Overexpression of lncRNA AFAP1-AS1 correlates with poor prognosis and promotes tumorigenesis in colorectal cancer

Accumulating evidence has shown that long non-coding RNAs (lncRNAs) are emerging as key molecules in human malignancies. The lncRNA actin filament associated protein 1 antisense RNA1 (AFAP1-AS1) was recently found deregulated in several cancers. However, its expression pattern, clinical performance and functional roles in colorectal cancer (CRC) had not been addressed. In this study, we found that AFAP1-AS1 was aberrantly over-expressed in CRC tissues and closely correlated with tumor size, TNM stage and distant metastasis. Kaplan-Meier analysis indicated that patients with high level of AFAP1-AS1 expression had poorer overall survival (OS) and disease-free survival (DFS). Univariate and multivariable Cox regression analyses further identified that up-regulated AFAP1-AS1 might act as an independent prognostic factor for CRC patients. Moreover, AFAP1-AS1 depletion resulted in the inhibition of CRC cell proliferation and colony formation. In addition, AFAP1-AS1 knockdown induced G0/G1 cell cycle arrest in CRC cells. Taken together, our findings indicate that AFAP1-AS1 is significantly up-regulated in CRC, which may act as an oncogene and correlate with tumor malignant progression and poor prognosis of CRC. This study may shed a new light on better understanding the pathogenesis of CRC. Moreover, AFAP1-AS1 also may be a promising diagnostic and therapeutic target for this deadly disease.     

成人Chiari畸形Ⅰ型后颅窝线性容积特征与小脑扁桃体下疝程度和脊髓空洞的相关性分析

目的 :探讨成人Chiari畸形Ⅰ型(Chiari malformation typeⅠ,CMⅠ)患者后颅窝线性容积特征及其与脊髓空洞和小脑扁桃体下疝程度之间的相关性。方法:收集2010年6月~2014年6月在我院接受治疗的CMⅠ患者,入选标准为:(1)年龄30岁;(2)经头颈部MRI确诊为CMⅠ伴或不伴脊髓空洞;所有入选患者均排除颅内占位性病变、颅骨破坏、后颅窝手术史或获得性Chiari畸形。选取年龄匹配的正常成人作为对照组,测量两组头颅正中矢状位MRI中斜坡长度、枕骨大孔横径、枕上长度、后颅窝矢状径、后颅窝高径和后颅窝斜坡倾斜角α等指标,并将两组按性别分组后比较后颅窝线性容积差异。同时根据小脑扁桃体下疝程度及是否伴发脊髓空洞进行分组,分析后颅窝线性容积特征与小脑扁桃体下疝程度及脊髓空洞的关系。结果:共纳入CMⅠ患者37例,男18例,女19例;年龄38.5±5.5岁(31~56岁)。正常对照组41例,男19例,女22例;年龄36.4±6.3岁(33~58岁),成人CMⅠ患者后颅窝斜坡长度、枕上长度、后颅窝矢状径、后颅窝高径及斜坡倾斜角分别为35.9±4.2mm、38.2±5.8mm、77.4±6.1mm、28.2±3.9mm和47.4°±6.4°,均明显小于正常对照组(43.3±2.9mm、43.5±5.6mm、82.5±4.5mm、35.4±3.4mm、58.6°±5.7°,P0.05);伴脊髓空洞的成人CMⅠ组患者斜坡倾斜角(45.8°±7.6°)较单纯CMⅠ组(49.7°±5.1°)显著减小;Ⅱ度扁桃体下疝CMⅠ患者的后颅窝斜坡长度(31.4±3.6mm)及倾斜角(42.3°±5.4°)明显小于Ⅰ度扁桃体下疝CMⅠ患者(36.2±3.8mm、48.1°±5.2°;P0.05),余指标未见明显差异。结论 :成人CMⅠ患者的后颅窝容积明显减少,但与脊髓空洞和扁桃体下疝程度之间无显著相关性;CMⅠ患者斜坡发育不良与脊髓空洞的形成以及小脑扁桃体下疝程度存在一定相关性。     

Effects of Different Levels of Weightlifting Training on Bone Mineral Density in a Group of Adolescents

The aim of the current study was to evaluate the effects of different levels of weightlifting training on bone mineral density (BMD) at different body sites (whole body (WB), lumbar spine (LS), femoral neck (FN), upper limbs (UL) and lower limbs (LL)) in a group of adolescents. Three groups of pubertal boys aged 13-15 years were recruited, including a control group (which included 13 untrained adolescents), a moderately trained group (which included 13 non-elite weightlifters, with four sessions of 2 hours per week) and a highly trained group (which included 13 elite weightlifters, with eight sessions of 2 hours per week). The three groups were paired for age and maturation index (using Tanner stages). Body composition, bone mineral content (BMC) and BMD were evaluated by dual-energy X ray absorptiometry (DXA). Physical performance variables (including weightlifting specific exercises, counter movement jump and squat jump) were measured using validated methods. Results showed that the values of BMD and physical performance variables were greater in the group of elite weightlifters compared to the group of non-elite weightlifters and the control group. In addition, the values of BMD and physical performance variables were higher in the group of the non-elite weightlifters compared to those of the control group. After adjusting for lean mass and squat jump, lumbar spine BMD, FN BMD, UL BMD and LL BMD remained significantly higher in the elite weightlifters’ group compared to the two other groups. In conclusion, the current study suggests that elite adolescent weightlifters have greater bone health parameters compared to moderately-trained adolescent weightlifters and untrained adolescents.     

Cerebrospinal fluid biomarkers of white matter injury and astrogliosis are associated with the severity and surgical outcome of degenerative cervical spondylotic myelopathy

BACKGROUND CONTEXTDegenerative cervical spondylotic myelopathy (DCM) is the commonest form of spinal cord injury in adults. However, a limited number of clinical reports have assessed the role of biomarkers in DCM.PURPOSEWe evaluated cerebrospinal fluid (CSF) biomarkers in patients scheduled for DCM surgery and hypothesized that CSF biomarkers levels (1) would reflect the severity of preoperative neurological status; and (2) correlate with radiological appearance; and (3) correlate with clinical outcome.STUDY DESIGN/SETTINGProspective clinical and laboratory study.PATIENT SAMPLETwenty-three DCM patients, aged 66.4±12.8 years and seven controls aged 45.4±5.3 years were included.OUTCOME MEASURESThe American Spinal Injury Association Impairment Scale, the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire and EuroQol 5-dimensions were assessed preoperatively and at 3 months post-surgery.METHODSWe measured preoperative biomarkers (glial fibrillary acidic protein [GFAP], neurofilament light [NFL], phosphorylated neurofilament-H [pNF-H] and Ubiquitin C-terminal hydrolase L1) in CSF samples collected from patients with progressive clinical DCM who underwent surgical treatment. Biomarker concentrations in DCM patients were compared with those of cervical radiculopathy controls.RESULTSThe median symptom duration was 10 (interquartile range 6) months. The levels of GFAP, NFL, pNF-H, Ubiquitin C-terminal hydrolase L1 were significantly higher in the DCM group compared to controls (p=.044, p=.002, p=.016, and p=.006, respectively). Higher pNF-H levels were found in patients with low signal on T1 Magnetic Resonance Imaging sequence compared to those without (p=.022, area under the receiver operating characteristic curve [AUC] 0.780, 95% Confidence Interval: 0.59–0.98). Clinical improvement following surgery correlated mainly with NFL and GFAP levels (p<.05).CONCLUSIONSOur results suggest that CSF biomarkers of white matter injury and astrogliosis may be a useful tool to assess myelopathy severity and predict outcome after surgery, while providing valuable information on the underlying pathophysiology.     

The surgical treatment of Andersson lesions associated with ankylosing spondylitis

Eight men with Andersson lesions associated with ankylosing spondylitis who underwent surgical treatment were reviewed for this study. Eight Andersson lesions were found in the 8 patients, and all presented as pseudoarthrosis. Including a patient with obvious vertebral body destruction, no obvious local kyphosis was observed. Spinal cord compression and neural deficit were observed in 1 patient. Without established instructions for the surgical treatment of Andersson lesions, we alternated the surgical technique for each patient. Therefore, 5 patients, including the patient with obvious anterior destruction requiring reconstruction, underwent surgical treatment with lesion curettage and anterior bone graft and fusion; 3 other patients underwent surgical treatment without lesion curettage and anterior bone graft. All surgeries were performed from a posterior approach. Posterolateral autograft was supplemented to posterior instrumentation with or without anterior bone graft.All 8 patients experienced pain relief immediately postoperatively. No evidence of non-union was observed on radiographs at the level of pseudoarthrosis at final follow-up, and no neural and infectious complications were observed. Based on these results, surgical treatment with only posterior instrumentation supplemented by posterolateral autograft was effective for patients with Andersson lesions without obvious vertebral body destruction requiring reconstruction. Anterior lesion curettage and bone graft were not necessary. Solid immobilization, achieved by posterior instrumentation, should be the focus of the treatment of Andersson lesions with ankylosing spondylitis.     

Vertebral body resection and lumbar corpectomies

Corpectomies in the lumbar spine are unique operations with important and well-deserving nuances that determine their ultimate safety and efficacy. Lumbar vertebral resections are indicated in deformity and non-deformity settings. For deformities, they are reserved for those that are severe and rigid. Infections, fractures, and tumors that compromise the weight-bearing capacity of the anterior and middle columns of the spine are also indicated for lumbar vertebrectomy. Anterior column structural support is required in non-deformity situations and may be accomplished with the use of polymethyl methacrylate (PMMA) cement, osseous strut grafts (i.e. allografts/autograft), or titanium cages (static vs. expandable). The newest generation of cages have wide, rectangular footprints that span the apophyseal ring and provide a sound biomechanical environment and minimize the risk of cage subsidence compared to those with circular footprints. Neural decompression and placement of structural support can be accomplished by a variety of surgical approaches. While a traditional anterior approach is the gold-standard for lumbar vertebrectomies, minimally invasive lateral approaches and a posterior-only approach are viable management strategies. Supplemental fixation is also required and may be achieved with anterior-only instrumentation, posterior-only instrumentation, and circumferential instrumentation. In the review to follow, an evidence-based approach will be used to outline appropriate indications, surgical technique, and concomitant reconstructive and stabilization options for lumbar corpectomies. The discussion to follow ideally will help optimize outcomes for patients treated with vertebral resection and lumbar corpectomies in the lumbar spine.     

Development and validation of machine learning-based predictive model for clinical outcome of decompression surgery for lumbar spinal canal stenosis

BACKGROUND CONTEXTAlthough the results of decompression surgery for lumbar spinal canal stenosis (LSS) are favorable, it is still difficult to predict the postoperative health-related quality of life of patients before surgery.PURPOSEThe purpose of this study was to develop and validate a machine learning model to predict the postoperative outcome of decompression surgery for patients with LSS.STUDY DESIGN/SETTINGA multicentered retrospective study.PATIENT SAMPLEA total of 848 patients who underwent decompression surgery for LSS at an academic hospital, tertiary center, and private hospital were included (age 71±9 years, 68% male, 91% LSS, level treated 1.8±0.8, operation time 69±37 minutes, blood loss 48±113 mL, and length of hospital stay 12±5 days).OUTCOME MEASURESBaseline and 2 years postoperative health-related quality of life.METHODSThe subjects were randomly assigned in a 7:3 ratio to a model building cohort and a testing cohort to test the models’ accuracy. Twelve predictive algorithms using 68 preoperative factors were used to predict each domain of the Japanese Orthopedic Association Back Pain Evaluation Questionnaire and visual analog scale scores at 2 years postoperatively. The final predictive values were generated using an ensemble of the top five algorithms in prediction accuracy.RESULTSThe correlation coefficients of the top algorithms for each domain established using the preoperative factors were excellent (correlation coefficient: 0.95–0.97 [relative error: 0.06–0.14]). The performance evaluation of each Japanese Orthopedic Association Back Pain Evaluation Questionnaire domain and visual analog scale score by the ensemble of the top five algorithms in the testing cohort was favorable (mean absolute error [MAE] 8.9–17.4, median difference [MD] 8.1–15.6/100 points), with the highest accuracy for mental status (MAE 8.9, MD 8.1) and the lowest for buttock and leg numbness (MAE 1.7, MD 1.6/10 points). A strong linear correlation was observed between the predicted and measured values (linear correlation 0.82–0.89), while 4% to 6% of the subjects had predicted values of greater than±3 standard deviations of the MAE.CONCLUSIONSWe successfully developed a machine learning model to predict the postoperative outcomes of decompression surgery for patients with LSS using patient data from three different institutions in three different settings. Thorough analyses for the subjects with deviations from the actual measured values may further improve the predictive probability of this model.     

Outcomes in surgical treatment for tandem spinal stenosis: systematic literature review

BACKGROUND CONTEXTTandem spinal stenosis (TSS) refers to a narrowing of the spinal canal in distinct, noncontiguous regions. TSS most commonly occurs in the cervical and lumbar regions. Decompressive surgery is indicated for those with cervical myelopathy or persistent symptoms from lumbar stenosis despite conservative management. Surgical management typically involves staged procedures, with cervical decompression taking precedence in most cases, followed by lumbar decompression at a later time. However, several studies have shown favorable outcomes in simultaneous decompression.PURPOSEThe aim of this study is to provide a literature review and compare surgical outcomes in patients undergoing staged vs simultaneous surgery for TSS.STUDY DESIGN/SETTINGSystematic literature review.METHODSA systematic review using PRISMA guidelines to identify original research articles for tandem spinal stenosis. PubMed, Cochrane, Ovid, Scopus, and Web of Science were used for electronic literature search. Original articles from 2005 to 2021 with more than eight adult patients treated surgically for cervical and lumbar TSS in staged or simultaneous procedures were included. Articles including pediatric patients, primarily thoracic stenosis, stenosis secondary to neoplasm or infectious disease, minimally invasive surgery, and non-English language were excluded. Demographic, perioperative, complications, functional outcome, and neurologic outcome data including mJOA (modified Japanese Orthopaedic Association), Nurick grade (NG), and ODI (Oswestry disability index), were extracted and summarized.RESULTSA total of 667 articles were initially identified. After preliminary screening, 21 articles underwent full-text screening. Ten articles met our inclusion criteria. A total of 831 patients were included, 571 (68%) of them underwent staged procedures, and 260 (32%) underwent simultaneous procedures for TSS. Mean follow-ups ranged from 12 to 85 months. There was no difference in estimated blood loss (EBL) between staged and simultaneous groups (p=.639). Simultaneous surgeries had shorter surgical time than staged surgeries (p<.001). Mean changes in mJOA, NG, and ODI was comparable between staged and simultaneous groups. Complications were similar between the groups. There were more major complications reported in simultaneous operations, although this was not statistically significant (p=.301).CONCLUSIONStaged and simultaneous surgery for TSS have comparable perioperative, functional, and neurologic outcomes, as well as complication rates. Careful selection of candidates for simultaneous surgery may reduce the length of stay and consolidate rehabilitation, thereby reducing hospital-associated costs.     

Anterolateral Retroperitoneal Psoas-Sparing (Anterior to Psoas: ATP) Lumbar Interbody Fusion for Degenerative Spine and Adult Deformity: Surgical Technique and the Evidence

Corrective multilevel spinal surgeries are notorious for high complication rate. In effort to reduce morbidities, various minimally invasive surgical techniques have been described. Posterior interbody fusions, while familiar to most surgeons, are limited in their ability to address multilevel pathology. Contrastingly, anterior lumbar fusion is effective in correcting multilevel deformities, yet it is notorious for vascular injuries and often warrants the assistance of an exposure surgeon. Moreover, the attractive lateral transpsoas approach has been associated with catastrophic neurovascular and visceral complications. Therefore, a novel retroperitoneal anterolateral psoas sparing access will be presented as a promising alternative to the preexisting techniques.