From bench to bedside: Advancing towards therapeutic treatment of vestibular schwannomas.

Vestibular schwannomas are rare intracranial tumors originating from Schwann cells of the vestibular nerve. Despite their benign nature, these tumors can exert significant mass effects and debilitating symptoms, including gradual hearing loss, vertigo, facial nerve dysfunction, and headaches. Current clinical management options encompass wait-and-scan, surgery, radiation therapy, and off-label medication. However, each approach exhibits its own challenges and harbors limitations that underscore the urgent need for therapeutic treatments. Over the past 2 decades, extensive elucidation of the molecular underpinnings of vestibular schwannomas has unraveled genetic anomalies, dysregulated signaling pathways, downstream of receptor tyrosine kinases, disrupted extracellular matrix, inflammatory tumor microenvironment, and altered cerebrospinal fluid composition as integral factors in driving the development and progression of the disease. Armed with this knowledge, novel therapeutic interventions tailored to the unique molecular characteristics of those conditions are actively being pursued. This review underscores the urgency of addressing the dearth of Food and Drug Administration-approved drugs for vestibular schwannoma, highlighting the key molecular discoveries and their potential translation into therapeutics. It provides an in-depth exploration of the evolving landscape of therapeutic development, which is currently advancing from bench to bedside. These ongoing efforts hold the promise of significantly transforming the lives of vestibular schwannoma patients in the future.

Regulation of ferroptosis by nanotechnology for enhanced cancer immunotherapy.

INTRODUCTION: This review explores the innovative intersection of ferroptosis, a form of iron-dependent cell death, with cancer immunotherapy. Traditional cancer treatments face limitations in efficacy and specificity. Ferroptosis as a new paradigm in cancer biology, targets metabolic peculiarities of cancer cells and may potentially overcome such limitations, enhancing immunotherapy. AREA COVERED: This review centers on the regulation of ferroptosis by nanotechnology to augment immunotherapy. It explores how nanoparticle-modulated ferroptotic cancer cells impact the TME and immune responses. The dual role of nanoparticles in modulating immune response through ferroptosis are also discussed. Additionally, it investigates how nanoparticles can be integrated with various immunotherapeutic strategies, to optimize ferroptosis induction and cancer treatment efficacy. The literature search was conducted using PubMed and Google Scholar, covering articles published up to March 2024. EXPERT OPINION: The manuscript underscores the promising yet intricate landscape of ferroptosis in immunotherapy. It emphasizes the need for a nuanced understanding of ferroptosis' impact on immune cells and the TME to develop more effective cancer treatments, highlighting the potential of nanoparticles in enhancing the efficacy of ferroptosis and immunotherapy. It calls for deeper exploration into the molecular mechanisms and clinical potential of ferroptosis to fully harness its therapeutic benefits in immunotherapy.

Photosynthetic bacteria-based whole-cell inorganic-biohybrid system for multimodal enhanced tumor radiotherapy.

The whole-cell inorganic-biohybrid systems show special functions and wide potential in biomedical application owing to the exceptional interactions between microbes and inorganic materials. However, the hybrid systems are still in stage of proof of concept. Here, we report a whole-cell inorganic-biohybrid system composed of Spirulina platensis and gold nanoclusters (SP-Au), which can enhance the cancer radiotherapy through multiple pathways, including cascade photocatalysis. Such systems can first produce oxygen under light irradiation, then convert some of the oxygen to superoxide anion (•O2-), and further oxidize the glutathione (GSH) in tumor cells. With the combination of hypoxic regulation, •O2- production, GSH oxidation, and the radiotherapy sensitization of gold nanoclusters, the final radiation is effectively enhanced, which show the best antitumor efficacy than other groups in both 4T1 and A549 tumor models. Moreover, in vivo distribution experiments show that the SP-Au can accumulate in the tumor and be rapidly metabolized through biodegradation, further indicating its application potential as a new multiway enhanced radiotherapy sensitizer.

Treatment and Diagnose of Spinal Phosphaturic Mesenchymal Tumor: A Case Report and a Systematic Literature Review.

BACKGROUND: Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases. METHODS: A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were ("PMT" or "TIO" or "Tumor-induced osteomalacia" or "phosphaturic mesenchymal tumor") and ("spine" or "spinal"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented. RESULTS: We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options. CONCLUSIONS: Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect.

Long-term postoperative outcomes of spinal cellular schwannoma: study of 93 consecutive cases.

BACKGROUND CONTEXT: Cellular schwannoma (CS) is a rare tumor that accounts for 2.8%-5.2% of all benign schwannomas. There is a dearth of up-to-date information on spinal CS in the literature. PURPOSE: The aims of this study were to identify the proportion of CS cases amongst spinal benign schwannoma, describe the clinical features of spinal CS, and identify prognostic factors for local recurrence by analyzing data from 93 consecutive CS cases. STUDY DESIGN: Retrospective review. PATIENT SAMPLE: We analyzed 93 PSGCT screened from 1,706 patients with spine CS who were treated at our institute between 2008 and 2021. OUTCOME MEASURES: Demographic, radiographic, operative and postoperative data were recorded and analyzed. METHODS: We compared the clinical features of spinal CS from the cervical, thoracic, lumbar and sacral segments. Prognostic factors for local recurrence-free survival (RFS) were identified by the Kaplan-Meier method. Factors with p≤.05 in univariate analysis were subjected to multivariate analysis by Cox regression analysis. RESULTS: The proportion of spinal CS in all benign schwannomas was 6.7%. The mean and median follow-up times for the 93 patients in this study were 92.2 and 91.0 months respectively (range 36-182 months). Local recurrence was detected in 11 cases, giving an overall recurrence rate of 11.7%, with one patient death. Statistical analysis revealed that tumor size ≥5 cm, intralesional resection, and Ki-67 ≥5% were independent negative prognostic factors for RFS in spinal CS. CONCLUSIONS: Whenever possible, en bloc resection is recommended for spinal CS. Long-term follow-up should be carried out for patients with tumor size ≥5 cm and postoperative pathological Ki-67 ≥5%.

LncRNA NEAT1 aggravates human microvascular endothelial cell injury by inhibiting the Apelin/Nrf2/HO-1 signalling pathway in type 2 diabetes mellitus with obstructive sleep apnoea.

Long noncoding RNAs (lncRNAs) regulate the progression of type 2 diabetes mellitus complicated with obstructive sleep apnoea (T2DM-OSA). However, the role of the lncRNA nuclear paraspeckle assembly transcript 1 (NEAT1) in T2DM-OSA remains unknown. This study aimed to reveal the function of NEAT1 in T2DM-OSA and the underlying mechanism. KKAy mice were exposed to intermittent hypoxia (IH) or intermittent normoxia to generate a T2DM-OSA mouse model. HMEC-1 cells were treated with high glucose (HG) and IH to construct a T2DM-OSA cell model. RNA expression was detected by qRT-PCR. The protein expression of Apelin, NF-E2-related factor 2 (Nrf2), haem oxygenase-1 (HO-1), and up-frameshift suppressor 1 (UPF1) was assessed using western blot. Cell injury was evaluated using flow cytometry, enzyme-linked immunosorbent assay, and oxidative stress kit assays. RIP, RNA pull-down, and actinomycin D assays were performed to determine the associations between NEAT1, UPF1, and Apelin. NEAT1 expression was upregulated in the aortic vascular tissues of mice with T2DM exposed to IH and HMEC-1 cells stimulated with HG and IH, whereas Apelin expression was downregulated. The absence of NEAT1 protected HMEC-1 cells from HG- and IH-induced damage. Furthermore, NEAT1 destabilized Apelin mRNA by recruiting UPF1. Apelin overexpression decreased HG- and IH-induced injury to HMEC-1 cells by activating the Nrf2/HO-1 pathway. Moreover, NEAT1 knockdown reduced HG- and IH-induced injury to HMEC-1 cells through Apelin. NEAT1 silencing reduced HMEC-1 cell injury through the Apelin/Nrf2/HO-1 signalling pathway in T2DM-OSA.Abbreviations: LncRNAs, long non-coding RNAs; T2DM, type 2 diabetes mellitus; OSA, obstructive sleep apnoea; NEAT1, nuclear paraspeckle assembly transcript 1; IH, intermittent hypoxia; HMEC-1, human microvascular endothelial cells; HG, high glucose; Nrf2, NF-E2-related factor 2; UPF1, up-frameshift suppressor 1; HO-1, haem oxygenase-1; qRT-PCR, quantitative real-time polymerase chain reaction; ELISA, enzyme-linked immunosorbent assay; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; TNF-α, tumour necrosis factor-α; CCK-8, Cell Counting Kit-8; IL-1ß, interleukin-1ß; ROS, reactive oxygen species; MDA, malondialdehyde; SOD, superoxide dismutase; RIP, RNA immunoprecipitation; SD, standard deviations; GSH, glutathione; AIS, acute ischaemic stroke; HMGB1, high mobility group box-1 protein; TLR4, toll-like receptor 4.

Measurement properties of health-related quality of life measures for people living with metastatic disease of the spine: a systematic review.

PURPOSE: Patients with spinal metastases (SM) suffer from a significant quality of life (QoL) deterioration. The measurement of QoL has garnered significant attention. In this study, the authors aimed to investigate the frequency of QoL measurement, systematically appraise the measurement properties of identified instruments, and facilitate the effective selection of an appropriate QoL instrument for patients with SM. METHODS: This systematic review adhered to the newly revised Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement guidelines. The methodological quality of the studies was assessed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) checklist. Measurement property results were assessed using the adapted criteria. Each measurement property was allocated a separate rating (excellent, good, fair, or poor). 'Best evidence synthesis' was performed using COSMIN outcomes and the quality of findings. RESULT: Two hundred and nine publications were included, and 18 instruments were identified. ECOG, EuroQol-5D, SF-36, SOSGOQ, and EORTC-QLQ-C30 were the top five instruments used for patients with SM in published literature. The measurement properties evaluated included internal consistency (four instruments), reliability (three instruments), validity (five instruments), validity (nine measures), floor and ceiling effects (four instruments), responsiveness (four instruments), and interpretability (three measures). Based on the limited evidence, the Brief Pain Inventory (BPI) had the best methodological quality. CONCLUSIONS: Owing to the limitations of BPI in assessment domains, we cannot fully support the use of BPI. For the lack of high-quality research, it is challenging to nominate a single appropriate measure. Additional studies are needed to explore the evidence before a confirmatory decision is made.

Assessing Cross-Cultural Adaptation of the Spine Oncology Study Group Outcomes Questionnaire 2.0: A Methodological Systematic Review Regard to Consensus-Based Standards for the Selection of Health Measurement Instruments Guideline.

STUDY DESIGN: systematic review of cross-cultural adaptation. OBJECTIVES: SOSGOQ 2.0 was widely used to assess the HRQQOL of patients with spinal metastasis. Due to the lack of methodological quality assessment, it is a challenge to use the questionnaire in routine practice. This study aims to comprehensively evaluate the translation procedures and measurement attributes of SOSGOQ 2.0 according to COSMIN guidelines. METHODS: The literature was reviewed adhering to the PRISMA guidelines. Each translation process and different cultural adaptation methods were classified according to the guidelines for Cross cultural Adaptation Process of Self Reporting Measures, and the methodological quality of the identified research was evaluated according to the consensus based on the selection criteria of health measurement tools. RESULTS: 6 publications finally met the inclusion criteria. As for the evaluation of translation procedures and cross-cultural adaptability, two adaptations did not report the detailed information in translation and cross-cultural adaptation (synthesis, back translation, review by expert committee, pre-test), factor analysis and sample size calculation were only mentioned in two studies, and only one adaptation met the minimum sample size standard. Regard to the methodological quality assessment of measurement attributes, all adaptations completed internal consistency, structural effectiveness and reliability. However, none of the adaptations reported measurement errors and only one reported response sensitivity. CONCLUSIONS: We found that the methodological quality of the current adaptation was uneven, and the report of measurement attribute results was not comprehensive. We recommend higher quality German, Italian and Chinese adaptation.

Comparison of Imaging Characteristics of Gangliogliomas between Child/Adolescent Group and Adult Group.

BACKGROUND: Ganglioglioma is a rare, slowly proliferating mixed glioneuronal tumor, with the highest incidence observed in children and young adults, but it can also occur in adults. OBJECTIVE: This study aimed to compare the imaging characteristics of ganglioglioma in children/adolescents and adults to facilitate radiographic diagnosis. METHODS: In this retrospective study, a total of 32 patients were included and divided into two groups: the child/adolescent group (age < 18 years, n=19) and the adult group (age ≥ 18 years, n=13). Various variables were analyzed, including maximum diameter, location, periphery, border, calcification, unenhanced CT attenuation, T1WI, T2WI/FLAIR, and DWI signal intensity, enhancement pattern, degree of enhancement, homogeneity of enhancement, solid/cystic component, peri-tumoral edema, intra-tumoral septa, peri-tumoral capsule, and intra-tumoral hemorrhage. RESULTS: Most gangliogliomas were situated in the peripheral regions, particularly in the temporal lobe. The majority exhibited hypointense/isointense signals on T1WI and hyperintense signals on T2WI/FLAIR and DWI, with predominantly heterogeneous nodular enhancement. Peri-tumoral edema was significantly less frequent in the child/adolescent group, while marked enhancement was significantly more common in the adult group. There was no significant difference in maximum diameter between the child/adolescent group and the adult group. CONCLUSION: Peri-tumoral edema was significantly less prevalent in the child/adolescent group, whereas marked enhancement was significantly more frequent in the adult group. To ensure accurate results, a larger case series should be conducted to validate our findings.

MSIF-LNP: microbial and human health association prediction based on matrix factorization noise reduction for similarity fusion and bidirectional linear neighborhood label propagation.

Studies have shown that microbes are closely related to human health. Clarifying the relationship between microbes and diseases that cause health problems can provide new solutions for the treatment, diagnosis, and prevention of diseases, and provide strong protection for human health. Currently, more and more similarity fusion methods are available to predict potential microbe-disease associations. However, existing methods have noise problems in the process of similarity fusion. To address this issue, we propose a method called MSIF-LNP that can efficiently and accurately identify potential connections between microbes and diseases, and thus clarify the relationship between microbes and human health. This method is based on matrix factorization denoising similarity fusion (MSIF) and bidirectional linear neighborhood propagation (LNP) techniques. First, we use non-linear iterative fusion to obtain a similarity network for microbes and diseases by fusing the initial microbe and disease similarities, and then reduce noise by using matrix factorization. Next, we use the initial microbe-disease association pairs as label information to perform linear neighborhood label propagation on the denoised similarity network of microbes and diseases. This enables us to obtain a score matrix for predicting microbe-disease relationships. We evaluate the predictive performance of MSIF-LNP and seven other advanced methods through 10-fold cross-validation, and the experimental results show that MSIF-LNP outperformed the other seven methods in terms of AUC. In addition, the analysis of Cystic fibrosis and Obesity cases further demonstrate the predictive ability of this method in practical applications.

Large pneumothorax following thoracic and lumbar tumor surgery: Risk factors and management strategies.

Objective: Large pneumothorax is a rare but dangerous complication following thoracic and lumbar tumor surgery. There is little discussion about the features of large pneumothorax following spinal tumor surgery. The purpose of this study was to analyze the characteristics of postoperative pneumothorax, identify factors related to large pneumothorax, and propose a management algorithm for prevention, diagnosis, and treatment. Methods: Included in this retrospective study were 118 patients who developed pneumothorax after receiving thoracic and lumbar tumor surgery between January 2015 and October 2021. A measurement of lung compression ≥20% on chest CT or x-ray was defined as large pneumothorax, and potential risk factors for large pneumothorax were identified by univariate analysis. Results: Spinal tumor history and intraoperative blood loss were risk factors for large pneumothorax. The common symptoms of postoperative pneumothorax were chest pain, chest tightness and dyspnea. The mean longest transverse diameter of tumors was 6.63 ± 2.4 cm. En bloc resection was performed in 70 patients, with a mean operation time of 6.9 ± 2.5 h and mean intraoperative blood loss of 1771 ± 1387 ml. The most common pathologies were chondrosarcoma, giant cell tumors of bone, and neurogenic tumors. Conclusion: During surgery, an artificial dura mater patch and a prolene suture can be used to repair the pleural and lung defects. We recommend chest CT as the preferred method for identifying postoperative pneumothorax. If a patient presents severe dyspnea, a large pneumothorax or concurrent pleural effusion, application of chest drainage is strongly recommended.

Identification and validation of DPY30 as a prognostic biomarker and tumor immune microenvironment infiltration characterization in esophageal cancer.

Esophageal cancer (ESCA) is a lethal malignancy and is associated with the alterations of various genes and epigenetic modifications. The protein dpy-30 homolog (DPY30) is a core member of histone H3K4 methylation catalase and its dysfunction is associated with the occurrence and development of cancer. Therefore, the present study investigated the role of DPY30 in ESCA and evaluated the association between the expression of DPY30, the clinicopathological characteristics of ESCA and the tumor immune microenvironment. It conducted a comprehensive analysis of DPY30 in patients with ESCA using The Cancer Genome Atlas (TCGA) database and clinical tissue microarray specimens of ESCA. Immunohistochemistry was performed to assess the expression levels of DPY30 in tissues. Receiver operating curve analysis, Kaplan-Meier survival analysis and Cox regression analysis were performed to identify the diagnostic and prognostic value of DPY30. Gene Set Enrichment Analysis, protein-protein interaction network and Estimation of Stromal and Immune cells in Malignant Tumor tissues using the Expression data were used to screen DPY30-associated genes and evaluate the immune score of the TCGA samples. The results demonstrated that the expression of mRNA and protein levels of DPY30 were significantly upregulated in tumor tissues compared with normal tissue samples. The expression of DPY30 was closely associated with the poor prognosis of patients with ESCA. The present study also found that DPY30 expression and the pathological characteristics of ESCA were significantly correlated. Additionally, the expression of DPY30 demonstrated a significant positive correlation with various immune cells infiltration. The results suggested that DPY30 might influence tumor immune infiltration. In conclusion, the findings suggested that DPY30 might be a potential prognostic biomarker and an immunotherapeutic target in ESCA.

A novel molecular classification method for osteosarcoma based on tumor cell differentiation trajectories.

Subclassification of tumors based on molecular features may facilitate therapeutic choice and increase the response rate of cancer patients. However, the highly complex cell origin involved in osteosarcoma (OS) limits the utility of traditional bulk RNA sequencing for OS subclassification. Single-cell RNA sequencing (scRNA-seq) holds great promise for identifying cell heterogeneity. However, this technique has rarely been used in the study of tumor subclassification. By analyzing scRNA-seq data for six conventional OS and nine cancellous bone (CB) samples, we identified 29 clusters in OS and CB samples and discovered three differentiation trajectories from the cancer stem cell (CSC)-like subset, which allowed us to classify OS samples into three groups. The classification model was further examined using the TARGET dataset. Each subgroup of OS had different prognoses and possible drug sensitivities, and OS cells in the three differentiation branches showed distinct interactions with other clusters in the OS microenvironment. In addition, we verified the classification model through IHC staining in 138 OS samples, revealing a worse prognosis for Group B patients. Furthermore, we describe the novel transcriptional program of CSCs and highlight the activation of EZH2 in CSCs of OS. These findings provide a novel subclassification method based on scRNA-seq and shed new light on the molecular features of CSCs in OS and may serve as valuable references for precision treatment for and therapeutic development in OS.

Prognostic factors and outcomes of surgical intervention for patients with spinal metastases secondary to lung cancer: an update systematic review and meta analysis.

PURPOSE: Lung cancer is one of the most common malignant tumors. Most patients develop spinal metastases during the course of cancer and suffer skeletal-related events. Currently, no consensus has been reached on the prognostic factors in patients undergoing surgeries. This study aimed to answer two questions: (1) what are the effects of surgical intervention, and (2) what are the factors associated with postoperative survival. METHODS: Searches were performed on electronic databases including PubMed, Ovid/MEDLINE, Cochrane, and Scopus for articles published before February of 2022, involving the survival factors of patients with spinal metastasis. Multiple data items were considered, such as baseline demographics, surgical details, clinical outcome, and prognostic factors. The analysis was performed in Review Manager (RevMan) 5.5. The prognostic factors of survival were analyzed with univariate and multivariate cox regression analysis. RESULTS: Finally, 14 studies with 813 patients were identified. Their 6, 12, and 24 months survival rates ranged from 18 to 58%, 18 to 22.4%, and 0 to 58.5%, respectively. The pooled hazard ratio of preoperative ambulatory status and the number of involved vertebrae demonstrated statistical significance, while no significant prognostic effect on the overall survival was found for targeted therapy, visceral metastases, chemotherapy, radiotherapy, or postoperative ambulatory status. CONCLUSION: Overall, surgical intervention could achieve significant pain relief and neurological function improvements. For patients receiving surgery for spinal metastasis from lung cancer, preoperative ambulatory status and the number of involved vertebrae were significant prognostic factors associated with their survival.

Pediatric meningioma with a Novel MAML2-YAP1 fusion variant: a case report and literature review.

BACKGROUND: Pediatric meningioma with YAP1 fusion is a rare subset of meningiomas. Currently, there are lack of integrated clinical, radiological, and pathological features on this subset. Here, we reported a case of pediatric meningioma with a novel MAML2-YAP1 fusion variant and reviewed the relevant literature. CASE PRESENTATION: We presented a case of 12-year-old boy with meningioma adjacent to the superior sagittal sinus and falx. Simpson grade II gross total resection was performed after diagnosis. Pathologically, he was diagnosed as WHO grade I meningothelial meningioma with rhabdoid features. A next-generation sequencing-based gene panel was performed to determine the molecular features for potential treatment, and a novel MAML2-YAP1 fusion break point was identified. CONCLUSION: Pediatric meningioma with the fusion of YAP1 and MAML2 genes is more likely to have pathological features of rhabdiod cells, which needs to be validated in large-scale studies for exploring better treatment under the integrated diagnosis.

Construction and validation of a novel web-based nomogram for patients with lung cancer with bone metastasis: A real-world analysis based on the SEER database.

Purpose: Patients with lung cancer with bone metastasis (LCBM) often have a very poor prognosis. The purpose of this study is to characterize the prevalence and associated factors and to develop a prognostic nomogram to predict the overall survival (OS) and cancer-specific survival (CSS) for patients with LCBM using multicenter population-based data. Methods: Patients with LCBM at the time of diagnosis were identified using the Surveillance, Epidemiology, and End Results (SEER) Program database of the National Cancer Institute (NCI) from 2010 to 2015. Multivariable and univariate logistic regression analyses were performed to identify factors associated with all-cause mortality and lung cancer (LC)-specific mortality. The performance of the nomograms was evaluated with the calibration curves, area under the curve (AUC), and decision curve analysis (DCA). Kaplan-Meier analysis and log-rank tests were used to estimate the survival times of patients with LCBM. Results: We finally identified 26,367 patients with LCBM who were selected for survival analysis. Multivariate analysis demonstrated age, sex, T stage, N stage, grade, histology, radiation therapy, chemotherapy, primary site, primary surgery, liver metastasis, and brain metastasis as independent predictors for LCBM. The AUC values of the nomogram for the OS prediction were 0.755, 0.746, and 0.775 in the training cohort; 0.757, 0.763, and 0.765 in the internal validation cohort; and 0.769, 0.781, and 0.867 in the external validation cohort. For CSS, the values were 0.753, 0.753, and 0.757 in the training cohort; 0.753, 0.753, and 0.757 in the internal validation cohort; and 0.767, 0.774, and 0.872 in the external validation cohort. Conclusions: Our study constructs a new prognostic model and clearly presents the clinicopathological features and survival analysis of patients with LCBM. The result indicated that the nomograms had favorable discrimination, good consistency, and clinical benefits in patients. In addition, our constructed nomogram prediction models may assist physicians in evaluating individualized prognosis and deciding on treatment for patients.

Cross-cultural adaptation and validation of simplified Chinese version of the Spine Oncology Study Group Outcomes Questionnaire (SOSGOQ) 2.0 with its assessment in clinical setting.

BACKGROUND CONTEXT: The treatment of spinal metastases (SM) has been significantly improved in recent years, which gives health-related quality of life (HRQOL) further significance in management of SM. The Spine Oncology Study Group Outcomes Questionnaire version 2.0 (SOSGOQ 2.0) was a specific targeted SM HRQOL criterion that was previously reported to pose good reliability and validity. However, there is no culturally adapted, reliable, and validated version of SOSGOQ 2.0 in mainland China. PURPOSE: The current study aimed to translate the SOSGOQ 2.0 in a cross-cultural fashion, before evaluating the reliability and validity of the adapted simplified Chinese version of (SC-SOSGOQ 2.0) for patients with spinal metastases (SM). STUDY DESIGN/SETTING: Translation, cross-cultural adaptation, and validation were performed on the Chinese version of the SOSGOQ 2.0. PATIENT SAMPLE: Patients who were diagnosed with metastatic spinal disease, posing at least 6-years experience of education and the ability to read and speak Chinese. OUTCOME MEASURES: Reliability and Validity of the SC-SOSGOQ 2.0 were measured to assess HRQOL in patients with SM. METHODS: The cross-cultural adaptation of the SOSGOQ 2.0 was conducted following international guidelines. The reliability and validity of the SC-SOSGOQ 2.0 was assessed in a multi-center, prospective observational study. The test-retest reliability was assessed by comparing the results of the first and final SC-SOSGOQ 2.0 scales, with 2 weeks apart. The discriminative, concurrent, and construct validity of the cross-culturally adapted questionnaire was individually evaluated. The relationship among the SC-SOSGOQ 2.0, SC-EQ-5D-5L and SC-SF-36 was assessed using the correlation coefficients. RESULTS: One hundred and twenty patients were included in this study. No floor or ceiling effects were observed for the SC-SOSGOQ 2.0. The Cronbach's α for domains of neurological function, pain, mental health, social function, and post-therapy were 0.825, 0.876, 0.896, 0.897, 0.943, and 0.835, respectively. The value of inter-class correlation coefficient ranged from 0.55 to 0.83, which reflected a satisfactory test-retest reliability. Concurrent assessment of criterion validity demonstrated a moderate-to-strong correlation in all domains of SC-SOSGOQ 2.0 with the SC-EQ-5D-5L (0.34-0.74) and SC-SF-36 (0.33-0.76). The best-correlated domain was physical function (0.741 in the EQ-5D-5L and 0.722 in the SF-36). CONCLUSIONS: The SC-SOSGOQ 2.0 demonstrated an excellent acceptability, score distribution, internal consistency, test-retest reliability and validity. It was therefore considered as a tool effective for evaluating HRQOL of Chinese patients with SM.

Factors Related to Instrumentation Failure in Titanium Mesh Reconstruction for Thoracic and Lumbar Tumors: Retrospective Analysis of 178 Patients.

PURPOSE: To investigate risk factors for instrumentation failure (IF) in titanium (Ti) mesh reconstruction for thoracic and lumbar tumors. PATIENTS AND METHODS: The clinical data of patients with thoracic or lumbar tumors who received Ti mesh reconstruction via the posterior approach in our hospital from 2013 to 2018 were analyzed retrospectively. The observation indexes included sex, age, BMI, the vertebra resection mode, the number of resected vertebral segments, application of bone cement, radiotherapy, chemotherapy, revision or primary surgery, and primary tumor metastasis. Correlations between these factors and IF were analyzed by Kaplan-Meier survival and logistics regression analyses. RESULTS: The 178 patients included 108 males and 70 females with a mean age of 48.09±16.21 (6-78) years and a mean follow-up period of 51.18 (24-90) months. The data showed that 17 patients (9.55%) were inflicted with IF, involving the thoracic vertebra in 11 cases, thoracolumbar vertebrae (T12-L1) in 2 cases, and lumbar vertebrae in 4 cases. The mean interval between surgery to IF was 35.18±14.17 (14-59) months. Univariate analysis showed that total vertebral body resection, the number of resected vertebral segments, radiotherapy and multiple tumor resection were potential factors for IF, while multivariate analysis showed that only total vertebral body resection, the number of resected vertebral segments and radiotherapy were independent factors. CONCLUSION: Total vertebra resection, the number of resected vertebral segments (≥2) and radiotherapy before and after operation were significant risk factors related to IF.

Targeting nanoparticles for diagnosis and therapy of bone tumors: Opportunities and challenges.

A variety of targeted nanoparticles were developed for the diagnosis and therapy of orthotopic and metastatic bone tumors during the past decade. This critical review will focus on principles and methods in the design of these bone-targeted nanoparticles. Ligands including bisphosphonates, aspartic acid-rich peptides and synthetic polymers were grafted on nanoparticles such as PLGA nanoparticles, liposomes, dendrimers and inorganic nanoparticles for bone targeting. Besides, other ligands such as monoclonal antibodies, peptides and aptamers targeting biomarkers on tumor/bone cells were identified for targeted diagnosis and therapy. Examples of targeted nanoparticles for the early detection of bone metastatic tumors and the ablation of cancer via chemotherapy, photothermal therapy, gene therapy and combination therapy will be intensively reviewed. The development of multifunctional nanoparticles to break down the "vicious" cycle between tumor cell proliferation and bone resorption, and the challenges and perspectives in this area will be discussed.

Carrier-Free Platinum Nanomedicine for Targeted Cancer Therapy.

Numerous nanomedicines have been developed to improve the efficiency and safety of conventional anticancer drugs; however, the complexities in carrier materials and functional integration make it challenging to promote these candidates for clinical translation. In this study, a facile method to prepare carrier-free anticancer nanodrug with inherent bone targeting and osteoclastogenesis inhibition capabilities is reported. Phytic acid, a naturally occurring and nontoxic product, is reacted with cisplatin to form uniform nanoparticles of different sizes. The prepared nanoparticles possess high drug loading and pH-responsive drug release behaviors. Phytic acid in the nanomedicine ensures high bone targeting and osteoclastogenesis inhibition, and the released platinum drugs triggered by tumor extracellular acidity eradicate tumor cells. The nanomedicine around 100 nm shows high anticancer activity and much reduced side effects in a subcutaneous breast cancer model when compared with cisplatin. In addition, it shows high accumulation at osteolytic lesions, and efficiently inhibits tumor growth and tumor-associated osteolysis in a bone metastatic breast cancer model. Here, a facile and efficient strategy to prepare carrier-free nanomedicines with high anticancer drug loading, inherent bone targeting, and osteoclast inhibitory activities for cancer therapy is provided.