Low-dose metformin treatment in the subacute phase improves the locomotor function of a mouse model of spinal cord injury.

Metformin, a first-line drug for type-2 diabetes, has been shown to improve locomotor recovery after spinal cord injury. However, there are studies reporting no beneficial effect. Recently, we found that high dose of metformin (200 mg/kg, intraperitoneal) and acute phase administration (immediately after injury) led to increased mortality and limited locomotor function recovery. Consequently, we used a lower dose (100 mg/kg, i.p.) metformin in mice, and compared the effect of immediate administration after spinal cord injury (acute phase) with that of administration at 3 days post-injury (subacute phase). Our data showed that metformin treatment starting at the subacute phase significantly improved mouse locomotor function evaluated by Basso Mouse Scale (BMS) scoring. Immunohistochemical studies also revealed significant inhibitions of microglia/macrophage activation and astrogliosis at the lesion site. Furthermore, metformin treatment at the subacute phase reduced neutrophil infiltration. These changes were in parallel with the increased survival rate of spinal neurons in animals treated with metformin. These findings suggest that low-dose metformin treatment for subacute spinal cord injury can effectively improve the functional recovery possibly through anti-inflammation and neuroprotection. This study was approved by the Institute Animal Care and Use Committee at the University of Texas Medical Branch (approval No. 1008041C) in 2010.

Liproxstatin-1 is an effective inhibitor of oligodendrocyte ferroptosis induced by inhibition of glutathione peroxidase 4.

Our previous studies showed that ferroptosis plays an important role in the acute and subacute stages of spinal cord injury. High intracellular iron levels and low glutathione levels make oligodendrocytes vulnerable to cell death after central nervous system trauma. In this study, we established an oligodendrocyte (OLN-93 cell line) model of ferroptosis induced by RSL-3, an inhibitor of glutathione peroxidase 4 (GPX4). RSL-3 significantly increased intracellular concentrations of reactive oxygen species and malondialdehyde. RSL-3 also inhibited the main anti-ferroptosis pathway, i.e., SLC7A11/glutathione/glutathione peroxidase 4 (xCT/GSH/GPX4), and downregulated acyl-coenzyme A synthetase long chain family member 4. Furthermore, we evaluated the ability of several compounds to rescue oligodendrocytes from ferroptosis. Liproxstatin-1 was more potent than edaravone or deferoxamine. Liproxstatin-1 not only inhibited mitochondrial lipid peroxidation, but also restored the expression of GSH, GPX4 and ferroptosis suppressor protein 1. These findings suggest that GPX4 inhibition induces ferroptosis in oligodendrocytes, and that liproxstatin-1 is a potent inhibitor of ferroptosis. Therefore, liproxstatin-1 may be a promising drug for the treatment of central nervous system diseases.

Neuroprotective effect of deferoxamine on erastininduced ferroptosis in primary cortical neurons.

The iron chelator deferoxamine has been shown to inhibit ferroptosis in spinal cord injury. However, it is unclear whether deferoxamine directly protects neurons from ferroptotic cell death. By comparing the survival rate and morphology of primary neurons and SH-SY5Y cells exposed to erastin, it was found that these cell types respond differentially to the duration and concentration of erastin treatment. Therefore, we studied the mechanisms of ferroptosis using primary cortical neurons from E16 mouse embryos. After treatment with 50 µM erastin for 48 hours, reactive oxygen species levels increased, and the expression of the cystine/glutamate antiporter system light chain and glutathione peroxidase 4 decreased. Pretreatment with deferoxamine for 12 hours inhibited these changes, reduced cell death, and ameliorated cellular morphology. Pretreatment with the apoptosis inhibitor Z-DEVD-FMK or the necroptosis inhibitor necrostain-1 for 12 hours did not protect against erastin-induced ferroptosis. Only deferoxamine protected the primary cortical neurons from ferroptosis induced by erastin, confirming the specificity of the in vitro ferroptosis model. This study was approved by the Animal Ethics Committee at the Institute of Radiation Medicine of the Chinese Academy of Medical Sciences, China (approval No. DWLL-20180913) on September 13, 2018.

Epidemiology of traumatic spinal cord injury in Tianjin, China: An 18-year retrospective study of 735 cases.

Study Design: Hospital-based retrospective studyObjectives: To evaluate the pathogenetic features of traumatic spinal cord injury (TSCI) during 1999-2016 according to changed injury etiology with time, explore different characteristics of patients suffered a TSCI during 1999-2007 and 2008-2016 in Tianjin, China.Setting: Tianjin Medical University General HospitalMethods: In this study, the medical records of TSCI patients were obtained from Tianjin Medical University General Hospital (TMUGH) from 1st January 1999 to 31th December 2016. Variables were recorded, including age, gender occupation, etiology, the level of injury, America Spinal Injury Association (ASIA) impairment scale, the severity, concomitant injuries, death and its cause. To explore the differences in characteristics by etiology and by two periods, related statistical methods were used to calculate the correlation of some variables. Differences in etiology of TSCI during 1999-2016 were evaluated and differences in epidemiological characteristics were separately compared and analyzed between the 1999-2007 period and the 2008-2016 period.Results: From 1999-2016, 831 TSCI cases were identified and 96 cases were excluded from analyses. The male-to-female ratio was 2.9:1 and the mean age was 49.7±15.2 years, which changed significantly between 1999-2007 (45.1±14.2) and 2008-2016 (51.6±15.2). Traffic accidents (45.8%) were the leading cause of TSCI during the 1999-2007 period, followed by low falls (30.7%). However, the opposite result was observed during the 2008-2016 period. Significant difference was observed compared with thoracic, lumbar and sacral levels, cervical level was the most commonly affected levels and the percentage decreased to a certain degree between 1999-2007 and 2008-2016 (from 84.4% to 68.9%). The proportions of ASIA grades A, B, C, and D were 20.5%, 10.3%, 23.3%, and 45.9%, respectively. The percentage of complete tetraplegia decreased from 22.9% in 1999-2007 to 13.2% in 2008-2016, and the percentage of incomplete paraplegia increased from 9.7% to 27.9%.Conclusion: According to the changes in the epidemiological characteristics of TSCI, relevant health service, laws and regulations, preventative strategies should be readjusted to follow up the changing situation and epidemiological characteristics of TSCI.

Bone marrow mesenchymal stem cells stimulated with low-intensity pulsed ultrasound: Better choice of transplantation treatment for spinal cord injury: Treatment for SCI by LIPUS-BMSCs transplantation.

Stem cell transplantation, especially treatment with bone marrow mesenchymal stem cells (BMSCs), has been considered a promising therapy for the locomotor and neurological recovery of spinal cord injury (SCI) patients. However, the clinical benefits of BMSCs transplantation remain limited because of the considerably low viability and inhibitory microenvironment. In our research, low-intensity pulsed ultrasound (LIPUS), which has been widely applied to clinical applications and fundamental research, was employed to improve the properties of BMSCs. The most suitable intensity of LIPUS stimulation was determined. Furthermore, the optimized BMSCs were transplanted into the epicenter of injured spinal cord in rats, which were randomized into four groups: (a) Sham group (n = 10), rats received laminectomy only and the spinal cord remained intact. (b) Injury group (n = 10), rats with contused spinal cord subjected to the microinjection of PBS solution. (c) BMSCs transplantation group (n = 10), rats with contused spinal cord were injected with BMSCs without any priming. (d) LIPUS-BMSCs transplantation group (n = 10), BMSCs stimulated with LIPUS were injected at the injured epicenter after contusion. Rats were then subjected to behavioral tests, immunohistochemistry, and histological observation. It was found that BMSCs stimulated with LIPUS obtained higher cell viability, migration, and neurotrophic factors expression in vitro. The rate of apoptosis remained constant. After transplantation of BMSCs and LIPUS-BMSCs postinjury, locomotor function was significantly improved in LIPUS-BMSCs transplantation group with higher level of brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in the epicenter, and the expression of neurotrophic receptor was also enhanced. Histological observation demonstrated reduced cavity formation in LIPUS-BMSCs transplantation group when comparing with other groups. The results suggested LIPUS can improve BMSCs viability and neurotrophic factors expression in vitro, and transplantation of LIPUS-BMSCs could promote better functional recovery, indicating possible clinical application for the treatment of SCI.

The association of rs11190870 near LBX1 with the susceptibility and severity of AIS, a meta-analysis.

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is the most common structural deformity of the spine. Genetics constitute largely to AIS, and the rs11190870 polymorphism has the potential for use in public health and clinical settings as a predictor of AIS risk. The aim of the present meta-analysis was to provide exhaustive evidence to evaluate the association of rs11190870 with the susceptibility and severity of adolescent idiopathic scoliosis (AIS) in multiple ethnic groups and different genders. MATERIALS AND METHODS: The professional databases, including PubMed, Embase, Social Sciences Citation Index, CINAHL, and International Bibliography of the Social Sciences, were searched from 1966 to October 2015. No language restriction was applied. Reference lists of all the selected articles were hand-searched for any additional studies. Three authors independently extracted data from all eligible studies. The data were analyzed by meta-analysis using fixed-effects or random-effects models with mean differences and risk ratios for continuous and dichotomous variables, respectively. RESULTS: Eight studies were included, and the pooled analysis suggested that the T genotype of SNP rs11190870 leads to a higher risk of AIS in multiple ethnic groups regardless of gender (Total:OR, 1.66, 95% CI 1.53, 1.79; I2 = 37.3%, P = 0.000, Female: OR, 1.62, 95% CI 1.50, 1.73; I2 = 26.7%, P = 0.000, Male: OR, 1.79, 95% CI 1.38, 2.20; I2 = 0.00%, P = 0.000). Additionally, the TT and TC genotype had a larger Cobb angle than those with the CC genotype in the overall and female Asian populations. CONCLUSION: A significant association of rs11190870 with AIS was observed in multiple ethnic groups regardless of gender. Additionally, a significant association was found between rs11190870 and curve severity in the overall and female Asian populations. Due to the limited data and clinical heterogeneity, further studies with large sample sizes are required.

Comparison of Mobi-C Cervical Disc Arthroplasty Versus Fusion for the Treatment of Symptomatic Cervical Degenerative Disc Disease.

OBJECTIVE: Mobi-C cervical disc arthroplasty (MCDA) is an alternative to anterior cervical discectomy and fusion (ACDF). This study evaluated the effectiveness and safety of MCDA and ACDF for symptomatic cervical degenerative disc disease. METHODS: Databases were systematically searched for randomized controlled trials. Studies were included based on eligibility criteria. Risk of bias assessment and quality of evidence assessment were performed. RESULTS: Four studies with 785 patients were included. For clinical outcomes, MCDA were superior to ACDF with fewer subsequent surgical interventions (P < 0.00001), lower neck pain scores (P = 0.01), lower incidences of adjacent segment degeneration at both superior and inferior levels (P = 0.0003 and P = 0.01, respectively), greater range of motion of the operated segment (P < 0.0001), and higher patient satisfaction (P = 0.007). No significant differences were observed between groups regarding operative time, blood loss, duration of hospitalization, and neck disability index and arm pain scores (P > 0.05). Subgroup analyses indicated that for patients with 2-level cervical degenerative disc disease, MCDA demonstrated lower neck disability index and arm pain scores and higher patient satisfaction (P < 0.05) compared with ACDF. CONCLUSIONS: MCDA had fewer subsequent surgical interventions, lower neck pain scores, lower incidences of adjacent segment degeneration at superior and inferior levels, greater range of motion, and higher patient satisfaction scores than ACDF. MCDA was similar to ACDF regarding operative time, blood loss, duration of hospitalization, and neck disability index and neck pain scores.

Dysregulated MiR-3150a-3p Promotes Lumbar Intervertebral Disc Degeneration by Targeting Aggrecan.

BACKGROUND/AIMS: Low back pain has become one of the most common musculoskeletal diseases in the world. Studies have shown that intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the mechanisms underlying IDD remain largely unknown. Research over the past decade has suggested critical roles for microRNAs (miRNAs) in natural growth and disease progression. However, it remains poorly understood whether circular RNAs participate in IDD. METHODS: Clinical IDD samples were collected from 20 patients who underwent discectomy. Weighted gene co-expression network analysis was used to identify the co-expression miRNA network modules (highly co-expressed clusters of miRNAs) that were associated with IDD grade. RESULTS: miR-3150a-3p was the most significantly up-regulated miRNA in module "Blue." Notably, aggrecan (ACAN) was identified as a direct target gene of miR-3150a-3p and ACAN expression was regulated by miR-3150a-3p. Overexpression of miR-3150a-3p decreased ACAN expression in nucleus pulposus cells, whereas inhibition of miR-3150a-3p increased ACAN expression. In addition, ACAN expression was negatively correlated with IDD grade. CONCLUSION: Our study suggests that the reduction of ACAN expression induced by the upregulation of miR-3150a-3p might participate in the development of IDD.

Circular RNA GRB10 as a competitive endogenous RNA regulating nucleus pulposus cells death in degenerative intervertebral disk.

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the underlying mechanisms remain poorly understood. Compared with normal nucleus pulposus (NP) tissues, the expression of circ-GRB10 was downregulated in IDD. Furthermore, overexpression of circ-GRB10 inhibited NP cell apoptosis. circ-GRB10 could sequester miR-328-5p, which could potentially lead to the upregulation of target genes related to cell proliferation via the ErbB pathway. In conclusion, the present study revealed that circ-GRB10/miR-328-5p/ERBB2 signaling pathway is involved in IDD development, suggesting that circ-GRB10 might be a novel therapeutic target for IDD.

Anterior inferior plating versus superior plating for clavicle fracture: a meta-analysis.

BACKGROUND: The position of plate fixation for clavicle fracture remains controversial. Our objective was to perform a comprehensive review of the literature and quantify the surgical parameters and clinical indexes between the anterior inferior plating and superior plating for clavicle fracture. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized and non-randomized studies that compared the anterior inferior plating with the superior plating for clavicle fracture. The relative risk or standardized mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. RESULTS: Four randomized controlled trials and eight observational studies were identified to compare the surgical parameters and clinical indexes. For the surgical parameters, the anterior inferior plating group was better than the superior plating group in operation time and blood loss (P < 0.05). Furthermore, in terms of clinical indexes, the anterior inferior plating was superior to the superior plating in reducing the union time, and the two kinds of plate fixation methods were comparable in constant score, and the rate of infection, nonunion, and complications (P > 0.05). CONCLUSIONS: Based on the current evidence, the anterior inferior plating may reduce the blood loss, the operation and union time, but no differences were observed in constant score, and the rate of infection, nonunion, and complications between the two groups. Given that some of the studies have low quality, more randomized controlled trails with high quality should be conduct to further verify the findings.

Discover cervical disc arthroplasty versus anterior cervical discectomy and fusion in symptomatic cervical disc diseases: A meta-analysis.

OBJECTIVE: Symptomatic cervical disc disease (SCDD) is a common degenerative disease, and Discover artificial cervical disc, a new-generation nonconstrained artificial disk, has been developed and performed gradually to treat it. We performed this meta-analysis to compare the efficacy and safety between Discover cervical disc arthroplasty (DCDA) and anterior cervical discectomy and fusion (ACDF) for SCDD. METHODS: An exhaustive literature search of PubMed, EMBASE, and the Cochrane Library was conducted to identify randomized controlled trials that compared DCDA with ACDF for patients suffering SCDD. A random-effect model was used. Results were reported as standardized mean difference or risk ratio with 95% confidence interval. RESULTS: Of 33 articles identified, six studies were included. Compared with ACDF, DCDA demonstrated shorter operation time (P < 0.0001), and better range of motion (ROM) at the operative level (P < 0.00001). But no significant differences were observed in blood loss, neck disability index (NDI) scores, neck and arm pain scores, Japanese orthopaedic association (JOA) scores, secondary surgery procedures and adverse events (P > 0.05). Subgroup analyses did not demonstrated significant differences. CONCLUSION: In conclusion, DCDA presented shorter operation time, and better ROM at the operative level. However, no significant differences were observed in blood loss, NDI scores, neck and arm pain scores, JOA scores, secondary surgery procedures and adverse events between the two groups. Additionally, more studies of high quality with mid- to long-term follow-up are required in future.

Which is best for osteoporotic vertebral compression fractures: balloon kyphoplasty, percutaneous vertebroplasty or non-surgical treatment? A study protocol for a Bayesian network meta-analysis.

INTRODUCTION: Osteoporotic vertebral compression fractures (OVCFs) commonly cause both acute and chronic back pain, substantial spinal deformity, functional disability and decreased quality of life and increase the risk of future vertebral fractures and mortality. Percutaneous vertebroplasty (PVP), balloon kyphoplasty (BK) and non-surgical treatment (NST) are mostly used for the treatment of OVCFs. However, which treatment is preferred is unknown. The purpose of this study is to comprehensively review the literature and ascertain the relative efficacy and safety of BK, PVP and NST for patients with OVCFs using a Bayesian network meta-analysis. METHODS AND ANALYSIS: We will comprehensively search PubMed, EMBASE and the Cochrane Central Register of Controlled Trials, to include randomided controlled trials that compare BK, PVP or NST for treating OVCFs. The risk of bias for individual studies will be assessed according to the Cochrane Handbook. Bayesian network meta-analysis will be performed to compare the efficacy and safety of BK, PVP and NST. The quality of evidence will be evaluated by GRADE. ETHICS AND DISSEMINATION: Ethical approval and patient consent are not required since this study is a meta-analysis based on published studies. The results of this network meta-analysis will be submitted to a peer-reviewed journal for publication. PROSPERO REGISTRATION NUMBER: CRD42016039452; Pre-results.

New approach to treating spinal cord injury using PEG-TAT-modified, cyclosporine-A-loaded PLGA/polymeric liposomes.

Cyclosporine-A (CsA) is an immunosuppressant agent that has shown effectiveness as a neuroprotective drug; however, it does not readily cross the blood-spinal cord barrier (BSCB), which constrains the clinical applications of CsA for the treatment of spinal cord injury (SCI). Our group recently tested the ability of novel polyethylene glycol (PEG)-transactivating-transduction protein (TAT)-modified CsA-loaded cationic multifunctional polymeric liposome-poly(lactic-co-glycolic acid) (PLGA) core/shell nanoparticles (PLGA/CsA NPs) to transport and deliver CsA across the BSCB to treat SCI. The PLGA/CsA NPs were successfully constructed. In vitro drug release studies have demonstrated that the sustained release of CsA from PLGA/CsA NPs occurs over ∼25 h. The in vivo study presented here showed that injured animals that received PLGA/CsA NPs through the tail vein, exhibited a significant up-regulation of growth-associated protein-43 (GAP-43) expression and an increased number of GAP-43-stained neurons compared with animals that received CsA or the vehicle alone. The improvement in neurological function was also evaluated by the Basso-Beattie-Bresnahan (BBB) open-field test. Moreover, fluorescein isothiocyanate (FITC)-attached PLGA/CsA NPs were successfully aggregated in the intact spinal cord 4 h after injection. Our data suggest that PLGA/CsA NPs have the potential for use as a new treatment method for SCI.

Cervical disc arthroplasty for symptomatic cervical disc disease: Traditional and Bayesian meta-analysis with trial sequential analysis.

OBJECTIVE: Cervical disc arthroplasty (CDA) has been designed as a substitute for anterior cervical discectomy and fusion (ACDF) in the treatment of symptomatic cervical disc disease (CDD). Several researchers have compared CDA with ACDF for the treatment of symptomatic CDD; however, the findings of these studies are inconclusive. Using recently published evidence, this meta-analysis was conducted to further verify the benefits and harms of using CDA for treatment of symptomatic CDD. METHODS: Relevant trials were identified by searching the PubMed, EMBASE, and Cochrane Library databases. Outcomes were reported as odds ratio or standardized mean difference. Both traditional frequentist and Bayesian approaches were used to synthesize evidence within random-effects models. Trial sequential analysis (TSA) was applied to test the robustness of our findings and obtain more conservative estimates. RESULTS: Nineteen trials were included. The findings of this meta-analysis demonstrated better overall, neck disability index (NDI), and neurological success; lower NDI and neck and arm pain scores; higher 36-Item Short Form Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores; more patient satisfaction; greater range of motion at the operative level; and fewer secondary surgical procedures (all P < 0.05) in the CDA group compared with the ACDF group. CDA was not significantly different from ACDF in the rate of adverse events (P > 0.05). TSA of overall success suggested that the cumulative z-curve crossed both the conventional boundary and the trial sequential monitoring boundary for benefit, indicating sufficient and conclusive evidence had been ascertained. CONCLUSIONS: For treating symptomatic CDD, CDA was superior to ACDF in terms of overall, NDI, and neurological success; NDI and neck and arm pain scores; SF-36 PCS and MCS scores; patient satisfaction; ROM at the operative level; and secondary surgical procedures rate. Additionally, there was no significant difference between CDA and ACDF in the rate of adverse events. However, as the CDA procedure is a relatively newer operative technique, long-term results and evaluation are necessary before CDA is routinely used in clinical practice.

Autograft versus allograft in anterior cruciate ligament reconstruction: A meta-analysis with trial sequential analysis.

BACKGROUND: Anterior cruciate ligament (ACL) reconstruction is considered as the standard surgical procedure for the treatment of ACL tear. However, there is a crucial controversy in terms of whether to use autograft or allograft in ACL reconstruction. The purpose of this meta-analysis is to compare autograft with allograft for patients undergoing ACL reconstruction. METHODS: PubMed, EMBASE, and the Cochrane Library were searched for randomized controlled trials that compared autograft with allograft in ACL reconstruction up to January 31, 2016. The relative risk or mean difference with 95% confidence interval was calculated using either a fixed- or random-effects model. The risk of bias for individual studies according to the Cochrane Handbook. The trial sequential analysis was used to test the robustness of our findings and get more conservative estimates. RESULTS: Thirteen trials were included, involving 1636 participants. The results of this meta-analysis indicated that autograft brought about lower clinical failure, better overall International Knee Documentation Committee (IKDC) level, better pivot-shift test, better Lachman test, greater Tegner score, and better instrumented laxity test (P < 0.05) than allograft. Autograft was not statistically different from allograft in Lysholm score, subjective IKDC score, and Daniel 1-leg hop test (P > 0.05). Subgroup analyses demonstrated that autograft was superior to irradiated allograft for patients undergoing ACL reconstruction in clinical failure, Lysholm score, pivot-shift test, Lachman test, Tegner score, instrumented laxity test, and subjective IKDC score (P < 0.05). Moreover, there were no significant differences between autograft and nonirradiated allograft. CONCLUSIONS: Autograft is superior to irradiated allograft for patients undergoing ACL reconstruction concerning knee function and laxity, but there are no significant differences between autograft and nonirradiated allograft. However, our results should be interpreted with caution, because the blinding methods were not well used.

Tanezumab for Patients with Osteoarthritis of the Knee: A Meta-Analysis.

OBJECTIVE: Tanezumab is a new therapeutic intervention for patients with osteoarthritis (OA) of the knee. We performed the present meta-analysis to appraise the efficacy and safety of tanezumab for patients with knee OA. METHODS: We systematically searched randomized controlled trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL). The primary outcomes were mean change in the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, the WOMAC physical function and patient's global assessment (PGA). Outcomes were reported as the standard mean difference (SMD) or relative risk (RR) with 95% confidence interval (CI). We assessed the pooled data using a random-effects model. RESULTS: Of the identified studies, four were eligible and were included in this meta-analysis (N = 1839 participants). Compared with the placebo groups, tanezumab yielded a significant reduction in mean change in the WOMAC pain (SMD = 0.51, 95% CI 0.34 to 0.69, P<0.00001), the WOMAC physical function (SMD = 0.56, 95% CI 0.38 to 0.74, P<0.00001) and PGA (SMD = 0.34, 95% CI 0.22 to 0.47, P<0.00001). There was no significant difference in serious adverse events (RR = 1.06, 95% CI 0.59 to 1.92, P = 0.84) between the tanezumab and placebo groups. Tanezumab significantly increased discontinuations due to adverse events (RR = 2.89, 95% CI 1.59 to 5.26, P = 0.0005), abnormal peripheral sensations (RR = 3.14, 95% CI 2.12 to 4.66, P<0.00001), and peripheral neuropathy (RR = 6.05, 95% CI 2.32 to 15.81, P = 0.0002). CONCLUSION: Tanezumab can alleviate pain and improve function for patients with OA of the knee. However, considering the limited number of studies, this conclusion should be interpreted cautiously and more clinical randomized controlled trials are needed to verify the efficacy and safety of tanezumab for OA of the knee.

Rivaroxaban for thromboprophylaxis after total hip or knee arthroplasty: a meta-analysis with trial sequential analysis of randomized controlled trials.

Venous thromboembolism (VTE) is the most widespread severe complication after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We conducted this meta-analysis to further validate the benefits and harms of rivaroxaban use for thromboprophylaxis after THA or TKA. We thoroughly searched PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials. Trial sequential analysis (TSA) was applied to test the robustness of our findings and to obtain a more conservative estimation. Of 316 articles screened, nine studies were included. Compared with enoxaparin, rivaroxaban significantly reduced symptomatic VTE (P = 0.0001) and symptomatic deep vein thrombosis (DVT; P = 0.0001) but not symptomatic pulmonary embolism (P = 0.57). Furthermore, rivaroxaban was not associated with an increase in all-cause mortality, clinically relevant non-major bleeding and postoperative wound infection. However, the findings were accompanied by an increase in major bleeding (P = 0.02). The TSA demonstrated that the cumulative z-curve crossed the traditional boundary but not the trial sequential monitoring boundary and did not reach the required information size for major bleeding. Rivaroxaban was more beneficial than enoxaparin for preventing symptomatic DVT but increased the risk of major bleeding. According to the TSA results, more evidence is needed to verify the risk of major bleeding with rivaroxaban.

Efficacy and Safety of Bisphosphonates for Low Bone Mineral Density After Kidney Transplantation: A Meta-Analysis.

In patients with low bone mineral density (BMD) after kidney transplantation, the role of bisphosphonates remains unclear. We performed a systematic review and meta-analysis to investigate the efficacy and safety of bisphosphonates.We retrieved trials from PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (CENTRAL) from inception through May 2015. Only randomized controlled trials that compared bisphosphonate-treated and control groups of patients with low bone mineral density after kidney transplantation were included. The primary outcomes were the percent change in BMD, the absolute change in BMD, and the BMD at the end of study at the lumbar spine. The results were expressed as the mean difference (MD) or relative risk (RR) with the 95% confidence interval (CI). We used a random-effects model to pool the outcomes.We included 17 randomized controlled trials with 1067 patients. Only 1 included trial was found to be at low risk of bias. The rest of the included studies were found to have high to uncertain risk of bias. Compared with the control group, those who received bisphosphonates had a significant increase in percent change in BMD (mean difference [MD] = 5.51, 95% confidence interval [CI] 3.22-7.79, P < 0.00001) and absolute change in BMD (MD = 0.05, 95% CI 0.04-0.05, P < 0.00001), but a nonsignificant increase in BMD at the end of the study (MD = 0.02, 95% CI -0.01 to 0.05, P = 0.25) at the lumbar spine. Bisphosphonates resulted in a significant improvement in percent change in BMD (MD = 4.95, 95% CI 2.57-7.33, P < 0.0001), but a nonsignificant improvement in absolute change in BMD (MD = 0.03, 95% CI -0.00 to 0.06, P = 0.07) and BMD at the end of the study (MD = -0.01, 95% CI -0.04 to 0.02, P = 0.40) at the femoral neck. No significant differences were found in vertebral fractures, nonvertebral fractures, adverse events, and gastrointestinal adverse events.Bisphosphonates appear to have a beneficial effect on BMD at the lumbar spine and do not significantly decrease fracture events in recipients. However, the results should be interpreted cautiously due to the lack of robustness and the heterogeneity among studies.

Epidemiological features of traumatic spinal cord injury in Chongqing, China.

OBJECTIVE: To describe the epidemiological characteristics and trends of traumatic spinal cord injury in Chongqing, China. STUDY DESIGN: Hospital-based retrospective research. SETTING: Xinqiao Hospital, Chongqing. METHODS: We reviewed medical records of 554 patients with traumatic spinal cord injury (TSCI) admitted to Xinqiao Hospital from 2009 to 2013. Variables included gender, age, marital status, etiology, occupation, time of injury, level of injury, and severity of injury, the length of hospital stay, and treatment. RESULTS: The mean age of patients with TSCI was 45.6 ± 13.8 years, and the male/female ratio was 4.33:1. 94.2% (522 patients) of all patients with TSCI were married. Falls, comprising low falls and high falls (10.8% and 50.9%, respectively), were the leading reason for a hospital visit. And the second reason was MVCs (21.8%). The most common injury site was the cervical spinal cord, accounting for nearly more than 54%. The length of hospital stay ranged between 1 and 219 days (mean: 28.3 days). The proportions of complete tetraplegia, incomplete tetraplegia, complete paraplegia and incomplete paraplegia were 17.1%, 37.8%, 22.2%, and 22.9%, respectively. CONCLUSION: The result revealed that the proportion of males was higher, as well as falls and MVCs were the first two main reasons, with older mean age of patients with TSCI than other countries. The occupations with highest risk for TSCI were peasants and laborers. All of these results prompted that preventive methods should be based on the characteristics of different type of patients with TSCI.