Prognostic scoring system for osteosarcoma using network-regularized high-dimensional Cox-regression analysis and potential therapeutic targets.

With the recent emphasis on the importance of personalized genomic medicine, studies have performed prognostic stratification using gene signatures in cancers. However, these studies have not considered gene networks with clinical data. Therefore, this study aimed to develop a novel prognostic score using grouped variable selection for patients with osteosarcoma. We assessed messenger RNA (mRNA) expression and clinical data from Gene Expression Omnibus to develop a novel prognostic scoring system for patients with osteosarcoma. Variable selection using Network-Regularized high-dimensional Cox-regression analysis with information regarding gene networks obtained from six large pathway databases was performed. We determined the risk score on the linear combination of regression coefficients and mRNA expression values. Log-rank test, UNO's c-index, and area under the curve (AUC) values were determined to evaluate the discriminatory power between the low- and high-risk groups. A recently reported next-generation Connectivity Map was used to identify future therapeutic targets for osteosarcoma. Our novel model had significantly high discriminatory power in predicting overall survival. An optimal c-index of 0.967 was obtained and time-dependent receiver operating characteristic analysis revealed an acceptable predictive value of AUC between 0.953 and 1.000. Knockdown of BACE2 or ING2 and linifanib treatment may improve the prognosis of patients with osteosarcoma. Herein, this novel prognostic scoring system would not only facilitate a more accurate prediction of patient prognosis, but also contribute to the selection of suitable therapeutic alternatives for osteosarcoma patients.

Relationships between Clinical Status and Gait Parameters in Ankylosing Spondylitis.

Background: This study aimed to identify the relationship between gait parameters and health-related quality of life (HRQOL) in patients with ankylosing spondylitis (AS). Methods: The study group comprised 134 patients with AS and 124 patients were enrolled as controls. All study participants underwent instrumented gait analysis and completed clinical questionnaires. The kinematic parameters of gait were walking speed, step length, cadence, stance phase, single support, double support, phase coordination index (PCI), and gait asymmetry (GA). For each patient, a visual analog scale (VAS; 0-10) score was used to assess back pain, 36-item short form survey (SF-36) questionnaire was administered to evaluate the HRQOL, and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) was calculated. Using kinematic parameters and questionnaires, statistical analyses were done to investigate significant differences between the groups. Relationship of gait kinematic data and questionnaires of clinical outcome was also evaluated. Results: Among the 134 patients with AS, 34 were women and 100 were men. In the control group, 26 were women and 98 were men. The patients with AS and control group patients had significant differences in terms of walking speed, step length, single support, PCI, and GA. However, such differences were not observed in cadence, stance phase, and double support (p > 0.05). In correlation analyses, gait kinematic parameters and clinical outcomes were significantly related with each other. In multiple regression analysis performed to identify predictive factors for clinical outcome, walking speed was found to predict VAS, and walking speed and step length were found to predict the BASDAI and SF-36 scores. Conclusions: Patients with and without AS had significant differences in the gait parameters. Correlation analysis showed significant correlation between the gait kinematic data and clinical outcomes. In particular, walking speed and step length successfully predicted clinical outcomes in patients with AS.

Double-Layered Lateral Meniscus Including a Ring-Shaped Accessory Meniscus: A Case Report.

CASE: We report the rare case of a double-layered lateral meniscus that was comprised of a normal meniscus and a ring-shaped accessory meniscus. An 11-year-old boy presented with left knee pain, and magnetic resonance imaging initially was interpreted as showing a horizontal meniscal tear. However, arthroscopic exploration revealed a double-layered meniscus. A superior accessory meniscus was fused with the inferior normal meniscus at the posterior horn and had more mobility compared with the normal meniscus. The symptoms improved substantially after resection of the superior accessory meniscus. The patient returned to sports at 4 months postoperatively; at 15 months postoperatively, radiographs demonstrated no evidence of degenerative changes. CONCLUSION: A double-layered lateral meniscus that includes a ring-shaped accessory meniscus is a rare abnormality that can be corrected arthroscopically by resection of the accessory meniscus.