Radiomics model based on MRI to differentiate spinal multiple myeloma from metastases: A two-center study.

Purpose: Spinal multiple myeloma (MM) and metastases are two common cancer types with similar imaging characteristics, for which differential diagnosis is needed to ensure precision therapy. The aim of this study is to establish radiomics models for effective differentiation between them. Methods: Enrolled in this study were 263 patients from two medical institutions, including 127 with spinal MM and 136 with spinal metastases. Of them, 210 patients from institution I were used as the internal training cohort and 53 patients from Institution II were used as the external validation cohort. Contrast-enhanced T1-weighted imaging (CET1) and T2-weighted imaging (T2WI) sequences were collected and reviewed. Based on the 1037 radiomics features extracted from both CET1 and T2WI images, Logistic Regression (LR), AdaBoost (AB), Support Vector Machines (SVM), Random Forest (RF), and multiple kernel learning based SVM (MKL-SVM) were constructed. Hyper-parameters were tuned by five-fold cross-validation. The diagnostic efficiency among different radiomics models was compared by accuracy (ACC), sensitivity (SEN), specificity (SPE), area under the ROC curve (AUC), YI, positive predictive value (PPV), negative predictive value (NPY), and F1-score. Results: Based on single-sequence, the RF model outperformed all other models. All models based on T2WI images performed better than those based on CET1. The efficiency of all models was boosted by incorporating CET1 and T2WI sequences, and the MKL-SVM model achieved the best performance with ACC, AUC, and F1-score of 0.862, 0.870, and 0.874, respectively. Conclusions: The radiomics models constructed based on MRI achieved satisfactory diagnostic performance for differentiation of spinal MM and metastases, demonstrating broad application prospects for individualized diagnosis and treatment.

Development and validation of a machine learning-based postoperative prognostic model for plasma cell neoplasia with spinal lesions as initial clinical manifestations: a single-center cohort study.

BACKGROUND: Spinal multiple myeloma (MM) and solitary plasmacytoma of bone (SPB), both plasma cell neoplasms, greatly affect patients' quality of life due to spinal involvement. Accurate prediction of surgical outcomes is crucial for personalized patient care, but systematic treatment guidelines and predictive models are lacking. OBJECTIVE: This study aimed to develop and validate a machine learning (ML)-based model to predict postoperative outcomes and identify prognostic factors for patients with spinal MM and SPB. METHODS: A retrospective analysis was conducted on patients diagnosed with MM or SPB from 2011 to 2015, followed by prospective data collection from 2016 to 2017. Patient demographics, tumor characteristics, clinical treatments, and laboratory results were analyzed as input features. Four types of ML algorithms were employed for model development. The performance was assessed using discrimination and calibration measures, and the Shapley Additive exPlanations (SHAP) method was applied for model interpretation. RESULTS: A total of 169 patients were included, with 119 for model training and 50 for validation. The Gaussian Naïve Bayes (GNB) model exhibited superior predictive accuracy and stability. Prospective validation on the 50 patients revealed an area under the curve (AUC) of 0.863, effectively distinguishing between 5-year survivors and non-survivors. Key prognostic factors identified included International Staging System (ISS) stage, Durie-Salmon (DS) stage, targeted therapy, and age. CONCLUSIONS: The GNB model has the best performance and high reliability in predicting postoperative outcomes. Variables such as ISS stage and DS stage were significant in influencing patient prognosis. This study enhances the ability to identify patients at risk of poor outcomes, thereby aiding clinical decision-making.

ε-Poly-l-lysine-hydroxyphenyl propionic acid/IL-4 composite hydrogels with inflammation regulation and antibacterial activity for improving integration stability of soft tissues and orthopedic implants.

The failure of orthopedic implants is usually caused by inflammation, poor tissue integration, and infection, which can lead to pain, limited mobility, dysfunction of patients. This may require additional surgical interventions, such as removal, replacement, or repair of implants, as well as related treatment measures such as antibiotic therapy, physical therapy. Here, an injectable hydrogel carrier was developed for the steady release of inflammatory regulators to reduce the surface tissue inflammatory response of orthopedic implants and induce soft tissue regeneration, ultimately achieving the promotion of implants stability. The hydrogels carrier was prepared by hydroxyphenyl propionic acid-modified ε-Poly-l-lysine (EPA), hydrogen peroxide and horseradish peroxidase, which showed antibacterial bioactive and stable factor release ability. Due to the introduction of IL-4, EPA@IL-4 hydrogels showed good inflammatory regulation. EPA@IL-4 hydrogels regulated the differentiation of macrophages into M2 in inflammatory environment in vitro, and promoted endothelial cells to show a more obvious trend of tube formation. The composite hydrogels reduced the inflammation on the surface of the implants in vivo, induced local endothelial cell angiogenesis, and had more collagen deposition and new granulation tissue. Therefore, EPA hydrogels based on IL-4 release are promising candidates for promoting of implants surface anti-inflammatory, soft tissue regeneration, and anti-infection.

BARX1 promotes osteosarcoma cell proliferation and invasion by regulating HSPA6 expression.

Osteosarcoma (OS) is a bone tumour affecting adolescents. Dysregulation of Barx homeobox 1 (BARX1) expression is involved in various cancers, but its function and mechanism in the process of OS are undefined. This study revealed that BARX1 expression is higher in OS tissue than in adjacent normal tissue. Downregulation of BARX1 in OS cells significantly suppressed their proliferation and migration, whereas enforced expression of exogenous BARX1 exerted the opposite effects on OS cells. Subsequently, heat shock 70-kDa protein 6 (HSPA6) expression was clearly increased after BARX1 overexpression in OS cells, as confirmed by RNA sequencing. The dual-luciferase reporter assay confirmed that HSPA6 expression is directly regulated by BARX1. The in vitro assay indicated that silencing HSPA6 expression attenuated OS proliferation and migration induced by BARX1. A dual immunofluorescence labelling assay provided further evidence that BARX1 was overexpressed and associated with HSPA6 overexpression in OS tumour tissue. In conclusion, BARX1 promotes OS cell proliferation and migration by inducing the expression of HSPA6, which plays an oncogenic role in OS. BARX1 and HSPA6 can potentially act as novel therapeutic targets for OS.

Prognostic factors and treatment outcomes of spinal osteosarcoma: Surveillance, epidemiology, and end results database analysis.

Objective: Spinal osteosarcoma is a rare osseous neoplasm. The aim of this study is to make a comprehensive analysis of the demographic features, clinicopathologic characteristics and factors affecting prognosis of spinal osteosarcoma using the Surveillance, Epidemiology and End Results (SEER) database. Methods: SEER data were reviewed to identify patients diagnosed with spinal osteosarcoma between 1975 and 2016 and determine their overall survival (OS) and disease-specifc survival (DSS). Univariate and multivariate analyses were performed using the Cox-regression proportional hazards model and Kaplan-Meier method. Results: A total of 668 patients (53.1% males) with spinal osteosarcoma were identified. The mean age at diagnosis was 45.2 years, including 67.5% patients younger than 60 years. The median OS of these patients was 15 months, and the 5-year OS was 16.8%. Multivariate analysis showed that age ≥60 year (HR=2.271, p = 0.008), high grade (HR=1.323, p = 0.008), regional stage (HR=1.658, p = 0.017), metastasis stage (HR=3.045, p < 0.001) and no-surgery treatment (HR=1.761, p < 0.001) were adversely associated with OS; gender (HR=0.657, p = 0.044), tumor grade (HR=1.616, p = 0.006), tumor stage (HR=3.329, p = 0.011; HR=7.983, p < 0.001) and radiotherapy (HR=0.606, p = 0.031) were independent prognostic factors affecting DSS. Conclusion: Based on SEER data analysis, male, high tumor grade, regional stage, metastasis stage and radiotherapy are independent predictors of poor survival of patients with spinal osteosarcoma. The clinical treatment of spinal osteosarcoma still faces serious challenges. Future research should focus on the clinical impact and survival outcomes of the emerging targeted and immune therapies for the sake of improving the survival stalemate of spinal osteosarcoma.

Surgical management and outcomes of spinal metastasis of malignant adrenal tumor: A retrospective study of six cases and literature review.

Purpose: Spinal metastasis of malignant adrenal tumor (SMMAT) is an extremely rare and poorly understood malignant tumor originating from the adrenal gland. The objective of this study is to elucidate the clinical characteristics and discuss surgical management and outcomes of SMMAT. Methods: Included in this study were six SMMAT patients who received surgical treatment in our center between February 2013 and May 2022. Their clinical data and outcomes were retrospectively analyzed to gain a better understanding of SMMAT. In addition, ten cases from the literature focusing on SMMAT were also reviewed. Results: Surgery was performed successfully, and the associated symptoms were relieved significantly in all patients postoperatively. The mean follow-up duration was 26.2 (range 3-55) months. Two patients died of tumor recurrence 12 and 48 months after operation respectively. The other four patients were alive at the last follow-up. Conclusions: The prognosis of SMMAT is usually poor. Preoperative embolization and early surgical radical resection can offer satisfactory clinical outcomes. The patient's health status, preoperative neurological function, tumor location and the resection mode are potential prognostic factors of SMMAT.

Efficacy and safety of erythropoietin in isolated spinal metastasis patients with total en bloc spondylectomy surgery: a case-control study.

OBJECTIVE: The purpose of our study is to identify the effect of short-term and high-dose use of erythropoietin (EPO) in spinal isolated metastatic patients with Total en bloc spondylectomy (TES) surgery by assessing hematological parameters, transfusion volume, postoperative complications, recurrence-free survival (RFS), and overall survival (OS). METHODS: From January 2015 and January 2022, 93 isolated spinal metastasis patients were selected and separated into 2 groups based on the treatment method used (EPO + TXA (Tranexamic acid) group, n = 47; and TXA group, n = 46). Indexes for evaluation included hemoglobin (Hb), hematocrit (Hct), red blood cells (RBC), RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, transfusion rate, and mean units transfused. RESULTS: The average follow-up duration was 38.13 months. There was no significant difference (P > 0.05) in RFS, OS, postoperative complications, postoperative Frankel Grade, drainage volume, and transfusion rate between the two groups. However, patients in EPO + TXA group have significantly higher Hb, Hct, and RBC values than those in the TXA group on postoperative days 1, 2, 3, and 5. Moreover, the mean transfusion volume in EPO + TXA group was significantly lower than those in the TXA group (P = 0.011). CONCLUSIONS: Perioperative short-term and high-dose administration of EPO could improve the anemia-related hematological parameters and reduce the requirement for blood transfusion without increasing the risk of deep vein thrombosis and tumor progression in solitary spinal metastatic patients with TES surgery.

Differentiation of benign and malignant spinal schwannoma using guided attention inference networks on multi-source MRI: comparison with radiomics method and radiologist-based clinical assessment.

BACKGROUND: Differentiating diagnosis between the benign schwannoma and the malignant counterparts merely by neuroimaging is not always clear and remains still confounding in many cases because of atypical imaging presentation encountered in clinic and the lack of specific diagnostic markers. PURPOSE: To construct and validate a novel deep learning model based on multi-source magnetic resonance imaging (MRI) in automatically differentiating malignant spinal schwannoma from benign. MATERIAL AND METHODS: We retrospectively reviewed MRI imaging data from 119 patients with the initial diagnosis of benign or malignant spinal schwannoma confirmed by postoperative pathology. A novel convolutional neural network (CNN)-based deep learning model named GAIN-CP (Guided Attention Inference Network with Clinical Priors) was constructed. An ablation study for the fivefold cross-validation and cross-source experiments were conducted to validate the novel model. The diagnosis performance among our GAIN-CP model, the conventional radiomics model, and the radiologist-based clinical assessment were compared using the area under the receiver operating characteristic curve (AUC) and balanced accuracy (BAC). RESULTS: The AUC score of the proposed GAIN method is 0.83, which outperforms the radiomics method (0.65) and the evaluations from the radiologists (0.67). By incorporating both the image data and the clinical prior features, our GAIN-CP achieves an AUC score of 0.95. The GAIN-CP also achieves the best performance on fivefold cross-validation and cross-source experiments. CONCLUSION: The novel GAIN-CP method can successfully classify malignant spinal schwannoma from benign cases using the provided multi-source MR images exhibiting good prospect in clinical diagnosis.

A Discussion on the Criteria for Surgical Decision-Making in Elderly Patients With Metastatic Spinal Cord Compression.

STUDY DESIGN: Retrospective study. OBJECTIVES: Although the role of surgery in the management of metastatic spinal cord compression (MSCC) has been well established, elderly patients may still be denied surgery because of higher risk of complications and shorter life expectancy. The purpose of this study was to determine whether elderly patients with MSCC could benefit from surgery and discuss the criteria for surgical decision-making in such patients. METHODS: Enrolled in this study were 55 consecutive patients aged 75 years or older who were surgically treated for MSCC in our center. Prognostic factors predicting overall survival (OS) were explored by the Kaplan-Meier method and Cox regression model. The quality of life (QoL) of the patients was evaluated by the SOSGOQ and compared using Student's t test. Risk factors for postoperative complications were identified by Chi-square test and multiple logistic regression analysis. RESULTS: Surgical treatment for MSCC substantially improved the neurological function in 55.8% patients and QoL in 88.5% patients with acceptable rates of postoperative complications (16.4%), reoperation (9.1%), and 30-day mortality (1.8%). Postoperative ECOG-PS of 1-2, total en-bloc spondylectomy (TES), and postoperative chemotherapy were favorable prognostic factors for OS, while a high Charlson Comorbidity Index (CCI) and a long operation time were risk factors for postoperative complications. CONCLUSIONS: Surgery should be encouraged for elderly patients with MSCC 1) who are compromised by the current or potential neurological dysfunction; 2) with radioresistant tumors; 3) with spinal instability; and 4) with no comorbidity, ECOG-PS of 0-2, and systemic treatment adherence. In addition, surgery should be performed by a skilled and experienced surgical team.

Differentiation between spinal multiple myeloma and metastases originated from lung using multi-view attention-guided network.

Purpose: Multiple myeloma (MM) and metastasis originated are the two common malignancy diseases in the spine. They usually show similar imaging patterns and are highly demanded to differentiate for precision diagnosis and treatment planning. The objective of this study is therefore to construct a novel deep-learning-based method for effective differentiation of two diseases, with the comparative study of traditional radiomics analysis. Methods: We retrospectively enrolled a total of 217 patients with 269 lesions, who were diagnosed with spinal MM (79 cases, 81 lesions) or spinal metastases originated from lung cancer (138 cases, 188 lesions) confirmed by postoperative pathology. Magnetic resonance imaging (MRI) sequences of all patients were collected and reviewed. A novel deep learning model of the Multi-view Attention-Guided Network (MAGN) was constructed based on contrast-enhanced T1WI (CET1) sequences. The constructed model extracts features from three views (sagittal, coronal and axial) and fused them for a more comprehensive differentiation analysis, and the attention guidance strategy is adopted for improving the classification performance, and increasing the interpretability of the method. The diagnostic efficiency among MAGN, radiomics model and the radiologist assessment were compared by the area under the receiver operating characteristic curve (AUC). Results: Ablation studies were conducted to demonstrate the validity of multi-view fusion and attention guidance strategies: It has shown that the diagnostic model using multi-view fusion achieved higher diagnostic performance [ACC (0.79), AUC (0.77) and F1-score (0.67)] than those using single-view (sagittal, axial and coronal) images. Besides, MAGN incorporating attention guidance strategy further boosted performance as the ACC, AUC and F1-scores reached 0.81, 0.78 and 0.71, respectively. In addition, the MAGN outperforms the radiomics methods and radiologist assessment. The highest ACC, AUC and F1-score for the latter two methods were 0.71, 0.76 & 0.54, and 0.69, 0.71, & 0.65, respectively. Conclusions: The proposed MAGN can achieve satisfactory performance in differentiating spinal MM between metastases originating from lung cancer, which also outperforms the radiomics method and radiologist assessment.

Surgical management and outcome of Extra-adrenal myelolipomas at unusual locations: A report of 11 cases in a single center.

Purpose: Extra-adrenal myelolipomas (EAMs) are rare benign tumors composed of both mature adipose and hematopoietic tissues with unclear etiology. There have been only sporadic case reports about the clinical characteristics and management of EAMs. Here we present our experience and practice in the clinical diagnosis and treatment of 11 consecutive patients with EAMs. Method: We retrospectively reviewed 11 consecutive patients, who received surgeries in our department and were confirmed as having EAMs by postoperative histopathology from April 2016 to December 2021. Clinical information and follow-up data of all patients were collected and analyzed afterwards. Results: Of the 11 EAM patients (7 male and 4 female) with a mean age of 47.6 years, 3 were asymptomatic and 8 were symptomatic with a mean symptom duration of 6.07 months. EAMs were found in the thoracic spine in 4 cases, paravertebral mediastinal regions in 3 cases, ilium in 2 cases, humerus in 1 case, and rib in 1 case. All patients were initially misdiagnosed as other tumors by radiologists. All 11 patients received gross total excision or curettage with a mean intraoperative blood loss of 781.82 ± 1143.3 ml and a mean operation duration of 180.91 ± 98.41 min. Patients' Frankel scores and Karnofsky Performance Status score were improved or at least preserved postoperatively. No significant complications occurred postoperatively. All the 11 patients survived, and no local recurrence or distant metastasis occurred during the mean follow-up period of 42.0 months. Conclusion: The surgical outcome and prognosis of EAMs are excellent and surgery can serve as the method of radical treatment.

m6A-dependent upregulation of TRAF6 by METTL3 is associated with metastatic osteosarcoma.

OBJECTIVES: RNA N6-methyladenosine (m6A) is associated with tumorigenesis. The importance of methyltransferase-like 3 (METTL3) has been reported in cancer progression and metastasis. However, its role and molecular mechanism in osteosarcoma (OS), the most common primary bone tumor, is poorly studied. In this study, we aimed to investigate the functional role and underlying mechanism of METTL3 in the metastasis of OS. METHODS: The expression differences of METTL3 between metastatic and non-metastatic OS tissues and patients with different Enneking stages were detected using RT-qPCR. METTL3 was artificially downregulated in the cells, followed by wound healing assay, Matrigel assay, immunofluorescence, in vivo tumorigenic assay, HE staining, and western blot. Transcriptome sequencing and m6A-seq was conducted to identify the downstream genes of METTL3, and RIP and dual-luciferase assays were performed for validation. The expression of TRAF6 in OS tissues was detected using RT-qPCR. Finally, the rescue experiments were conducted. RESULTS: METTL3 was overexpressed in metastatic OS tissues, and downregulation of METTL3 decreased cell migration, invasion, epithelial-mesenchymal transition, and tumorigenic and metastatic activities. The m6A site was highly enriched in cells poorly expressing METTL3, and the m6A peak was mainly enriched in the exon region. METTL3 was positively correlated with TRAF6 in metastatic OS, and depletion of METTL3 resulted in the loss of TRAF6 expression in OS cells. Upregulation of TRAF6 contributed to metastases in vitro and in vivo. CONCLUSION: METTL3 is highly expressed in OS and enhances TRAF6 expression through m6A modification, thereby promoting the metastases of OS cells.

RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating Runx2 mRNA and inhibiting osteogenic differentiation.

As a systemic disease, osteoporosis (OP) results in bone density loss and fracture risk, particularly in the hip and vertebrae. However, the underlying molecular mechanisms of OP development have not been fully illustrated. N6-Methyladenosine (m6A) is the most abundant modification of mRNAs, which is involved in many of pathological processes in aging disease. However, its role and regulatory mechanism in OP remains unknown. Here, we aimed to investigate the roles of m6A and its demethylase FTO in OP development. The results showed that m6A methylated RNA level was up-regulated in the bone marrow mesenchymal stem cells (BMSCs) from patients with OP. The level of N6-methyladenosine demethylase FTO was consistently decreased in the BMSCs from patients with OP. Functionally, lentivirus-mediated FTO overexpression in normal BMSCs to compromised osteogenic potential. Mechanism analysis further suggested that FTO overexpression decreased the m6A methylated and total level of runt related transcription factor 2 (Runx2) mRNA, subsequently inhibited osteogenic differentiation. We found that FTO inhibition could effectively improve the bone formation in ovariectomized osteoporotic mice in vivo. Together, these results reveal that RNA N6-methyladenosine demethylase FTO promotes osteoporosis through demethylating runx2 mRNA and inhibiting osteogenic differentiation.

Development and Validation of a Scoring System for Differential Diagnosis of Tuberculosis and Metastatic Tumor in the Spine.

PURPOSE: Spinal tuberculosis (TB) and metastatic tumor (MT) are common diseases with similar manifestations. Although pathological evaluation is the gold standard to confirm diagnosis, performing biopsies in all patients is not feasible. This study is aimed to create a scoring system to facilitate the differential diagnosis of spinal TB and MT before invasive procedures. METHODS: Altogether, 447 patients with spinal TB (n=198) and MT (n=249) were retrospectively analyzed. Patients were randomly assigned at 2:1 ratio to a training cohort and a validation cohort. Clinical, laboratory, and radiological diagnostic factors were identified by χ2 and multiple logistic regression analyses. The scoring system was then established based on the identified independent diagnostic factors scored by regression coefficient ß value, with the cut-off value being determined by ROC curve. The sensitivity and specificity of the system was calculated by comparing the predicted diagnosis with their actual pathological diagnosis. RESULTS: This scoring system was composed of 5 items: pain worsens at night (0 or 2 points), CRP value (0 or 3 points), tumor marker values (0 or 2 points), skip lesions (0 or 3 points), and intervertebral space destruction (0 or 3 points). Patients scoring higher than 7.5 could be diagnosed as spinal TB, otherwise, MT. According to the internal validation, the sensitivity and specificity of the system were 87.9% and 91.6%, respectively. CONCLUSION: This study established and validated a scoring system which could be used to differentiate spinal TB from MT, thus helping clinicians in quick and accurate differential diagnosis.

The CD24+ cell subset promotes invasion and metastasis in human osteosarcoma.

BACKGROUND: Osteosarcoma is the most common primary aggressive bone tumor affecting children and young adolescents. Metastases are often resistant to conventional chemotherapy and mean short-term survival. Development of valuable diagnostic indicators and targeting agents will have important implications for clinical diagnosis by the identification and characterization of molecules that contribute to its aggressive behavior. METHODS: We examined differential expression levels of common stem cell markers in osteosarcoma parental and sphere cells. In addition, we further analyzed the changes of candidate common stem cell markers before and after in vitro chemotherapy of osteosarcoma cells. The biological functions of CD24+ subpopulation in osteosarcoma such as proliferation, migration, invasion, tumorigenesis and metastasis were systematically investigated, and the correlations of CD24 levels with prognosis in patients with osteosarcoma were analyzed. FINDINGS: CD24+ Cells presented characteristics of TICs and resist drug-induced apoptosis. The prevention of tumor formation and metastasis by CD24 knockdown highlights the potential of CD24 as a therapeutic target for osteosarcoma. Moreover, the levels of CD24 in osteosarcoma samples were significantly correlated with the prognosis of patients. INTERPRETATION: CD24+ cell subset played an important role in osteosarcoma invasion and metastasis. FUNDING: National Natural Science Foundation of China (No.81772857); Shanghai Science and Technology Commission (18140902000); Shanghai Municipal Health Commission (2017ZZ01017; 17411950301).

Symptomatic postoperative spinal epidural hematoma after spine tumor surgery: Incidence, clinical features, and risk factors.

STUDY DESIGN: Case-control study. OBJECTIVES: The objective of this study was to provide some useful information concerning the incidence, clinical features, and risk factors for symptomatic postoperative spinal epidural hematoma (SPSEH) in an isolated cohort of patients undergoing spine tumor surgery. SETTING: Hospital in Shanghai, China. METHODS: We retrospectively reviewed all patients who underwent surgery for spine tumors between August 2012 and August 2017, and conducted a case-control study involving 16 patients who received evacuation surgery due to SPSEH after spine tumor surgery and 48 controls without SPSEH. Case and control subjects were matched at 1:3 by pathological diagnosis, tumor size (±1 cm), resection mode, surgical approach, and the operation team. Data of SPSEH subjects along with 48 matched controls were further obtained from a detailed review of the medical records. Univariate and multivariate analyses were conducted to identify the risk factors for developing SPSEH. RESULTS: SPSEH evacuation surgery was performed after 16 of 5421 (0.30%) spine tumor surgeries. Angiogenic tumors were the most susceptible tumors developing SPSEH. Very large hematomas, continuous blood loss, and delayed hematomas were characteristic clinical presentations for SPSEH after spine tumor surgery. Multiple logistic regression analysis suggested that patients suffering from at least one medical comorbidity and patients with Frankel grade of A-C had a significantly higher risk of developing SPSEH. CONCLUSIONS: The incidence of SPSEH after spine tumor surgery requiring surgical evacuation was 0.30%. Medical comorbidity and Frankel grade were identified as independent risk factors for SPSEH development.

Clinical features and prognostic factors of pediatric spine giant cell tumors: report of 31 clinical cases in a single center.

BACKGROUND CONTEXT: Giant cell tumors (GCTs) of the bone are benign but locally aggressive. Pediatric spine giant-cell tumors (PSGCTs) have been infrequently reported in the literature because of the rarity of the disease. PURPOSE: The purpose of this study was to define the overall occurrence rate of PSGCTs among all spinal GCTs in our center and investigate the clinical features and prognostic factors of this rare disease. STUDY DESIGN: A retrospective review. PATIENT SAMPLE: Thirty-one PSGCT patients, screened from 226 patients with spine GCTs who received treatment in our center between 1998 to 2017. OUTCOME MEASURES: The clinical symptoms, neurologic status, radiologic manifestations, treatment, outcome, and complications were recorded and analyzed. METHODS: The postoperative recurrence-free survival (RFS) rate was estimated by the Kaplan-Meier method. Factors with p values ≤.1 were subjected to multivariate analysis for RFS by proportional hazard analysis, among which p values ≤.05 were considered statistically significant. RESULTS: A total of 31 (31 of 226, 13.7%) PSGCTs patients (9 male and 22 female) were included in the study, with a mean age of 15.9 years and a mean follow-up period of 85.1 (median 84.0; range 12-221) months. The majority of patients (80.6 %) were 14-18 years of age. Recurrence was detected in 12 (38.7%) of the 31 patients. Univariate and multivariate analyses suggested that Jaffe grade II-III was an adverse prognostic factor for RFS, while total spondylectomy and bisphosphonate treatment were positive prognostic factors. CONCLUSIONS: Total en bloc spondylectomy (TES) is associated with excellent prognosis for PSGCTs, and total piecemeal spondylectomy is a viable alternative if total en bloc spondylectomy is unfeasible. Long-term bisphosphonate administration could significantly reduce the recurrence risk of PSGCTs. Denosumab treatment is recommended, especially for advanced PSGCTs. Jaffe grade II-III is an adverse prognostic factor for recurrence.

ILKAP Binding to and Dephosphorylating HIF-1α is Essential for Apoptosis Induced by Severe Hypoxia.

BACKGROUND/AIMS: Integrin-linked kinase-associated phosphatase (ILKAP), a serine/threonine phosphatase that belongs to the protein phosphatase 2C family, has a role in cell survival and apoptosis. Hypoxia-inducible factor 1α (HIF-1α) is the key transcription factor in the response to oxygen deficiency in mammals. Direct phosphorylation and dephosphorylation of HIF-1α affect its function. The present study investigated the role of ILKAP on HIF-1α dephosphorylation and cell behavior. METHODS: HIF-1α was induced by hypoxia. Physical binding between ILKAP and HIF-1α was demonstrated by a co-immunoprecipitation assay. HIF-1α transcriptional activity was investigated using a hypoxia-response element-containing luciferase reporter plasmid. Cell viability was evaluated by a trypan blue dye exclusion assay. ILKAP function was explored by a gain and loss assay with an overexpression plasmid and shRNA infection. RESULTS: ILKAP physically interacted with HIF-1α and induced its dephosphorylation. Both the HIF-1α-p53 interaction and apoptosis relied on ILKAP. CONCLUSION: The results indicated that the ILKAP directly binds and dephosphorylates HIF-1α and responsible for severe hypoxia-induced cell apoptosis.

Possible Epithelial Ovarian Cancer Association with HPV18 or HPV33 Infection.

The present study was conducted to investigate the prevalence of HPV infection in epithelial ovarian cancer (EOC) in Hunan province. DNA samples were collected from paraffin embedded ovarian tissue from 322 patients with EOC, 99 with ovarian benign tumors and 199 normal persons. The polymerase chain reaction and direct sequencing were used to identify the HPV types in the samples. The relationship between the infection of human papillomavirus (HPV) and the epithelial ovarian carcinoma (EOC) was investigated combined with clinical data. The prevalence of HPV18 and HPV33 in EOC group and benign group was higher than in the normal group. HPV18 and HPV33 may play a role in the development of both EOC and ovarian benign tumor and may participate in the development of EOC with traditional risk factors, family history and abortion, possibly exerting synergistic effects..