CircEYA3 aggravates intervertebral disc degeneration through the miR-196a-5p/EBF1 axis and NF-κB signaling.

Intervertebral disc degeneration (IDD) is a well-established cause of disability, and extensive evidence has identified the important role played by regulatory noncoding RNAs, specifically circular RNAs (circRNAs) and microRNAs (miRNAs), in the progression of IDD. To elucidate the molecular mechanism underlying IDD, we established a circRNA/miRNA/mRNA network in IDD through standardized analyses of all expression matrices. Our studies confirmed the differential expression of the transcription factors early B-cell factor 1 (EBF1), circEYA3, and miR-196a-5p in the nucleus pulposus (NP) tissues of controls and IDD patients. Cell proliferation, apoptosis, and extracellular mechanisms of degradation in NP cells (NPC) are mediated by circEYA3. MiR-196a-5p is a direct target of circEYA3 and EBF1. Functional analysis showed that miR-196a-5p reversed the effects of circEYA3 and EBF1 on ECM degradation, apoptosis, and proliferation in NPCs. EBF1 regulates the nuclear factor kappa beta (NF-кB) signalling pathway by activating the IKKß promoter region. This study demonstrates that circEYA3 plays an important role in exacerbating the progression of IDD by modulating the NF-κB signalling pathway through regulation of the miR196a-5p/EBF1 axis. Consequently, a novel molecular mechanism underlying IDD development was elucidated, thereby identifying a potential therapeutic target for future exploration.

Metabolic reprogramming based on RNA sequencing of gemcitabine-resistant cells reveals the FASN gene as a therapeutic for bladder cancer.

Bladder cancer (BLCA) is the most frequent malignant tumor of the genitourinary system. Postoperative chemotherapy drug perfusion and chemotherapy are important means for the treatment of BLCA. However, once drug resistance occurs, BLCA develops rapidly after recurrence. BLCA cells rely on unique metabolic rewriting to maintain their growth and proliferation. However, the relationship between the metabolic pattern changes and drug resistance in BLCA is unclear. At present, this problem lacks systematic research. In our research, we identified and analyzed resistance- and metabolism-related differentially expressed genes (RM-DEGs) based on RNA sequencing of a gemcitabine-resistant BLCA cell line and metabolic-related genes (MRGs). Then, we established a drug resistance- and metabolism-related model (RM-RM) through regression analysis to predict the overall survival of BLCA. We also confirmed that RM-RM had a significant correlation with tumor metabolism, gene mutations, tumor microenvironment, and adverse drug reactions. Patients with a high drug resistance- and metabolism-related risk score (RM-RS) showed more active lipid synthesis than those with a low RM-RS. Further in vitro and in vivo studies were implemented using Fatty Acid Synthase (FASN), a representative gene, which promotes gemcitabine resistance, and its inhibitor (TVB-3166) that can reverse this resistance effect.

Development and validation of a newly developed nomogram for predicting the risk of deep vein thrombosis after surgery for lower limb fractures in elderly patients.

Background: Prevention of deep vein thrombosis (DVT) is indispensable in the treatment of lower limb fractures during the perioperative period. This study aimed to develop and validate a novel model for predicting the risk of DVT in elderly patients after orthopedic surgeries for lower limb fractures. Methods: This observational study included 576 elderly patients with lower limb fractures who were surgically treated from January 2016 to December 2018. Eleven items affecting DVT were optimized by least absolute shrinkage and selection operator regression analysis. Multivariable logistic regression analysis was performed to construct a predictive model incorporating the selected features. C-index was applied to evaluate the discrimination. Decision curve analysis was employed to determine the clinical effectiveness of this model and calibration plot was applied to evaluate the calibration of this nomogram. The internal validation of this model was assessed by bootstrapping validation. Results: Predictive factors that affected the rate of DVT in this model included smoking, time from injury to surgery, operation time, blood transfusion, hip replacement arthroplasty, and D-dimer level after operation. The nomogram showed significant discrimination with a C-index of 0.919 (95% confidence interval: 0.893-0.946) and good calibration. Acceptable C-index value could still be reached in the interval validation. Decision curve analysis indicated that the DVT risk nomogram was useful within all possibility threshold. Conclusion: This newly developed nomogram could be used to predict the risk of DVT in elderly patients with lower limb fractures during the perioperative period.

Effect of Anterior Cervical Decompression Fusion and Partial Resection of Uncinate Vertebra Joint on Cervical Sagittal Sequence in Patients with Non-Single-Segment Radiculopathy and its Correlation with Curative Effect: A Retrospective Analysis.

OBJECTIVE: Analyze the effect of preservation or resection of the partial uncinate joint on the sagittal sequence of the cervical vertebrae in patients with non-single-segment radiculopathy and the correlation between the sagittal sequence of the cervical vertebrae and the long-term effect after surgery, we explored whether it is necessary to perform partial resection of the uncinate joint in patients with cervical spondylotic radiculopathy undergoing anterior cervical decompression and fusion (ACDF). METHODS: The study retrospectively analyzed 96 patients with cervical spondylotic radiculopathy with more than two segments from August 2016 to January 2021, who underwent ACDF (ACDF group, 45 patients) or ACDF combined with partial uncinate joint resection (ACDF + UT group, 51 patients). Partial resection of the uncinate joint indicated removal of part of the uncinate joint and osteophyte based on the compression of the nerve root during surgery, whereas the uncinate joints in the ACDF group were retained completely. The imaging data and functional scores of the two groups were recorded before surgery, 1 month after surgery, and at the last follow-up. A paired t-test or rank sum test was applied to analyze the data. In addition, the correlation between the imaging parameters and functional scores was validated using the Pearson's test. RESULTS: All 96 patients successfully completed the surgery and were followed up for at least 12 months, with an average follow-up time of 14 months. At the last follow-up, the pain visual analog scale (VAS), neck disability index (NDI), and neck pain and disability scale (NPAD) scores of the two groups were significantly lower than those before surgery, and the Japanese Orthopaedic Association (JOA) score was significantly higher than that before surgery. At the last follow-up, compared with the ACDF+UT group, the NDI and NPAD scores in the ACDF group decreased more significantly (p < 0.05), and C2-7SVA, △C2-7SVA (the difference between C2-7 SVA at last follow-up and before operation), and T1S values decreased significantly (p < 0.05). The C2-7 Cobb angle was positively correlated with the JOA score and T1S (p < 0.05) and negatively correlated with the VAS, NDI, and NPAD scores and CGH-C7SVA (p < 0.05). C2-7SVA was positively correlated with CGH-C7SVA and T1S (p < 0.05). CONCLUSION: Patients with non-single-segmental cervical spondylotic radiculopathy and ACDF with or without uncinate joint resection can have effective improvement in the clinical effect and sagittal balance; however, partial uncinate joint resection has a certain negative impact on the long-term reconstruction of sagittal balance and long-term effects in patients after surgery.

Point-Guided Contrastive Learning for Monocular 3-D Object Detection.

3-D object detection is a fundamental task in the context of autonomous driving. In the literature, cheap monocular image-based methods show a significant performance drop compared to the expensive LiDAR and stereo-images-based algorithms. In this article, we aim to close this performance gap by bridging the representation capability between 2-D and 3-D domains. We propose a novel monocular 3-D object detection model using self-supervised learning and auxiliary learning, resorting to mimicking the representations over 3-D point clouds. Specifically, given a 2-D region proposal and the corresponding instance point cloud, we supervise the feature activation from our image-based convolution network to mimic the latent feature of a point-based neural network at the training stage. While state-of-the-art (SOTA) monocular 3-D detection algorithms typically convert images to pseudo-LiDAR with depth estimation and regress 3-D detection with LiDAR-based methods, our approach seeks the power of the 2-D neural network straightforwardly and essentially enhances the 2-D module capability with latent spatial-aware representations by contrastive learning. We empirically validate the performance improvement from the feature mimicking the KITTI and ApolloScape datasets and achieve the SOTA performance on the KITTI and ApolloScape leaderboard.

BMSC-EV-derived lncRNA NORAD Facilitates Migration, Invasion, and Angiogenesis in Osteosarcoma Cells by Regulating CREBBP via Delivery of miR-877-3p.

Bone marrow mesenchymal stem cells (BMSCs) can boost osteosarcoma (OS) cell proliferation and invasion, yet the function of extracellular vesicles (EVs) derived from BMSCs on OS is scarcely known. This study is aimed at examining the role of BMSC-EVs in OS cells. BMSCs and BMSC-EVs were isolated and identified. The effect of EVs and EVs-si-NORAD on OS cell proliferation, invasion, migration, and angiogenesis was determined. Expressions of NORAD, miR-877-3p, and CREBBP were detected. The binding relationship among NORAD, miR-877-3p, and CREBBP was verified. The miR-877-3p inhibitor or pc-CREBBP was delivered into OS cells treated with EVs-si-NORAD for in vitro analysis. The nude mouse model of the subcutaneous tumor xenograft was established for in vivo analysis. BMSC-EVs promoted OS cell proliferation, invasion, migration, and angiogenesis. BMSC-EVs carried NORAD into OS cells and upregulated CREBBP by sponging miR-877-3p. miR-877-3p downregulation or CREBBP overexpression partly inverted the inhibitory effect of EVs by silencing NORAD on OS cell proliferation, invasion, migration, and angiogenesis. In vivo experiments validated that BMSC-EV-derived NORAD facilitated tumor growth by upregulating CREBBP via miR-877-3p. To conclude, BMSC-EV-derived NORAD facilitated OS cell proliferation, invasion, migration, and angiogenesis by modulating CREBBP via miR-877-3p, which may offer new insights into OS treatment.

From calibration to parameter learning: Harnessing the scaling effects of big data in geoscientific modeling.

The behaviors and skills of models in many geosciences (e.g., hydrology and ecosystem sciences) strongly depend on spatially-varying parameters that need calibration. A well-calibrated model can reasonably propagate information from observations to unobserved variables via model physics, but traditional calibration is highly inefficient and results in non-unique solutions. Here we propose a novel differentiable parameter learning (dPL) framework that efficiently learns a global mapping between inputs (and optionally responses) and parameters. Crucially, dPL exhibits beneficial scaling curves not previously demonstrated to geoscientists: as training data increases, dPL achieves better performance, more physical coherence, and better generalizability (across space and uncalibrated variables), all with orders-of-magnitude lower computational cost. We demonstrate examples that learned from soil moisture and streamflow, where dPL drastically outperformed existing evolutionary and regionalization methods, or required only ~12.5% of the training data to achieve similar performance. The generic scheme promotes the integration of deep learning and process-based models, without mandating reimplementation.

From Hydrometeorology to River Water Quality: Can a Deep Learning Model Predict Dissolved Oxygen at the Continental Scale?

Dissolved oxygen (DO) reflects river metabolic pulses and is an essential water quality measure. Our capabilities of forecasting DO however remain elusive. Water quality data, specifically DO data here, often have large gaps and sparse areal and temporal coverage. Earth surface and hydrometeorology data, on the other hand, have become largely available. Here we ask: can a Long Short-Term Memory (LSTM) model learn about river DO dynamics from sparse DO and intensive (daily) hydrometeorology data? We used CAMELS-chem, a new data set with DO concentrations from 236 minimally disturbed watersheds across the U.S. The model generally learns the theory of DO solubility and captures its decreasing trend with increasing water temperature. It exhibits the potential of predicting DO in "chemically ungauged basins", defined as basins without any measurements of DO and broadly water quality in general. The model however misses some DO peaks and troughs when in-stream biogeochemical processes become important. Surprisingly, the model does not perform better where more data are available. Instead, it performs better in basins with low variations of streamflow and DO, high runoff-ratio (>0.45), and winter precipitation peaks. Results here suggest that more data collections at DO peaks and troughs and in sparsely monitored areas are essential to overcome the issue of data scarcity, an outstanding challenge in the water quality community.

Tim3+ Foxp3 + Treg Cells Are Potent Inhibitors of Effector T Cells and Are Suppressed in Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disorder. Earlier studies have demonstrated that regulatory T (Treg) cells, the main cell type mediating immune tolerance, appeared to be enriched in the inflamed synovial tissues. It is still unclear why the Treg cells in RA patients are unable to limit exacerbated inflammation. Here, we found that the frequency of Tim3+Foxp3+ Treg cells, which were potent suppressors of proinflammatory responses, was downregulated in RA patients. Reduction in Tim3+Foxp3+ Treg frequency was correlated with increased RA disease activity. Furthermore, we observed that Tim3+Foxp3+ Tregs were expressed more interleukin (IL)-10 than Tim3-Foxp3+ Tregs. CD4+CD25+Tim3+ T cells had higher capability of inhibiting interferon (IFN)-γ and tumor necrosis factor (TNF)-α secretion from T cells and peripheral blood mononuclear cells (PBMCs) than CD4+CD25+Tim3- T cells. Compared to that in healthy individuals, CD4+CD25+ T cells in RA patients were less potent in suppressing IFN-γ and TNF-α production from PBMCs. Blocking Tim3 on CD4+CD25+ T cells from healthy controls resulted in an elevation of IFN-γ and TNF-α production from PBMCs, suggesting that Tim3 expression on CD4+CD25+ T cells was required for optimal Treg function. However, this phenomenon was not observed in RA patients. In conclusion, our study suggested that the CD4+CD25+Foxp3+ Treg cells from RA patients demonstrated a reduction of Tim3 and were less functional than Treg cells from healthy controls in a Tim3-related manner.

Loss of B cell regulatory function is associated with delayed healing in patients with tibia fracture.

The process of bone regeneration after fracture is a complex and well-orchestrated process usually requiring 3-12 weeks. A subset of patients, however, exhibit delayed healing time and even incomplete restoration of the normal bone structure. Although the precise mechanism is unknown, studies have shown that smurf1 may play a role during the process. Here, we sought to determine the involvement of the immune system in impaired bone healing. We found that immediately after fracture, the B-cell composition was shifted toward increased frequency of plasmablasts and decreased frequency of naïve B cells, reflecting higher inflammatory status. The percentage of CD19(+) CD24(+) CD38(+) regulatory B cells was also upregulated in response to bone fracture. The production of IL-10, a pivotal cytokine in regulatory B-cell function, was upregulated in all patients. Interestingly, the increase in IL-10 production was only sustained throughout the healing course in normal healing patients but not in delayed healing patients. Rather, delayed healing patients downregulated B-cell IL-10 secretion early and had reduced level of regulatory B-cell activity. Together, these data revealed a role of regulatory B cells in the endogenous bone regeneration process and an alternation in B-cell-mediated regulation in delayed healing patients.

[Effect of water depths on hydraulic performance of pond wetlands].

Pond wetlands have been widely used in the treatment of drainage water from paddy fields. However, wetland hydraulic performance and purification effects are affected by many factors, such as water depth, flow rate, aspect ratio and vegetation distribution, and the better understanding of these factors would be helpful to improve the quality of wetland design, operation and management. This paper analyzed the effect of three different water depths (20, 40 and 60 cm) on the hydraulic performance of pond wetland through the dye tracer experiments with Rhodamine WT. The hydraulic indices, i. e., effective volume ratio, nominal serial complete mixing tanks (N), hydraulic efficiency (λ), were selected for analysis through the hydraulic residence time distribution (RTD) curve. The results showed that the effective volume rate rose from 0.421 to 0.844 and the hydraulic efficiency from 0.281 to 0.604 when the water depth declined from 60 cm to 20 cm. This indicated that the wetland hydraulic performance improved as the water depth decreased. In addition, the hydraulic performance of the first half of the wetland was significantly better than that of the second half. The flow regime of the first half approached complete mixing because of the mixing index (N) approaching 1 and its effective volume rate was above 0.9 when the water depth was relatively low (20 and 40 cm). The normalized RTD curves demonstrated a good agreement between moment analysis parameters and hydraulic parameters, and a great consistency between the hydraulic parameters and moment index which was not affected by tail truncation error. The experimental study concluded that a lower water depth was favorable to improve the hydraulic performance of pond wetlands.

Osteosarcoma of the spine: surgical treatment and outcomes.

BACKGROUND: The goal of this study was to determine whether there are correlations between various options of surgical treatment and long-term outcome for spinal osteosarcoma. METHODS: This was a retrospective review of 16 patients with spinal osteosarcoma, who underwent surgical treatment from 1999 to 2010. Seven patients were given total en bloc spondylectomy (TES), while nine received piecemeal resection (there were seven cases of total piecemeal spondylectomy, one of sagittal resection, and one of vertebrectomy). The outcome and prognosis of the patients were evaluated, grouped by surgical treatment. RESULTS: All 16 cases were followed for an average of 42.4 months. At follow-up, all patients noted that pain had eased or had gradually disappeared. Three months after surgery, eight patients (50.0%) had improved 1 to 2 grades in their neurological status, based on Frankel scoring. Six (37.5%) patients experienced local recurrence of the tumor, nine (56.3%) had metastases, and five (31.3%) died of the disease. Of the six patients who received a wide or marginal en bloc resection, none developed local recurrence or died from the disease. Conversely, of the ten patients who received intralesional or contaminated resections, six (60%) relapsed and five (50%) died from the disease. CONCLUSIONS: TES, with a wide margin, should be planned for patients with osteosarcoma of the cervical and thoracolumbar spine, whenever possible. When the patients are not candidates for en bloc resection, total piecemeal spondylectomy is an appropriate choice for osteosarcoma in the mobile spine.

Cytotoxic T-lymphocyte antigen-4 genetic variants and risk of Ewing's sarcoma.

Despite the knowledge of many genetic alterations present in Ewing's sarcoma (ES), the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) can decrease T-cell activation and attenuate antitumor responses. Polymorphisms in the CTLA-4 gene have been shown to be associated with different diseases. Here, we investigated the association of four CTLA-4 gene polymorphisms, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with ES in the Chinese population. A total of 308 ES cases and 362 healthy controls were recruited and CTLA-4 polymorphisms were tested by polymerase chain reaction-restriction fragment length polymorphism. Results showed that frequencies of the CTLA-4 gene +49AA genotype, +49A allele, and GTAG haplotype were significantly increased in ES patients compared to healthy controls (odds ratio [OR]=2.42, 95% confidence interval [CI] 1.43-4.09, p<0.001; OR 1.38, 95% CI 1.11-1.73, p=0.005, and OR=1.46, 95% CI 1.06-2.02, p=0.020, respectively). We further compared CTLA-4 polymorphisms in ES patients based on different clinical parameters and data revealed that ES patients with metastasis had higher numbers of the +49AA genotype than those without metastasis (p=0.004). These results indicated that the CTLA-4 polymorphism could be a risk factor for ES and suggested a potential role of CTLA-4 in the metastasis of this malignancy.

Pterostilbene exerts antitumor activity against human osteosarcoma cells by inhibiting the JAK2/STAT3 signaling pathway.

Osteosarcoma is a high-grade malignant bone tumor. Pterostilbene (PTE) is a natural, dimethylated analog of resveratrol with higher bioavailability. While PTE has been shown to have potent antitumor activity against various types of cancer, the molecular mechanisms underlying the effects of PTE remain largely unknown. The Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway plays a crucial role in tumorigenesis and immune development. In this study, we assessed the antitumor activity of PTE against human osteosarcoma cells and explored the role of JAK2/STAT3 and apoptosis-related signaling pathways on the activity of PTE. PTE treatment resulted in a dose- and time-dependent inhibition of osteosarcoma cell viability. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration and mitochondrial membrane potential (MMP) but also by increases in the apoptotic index, reactive oxygen species (ROS) and several biochemical parameters. Furthermore, PTE treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of STAT3. PTE also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. PTE, used in combination with a known JAK2/STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells. Taken together, PTE is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/STAT3 signaling pathway. These data suggest that inhibition of JAK2/STAT3 signaling is a novel mechanism of action for PTE during therapeutic intervention in osteosarcoma cancers.

CD86 +1057G/A polymorphism and susceptibility to Ewing's sarcoma: a case-control study.

The development of Ewing's sarcoma (ES) is a complex process resulting from interplay between mutations in oncogenes and tumor suppressors, host susceptibility factors, and cellular context. CD86 (B7-2) may affect cancer susceptibility by modulating T cell response. CD86 +1057G/A polymorphism (rs1129055) has been reported to be associated with various diseases. Here, we investigated the association between CD86 +1057G/A polymorphism and the risk of ES in a Chinese population. The CD86 +1057G/A polymorphism was detected by polymerase chain reaction-restriction fragment length polymorphism in 158 ES cases and 212 age-matched healthy controls. Frequencies of CD86 +1057 AA genotype and +1057 A allele were significantly increased in patients with ES compared to healthy controls (odds ratio [OR]=2.12, 95% confidence interval [CI], 1.11-3.79, p=0.021; and OR=1.41, 95% CI, 1.10-1.91, p=0.018). Our data suggest that the +1057G/A polymorphism of the CD86 gene is associated with increased susceptibility to ES.

Chondrosarcomas of the cervical and cervicothoracic spine: surgical management and long-term clinical outcome.

STUDY DESIGN: A retrospective review study. OBJECTIVES: To estimate the clinical outcome of various resection protocols in patients with chondrosarcoma (CHS) at the challenging region of cervical and cervicothoracic spine (CCT). SUMMARY OF BACKGROUND DATA: It is challenging to surgically manage CHS of the spine. Although total en-bloc resection has proven to be an ideal treatment, this option is not always feasible in the spine because of the constrains of critical neurovascular structures in the vicinity. Lesions at the CCT region pose even more difficulties, and few large clinical series concerning various protocols and long-term outcomes of these lesions exist at present. METHODS: Fifteen patients with CHS at the CCT region who underwent surgical management in our institute were retrospectively studied. Twelve piecemeal resections and 3 en-bloc resections were performed. Intraoperative local chemotherapy and postoperative cyberknife radiotherapy were given as adjuvant therapy. Neurologic status, local recurrence, distant metastasis, and treatment-related complications were evaluated. RESULTS: The mean follow-up time was 58.7 months (median 37 mo; ranging from 18 to 141 mo). Local recurrence was detected in 5 of 5 cases (100%) treated by intracapsular piecemeal resection, and in 1 of 7 cases (14.3%) treated by extracapsular piecemeal resection, whereas no recurrence was found in 3 cases treated by en-bloc resection. Of the 6 recurrent patients, 5 died of disease 24 to 46 months after present surgery, and the remaining patient was alive with disease in the final follow-up. There were no signs of recurrence in the remaining 9 patients. CONCLUSIONS: For CHS at the CCT region, intralesional piecemeal resection has a poor prognosis and should be avoided. Oncologically, en-bloc resection remains the best form of disease management and should be the primary treatment of choice. For cases in which an uncontaminated en-bloc resection could not be achieved, the extracapsular piecemeal resection with adjuvant therapy including local chemotherapy and cyberknife radiotherapy is an effective and achievable option.

Cytotoxic T-lymphocyte antigen-4 polymorphisms and susceptibility to osteosarcoma.

Despite the knowledge of many genetic alterations present in osteosarcoma, the complexity of this disease precludes placing its biology into a simple conceptual framework. Cytotoxic T-lymphocyte antigen-4 (CTLA-4) plays important roles in downregulating T-cell activation, thereby attenuating anti-tumor responses and increasing cancer susceptibility. Polymorphisms in the CTLA-4 gene are associated with different autoimmune diseases and cancers. The current study evaluated the association of four CTLA-4 gene mutations, -1661A/G (rs4553808), -318C/T (rs5742909), +49G/A (rs231775), and CT60A/G (rs3087243), with osteosarcoma in the Chinese population. CTLA-4 polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism in 267 osteosarcoma patients and 282 age-matched healthy controls. Results showed that the CTLA-4 gene +49 AA genotype, +49 A allele, and GTAG haplotype were significantly more frequent in osteosarcoma patients than in controls (odds ratio [OR] 2.20, 95% confidence interval [CI] 1.23-2.95, p = 0.007; OR 1.32, 95% CI 1.03-1.69, p = 0.029, and OR = 1.47, 95% CI 1.03-2.09, p = 0.033, respectively). The CTLA-4 +49G/A polymorphism and GTAG haplotype are associated with increased risk of osteosarcoma.

Sequentially staged resection and 2-column reconstruction for C2 tumors through a combined anterior retropharyngeal-posterior approach: surgical technique and results in 11 patients.

BACKGROUND: Surgical treatment of C2 tumors remains challenging. Because of the deep location and unique anatomical complexity, anterior exposure in this region is considered difficult and dangerous, and few reports concerning anterior tumor resection and reconstruction exist. OBJECTIVE: To describe a technique of sequentially staged resection and 2-column reconstruction for C2 tumors through a combined anterior retropharyngeal-posterior approach. METHODS: Eleven patients with C2 tumors underwent sequentially staged tumor resection and 2-column reconstruction in our institute. Eight primary lesions and 3 metastases were involved. Tumor resections and anterior reconstructions with conventional constructs were accomplished by an anterior retropharyngeal approach, and occipitocervical fusions through posterior access were performed in the same anesthesia. RESULTS: No operative mortality occurred in this series. All patients experienced pain relief and neurological improvement after surgery. Except for 1 incidence of screw pullout, which was corrected by revision surgery, solid fusion was achieved in all patients. A follow-up period of 12 to 37 months was available for this study. Two patients with chordoma relapsed; 1 died of disease, and the other was alive with disease. Two patients with metastasis died of multiple remote metastases. No evidence of local recurrence was found in the other patients. CONCLUSION: The anterior retropharyngeal approach is a favorable route to treat tumor lesions of the C2 vertebral body that allows tumor resection and placement of anterior constructs between C1 and the subaxial vertebral body. Tumor resection and 2-column reconstruction could safely be accomplished simultaneously through the combined anterior retropharyngeal-posterior approach.

Aneurysmal bone cyst secondary to giant cell tumor of the mobile spine: a report of 11 cases.

STUDY DESIGN: A retrospective analysis was performed. OBJECTIVE: To analyze the characteristics of aneurysmal bone cyst arising from giant cell tumor of the mobile spine and to discuss the outcome of corresponding surgical and nonsurgical treatment. SUMMARY OF BACKGROUND DATA: Giant cell tumors are generally benign neoplasms that exhibit aggressive behavior with a tendency to recur locally. Aneurysmal bone cysts are benign, highly vascular osseous lesions. Although both of them have been described separately in previous literatures, few reports have described aneurysmal bone cyst secondary to giant cell tumor of the mobile spine. METHODS: Between January 2004 and December 2009, 11 patients were identified with an aneurysmal bone cyst arising from giant cell tumor of the mobile spine. Four patients underwent subtotal tumor resection followed by radiotherapy, and the other 7 patients underwent total tumor resection. Patients with lesions located below T6 were treated with selective arterial embolization before surgery. Clinical data and the efficacy of surgery were analyzed via chart review RESULTS: Of the eleven patients identified for inclusion in this study, the average age was 33 months (range ∇ 14-65 months). The mean length of follow-up was 31 months. Seven patients kept disease-free during the follow-ups. The remaining four patients recurred and one died of local re-recurrence and lung metastasis. CONCLUSION: Unlike primary aneurysmal bone cyst, secondary aneurysmal bone cyst arising from giant cell tumor of the mobile spine has a more aggressive tendency to recurrence locally. Complete resection with systematic radiotherapy should be undertaken for the treatment of aneurysmal bone cyst secondary to giant cell tumor of the mobile spine, which is associated with a good prognosis for local tumor control. As complete or as radical an operation as possible should be performed at first presentation. The best chance for the patient is the first chance. Selective preoperative embolization is advised to minimize intraoperative blood loss.

Combined pre- and retrovascular extraoral approach for tumors at lateral mass of the atlas.

STUDY DESIGN: a series of 9 patients surgically treated with a novel combined pre-and retrovascular extraoral approach to lateral mass of the atlas (LMA) is examined. OBJECTIVE: to describe the efficacy of combined pre- and retrovascular extraoral approach in achieving a wide exposure and aggressive resection of tumors at the LMA. SUMMARY OF BACKGROUND DATA: the anatomic complexity and closeness to vital neurovascular structures raise technical difficulties in the surgical access to the LMA. Although various approaches, such as transoral approach, high anterior cervical approach, anterior lateral approach, and far lateral approach, have been reported in literature, wide exposure for the tumors at the LMA remains a unique challenge. METHODS: for our experience in the surgical exposure of the upper cervical spine, we have developed a combined pre- and retrovascular extraoral approach to the atlas since 2001. Nine patients with neoplastic lesions at the LMA were surgically treated through this combined approach. Reconstruction of stability was achieved by a posterior occipitocervical fusion through a posterior approach under the same anesthesia. RESULTS: this combined approach provided an excellent surgical field exposure to ensure the successful tumor resection while preventing the vertebral artery or nerve from injury. There was no operative mortality or severe morbidity in this series. Complications included 1 instance of transient dysphagia and 2 instances of transient trouble swallowing liquids. The symptoms of local pain and pharyngeal discomfort relieved, and patients suffering from spinal cord compression recovered well with 1 level of the Frankel scale when reevaluated 3 months after operation. With a follow-up period of 16 to 100 months, 1 patient with chondrosarcoma developed local recurrence at the 14th month of postoperation and died of respiratory and circulatory failure 39 months after surgery. No evidence of local recurrence was found in other patients. CONCLUSION: the combined pre- and retrovascular extraoral approach provides an advantageous alternative to previous reported approaches. For selected cases with tumor lesions at the LMA, this combined approach offers more benefits, through which a wide exposure with well-protected vertebral artery favoring radical excision could be achieved without complications normally associated with transoral surgery.