Comparative effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with chronic low back pain.

OBJECTIVES: Chronic low back pain (CLBP) can seriously impair the quality of life of patients and has a remarkable comorbidity with psychological symptoms, which, in turn, can further exacerbate the symptoms of CLBP. Psychological treatments are critical and nonnegligent for the management of CLBP, and thus, should attract sufficient attention. However, current evidence does not suggest the superiority and effectiveness of nonpharmacological interventions in reducing psychological symptoms among patients with CLBP.Thus, this study was designed to compare the effectiveness of nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP and to recommend preferred strategies for attenuating psychological symptoms in clinical practice. METHODS: In this systematic review and network meta-analysis (NMA), PubMed, Embase Database, Web of Science, and Cochrane Library were searched from database inception until March 2022. Randomized clinical trials (RCTs) that compare different nonpharmacological interventions for depression, anxiety, and mental health among patients with CLBP were eligible. The Preferred Reporting Items for Systematic Reviews and Meta-analyses statement was used. Four reviewers in pairs and divided into two groups independently performed literature selection, data extraction, and risk of bias, and certainty of evidence assessments. This NMA was conducted with a random effects model under a frequentist framework. The major outcomes were depression, anxiety, and mental health presented as the standardized mean difference (SMD) with the corresponding 95% CI. RESULTS: A total of 66 RCTs that randomized 4806 patients with CLBP met the inclusion criteria. The quality of evidence was typically low or some risks of bias (47 out of 66 trials, 71.3%), and the precision of summary estimates for effectiveness varied substantially. In addition, 7 categories of interventions with 26 specific treatments were evaluated. For depression, mind body therapy (pooled SMD = -1.20, 95% CI: -1.63 to -0.78), biopsychosocial approach (pooled SMD = -0.41, 95% CI: -0.70 to -0.12), and physical therapy (pooled SMD = -0.26, 95% CI: -0.50 to -0.02) exhibited remarkable effectiveness in reducing depression compared with the control group. For managing anxiety, mind body therapy (pooled SMD = -1.35, 95% CI: -1.90 to -0.80), multicomponent intervention (pooled SMD = -0.47, 95% CI: -0.88 to -0.06), and a biopsychosocial approach (pooled SMD = -0.46, 95% CI: -0.79 to -0.14) were substantially superior to the control group. For improving mental health, multicomponent intervention (pooled SMD = 0.77, 95% CI: 0.14 to 1.39), exercise (pooled SMD = 0.60, 95% CI: 0.08 to 1.11), and physical therapy (pooled SMD = 0.47, 95% CI: 0.02-0.92) demonstrated statistically substantial effectiveness compared with the control group. The rank probability indicated that mind body therapy achieved the highest effectiveness in reducing depression and anxiety among patients with CLBP. Besides, the combined results should be interpreted cautiously based on the results of analyses evaluating the inconsistency and certainty of the evidence. CONCLUSION: This systemic review and NMA suggested that nonpharmacological interventions show promise for reducing psychological symptoms among patients with CLBP. In particular, mind body therapy and a biopsychosocial approach show considerable promise, and mind body therapy can be considered a priority choice in reducing depression and anxiety. These findings can aid clinicians in assessing the potential risks and benefits of available treatments for CLBP comorbidity with psychological symptoms and provide evidence for selecting interventions in clinical practice. More RCTs involving different interventions with rigorous methodology and an adequate sample size should be conducted in future research.

Clinical application of spinal robot in cervical spine surgery: safety and accuracy of posterior pedicle screw placement in comparison with conventional freehand methods.

The novel robot-assisted (RA) technique has been utilized increasingly to improve the accuracy of cervical pedicle screw placement. Although the clinical application of the RA technique has been investigated in several case series and comparative studies, the superiority and safety of RA over conventional freehand (FH) methods remain controversial. Meanwhile, the intra-pedicular accuracy of the two methods has not been compared for patients with cervical traumatic conditions. This study aimed to compare the rate and risk factors of intra-pedicular accuracy of RA versus the conventional FH approach for posterior pedicle screw placement in cervical traumatic diseases. A total of 52 patients with cervical traumatic diseases who received cervical screw placement using RA (26 patients) and FH (26 patients) techniques were retrospectively included. The primary outcome was the intra-pedicular accuracy of cervical pedicle screw placement according to the Gertzbin-Robbins scale. Secondary outcome parameters included surgical time, intraoperative blood loss, postoperative drainage, postoperative hospital stay, and complications. Moreover, the risk factors that possibly affected intra-pedicular accuracy were assessed using univariate analyses. Out of 52 screws inserted using the RA method, 43 screws (82.7%) were classified as grade A, with the remaining 7 (13.5%) and 2 (3.8%) screws classified as grades B and C. In the FH cohort, 60.8% of the 79 screws were graded A, with the remaining screws graded B (21, 26.6%), C (8, 10.1%), and D (2, 2.5%). The RA technique showed a significantly higher rate of optimal intra-pedicular accuracy than the FH method (P = 0.008), but there was no significant difference between the two groups in terms of clinically acceptable accuracy (P = 0.161). Besides, the RA technique showed remarkably longer surgery time, less postoperative drainage, shorter postoperative hospital stay, and equivalent intraoperative blood loss and complications than the FH technique. Furthermore, the univariate analyses showed that severe obliquity of the lateral atlantoaxial joint in the coronal plane (P = 0.003) and shorter width of the lateral mass at the inferior margin of the posterior arch (P = 0.014) were risk factors related to the inaccuracy of C1 screw placement. The diagnosis of HRVA (P < 0.001), severe obliquity of the lateral atlantoaxial joint in the coronal plane (P < 0.001), short pedicle width (P < 0.001), and short pedicle height (P < 0.001) were risk factors related to the inaccuracy of C2 screw placement. RA cervical pedicle screw placement was associated with a higher rate of optimal intra-pedicular accuracy to the FH technique for patients with cervical traumatic conditions. The severe obliquity of the lateral atlantoaxial joint in the coronal plane independently contributed to high rates of the inaccuracy of C1 and C2 screw placements. RA pedicle screw placement is safe and useful for cervical traumatic surgery.

Robotics in Cervical Spine Surgery: Feasibility and Safety of Posterior Screw Placement.

OBJECTIVE: Robot-assisted (RA) techniques have been widely investigated in thoracolumbar spine surgery. However, the application of RA methods on cervical spine surgery is rare due to the complex morphology of cervical vertebrae and catastrophic complications. Thus, the feasibility and safety of RA cervical screw placement remain controversial. This study aims to evaluate the feasibility and safety of RA screw placement on cervical spine surgery. METHODS: A comprehensive search on PubMed, Cochrane Library, Embase Database, Web of Science, Chinese National Knowledge Databases, and Wanfang Database was performed to select potential eligible studies. Randomized controlled trials (RCTs), comparative cohort studies, and case series reporting the accuracy of cervical screw placement were included. The Cochrane risk of bias criteria and Newcastle-Ottawa Scale criteria were utilized to rate the risk of bias of the included literatures. The primary outcome was the rate of cervical screw placement accuracy with robotic guidance; subgroup analyses based on the screw type and insertion segments were also performed. RESULTS: One RCT, 3 comparative cohort studies, and 3 case series consisting of 160 patients and 719 cervical screws were included in this meta-analysis. The combined outcomes indicated that the rates of optimal and clinically acceptable cervical screw placement accuracy under robotic guidance were 88.0% (95% confidence interval [CI], 84.1%-91.4%; p = 0.073; I2 = 47.941%) and 98.4% (95% CI, 96.8%-99.5%; p = 0.167; I2 = 35.954%). The subgroup analyses showed that the rate of optimal pedicle screw placement accuracy was 88.2% (95% CI, 83.1%-92.6%; p = 0.057; I2 = 53.305%); the rates of optimal screw placement accuracy on C1, C2, and subaxial segments were 96.2% (95% CI, 80.5%-100.0%; p = 0.167; I2 = 44.134X%), 89.7% (95% CI, 80.6%-96.6%; p = 0.370; I2 = 0.000X%), and 82.6% (95% CI, 70.9%-91.9%; p = 0.057; I2 = 65.127X%;), respectively. CONCLUSION: RA techniques were associated with high rates of optimal and clinically acceptable screw positions. RA cervical screw placement is accurate, safe, and feasible in cervical spine surgery with promising clinical potential.

Medium and long-term radiographic and clinical outcomes of Dynesys dynamic stabilization versus instrumented fusion for degenerative lumbar spine diseases.

BACKGROUND: Dynesys stabilization (DS) is utilized to preserve mobility at the instrumental segments and prevent adjacent segment pathology in clinical practice. However, the advantages of DS method in medium and long-term follow-up remain controversial. OBJECTIVE: To compare the radiographic and clinical outcomes between DS and instrumented fusion in the treatment of degenerative lumbar spine disease with or without grade I spondylolisthesis with a minimum follow-up period of 2 years. METHODS: We conducted a comprehensive search of PubMed, EMBASE, Cochrane, and Web of Science databases, Chinese National Knowledge Databases, and Wanfang Database for potentially eligible articles. Clinical outcomes were assessed in terms of VAS and ODI scores, screw loosening and breakage, and surgical revision. Radiographic outcomes were assessed in terms of postoperative range of movement (ROM) and disc heigh. Moreover, adjacent segment degeneration (ASDeg) and adjacent segment disease (ASDis) were evaluated. RESULTS: Seventeen studies with 1296 patients were included in the meta-analysis. The DS group was associated with significantly lower postoperative VAS scores for low-back and leg pain, and lower rate of surgical revision than the fusion group. Moreover, the Dynesys group showed significantly less ASDeg than the fusion group but showed no significant advantage over the fusion group in terms of preventing ASDis. Additionally, the ROM at the stabilized segments of the fusion group decreased significantly and that at the adjacent segments increased significantly compared with those of the DS group. CONCLUSION: DS showed comparable clinical outcomes and provided benefits in preserving the motion at the stabilized segments, thus limiting the hypermobility at the adjacent segments and preventing ASDeg compared with the fusion method in degenerative disease with or without grade I spondylolisthesis.

Ferroptosis: A potential target for the intervention of intervertebral disc degeneration.

Ferroptosis, an iron-dependent form of programmed cell death marked by phospholipid peroxidation, is regulated by complex cellular metabolic pathways including lipid metabolism, iron balance, redox homeostasis, and mitochondrial activity. Initial research regarding the mechanism of ferroptosis mainly focused on the solute carrier family 7 member 11/glutathione/glutathione peroxidase 4 (GPX4) signal pathway. Recently, novel mechanisms of ferroptosis, independent of GPX4, have been discovered. Numerous pathologies associated with extensive lipid peroxidation, such as drug-resistant cancers, ischemic organ injuries, and neurodegenerative diseases, are driven by ferroptosis. Ferroptosis is a new therapeutic target for the intervention of IVDD. The role of ferroptosis in the modulation of intervertebral disc degeneration (IVDD) is a significant topic of interest. This is a novel research topic, and research on the mechanisms of IVDD and ferroptosis is ongoing. Herein, we aim to review and discuss the literature to explore the mechanisms of ferroptosis, the relationship between IVDD and ferroptosis, and the regulatory networks in the cells of the nucleus pulposus, annulus fibrosus, and cartilage endplate to provide references for future basic research and clinical translation for IVDD treatment.

Safety and risk factors of TINAVI robot-assisted percutaneous pedicle screw placement in spinal surgery.

OBJECTIVE: To determine the rates and risk factors of pedicle screw placement accuracy and the proximal facet joint violation (FJV) using TINAVI robot-assisted technique. METHODS: Patients with thoracolumbar fractures or degenerative diseases were retrospectively recruited from June 2018 and June 2020. The pedicle penetration and proximal FJV were compared in different instrumental levels to identify the safe and risk segments during insertion. Moreover, the factors were also assessed using univariate and multivariate analyses. RESULTS: A total of 72 patients with 332 pedicle screws were included in the current study. The optimal and clinically acceptable screw positions were 85.8% and 93.4%. Of the 332 screws concerning the intra-pedicular accuracy, 285 screws (85.8%) were evaluated as Grade A according to the Gertzbein and Robbins scale, with the remaining 25 (7.6%), 10 (3.0%), 6 (1.8%), and 6 screws (1.8%) as Grades B, C, D, and E. Moreover, in terms of the proximal FJV, 255 screws (76.8%) screws were assessed as Grade 0 according to the Babu scale, with the remaining 34 (10.3%), 22 (6.6%), and 21 screws (6.3%) as Grades 1, 2, and 3. Furthermore, the univariate analysis showed significantly higher rate of penetration for patients with age < 61 years old, sex of female, thoracolumbar insertion, shorter distance from skin to insertion point, and smaller facet angle. Meanwhile, the patients with the sex of female, BMI < 25.9, grade I spondylolisthesis, lumbosacral insertion, longer distance from skin to insertion point, and larger facet angle had a significantly higher rate of proximal FJV. The outcomes of multivariate analyses showed that sex of male (adjusted OR 0.320, 95% CI 0.140-0.732; p = 0.007), facet angle ≥ 45° (adjusted OR 0.266, 95% CI 0.090-0.786; p = 0.017), distance from skin to insertion point ≥ 4.5 cm (adjusted OR 0.342, 95% CI 0.134-0.868; p = 0.024), and lumbosacral instrumentation (adjusted OR 0.227, 95% CI 0.091-0.566; p = 0.001) were independently associated with intra-pedicular accuracy; the L5 insertion (adjusted OR 2.020, 95% CI 1.084-3.766; p = 0.027) and facet angle ≥ 45° (adjusted OR 1.839, 95% CI 1.026-3.298; p = 0.041) were independently associated with the proximal FJV. CONCLUSION: TINAVI robot-assisted technique was associated with a high rate of pedicle screw placement and a low rate of proximal FJV. This new technique showed a safe and precise performance for pedicle screw placement in spinal surgery. Facet angle ≥ 45° is independently associated with both the intra-pedicular accuracy and proximal FJV.

Lactate dehydrogenase as promising marker for prognosis of brain metastasis.

BACKGROUND: Lactate dehydrogenase (LDH) is a biomarker for cancer. However, the relationship between serum LDH levels and the survival of patients with brain metastasis has been fully revealed. We aimed to evaluate the serum LDH levels and assess its prognostic value in patients with BM. METHODS: The serum LDH levels were collected from 2507 patients with BM. Patients were categorized into four groups according to the quartile of serum LDH levels. The association between serum LDH levels and overall survival (OS) was evaluated using Cox regression models and Kaplan-Meier curves. Three predictive models were used to evaluate patients. RESULTS: The Kaplan-Meier curve for survival by the serum LDH group demonstrates clear separation between four groups (P < 0.001). The participants in the lower group had longer OS than those in the higher group. After adjusting in multivariate Cox regression models remained significant for patients in the Q4 compared with patients in the Q1 (Q4:Q1 OR 1.58, 95% CI 1.38-1.80). Furthermore, the GPA-LDH model generates a pooled area under the curve of 0.630 (95% CI 0.600, 0.660). CONCLUSIONS: Serum LDH levels and OS in patients with brain metastasis is an inverse association. Moreover, Serum LDH levels can improve the prognosis of the GPA model.

Predictors of accurate intrapedicular screw placement in single-level lumbar (L4-5) fusion: robot-assisted pedicle screw, traditional pedicle screw, and cortical bone trajectory screw insertion.

BACKGROUND: The superiorities in proximal facet joint protection of robot-assisted (RA) pedicle screw placement and screw implantation via the cortical bone trajectory (CBT) have rarely been compared. Moreover, findings on the screw accuracy of both techniques are inconsistent. Therefore, we analyzed the screw accuracy and incidence of facet joint violation (FJV) of RA and CBT screw insertion in the same study and compared them with those of conventional pedicle screw (PS) insertion. The possible factors affecting screw accuracy and FJV were also analyzed. METHODS: A total of 166 patients with lumbar degenerative diseases requiring posterior L4-5 fusion were retrospectively included and divided into the RA, PS, and CBT groups from March 2019 to December 2021. The grades of intrapedicular accuracy and superior FJV were evaluated according to the Gertzbin-Robbins scale and the Babu scale based on postoperative CT. Univariable and multivariable analyses were conducted to assess the possible risk factors associated with intrapedicular accuracy and superior FJV. RESULTS: The rates of optimal screw insertion in the RA, PS, and CBT groups were 87.3%, 81.3%, and 76.5%, respectively. The difference between the RA and CBT groups was statistically significant (P = 0.004). Superior FJVs occurred in 28.2% of screws in RA, 45.0% in PS, and 21.6% in CBT. The RA and CBT groups had fewer superior FJVs than the PS group (P = 0.008 and P < 0.001, respectively), and no significant difference was observed between the RA and CBT groups (P = 0.267). Multivariable analysis revealed that the CBT technique was an independent risk factor for intrapedicular accuracy. Furthermore, older age, the conventional PS technique and a smaller facet angle were independently associated with the incidence of superior FJVs. CONCLUSIONS: The RA and CBT techniques were associated with fewer proximal FJVs than the PS technique. The RA technique showed a higher rate of intrapedicular accuracy than the CBT technique. The CBT technique was independently associated with screw inaccuracy. Older age, conventional PS technique and coronal orientation of the facet join were independent risk factors for superior FJV.

Rates and risk factors of intrapedicular accuracy and cranial facet joint violation among robot-assisted, fluoroscopy-guided percutaneous, and freehand techniques in pedicle screw fixation of thoracolumbar fractures: a comparative cohort study.

BACKGROUND: Robot-assisted (RA) technique has been increasingly applied in clinical practice, providing promising outcomes of inserting accuracy and cranial facet joint protection. However, studies comparing this novel method with other assisted methods are rare, and the controversy of the superiority between the insertion techniques remains. Thus, we compare the rates and risk factors of intrapedicular accuracy and cranial facet joint violation (FJV) of RA, fluoroscopy-guided percutaneous (FP), and freehand (FH) techniques in the treatment of thoracolumbar fractures. METHODS: A total of 74 patients with thoracolumbar fractures requiring pedicle screw instruments were retrospectively included and divided into RA, FP, and FH groups from June 2016 to May 2020. The primary outcomes were the intrapedicular accuracy and cranial FJV. The factors that affected the intrapedicular accuracy and cranial FJV were assessed using multivariate analyses. RESULTS: The optimal intrapedicular accuracy of pedicle screw placement (Grade A) in the RA, FP, and FH groups was 94.3%, 78.2%, and 88.7%, respectively. This finding indicates no significant differences of RA over FH technique (P = 0.062) and FP technique (P = 0.025), but significantly higher accuracies of RA over FP (P < 0.001). In addition, the rates of proximal FJV in RA, FP, and FH groups were 13.9%, 30.8%, and 22.7%, respectively. RA had a significantly greater proportion of intact facet joints than the FP (P = 0.002). However, FP and FH (P = 0.157), as well as RA and FH (P = 0.035) showed significantly similar outcomes with respect to the proximal FJV. The logistic regression analysis showed that FP technique (OR = 3.056) was independently associated with insertion accuracy. Meanwhile, the age (OR = 0.974), pedicle angle (OR = 0.921), moderate facet joint osteoarthritis (OR = 5.584), and severe facet joint osteoarthritis (OR = 11.956) were independently associated with cranial FJV. CONCLUSION: RA technique showed a higher rate of intrapedicular accuracy and a lower rate of cranial FJV than FP technique, and similar outcomes to FH technique in terms of intrapedicular accuracy and cranial FJV. RA technique might be a safe method for pedicle screw placement in thoracolumbar surgery. LEVEL OF EVIDENCE: 3.

Efficacy and Safety of Establishing an Optimal Path Through Unilateral Pedicle Under the Assistance of Surgical Robot in Percutaneous Kyphoplasty.

BACKGROUND: Despite percutaneous kyphoplasty (PKP) being widely used to treat osteoporotic vertebral compression fractures (OVCFs), the details of puncture are still controversial. With the development of surgical robots in spine surgery, robotic-assisted PKP surgery will become a promising treatment strategy. OBJECTIVES: To evaluate the efficacy and safety of establishing an optimal working path through a unilateral pedicle approach to improve bone cement distribution under the assistance of a surgical robot in percutaneous kyphoplasty. STUDY DESIGN: Experimental and prospective study. METHODS: PKP surgery under the assistance of the TINAVI robot was performed on 78 patients with osteoporotic vertebral compression fractures (OVCFs) from May 2018 to January 2020 in a single spine center. During the operation, the optimal path of the working channel made through unilateral pedicle puncture was designed according to the details of the fractured vertebral body under the guidance of the TINAVI surgical robot. Visual analog scale (VAS) scores of back pain, intraoperative blood loss, surgical time, and complications were recorded and evaluated. Postoperative fluoroscopy and 3D-CT were used to evaluate the distribution of bone cement. RESULTS: We have successfully performed 78 PKP surgeries under the assistance of the TINAVI robot. The mean procedure time was 13.9 ± 2.6 minutes from the beginning of C-arm scan to finish the injection of bone cement, and the intraoperative blood loss was 5.4 ± 2.8 mL. Pain of all cases was relieved immediately and significantly after PKP surgery; the VAS score was 7.5 ± 2.3 before surgery and 1.4 ± 0.8 post-surgery. The mean volume of bone cement was 4.7 ± 1.9 mL, and bone cement leakage occurred at the anterior edge of the fractured vertebral body in 2 patients, with no neurological and vascular injury in any of the cases. Postoperative fluoroscopy and 3D-CT showed that a good bone cement distribution evenly through unilateral pedicle puncture in the fractured vertebral body in all cases except the bone cement leakage in 2 patients. LIMITATIONS: More cases are needed to evaluate the efficacy and stability of robot-assisted PKP surgery. A control group of PKP performed freehand should be included in this study. CONCLUSIONS: Robotic-assisted PKP surgery through the unilateral approach to establishing an optimal working channel is a safe and available procedure for treating OVCFs in terms of better distribution of bone cement, high accuracy, good repeatability, and less surgical trauma.

Accuracy of Pedicle Screw Placement and Four Other Clinical Outcomes of Robotic Guidance Technique versus Computer-Assisted Navigation in Thoracolumbar Surgery: A Meta-Analysis.

BACKGROUND: Robotic guidance (RG) pedicle screw placement has been increasingly used to improve the rate of insertion accuracy. However, the superiority of the RG technique over computer-assisted navigation (CAN) remains debatable. OBJECTIVE: To determine whether the Mazor RG technique is superior to CAN in terms of the rate of insertion accuracy and 4 other clinical indices, namely, intraoperative time, blood loss, complications and revision surgery caused by malposition. METHODS: A search of PubMed, Embase, Cochrane, Web of Science, CNKI, and WanFang was conducted. We mainly aimed to evaluate the accuracy of pedicle screw placement between the Mazor RG and CAN techniques. The secondary objectives were intraoperative time, blood loss, complications, and revision surgery caused by malposition. The meta-analysis was conducted using the RevMan 5.3 and Stata 15.1 software. RESULTS: A randomized controlled trial and 5 comparative cohort studies consisting of 529 patients and 4081 pedicle screws were included in this meta-analysis. The RG technique has a significantly higher accuracy than CAN in terms of optimal (odds ratio [OR], 2.26; 95% confidence interval [CI], 1.85-2.76; P < 0.01) and clinically acceptable (OR, 1.69; 95% CI, 1.22-2.34; P = 0.002) pedicle screw insertions. Furthermore, the RG technique showed significantly less blood loss (mean difference, -42.49; 95% CI, -78.38 to -6.61; P = 0.02) than did the CAN technique but has equivalent intraoperative time (mean difference, 0.75; 95% CI, -5.89 to 7.40; P = 0.82), complications (OR, 0.65; 95% CI, 0.32-1.33, P = 0.24), and revision surgery caused by malposition (OR, 0.46; 95% CI, 0.15-1.43, P = 0.18). CONCLUSIONS: The Mazor RG technique is superior to CAN concerning the accuracy of pedicle screw placement. Thus, the Mazor RG technique is accurate and safe in clinical application.

Identification of a Novel Immune-Related Prognostic Biomarker and Small-Molecule Drugs in Clear Cell Renal Cell Carcinoma (ccRCC) by a Merged Microarray-Acquired Dataset and TCGA Database.

Clear cell renal cell carcinoma (ccRCC) is one of the most common histological subtypes of renal cancer, with a poor prognosis. Our study aimed to identify a biomarker that is significantly associated with ccRCC prognosis and novel immunotherapeutic targets, as well as some novel molecular drugs for ccRCC. Based on the overlap of The Cancer Genome Atlas (TCGA)-Kidney Renal Clear Cell Carcinoma (KIRC) data and the ImmPort database, we obtained 1,292 immune-related genes (IRGs) and constructed a weighed co-expression network based on the IRGs. A total of 39 hub genes were screened out in three modules. CTLA4, which had the highest connectivity degree among the screened genes in a protein-protein interaction network (degree = 24), was selected. Internal validation based on the GEPIA database revealed that patients with a higher expression of CTLA4 had a significantly shorter overall survival time and disease-free survival time. Expression of CTLA4 was also closely correlated with local recurrence, pathologic stage, and immune infiltration level. External validation based on the Oncomine database and merged microarray-acquired dataset validated the mRNA expression level of hub genes. Gene-set enrichment analysis revealed that six KEGG signaling pathways, which were significantly associated with CTLA4, were enriched on immune-related pathways. Further analysis according to the TIMER database demonstrated that CTLA4 expression was positively related to dendritic cells (cor = 0.446, P = 1.32E-23) and negatively associated with tumor purity (cor = -0.267, P = 5.51E-09). Finally, we screened out 293 differentially expressed genes by integrating six datasets from the GEO database. The Connectivity Map (CMap) analysis revealed the strong potential of three small molecule drugs (monensin, quercetin, and fenbufen) for ccRCC treatment. In conclusion, CTLA4 was identified and validated in prognosis of ccRCC. CTLA4 may be a new prognostic biomarker and immunotherapeutic target for ccRCC. Monensin, quercetin, and fenbufen may be novel choices for ccRCC treatment.

Complement C7 (C7), a Potential Tumor Suppressor, Is an Immune-Related Prognostic Biomarker in Prostate Cancer (PC).

Objectives: Prostate cancer (PC) is the second most frequent tumor in men, which has a high recurrence rate and poor prognosis. Therefore, this study aimed to identify novel prognostic biomarkers and therapeutic targets for immunotherapy and small molecule drugs for PC treatment. Materials and Methods: The Estimation of Stromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) algorithm was applied to calculate immune scores and stromal scores of TCGA-PRAD data. Differentially expressed genes (DEGs) were identified using R package "limma." GO, KEGG, and DO analyses were performed to analyze DEGs. Overall survival and disease-free survival analyses were conducted for hub gene identification. To validate the hub gene at the mRNA and protein expression levels, genetic alterations were measured, and CCLE and Cox regression analyses were performed. Connectivity map (CMap) analysis and GSEA were performed for drug exploration and function analysis, respectively. Results: Immune scores ranged from -1795.98 to 2339.39, and stomal scores ranged from -1877.60 to 1659.96. In total, 45 tumor microenvironment (TME)-related DEGs were identified, of which Complement C7 (C7) was selected and validated as a hub gene. CMap analysis identified six small molecule drugs as potential agents for PC treatment. Further analysis demonstrated that C7 expression was significantly correlated with clinical T, pathological N, and immune infiltration level. Conclusions: In conclusion, of the 45 TME-related DEGs, C7 was shown to correlate with PC prognosis in patients, indicating it as a novel prognostic biomarker and immunotherapy target in PC. Additionally, six small molecule drugs showed strong therapeutic potential for PC treatment.

Associations between the hounsfield unit values of different trajectories and bone mineral density of vertebrae: cortical bone and traditional trajectories.

Cortical bone trajectory (CBT) is widely used in orthopedic surgery to improve fixation while minimizing soft tissue dissection. This study used radiological methods to assess the correlation between the bone mineral density (BMD) of vertebrae and Hounsfield unit (HU) values of CBT and traditional trajectory (TT). A total of 240 thoracic and lumbar (T9-L5) vertebrae from 40 cadaveric spines were obtained. The specimens were measured using computed tomography (CT). The axial CT images of TT were sliced in a plane horizontal to the pedicle, whereas those of CBT were sliced in a caudocranial plane. The regions of interest of TT and CBT were selected to calculate an average HU value within the area, wherein the screws were inserted and fixed at 6.0 mm × 40 mm and 4.0 mm × 30 mm, respectively. The BMD of vertebrae was measured by dual-energy X-ray absorptiometry (DEXA) and quantitative CT (QCT). The HU value of CBT (286.74 ± 120.80) was almost twice higher than that of TT (165.61 ± 92.38). The average lateral and anteroposterior BMDs of 240 vertebrae determined using DEXA were 0.540 ± 0.193 and 0.651 ± 0.180 g/cm2, respectively. The average cortical and cancellous BMDs of 240 vertebrae determined using QCT were 245.63 ± 80.09 and 88.24 ± 61.78 mg/cm3, respectively. The BMD determined using DEXA and QCT was significantly and positively associated with the HU values of CBT and TT. The ratio of the HU values of CBT and TT was significantly and negatively associated with the lateral BMD determined using DEXA and the cancellous BMD determined using QCT. However, it was significantly and positively associated with segments but not with the anteroposterior BMD determined using DEXA and the cortical BMD determined using QCT. Collectively, the HU values of CBT and TT significantly decreased with decreasing BMD. However, the CBT HU values significantly decreased less than the TT HU values, especially in low-BMD vertebrae and cauda lumbar segments.

Comparison of Cranial Facet Joint Violation Rate and Four Other Clinical Indexes Between Robot-assisted and Freehand Pedicle Screw Placement in Spine Surgery: A Meta-analysis.

STUDY DESIGN: A meta-analysis. OBJECTIVE: Through meta-analysis, whether RA techniques are superior to conventional freehand (FH) techniques was determined in terms of cranial facet joint protection and four other clinical indexes, namely, the accuracy of pedicle screw placement, the number of surgical revision due to malposition, intraoperative radiation dose, and operative time. SUMMARY OF BACKGROUND DATA: Cranial facet joint violation (FJV) is an important risk factor for adjacent segment degeneration. Some studies recommended the use of robot-assisted (RA) pedicle screw placement in reducing the rate of cranial FJV instead of conventional FH pedicle screw placement. However, the superiority of RA techniques to FH techniques remains controversial. METHODS: A comprehensive search on PubMed, EMBASE, Cochrane, Web of Science, CNKI, and WanFang was conducted for the selection of potential eligible literature. The outcomes were evaluated in terms of odds ratio (OR) or standardized mean difference and corresponding 95% confidence interval (CI). The meta-analysis was conducted using RevMan 5.3. The subgroup analyses of the violation of the cranial facet joint and the accuracy of pedicle screw placement were performed on the basis of robot type. RESULT: Three randomized controlled trials, two prospective cohort study, and one retrospective cohort study consisting of 783 patients and 2694 cranial pedicle screws were included in the meta-analysis. RA pedicle screw placement was associated with significantly fewer cranial FJVs than FH screw placement. Subgroup analyses showed that the Renaissance (OR = 0.19, 95% CI = 0.07-0.56) and TINAVI (OR = 0.19, 95% CI = 0.09-0.38) robots under RA techniques were associated with significantly fewer cranial FJVs than FH techniques. Furthermore, the RA techniques showed more accurate pedicle screw placement and lower intraoperative radiation dose, equivalent number of surgical revision due to malposition, but longer operative time than the FH techniques. CONCLUSION: The RA (Renaissance and TINAVI) techniques are superior to conventional FH techniques in terms of protecting the cranial facet joint. RA techniques are accurate and safe in clinical application. LEVEL OF EVIDENCE: 2.

Identification of transforming growth factor beta induced (TGFBI) as an immune-related prognostic factor in clear cell renal cell carcinoma (ccRCC).

Clear cell renal cell carcinoma (ccRCC) is the most common subtype among kidney cancer, which has poor prognosis. The aim of this study was to screen out novel prognostic biomarkers and therapeutic targets for immunotherapy, and some novel molecule drugs for ccRCC treatment. Immune scores ranged from -1109.36 to 2920.81 and stromal scores ranged from -1530.11 to 1955.39 were firstly calculated by applying ESTIMATE algorithm. Then 17 DEGs associated with immune score and stromal score were further identified. 6 candidate hub genes were screened out by performing overall survival (OS) and disease-free survival analyses based on TCGA-KIRC data, one of which including TGFBI was further regarded as hub gene associated with prognosis by calculating the R2 (R2 = 0.011, P = 0.018) and AUC (AUC = 0.874). The prognostic value of TGFBI was validated by performing OS, CSS, and PFS analyses based on GSE29609 and E-MTAB-3267. CMap analysis suggested that 3 molecule drugs might be novel choice for ccRCC treatment. Further analysis demonstrated that CNVs of TGFBI was associated with OS of patients with ccRCC. TGFBI expression was also correlated with histologic grade, pathologic stage, and immune infiltration level, significantly. TGFBI was the most relevant gene with OS among the candidate hub genes, which might be novel DNA methylation biomarkers for ccRCC. In conclusion, our findings indicated that TGFBI was correlated with prognosis of patients with ccRCC, which might be novel prognostic biomarkers, and targets for immunotherapy in ccRCC. Three small molecule drugs were also identified, which showed strong potential for ccRCC treatment.

Accuracy of Pedicle Screw Placement and Clinical Outcomes of Robot-assisted Technique Versus Conventional Freehand Technique in Spine Surgery From Nine Randomized Controlled Trials: A Meta-analysis.

STUDY DESIGN: A meta-analysis. OBJECTIVE: To investigate whether robot-assisted techniques are superior to conventional techniques in terms of the accuracy of pedicle screw placement and clinical indexes. SUMMARY OF BACKGROUND DATA: Robot-assisted techniques are increasingly applied to spine surgery to reduce the rate of screw misplacement. However, controversy about the superiority of robot-assisted techniques over conventional freehand techniques remains. METHODS: We conducted a comprehensive search of PubMed, EMBASE, and Cochrane Library for potentially eligible articles. The outcomes were evaluated in terms of risk ratio (RR) or standardized mean difference and the associated 95% confidence intervals (CIs). Meta-analysis was performed using the RevMan 5.3 software and subgroup analyses were performed based on the robot type for the accuracy of pedicle screw placement. RESULTS: Nine randomized controlled trials with 696 patients were included in this meta-analysis. The results demonstrated that the robot-assisted technique was more accurate in pedicle screw placement than the freehand technique. Subgroup analyses showed that the TINAVI robot-assisted technique was more accurate in screw positions Grade A (RR, 1.10; 95% CI, 1.06-1.14), Grade B (RR, 0.46; 95% CI, 0.28-0.75), and Grades C + D + E (RR, 0.21; 95% CI, 0.09-0.45) than the freehand technique, whereas the Renaissance robot-assisted technique showed the same accuracy as the freehand technique in screw positions Grade A, Grade B, and Grades C + D + E. Furthermore, the robot-assisted techniques showed equivalent postoperative stay, visual analogue scale scores, and Oswestry disability index scores to those of the freehand technique and shorter intraoperative radiation exposure time, fewer radiation dose and proximal facet violations but longer surgical time than the freehand technique. CONCLUSION: The robot-assisted technique is more accurate in pedicle screw placement than the freehand technique. And TINAVI robot-assisted pedicle screw placement is a more accurate alternative to conventional techniques and the Renaissance robot-assisted procedure. LEVEL OF EVIDENCE: 1.

Differences in radiographic and clinical outcomes of oblique lateral interbody fusion and lateral lumbar interbody fusion for degenerative lumbar disease: a meta-analysis.

BACKGROUND: In the current surgical therapeutic regimen for the degenerative lumbar disease, both oblique lateral interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) are gradually accepted. Thus, the objective of this study is to compare the radiographic and clinical outcomes of OLIF and LLIF for the degenerative lumbar disease. METHODS: We conducted an exhaustive literature search of MEDLINE, EMBASE, and the Cochrane Library to find the relevant studies about OLIF and LLIF for the degenerative lumbar disease. Random-effects model was performed to pool the outcomes about disc height (DH), fusion, operative blood loss, operative time, length of hospital stays, complications, visual analog scale (VAS), and Oswestry disability index (ODI). RESULTS: 56 studies were included in this study. The two groups of patients had similar changes in terms of DH, operative blood loss, operative time, hospital stay and the fusion rate (over 90%). The OLIF group showed slightly better VAS and ODI scores improvement. The incidence of perioperative complications of OLIF and LLIF was 26.7 and 27.8% respectively. Higher rates of nerve injury and psoas weakness (21.2%) were reported for LLIF, while higher rates of cage subsidence (5.1%), endplate damage (5.2%) and vascular injury (1.7%) were reported for OLIF. CONCLUSIONS: The two groups are similar in terms of radiographic outcomes, operative blood loss, operative time and the length of hospital stay. The OLIF group shows advantages in VAS and ODI scores improvement. Though the incidence of perioperative complications of OLIF and LLIF is similar, the incidence of main complications is significantly different.