Activation of Ventral Tegmental Area Dopaminergic Neurons Projecting to the Parabrachial Nucleus Promotes Emergence from Propofol Anesthesia in Male Rats.

Since the clinical introduction of general anesthesia, its underlying mechanisms have not been fully elucidated. The ventral tegmental area (VTA) and parabrachial nucleus (PBN) play pivotal roles in the mechanisms underlying general anesthesia. However, whether dopaminergic (DA) projections from the VTA to the PBN play a role in mediating the effects of general anesthesia is unclear. We microinjected 6-hydroxydopamine into the PBN to damage tyrosine hydroxylase positive (TH+) neurons and found a prolonged recovery time from propofol anesthesia. We used calcium fiber photometry recording to explore the activity of TH + neurons in the PBN. Then, we used chemogenetic and optogenetic approaches either activate the VTADA-PBN pathway, shortening the propofol anesthesia emergence time, or inhibit this pathway, prolonging the emergence time. These data indicate the crucial involvement of TH + neurons in the PBN in regulating emergence from propofol anesthesia, while the activation of the VTADA-PBN pathway facilitates the emergence of propofol anesthesia.

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.

Mesenchymal stem cell-derived exosomes as a new drug carrier for the treatment of spinal cord injury: A review.

Spinal cord injury (SCI) is a devastating traumatic disease seriously impairing the quality of life in patients. Expectations to allow the hopeless central nervous system to repair itself after injury are unfeasible. Developing new approaches to regenerate the central nervous system is still the priority. Exosomes derived from mesenchymal stem cells (MSC-Exo) have been proven to robustly quench the inflammatory response or oxidative stress and curb neuronal apoptosis and autophagy following SCI, which are the key processes to rescue damaged spinal cord neurons and restore their functions. Nonetheless, MSC-Exo in SCI received scant attention. In this review, we reviewed our previous work and other studies to summarize the roles of MSC-Exo in SCI and its underlying mechanisms. Furthermore, we also focus on the application of exosomes as drug carrier in SCI. In particular, it combs the advantages of exosomes as a drug carrier for SCI, imaging advantages, drug types, loading methods, etc., which provides the latest progress for exosomes in the treatment of SCI, especially drug carrier.

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.

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.

Improvement of sleep quality in isolated metastatic patients with spinal cord compression after surgery.

BACKGROUND: This study aimed to assess changes in quality of sleep (QoS) in isolated metastatic patients with spinal cord compression following two different surgical treatments and identify potential contributing factors associated with QoS improvement. METHODS: We reviewed 49 patients with isolated spinal metastasis at our spinal tumor center between December 2017 and May 2021. Total en bloc spondylectomy (TES) and palliative surgery with postoperative stereotactic radiosurgery (PSRS) were performed on 26 and 23 patients, respectively. We employed univariate and multivariate analyses to identify the potential prognostic factors affecting QoS. RESULTS: The total Pittsburgh Sleep Quality Index (PSQI) score improved significantly 6 months after surgery. Univariate analysis indicated that age, pain worsening at night, decrease in visual analog scale (VAS), increase in Eastern Cooperative Oncology Group performance score (ECOG-PS), artificial implant in focus, and decrease in epidural spinal cord compression (ESCC) scale values were potential contributing factors for QoS. Multivariate analysis indicated that the ESCC scale score decreased as an independent prognostic factor. CONCLUSIONS: Patients with spinal cord compression caused by the metastatic disease had significantly improved QoS after TES and PSRS treatment. Moreover, a decrease in ESCC scale value of > 1 was identified as a favorable contributing factor associated with PSQI improvement. In addition, TES and PSRS can prevent recurrence by achieving efficient local tumor control to improve indirect sleep. Accordingly, timely and effective surgical decompression and recurrence control are critical for improving sleep quality.

A comparison of two different surgical procedures in the treatment of isolated spinal metastasis patients with metastatic spinal cord compression: a case-control study.

OBJECTIVE: The aim of the study was to compare total en bloc spondylectomy (TES) and separation surgery with postoperative stereotactic radiosurgery (SSRS) for isolated metastatic patients with spinal cord compression by assessing recurrence-free survival (RFS), overall survival (OS), postoperative complications, and quality of life scores (QoL). METHODS: From October 2013 to December 2020, 52 isolated spinal metastasis patients with cord compression were selected and separated into two groups based on the surgical method used (TES group, n = 26; and SSRS group, n = 26). Indexes for evaluation included postoperative Frankel grade, postoperative ECOG-PS, RFS, OS, postoperative complications, operation time, intraoperative blood loss, and QoL. RESULTS: The average follow-up duration was 31.44 months. There was no significant difference (P > 0.05) in postoperative complications and OS between the two groups. However, a significant difference in operation time, intraoperative blood loss, postoperative ECOG-PS, RFS, and mental health domain (6 months after surgery) was found between the two groups (P < 0.05). According to The Spine Oncology Study Group Outcomes Questionnaire assessment, the total pain and physical function domains scores were also elevated after surgery in both groups. However, no significant difference was observed between groups A and B (p = 0.450 and 0.446, respectively). CONCLUSIONS: TES and SSRS were efficient methods for treating solitary spinal metastasis patients with metastatic spinal cord compression. Better local tumor control and mental health were found in the TES group, and most patients felt as if they were free of spinal tumors. Compared with TES, the SSRS caused less operation-related trauma. However, there was no significant difference in OS between the two groups.

Apatinib in patients with advanced chordoma: a single-arm, single-centre, phase 2 study.

BACKGROUND: No standard treatment exists for advanced chordoma. Apatinib has been found to have promising efficacy and manageable adverse effects for the treatment of solid tumours. We aimed to investigate the safety and antitumour activity of apatinib in patients with advanced chordoma. METHODS: We did a single-arm, phase 2 study at one tertiary hospital in Shanghai, China. Eligible patients were aged 18-75 years, with histologically confirmed advanced chordoma that was unresectable or resectable only through demolitive surgery, who had previously received surgical treatment, with at least one measurable lesion according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, evidence of tumour progression on enhanced CT or MRI in the previous 6 months, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients received oral 500 mg apatinib once daily until disease progression or unacceptable toxicity. The co-primary endpoints were progression-free survival and objective response rate according to RECIST 1.1 and Choi criteria by investigator assessment. Progression-free survival was assessed in the intention-to-treat population. Objective response rate was assessed in the per-protocol population, which included all enrolled patients who were compliant with the protocol and had at least one post-baseline assessment. Safety was analysed in all patients with complete safety data. This study is ongoing, but recruitment is complete. This study is registered with Chictr.org.cn, ChiCTR-OIC-17013586. FINDINGS: Between Aug 21, 2017, and May 31, 2019, we screened 32 patients, of whom 30 were enrolled. Median follow-up was 14·2 months (IQR 9·4-19·7). Of the 27 patients included in the per-protocol population, one patient (3·7%; 95% CI 0-11·3) achieved an objective response according to RECIST, and seven patients (25·9%; 8·3-43·6) achieved an objective response according to Choi criteria. Median progression-free survival was 18 months (95% CI 3-34) according to RECIST and 18 months (3-33) according to Choi criteria. The most common treatment-related grade 3 adverse events were hypertension (seven [24%] of 29 patients) and proteinuria (two [7%]). No treatment-related grade 4 adverse events or treatment-related deaths were observed. INTERPRETATION: To our knowledge, this is the first trial of apatinib for the treatment of advanced chordoma. Apatinib shows promising activity and manageable toxicity and thus might be an option for the treatment of advanced chordoma. FUNDING: None.

FOXD3 Suppresses Tumor-Initiating Features in Lung Cancer via Transcriptional Repression of WDR5.

The tumor-initiating cells (TICs) are a cell population that can initiate tumor occurrence, mediate drug resistance, and give rise to metastasis. FOXD3 is a forkhead box (Fox) transcription factor family that regulates the pluripotency of embryonic stem cell and tumorigenicity. However, it is unclear whether FOXD3 plays any role in TIC and tumor metastasis. The functional analysis of FOXD3 was performed by oncospheres formation and redifferentiation, drug resistance assay, and cell migration. Global genomic RNA-Seq and ChIP-Seq analysis were used to identify the direct target of FOXD3 in lung cancer. We demonstrated that downregulation of FOXD3 in TICs was positively correlated with higher histologic grades and positive lymph node metastasis. FOXD3 repressed TIC expansion and cell migration, drug resistance, and osteoclasts in vitro and in vivo. Mechanically, we found that FOXD3 represses WDR5, which regulates TIC-related signaling pathway. Moreover, WDR5 were positively correlated with the TIC abundance and tumor progression. Besides, patients with high expression of WDR5 presented a poorer overall survival. FOXD3 may suppress TIC accumulation by repressing the expression of WDR5 in lung cancer. Stem Cells 2019;37:582-592.

The efficacy of immersive virtual reality surgical simulator training for pedicle screw placement: a randomized double-blind controlled trial.

OBJECTIVE: To verify whether the pedicle screw placement (PSP) skills of young surgeons receiving immersive virtual reality surgical simulator (IVRSS) training could be improved effectively and whether the IVRSS-PSP training mode could produce a real clinical value in clinical surgery. METHODS: Twenty-four young surgeons were equally randomized to a VR group and a NON-VR group. Participants in VR group received IVRSS-PSP training, and those in NON-VR group used the conventional model of observing a spinal model first and then watching a teaching video of spinal surgery for 40 minutes x five. The nailing outcome of the participants before and after training was evaluated by statistical analysis in both groups. RESULTS: Post-training data analysis showed that the success rate and accuracy rate of screw placement in VR group and NON-VR group were 82.9% and 69.6% vs. 74.2% and 55.4%, respectively, showing statistically significant differences between the two groups by chi-square test (P < 0.05). CONCLUSION: The present study demonstrated that IVRSS-PSP was helpful to improve the success rate of PSP for young surgeons, and may provide valuable reference for PSP training of young surgeons. In addition, our study also showed a promising potential of the VR technology in surgical simulation training.

Treatments and outcomes of spinal metastasis from thymic epithelial tumors: 10-year experience with 15 patients in a single center.

PURPOSE: Although thymic epithelial tumors (TETs) are rare, their spinal metastases are even rarer, and they have only been described in a few case reports. The aim of the present study is to discuss the possible treatments and outcomes of patients with spinal metastasis from TETs. METHODS: Included in this retrospective study were 15 patients with metastasis of TETs who received either radical or debulking surgery plus radiochemotherapy as adjuvant therapy in our center between 2007 and 2017. Possible prognostic factors for progression-free survival (PFS) and overall survival (OS) were analyzed by log-rank analysis. RESULTS: Our series comprised seven men and eight women, with a median age of 52 years. The period from the primary diagnosis to spinal metastasis varied from 0 to 16 months. The metastatic lesions were mainly located in the thoracic spine (n = 11; 73.3%), followed by the cervical and lumbar spine (n = 2; 13.3%, respectively). The median follow-up period was 28 months. Local tumor progression was detected in four patients (26.7%), and seven patients (46.7%) died of the disease during the follow-up period. Log-rank analysis indicated that radical resection was associated with longer PFS, whereas PFS, response to systemic chemotherapy and WHO B1-B2 were favorable factors of OS for patients with spinal metastatic TETs. CONCLUSIONS: Radical surgery is associated with longer PFS, while PFS is associated with better OS. Postoperative radiotherapy seems to be a useful supplementary treatment after debulking surgery, and patients who respond to postoperative chemotherapy were demonstrated with greater OS. WHO type B3-C seemed to be an adverse factor for spinal metastasis from TETs. These slides can be retrieved under Electronic Supplementary Material.

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.

Recurrence or neurological loss? Resection mode selection for patients with large sacral chordoma: an analysis of prognostic factors and quality of life.

BACKGROUND: Surgical resection represents the main therapeutic method for sacral chordoma, but plans for resection mode must weigh neurological loss against complete tumor excision, a difficult balance to strike. The purpose of this study was to provide useful information contributing to surgical decision making in sacral chordoma. METHODS: A retrospective review was performed on 47 patients with large sacral chordoma. Prognostic factors affecting recurrence-free survival (RFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox proportional hazards model. Quality of life was assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) questionnaire and compared using Student's t test. RESULTS: Resection mode was the independent prognostic factor affecting RFS, while independent prognostic factors affecting OS were resection mode and postoperative recurrence. As for quality of life, the en bloc resection group showed a higher score in emotional well-being, while the piecemeal resection group scored better in function well-being. No significant difference was identified in total the FACT-G score between two groups. CONCLUSIONS: On the one hand, en bloc resection showed huge advantages in disease control for sacral chordoma. On the other hand, despite the unsatisfaction in functional well-being, en bloc resection did not sacrifice quality of life significantly in terms of the total FACT-G score.

Stromal Cell-Derived CCL20 Promotes Tumor Progression and Osteolysis in Giant Cell Tumor of Bone.

BACKGROUND/AIMS: Giant cell tumor of bone (GCTB), one of the most common primary bone tumors, leads to extensive bone destruction. However, the mechanisms underlying GCTB progression remain elusive and prognostic factors and treatment targets are required. In the current study, we explored the function of the chemokine family member CCL20 in GCTB progression. METHODS: We explored the expression of CCL20 in stromal cells (GCTSCs) using microarray. Clinical analyses of the role of CCL20 in tumor progression were performed based on the patient cohort of our institution. The role of CCL20 in tumor proliferation was evaluated by MTS assay, migration ability was measured by a Transwell assay, and osteoclastogenesis was induced by CCL20 or GCTSC-conditioned medium. Quantitative PCR and western blot were used to measure the expression levels of mRNAs and proteins related to tumor progression. RESULTS: CCL20 was upregulated in GCTSCs and correlated with tumor progression and prognosis. CCL20 induced GCTSC proliferation and migration in an autocrine manner. In addition, CCL20 recruited mononuclear cells and induced osteoclastogenesis by overactivating the AKT and NF-κB signaling pathways. Antibody blockade of CCL20 abolished the exacerbated osteoclastogenesis. CONCLUSION: Taken together, our data indicate that GCTSC secretion of CCL20 acts as a key modulator in the pathological progression of GCTB. It can promote GCTSC proliferation and migration in an autocrine manner and can recruit bone marrow monocytes to the tumor microenvironment and enhance osteoclastogenesis in a paracrine manner. These findings strongly indicate the potential prognostic and therapeutic value of CCL20 in GCTB.

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.

Treatment and outcomes of 28 patients with spinal metastasis from gynecological cancer.

The aim of this study was to provide some useful information concerning clinical characteristics, surgical treatment, potential contributing factor and prognostic factors for patients with gynecological cancer (GC) spinal metastasis. We reviewed 28 patients with GC spinal metastasis in our spine tumor center between July 2008 and July 2015. Surgeries were performed on 22 of them. Univariate and multivariate analyses were conducted to identify potential prognostic factors affecting spinal metastasis-free survival (SMFS) and overall survival. The operative patients responded favorably according to decrease of VAS score and increase of Frankel grade after surgery. The 1- and 2-year survival rates in all patients were 60.7 and 41.0%, respectively. Univariate analysis suggested that age at diagnosis with GC was the potential contributing factor for spinal metastasis, while Frankel grade, ECOG-PS, visceral metastasis and chemotherapy were the potential prognostic factors affecting survival. Multivariate analysis indicated that the independent prognostic factors came from visceral metastasis and chemotherapy. Surgery played an important role in improving patients' quality of life. Patients over 50 years old had a shorter SMFS after diagnosed with GC. Visceral metastasis was an adverse prognostic factor for patients with GC spinal metastasis, while chemotherapy was a favorable one.

Clinical features, treatments and long-term follow-up outcomes of spinal chondroblastoma: report of 13 clinical cases in a single center.

PURPOSE: Chondroblastoma (CB) in the spine is extremely rare and there is little published information regarding this subject. We attempt to explore the clinical features of spinal CB and address the importance of total resection, especially total en bloc spondylectomy (TES) for the treatment of spinal CB. METHODS: Clinical data of 13 consecutive CB patients who received surgical treatment in our center between January 2006 and December 2016 were reviewed retrospectively. Recurrence-free survival (RFS) was estimated by Kaplan-Meier method and Log-rank test. RESULTS: The 13 CB patients included 9 men and 4 women with a mean age of 32 years. The lesions were located in the cervical spine in 2 cases, thoracic spine in 5 cases, and lumbar spine in 6 cases. All the patients were treated surgically using either curettage, piecemeal total resection, or TES. Postoperative radiotherapy was administered in 2 cases. The mean follow-up period was 41.6 months. Relapse occurred in 3 (23.1%) cases, resulting in one death in 60 months. The mean RFS duration was 28.7 months. CONCLUSIONS: CB predominantly affects males and various age groups. Spinal CB more commonly involves the thoracic and lumbar segments. Spinal CB usually appears as an aggressive and destructive bony lesion with a soft tissue mass on imaging, forming compression on the spinal cord in some cases. Recurrence is not uncommon for spinal CB. Total resection, especially TES, has been confirmed as a powerful method to control the disease, while curettage is more likely to associate with local recurrence. Radiotherapy does not seem to reduce local recurrence.

Surgical management of spinal solitary fibrous tumor/hemangiopericytoma: a case series of 20 patients.

PURPOSE: Spinal solitary fibrous tumor/hemangiopericytoma (SFT/HPC), a rare mesenchymal tumor that arises from pericytes of Zimmerman, comprises only 0.08% of all primary bone tumors and 0.1% of primary malignant bone tumor and rarely occurs in the spine. We attempt to correlate the clinical factors and different treatment options with the recurrence rate and overall survival of SFT/HPC over time. METHODS: A retrospective study of 20 patients with spinal osseous SFT/HPCs who were surgically treated in our center between 2003 and 2015 was performed. Kaplan-Meier curves and log-rank tests were used to compare the survival probability or recurrence-free probability between groups, and P values < 0.05 were considered statistically significant. RESULTS: Three surgical management strategies, including subtotal resection, piecemeal total resection, and total en bloc spondylectomy (TES) were applied. Postoperative radiotherapy was carried out in 14 cases. The mean follow-up period was 38.3 (median 35, range 7-93) months, and 6 patients passed away with the mean follow-up time of 47.7 (median 41, range 24-77) months. Relapse was detected in 9 patients (45%) with the mean time from surgery to recurrence being 36.6 (median 28, range 12-73) months. Our results indicate that grade III is an adverse prognostic factor for both recurrence and over survival (OS) for spinal osseous SFT/HPC, while total resection, especially TES, is a positive prognostic factor. CONCLUSIONS: Spinal osseous SFT/HPC is a challenging clinical entity given its high local recurrence rate. Surgical management plays a crucial role in the whole treatment of spinal SFT/HPCs and total excision, especially TES, should be strived for whenever possible. Postoperative radiotherapy is recommended to lower the recurrent rate. This study also confirms that pathology grade III is an adverse prognostic factor for spinal osseous SFT/HPCs.

Single-stage multi-level construct design incorporating ribs and chest wall reconstruction after en bloc resection of spinal tumour.

PURPOSE: Multi-level reconstruction incorporating the chest wall and ribs is technically demanding after multi-segmental total en bloc spondylectomy (TES) of thoracic spinal tumours. Few surgical techniques are reported for effective reconstruction. A novel and straightforward technical reconstruction through posterior-lateral approach was presented to solve the extensive chest wall defect and prevent occurrences of severe respiratory dysfunctions after performing TES. The preliminary outcomes of surgery were reviewed. METHODS: Multi-level TES was performed for five patients with primary or recurrent thoracic spinal malignancies through posterior-lateral approach. The involved ribs and chest wall were removed to achieve tumour-free margin. Then titanium mesh with allograft bone and pedicle screw-rod system were adopted for the circumferential spinal reconstruction routinely. Titanium rods were modified accordingly to attach to the screw-rod system proximally, and the distal end of rods was dynamically inserted into the ribs. RESULTS: The mean surgery time was 6.7 hours (range 5-8), with the average blood loss of 3260 ml (range 2300-4500). No severe neurological complications were reported while three patients had complaints of slight numbness of chest skin (no. 1, 3, and 5). No severe respiratory complications occurred during peri-operative period. No implant failure and no local recurrence or distant metastases were observed with an average follow-up of 12.5 months. CONCLUSIONS: The single-stage reconstructions incorporating spine and chest wall are straightforward and easy to perform. The preliminary outcomes of co-reconstructions are promising and favourable. More studies and longer follow-up are required to validate this technique.

Hypoxia-induced microRNA-146a represses Bcl-2 through Traf6/IRAK1 but not Smad4 to promote chondrocyte autophagy.

It has been shown that hypoxia stimulation promotes chondrocytes autophagy partly through HIF-1α, miR-146a and Bcl-2 progressively, and this mechanism represented the connection among hypoxia, miR-146a and autophagy, and provides a possible therapeutic strategy for osteoarthritis. However, the interaction between miR-146a and Bcl-2 is still unclear. Here in a hypoxic environment, we quantified the three reported miR-146a targets: two inflammation related targets Traf6, IRAK1; and the only reported target in chondrocytes Smad4. We confirmed the regulative function of miR-146a between hypoxia and these genes, and explored the Bcl-2 expression and autophagy level under extrinsic up-regulation of these three gene separately. All the three genes were down-regulated by hypoxia. Surprisingly, Traf6 and IRAK, but not the unique Smad4 in chondrocytes, were restored by antagomiR-146a. Both Ad-Traf6 and Ad-IRAK1 reinstated hypoxia or miR-146a repressed Bcl-2. However, Ad-Smad4 did not affect Bcl-2 in hypoxia or normoxia. The autophagy level showed a reverse variability compared to Bcl-2. Taken together, our results provided evidence that Smad4, the unique reported target for miR-146a in chondrocytes is unusually not involved in the chondrocytes autophagy, while the Traf6 and IRAK1 are the new targets for miR-146a in chondrocytes during autophagy.