS: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3-12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). RESULTS: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004-1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. CONCLUSION: Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.

Long-Term Impairment of the Blood-Spinal Cord Barrier in Patients With Post-Traumatic Syringomyelia and its Effect on Prognosis.

STUDY DESIGN: Cohort study. OBJECTIVE: The aim of this study was to explore the association between blood-spinal cord barrier (BSCB) markers and other factors associated with an unfavorable outcome among patients with post-traumatic syringomyelia (PTS) who achieved successful intradural adhesion lysis (IAL). SUMMARY OF BACKGROUND DATA: Only approximately half of PTS patients receiving IAL have a favorable outcome. PATIENTS AND METHODS: Forty-six consecutive patients with PTS and 19 controls (CTRL) were enrolled. All PTS patients underwent physical and neurological examinations and spinal magnetic resonance imaging before and 3 to 12 months after IAL. All patients underwent myelography before surgery. BSCB disruption was detected by increased intrathecal and serum concentrations of albumin, immunoglobulin (Ig)G, IgA, and IgM. A multivariable analysis was performed with a logistic regression model to identify factors associated with unfavorable outcomes. Receiver operating characteristic curves were calculated to investigate the diagnostic value of biomarkers. RESULTS: The ages and general health of the PTS and CTRL groups did not differ significantly. QAlb, IGAQ, IGGQ, and IGMQ was significantly higher in PTS patients than in controls ( P =<0.001). The degree of intradural adhesion was significantly higher in the unfavorable outcome group than in the favorable outcome group ( P <0.0001). QAlb, immunoglobulin (Ig)AQ, IGGQ, and IGMQ was significantly correlated with clinical status ( R =-0.38, P <0.01; R =-0.47, P =0.03; R =-0.56, P =0.01; R =-0.43, P =0.05, respectively). Higher QAlb before surgery (odds ratio=2.66; 95% CI: 1.134-6.248) was significantly associated with an unfavorable outcome. The receiver operating characteristic curve analysis demonstrated a cutoff for QAlb higher than 10.62 with a specificity of 100% and sensitivity of 96.3%. CONCLUSION: This study is the first to detect increased permeability and BSCB disruption in PTS patients. QAlb>10.62 was significantly associated with unfavorable clinical outcomes following intradural decompression. LEVEL OF EVIDENCE: Level III-prognostic.

A Novel pedicle screw placement Surgery Based on Integration of Surgical guides and Augmented Reality.

BACKGROUND: Augmented reality is a new technology that, when applied to spinal surgery, offers the potential for efficient, safe, and accurate placement of pedicle screws. This study investigated whether augmented reality combined with a guide board improved the safety and accuracy of pedicle screw placement compared to traditional free-hand screw placement. METHODS: Four trainers were divided into augmented reality navigation and free-hand groups. Each group consisted of a novice and an experienced spine surgeon. A total of 80 pedicle screws were implanted. First, the AR group reconstructed the 3D model and planned the screw insertion route according to the CT data of L2 lumbar vertebrae. Next, the Microsoft HoloLens™ 2 was used to identify the vertebral model, and the planned virtual path was superimposed on the real cone model. Next, the screw was placed according to the projected trajectory. Finally, Micron Tracker was used to measure the deviation of screws from the preoperatively planned trajectory, and pedicle screws were evaluated using the Gertzbein-Robbins scale. RESULTS: In the augmented reality group, the linear deviation of experienced doctors and novices was 1.59 ± 0.39 mm and 1.73 ± 0.52 mm, and the angle deviation was 2.72 ± 0.61° and 2.87 ± 0.63°, respectively. In the free-hand group, the linear deviation of experienced doctors and novices was 2.88 ± 0.58mm and 5.25 ± 0.62mm, and the angle deviation was 4.41 ± 1.18° and 7.15 ±1.45°, respectively. The screw accuracy rate was 97.5% in the augmented reality navigation group and 77.5% in the free-hand group. CONCLUSIONS: Augmented reality navigation improves the accuracy and safety of pedicle screw implantation compared with the traditional free-hand method and can assist inexperienced doctors in completing the surgery.

Uncertainty-guided transformer for brain tumor segmentation.

Multi-model data can enhance brain tumor segmentation for the rich information it provides. However, it also introduces some redundant information that interferes with the segmentation estimation, as some modalities may catch features irrelevant to the tissue of interest. Besides, the ambiguous boundaries and irregulate shapes of different grade tumors lead to a non-confidence estimate of segmentation quality. Given these concerns, we exploit an uncertainty-guided U-shaped transformer with multiple heads to construct drop-out format masks for robust training. Specifically, our drop-out masks are composed of boundary mask, prior probability mask, and conditional probability mask, which can help our approach focus more on uncertainty regions. Extensive experimental results show that our method achieves comparable or higher results than previous state-of-the-art brain tumor segmentation methods, achieving average dice coefficients of [Formula: see text] and Hausdorff distance of 4.91 on the BraTS2021 dataset. Our code is freely available at https://github.com/chaineypung/BTS-UGT.

Detection of Glioma-Related Hotspot Mutations Through Sequencing of Cerebrospinal Fluid (CSF)-Derived Circulating Tumor DNA: A Pilot Study on CSF-Based Liquid Biopsy for Primary Spinal Cord Astrocytoma.

OBJECTIVE: Although cerebrospinal fluid (CSF)-based liquid biopsy was proved to be practical in molecular analysis of intracranial gliomas, liquid biopsy of primary intramedullary astrocytoma was rarely reported. Given the distinct genomic profiles between primary intramedullary glioma and intracranial astrocytoma, whether the feasibility of CSF-based molecular analysis of intracranial gliomas can be replicated in primary spinal cord astrocytoma needs to be investigated. The aim of this pilot study is to evaluate the feasibility of molecular analysis of primary intramedullary astrocytoma through sequencing CSF-derived circulating tumor DNA (ctDNA). METHODS: Two grade IV diffuse midline gliomas, 1 grade II, and 1 grade I astrocytoma were included. Intraoperative collection of peripheral blood and CSF samples was conducted, along with postoperative collection of matched tumor tissues. A panel covering the 1,021 most common driver genes of solid tumors was used for targeted DNA sequencing. RESULTS: CSF-derived ctDNA was detected in 3 CSF samples (2 grade IV diffuse midline gliomas and 1 grade I astrocytoma), 5 mutations were found in both tumor tissues and CSF samples, while 11 mutations and 20 mutations were detected exclusively in tumor tissues and CSF samples, respectively. Importantly, hotspot genetic alterations, including H3F3A K28M, TP53, and ATRX, were identified in CSF and the average mutant allele frequency was often higher in CSF than in tumor tissues. CONCLUSION: CSF-based liquid biopsy showed potential feasibility for molecular analysis of primary intramedullary astrocytoma through sequencing of ctDNA. This approach may assist in diagnosis and prognostic evaluation of this rare spinal cord tumor.

A sporadic pediatric case of a spinal dumbbell-shaped epithelioid malignant peripheral nerve sheath tumor with a novel germline mutation in SMARCB1: a case report and review of the literature.

Malignant peripheral nerve sheath tumors (MPNSTs) are commonly associated with poor prognosis and are primarily caused by germline mutations in the SMARCB1/INI-1 gene. However, these tumors are rarely found in the spine. This case report presents the case of a 3-year-old boy diagnosed with a lumbosacral dumbbell-shaped epithelioid MPNST, an extremely uncommon manifestation. Immunohistochemistry revealed the complete absence of the SMARCB1/INI-1 protein, and genetic testing identified a novel germline mutation in the SMARCB1/INI-1 gene in both the patient and his father, suggesting a "second-hit loss." One year of follow-up after the tumor's radical resection revealed no suspected metastasis. This case report offers novel genetic research results regarding spinal dumbbell-shaped MPNSTs. Six studies, including 13 cases associated with spinal dumbbell MPNST, were included in the literature. The range of age of these patients varied from 2 to 71 years. Of the 12 known patients diagnosed with spinal dumbbell MPNST, only one received radiation therapy, while the rest underwent surgery. Two patients who underwent partial resection had metastases after surgery, while one of the five patients who underwent complete surgical resection alone had no distant metastases and a good prognosis, indicating that radical resection is more likely to be effective in inhibiting distant metastasis and improving the prognosis.

Postoperative Spinal 18 F-FDG PET Pseudoprogression Mimicking Malignancy.

ABSTRACT: A 60-year-old woman presented with left upper limb weakness. Spinal MRI revealed C2-C3 heterogeneous mass with no hypermetabolic foci on 18 F-FDG PET. Total resection was performed, and the pathology showed gliosis. Her limb weakness worsened 3 months after surgery. Spinal MRI revealed long intramedullary mass from medulla oblongata to C5, which showed obvious hypermetabolism under 18 F-FDG PET with an SUV max of 7.11, but 18 F-FET PET indicated mild hypermetabolism with an SUV max of 2.29. Malignancy was suspected, and C2-C4 biopsy was performed. The pathology results confirmed the diagnosis of gliosis, and the postoperative spinal 18 F-FDG PET results were considered pseudoprogression.