Clinical Outcomes of Surgical Treatments for Traumatic Spinal Injuries due to Snowboarding.

STUDY DESIGN: Retrospective study. PURPOSE: To assess treatment outcomes of snowboarding-related spinal and spinal cord injuries. OVERVIEW OF LITERATURE: Snowboarding-related spinal or spinal cord injury have a great impact on social and sporting activities. METHODS: A retrospective review of 19 cases of surgically treated snowboard-related injury was done. Analyzed parameters included site of injury, type of fracture, peri- and postoperative complications, pre- and postoperative neurological status, activities of daily living, and participation in sports activities at the final follow-up. RESULTS: The major site of injury was the thoracolumbar junction caused by fracture-dislocation (13/19 cases). The remaining 6 cases had cervical spine injuries. Over 60% of the patients had Frankel A and B paralysis. All patients were surgically treated by posterior fusion with instrumentation. Five underwent additional anterior fusion. Surgical outcome was restoration of ambulatory capacity in 12 patients (63.2%). Ultimately, 15 patients (78.9%) could return to work. Patients with complete paralysis upon admission showed reduced ambulatory capacity compared to those with incomplete paralysis. None of the patients again participated in any sports activities, including snowboarding. CONCLUSIONS: Snowboarding-related spinal or spinal cord injury has a great impact on social as well as sports activities. It is necessary to enhance promotion of injury prevention emphasizing the snowboarders' responsibility code.

Hip pads reduce the overall risk of injuries in recreational snowboarders.

OBJECTIVE: The purpose is to determine common injuries in recreational snowboarding as targets of preventive strategy and protective gear that reduces the overall risk of these injuries. METHODS: The subjects comprised 5561 injured recreational snowboarders. On the basis of patients' self-reporting form, 'the common snowboarding injuries' (cut-off point >2.0% in prevalence) were decided, and all injured snowboarders were categorised into two groups: common injuries and the other injuries (control). Several factors such as age, gender, self-reported skill level, experienced seasons, experienced days, previous snowboarding school attendance and the use of protective gears (helmet, elbow pads, wrist guards, backbone guard, hip pads and knee pads) were recorded. Multiple logistic regression analysis was conducted to investigate which type of protective gear reduced the overall risk of the common injuries. RESULTS: The common snowboarding injuries consisted of eight types, in which distal radial fracture was the most common (17.7%), followed by head injury (9.4%) and clavicle fracture (6.5%). In univariate regression analysis, skill level, experienced seasons, experienced days and the use of hip pads and knee pads were manifested potential risk factors on the common injuries. In subsequent multivariate regression analysis, the use of hip pads was related with a lower overall risk of these common injuries (OR, 0.84; 95% CI, 0.75 to 0.95), specifically that of distal radial fracture and glenohumeral dislocation. CONCLUSIONS: The use of hip pads is recommended for snowboarders as it reduces the overall risk of common snowboarding injuries.

BLCAP induces apoptosis in human Ewing's sarcoma cells.

Bladder cancer-associated protein (BLCAP) is a novel candidate tumor suppressor gene identified from human bladder carcinoma and highly associated with the invasion of bladder cancer. We previously reported that it also plays a key role in the tumorigenesis and metastasis of human osteosarcoma. In the present study, we constructed a recombinant encoding BLCAP cDNA. Overexpression of BLCAP resulted in growth inhibition and induced apoptosis of human TC-135 Ewing's sarcoma cells in vitro. We further investigated the caspase-3/7 activity and expressions of the fusion transcription factor Ewing's sarcoma protein-friend leukemia virus integration 1 (EWS-FLI1) and the apoptosis regulator B-cell lymphoma 2 (BCL-2). Cell apoptosis was accompanied by the down-regulated expression of EWS-FLI1 and BCL-2. Our present results suggest that BLCAP may play a role not only in regulating cell proliferation but also in coordinating apoptosis through the down-regulation of BCL-2 and EWS-FLI1 in human Ewing's sarcoma cells.

Characteristics of upper extremity injuries sustained by falling during snowboarding: a study of 1918 cases.

BACKGROUND: Little epidemiological research on characteristics of upper extremity injuries resulting from snowboarding has been conducted, particularly in relation to snowboarding stance, falling direction, and the side of the body where the injury occurs. HYPOTHESIS: Snowboarding stance and the direction of the fall may influence the frequency of the side or the location of the upper extremity injury. STUDY DESIGN: Descriptive epidemiology study. METHODS: This study analyzed the information obtained from 1918 patients with fractures or dislocations of the upper extremity (excluding the fingers and scapula) sustained during snowboarding/sliding between 2000 and 2008. Diagnosis, injured part and side, stance (regular or goofy), and falling directions were prospectively analyzed. Associations among these parameters were also analyzed. RESULTS: As characterized by skill level, patients were beginners (57.9%), intermediates (38.0%), and experts (4.0%). Eighty-eight percent had not received instruction from licensed instructors. Diagnoses included wrist fractures (53.7%), upper arm fractures (16.8%), shoulder dislocations (11.5%), and elbow dislocations (9.8%). In sum, 1742 (90.8%) patients were in regular stance when they fell, whereas 176 (9.2%) were in goofy stance. There was a significant difference in the prevalence of the injured side between the 2 stances. When the injured sides were classified according to the sliding direction, wrist fractures (61.7%) occurred on the side opposite the sliding direction, whereas shoulder dislocations (65.6%), upper arm fractures (82.9%), and elbow dislocations (79.8%) occurred on the same side as the sliding direction. When the injured sides were classified according to the falling direction, wrist fractures (68.1%) and elbow dislocations (63.5%) occurred because of backward falls, and shoulder dislocations (68.9%) and upper arm fractures (60.7%) occurred because of forward falls. CONCLUSION: Two snowboarding stances as well as 2 falling directions had a significant influence on the frequency of the injured side in the upper extremity.

Surgical treatment of multiple spinal canal stenoses associated with vitamin D-resistant rickets.

We describe a 44-year-old woman who was diagnosed in childhood with vitamin D-resistant rickets, and who had paraparesis due to multiple spinal canal stenoses between C5 and L1 with ossification of the posterior longitudinal ligament and the yellow ligament. She was treated surgically with laminoplasty of the C2 through C7 levels and laminectomy from T8 through T11. Four months later, she underwent anterior fusion using an ilium graft by thoracotomy from the T12 to L1 levels. Six months after surgery, her symptoms improved. After 5 years, and with oral vitamin D, no progression of symptoms has been observed.

Simultaneous inhibition of mitogen-activated protein kinase and phosphatidylinositol 3-kinase pathways augment the sensitivity to actinomycin D in Ewing sarcoma.

PURPOSE: Ewing sarcoma cells, of which over 85% retain chimeric fusion gene EWS/Fli-1, are by and large more resistant to chemotherapeutics compared to nonneoplastic cells. The purpose of this study is to determine the role of EWS/Fli-1 fusion and its downstream targets regarding the cells' resistance against actinomycin D (ActD), which is one of the most commonly used antitumor agents in combination chemotherapy of Ewing sarcomas. METHODS: Cytotoxicity was measured by WST-8 assay. Caspase-dependent and -independent cell death was examined by fluorescence microscope. Protein expression was analyzed by western blotting. Caspase activity was determined by Caspase-Glo assay. RESULTS: ActD-induced caspase-dependent apoptotic cell death to Ewing sarcoma TC-135 cells in a dose- and time- dependent manner. Knockdown of EWS/Fli-1 fusion by siRNA resulted in enhancement of ActD-induced apoptosis. ActD treatment activated both mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and phosphatidylinositol 3-kinase (PI3K)/Akt pathways although in a distinctive manner. Combined administration of U0126 (MEK inhibitor) and LY294002 (PI3K inhibitor) significantly enhanced ActD-induced apoptosis in vitro and suppressed xenograft tumor growth in vivo. CONCLUSIONS: The present study demonstrated for the first time that combination of U0126 and LY294002 can augment the cytotoxicity of ActD against Ewing sarcoma cells in vitro and in vivo. Our results indicate that further study on combination of conventional chemotherapies with MEK and PI3K inhibitors may be considered for innovative treatments of Ewing sarcoma patients.

EWS-Fli1 up-regulates expression of the Aurora A and Aurora B kinases.

EWS-Fli1, a fusion gene resulting from the chromosomal translocation t(11;22, q24;q12), encodes a transcriptional activator, promotes cellular transformation, and is often found in Ewing sarcoma and primitive neuroectodermal tumor. The Aurora A and Aurora B kinases belong to a highly conserved family of serine/threonine protein kinases, are tightly regulated during the cell cycle, and are overexpressed in many carcinomas. Because the relationship between the Aurora A and/or Aurora B genes and the EWS-Fli1 fusion gene is unknown, we investigated the regulatory mechanism(s) by which Aurora kinases are controlled. Knockdown of EWS-Fli1 by small interfering RNA reduced mRNA levels not only of EWS-Fli1 but also of Aurora A and Aurora B. Luciferase assay using Aurora A and Aurora B promoters showed up-regulated activities compared with those of an empty vector. Experiments with deletion and point mutants showed positive regulatory Ets-binding sites located -84 and -71 bp upstream of the transcription initiation sites in Aurora A and Aurora B, respectively. Moreover, chromatin immunoprecipitation assay revealed that EWS-Fli1 gene products interact with both the Aurora A and Aurora B promoters. These results strongly suggest that the mitotic kinases Aurora A and Aurora B are regulated by EWS-Fli1 fusion protein in Ewing sarcoma cells.

Traumatic spinal cord injuries from snowboarding.

BACKGROUND: Little information has yet been made available on the types and mechanisms of snowboard-related spinal cord injuries or their neurologic involvement. PURPOSE: To review the cause and types of spinal cord injuries seen in snowboarders. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: The subjects were 18 patients (mean age, 24.0 years) referred to the authors' institution for neurologic deficits associated with spinal injuries between November 1, 1995, and April 9, 2005. The clinical features of these patients were reviewed with respect to epidemiologic factors, mechanism of injury, fracture pattern, and neurologic status. RESULTS: The 18 snowboarders with spinal cord injuries constituted a very homogeneous group. First, almost all patients (94.4%) were young men. Second, most of the patients were intermediate or expert boarders. Third, the most common cause of injury was a failure of intentional jumping (83.3%). Fourth, the most commonly affected site was the thoracolumbar junction (66.7%), and the most common type of fracture was an anterior dislocation fracture (66.7%). Finally, in the thoracolumbar group, most patients (83.3%) were classed as Frankel grade A or B. CONCLUSION: It is fundamentally important that snowboarders, especially young men, be made aware of the spinal injury risk associated with jumping.

Global gene expression profiling of pleural mesotheliomas: overexpression of aurora kinases and P16/CDKN2A deletion as prognostic factors and critical evaluation of microarray-based prognostic prediction.

Most gene expression profiling studies of mesothelioma have been based on relatively small sample numbers, limiting their statistical power. We did Affymetrix U133A microarray analysis on 99 pleural mesotheliomas, in which multivariate analysis showed advanced-stage, sarcomatous histology and P16/CDKN2A homozygous deletion to be significant independent adverse prognostic factors. Comparison of the expression profiles of epithelioid versus sarcomatous mesotheliomas identified many genes significantly overexpressed among the former, including previously unrecognized ones, such as uroplakins and kallikrein 11, both confirmed by immunohistochemistry. Examination of the gene expression correlates of survival showed that more aggressive mesotheliomas expressed higher levels of Aurora kinases A and B and functionally related genes involved in mitosis and cell cycle control. Independent confirmation of the negative effect of Aurora kinase B was obtained by immunohistochemistry in a separate patient cohort. A role for Aurora kinases in the aggressive behavior of mesotheliomas is of potential clinical interest because of the recent development of small-molecule inhibitors. We then used our data to develop microarray-based predictors of 1 year survival; these achieved a maximal accuracy of 68% in cross-validation. However, this was inferior to prognostic prediction based on standard clinicopathologic variables and P16/CDNK2A status (accuracy, 73%), and adding the microarray model to the latter did not improve overall accuracy. Finally, we evaluated three recently published microarray-based outcome prediction models, but their accuracies ranged from 63% to 67%, consistently lower than reported. Gene expression profiling of mesotheliomas is an important discovery tool, but its power in clinical prognostication has been overestimated.

Inhibition of platelet-derived growth factor-induced cell growth signaling by a short interfering RNA for EWS-Fli1 via down-regulation of phospholipase D2 in Ewing sarcoma cells.

EWS-Fli1, a fusion gene resulting from a chromosomal translocation t(11;22, q24;q12) and found in Ewing sarcoma and primitive neuroectodermal tumors, encodes a transcriptional activator and promotes cellular transformation. However, the precise biological functions of its products remain unknown. To investigate the role of EWS-Fli1 in cell growth signaling, we transfected Ewing sarcoma TC-135 cells with short interfering RNAs for EWS-Fli1. EWS-Fli1 knockdown reduced cell growth and platelet-derived growth factor (PDGF)-BB-induced activation of the growth signaling enzymes. Interestingly, phospholipase D2 (but not the PDGF-BB receptor) showed marked down-regulation in the EWS-Fli1-knocked down TC-135 cells compared with the control cells. In Ewing sarcoma TC-135 cells, the PDGF-BB-induced phosphorylation of growth signaling involving extracellular signal-regulated kinase, Akt, p70S6K, and the expression of cyclin D3 were markedly inhibited by transfection with short interfering RNA phospholipase (PL)-D2. The PDGF-BB-induced activation of growth signaling was also suppressed by 1-butanol, which prevents the production of phosphatidic acid by phospholipase D (but not by t-butyl alcohol), thereby implicating PLD2 in PDGF-BB-mediated signaling in TC-135 cells. These results suggest that EWS-Fli1 may play a role in the regulation of tumor proliferation-signaling enzymes via PLD2 expression in Ewing sarcoma cells.