EYA4 reduces chemosensitivity of osteosarcoma to doxorubicin through DNA damage repair.

Previous studies have demonstrated that Eyes Absent 4 (EYA4) influences the proliferation and migration of tumor cells. Notably, studies have established that EYA4 can also limit tumor sensitivity to chemotherapeutic agents. The objective of this study was to investigate the effect of EYA4 in conferring drug resistance in osteosarcoma (OS). Bioinformatics, histological, and cellular analyses revealed that the expression level of EYA4 was higher in OS tissues than in healthy tissues/cells and in resistant tissues/cells compared with sensitive tissues/cells. In vitro and in vivo experiments demonstrated that EYA4 knockdown increased the sensitivity of OS to doxorubicin (DOX). Conversely, overexpression of EYA4 decreased the sensitivity of OS to DOX. Exploration of the resistance mechanism exposed that EYA4 facilitates DNA double-strand break (DSB) repair, a typical mode of DNA damage repair (DDR). Subsequently, our findings indicated that EYA4 could directly interact with histone H2AX to activate the DDR pathway. Taken together, our observations indicated that EYA4 may serve as a target molecule for reversing drug resistance in OS patients.

Cytoplasmic Escape of Mitochondrial DNA Mediated by Mfn2 Downregulation Promotes Microglial Activation via cGas-Sting Axis in Spinal Cord Injury.

Neuroinflammation is associated with poor outcomes in patients with spinal cord injury (SCI). Recent studies have demonstrated that stimulator of interferon genes (Sting) plays a key role in inflammatory diseases. However, the role of Sting in SCI remains unclear. In the present study, it is found that increased Sting expression is mainly derived from activated microglia after SCI. Interestingly, knockout of Sting in microglia can improve the recovery of neurological function after SCI. Microglial Sting knockout restrains the polarization of microglia toward the M1 phenotype and alleviates neuronal death. Furthermore, it is found that the downregulation of mitofusin 2 (Mfn2) expression in microglial cells leads to an imbalance in mitochondrial fusion and division, inducing the release of mitochondrial DNA (mtDNA), which mediates the activation of the cGas-Sting signaling pathway and aggravates inflammatory response damage after SCI. A biomimetic microglial nanoparticle strategy to deliver MASM7 (named MSNs-MASM7@MI) is established. In vitro, MSNs-MASM7@MI showed no biological toxicity and effectively delivered MASM7. In vivo, MSNs-MASM7@MI improves nerve function after SCI. The study provides evidence that cGas-Sting signaling senses Mfn2-dependent mtDNA release and that its activation may play a key role in SCI. These findings provide new perspectives and potential therapeutic targets for SCI treatment.

Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women.

Background: There are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures. Methods: PubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events. Results: Fifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up. Conclusions: A variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21-72 months.

Comparison of posterior decompression techniques and conventional laminectomy for lumbar spinal stenosis.

Objectives: To compare the efficacy of posterior decompression techniques with conventional laminectomy for lumbar spinal stenosis. Methods: The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to January 13, 2022. The main outcomes were functional disability, perceived recovery, leg and back pain, complications. A random effects model was used to pooled data. Risk ratio (RR), mean difference (MD) and 95% confidence interval (CI) were used to report results. The study protocol was published in PROSPERO (CRD42022302218). Results: 14 trials including 1,106 participants were included in the final analysis. Bilateral laminotomy was significantly more efficacious in improve functionality than laminectomy [MD: -2.94; (95% CI, -4.12 to -1.76)]. Low incidence of iatrogenic instability due to bilateral laminectomy compared with laminectomy [RR: 0.11; (95% CI, 0.02 to 0.59)]. In addition, between those who received bilateral laminotomy and those undergoing laminectomy, the result showed significant difference regarding recovery [RR: 1.31; (95% CI, 1.03 to 1.67)]. Conclusions: This study provides evidence that bilateral laminotomy has advantages in functional recovery, postoperative stability, and postoperative rehabilitation outcomes. Further research is needed to determine whether posterior techniques provide a safe and effective option for conventional laminectomy.

The Anticancer Effect of Metformin Combined with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors in Non-small Cell Lung Cancer Patients with or Without Type 2 Diabetes Mellitus: A Systematic Review and Meta-analysis.

INTRODUCTION: Despite the growing evidence for the anticancer effect of metformin or its combination with epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs), the efficacies and side effects of such strategies in non-small cell lung cancer (NSCLC) patients with or without type 2 diabetes mellitus (T2DM) are not well understood. This meta-analysis was performed to determine the efficacy and side effects of metformin combined with EGFR-TKIs (MET-EGFR-TKIs) for the treatment of NSCLC with or without T2DM. METHODS: PubMed and Cochrane Library databases were used to retrieve relevant studies through August 2020 using the keywords "metformin", "EGFR-TKIs" ("gefitinib" or "erlotinib" or "afatinib" or "icotinib" or "dacomitinib") and "lung cancer". The patients in the experimental group received MET-EGFR-TKIs, while those in the control group received only EGFR-TKIs. The outcome analysis reported overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and disease control rate (DCR). Random-effect models and fixed-effect models were used to estimate the combined hazard ratio (HR) and odds ratio (OR) depending on the data heterogeneity. Three studies (including 1996 patients) were included in the current meta-analysis. RESULTS: There were significant differences in PFS (HR 0.84; 95% confidence interval (CI) 0.75-0.95; P = 0.004) and OS (HR 0.77; 95% CI, 0.50-1.04; P < 0.001) between the MET-EGFR-TKI and EGFR-TKI groups. Although the ORR (OR 1.38; 95% CI 0.66-2.88; P = 0.105) and DCR (OR 2.61, 95% CI 0.68-9.95, P = 0.160) were improved, there was no statistical significance. OS subgroup analysis showed that the combination was more effective in NSCLC with T2DM than in NSCLC without T2DM (HR 0.84; 95% CI 0.74-0.95; P < 0.005). CONCLUSIONS: MET-EGFR-TKIs provided benefits for PFS and OS, and OS subgroup analysis showed that patients with NSCLC with T2DM received greater benefit than NSCLC patients without T2DM. However, further large-scale, well-designed randomized controlled trials (RCTs) are warranted to confirm the findings in the present investigation.

Corrigendum: Sestrin2-mediated autophagy contributes to drug resistance via endoplasmic reticulum stress in human osteosarcoma.

[This corrects the article DOI: 10.3389/fcell.2021.722960.].

Physical exercise improved muscle strength and pain on neck and shoulder in military pilots.

Purpose: To evaluate the effects of physical exercise on neck and shoulder muscle strength and pain in military pilots. Method: Embase, PubMed, and Cochrane Library databases were searched studies published up to April 1, 2022. Studies that met the screening criteria were included in the final meta-analysis. We calculated neck and shoulder maximal voluntary isometric contractions (MVICs), prevalence of pain, and pain intensity. Heterogeneity was explored by subgroup and sensitivity analyses. Result: A total of 15 studies with 907 participants were included. In the exercise group, muscle strength was significantly increased in four directions of neck motion: flexion (standardized mean difference (SMD) = 0.45; 95% CI, 0.08-0.82), extension (SMD = 0.63; 95% CI, 0.27-1.00), right lateral flexion (Rtflx) (SMD = 0.53; 95% CI, 0.12-0.94), and left lateral flexion (Ltflx) (SMD = 0.50; 95% CI, 0.09-0.91). Subgroup analysis showed that fighter pilots, strength plus endurance training, and a follow-up period <20 weeks exhibited more significant muscle strength improvements than helicopter pilots, simple strength training, and a follow-up period ≥20 weeks. Overall, the pooled odds ratio (OR) for the effect of physical exercise on the prevalence of neck pain was not statistically significant (I2 = 60%). Sensitivity analysis revealed that the heterogeneity was restored after removing each of two studies (I2 = 47%), and the pooled OR was statistically significant (OR = 0.46; 95% CI, 0.23 to 0.94, or OR = 0.47; 95% CI, 0.24-0.91). Furthermore, compared with observational studies (OS), the reduction in the prevalence of neck pain was more significant in randomized controlled trials (RCTs) (OR = 0.37; 95% CI, 0.18-0.78). No significant differences in the effects of exercise on shoulder muscle strength and neck and shoulder pain intensity were observed. Conclusion: Physical exercise can improve neck muscle strength in military pilots. After removing studies that may be the source of heterogeneity, exercise showed a protective effect on neck pain, especially in RCTs. The conclusion that exercise had no effects on shoulder muscle strength and pain intensity should be taken with caution.

Clinical Efficacy and Safety of Surgical Treatments in Patients With Pure Cervical Radiculopathy.

Background: Traditionally paired meta-analysis revealed inconsistencies in the safety and effectiveness of surgical interventions. We conducted a network meta-analysis to assess various treatments' clinical efficacy and safety for pure cervical radiculopathy. Methods: The Embase, PubMed, and Cochrane Library databases were searched for randomized controlled trials (RCTs) comparing different treatment options for patients with pure cervical radiculopathy from inception until October 23, 2021. The primary outcomes were postoperative success rates, postoperative complication rates, and postoperative reoperation rates. The pooled data were subjected to a random-effects consistency model. The protocol was published in PROSPERO (CRD42021284819). Results: This study included 23 RCTs (n = 1,844) that evaluated various treatments for patients with pure cervical radiculopathy. There were no statistical differences between treatments in the consistency model in terms of major clinical effectiveness and safety outcomes. Postoperative success rates were higher for anterior cervical foraminotomy (ACF: probability 38%), posterior cervical foraminotomy (PCF: 24%), and anterior cervical discectomy with fusion and additional plating (ACDFP: 21%). Postoperative complication rates ranked from high to low as follows: cervical disc replacement (CDR: probability 32%), physiotherapy (25%), ACF (25%). Autologous bone graft (ABG) had better relief from arm pain (probability 71%) and neck disability (71%). Among the seven surgical interventions with a statistical difference, anterior cervical discectomy with allograft bone graft plus plating (ABGP) had the shortest surgery time. Conclusions: According to current results, all surgical interventions can achieve satisfactory results, and there are no statistically significant differences. As a result, based on their strengths and patient-related factors, surgeons can exercise discretion in determining the appropriate surgical intervention for pure cervical radiculopathy.Systematic Review Registration: CRD42021284819.

Association Between Vitamin D Supplementation and Fall Prevention.

Background: Falls occur frequently among older individuals, leading to high morbidity and mortality. This study was to assess the efficacy of vitamin D in preventing older individuals from falling. Methods: We searched the PubMed, Cochrane Library, and EMBASE databases systematically using the keywords "vitamin D" and "fall" for randomized controlled trials (RCTs) comparing the effects of vitamin D with or without calcium supplements with those of a placebo or no treatment on fall incidence in adults older than 50 years. A meta-analysis was performed to calculate risk ratios (RRs), absolute risk differences (ARDs) and 95% CIs with random-effects models. Results: A total of 38 RCTs involving 61 350 participants fulfilled the inclusion criteria. Compared with placebo, high-dose vitamin D (≥ 700 IU) can prevent falls [RR, 0.87 (95% CI 0.79 to 0.96); ARD, -0.06 (95% CI, -0.10 to -0.02)]. Low-dose vitamin D (<700 IU) was not significantly associated with falls. Subgroup analysis showed that supplemental calcium, 25(OH) D concentration and frequency influenced the effect of vitamin D in preventing falls. Sensitivity analysis showed that vitamin D prevented falls, which was consistent with the primary analysis. In addition, the active form of vitamin D also prevented falls. Conclusion: In this meta-analysis of RCTs, doses of 700 IU to 2000 IU of supplemental vitamin D per day were associated with a lower risk of falling among ambulatory and institutionalized older adults. However, this conclusion should be cautiously interpreted, given the small differences in outcomes. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42020179390.

Decompression alone or decompression and fusion in degenerative lumbar spondylolisthesis.

Background: Clinically, there are substantive practice variations in surgical management of degenerative lumbar spondylolisthesis. We aimed at evaluating whether decompression alone outcomes for patients with degenerative lumbar spondylolisthesis are comparable to those of decompression with fusion. Methods: In this meta-analysis, the Embase, PubMed, and Cochrane Library databases were searched from inception to February 16th, 2022. Randomised controlled trials (RCTs) and cohort studies comparing decompression alone with decompression and fusion for patients with degenerative lumbar spondylolisthesis were included in this study. There were no language limitations. Odds ratio (OR), mean difference (MD) and 95% confidence interval (CI) were used to report results in the random-effects model. Main outcomes included Oswestry disability index (ODI), pain, clinical satisfaction, complication and reoperation rates. The study protocol was published in PROSPERO (CRD42022310645). Findings: Thirty-three studies (6 RCTs and 27 cohort studies) involving 94 953 participants were included. Differences in post-operative ODI between decompression alone and decompression with fusion were not significant. A small difference for back (MD, 0.13; [95% CI, 0.08 to 0.18]; I 2:0.00%) and leg pain (MD, 0.30; [95% CI, 0.09 to 0.51]; I 2:48.35%) was observed on the 3rd post-operative month. The results did not reveal significant differences in leg pain and back pain between decompression alone and fusion groups on the 6th, 12th, and 24th post-operative months. Difference in clinical satisfaction between decompression alone and decompression with fusion were not significant from RCTs (OR, 0.26; [95% CI, 0.03 to 1.92]; I 2:83.27%). Complications (OR, 1.54; [95% CI, 1.16 to 2.05]; I 2:48.88%), operation time (MD, 83.39; [95% CI, 55.93 to 110.85]; I 2:98.75%), intra-operative blood loss (MD, 264.58; [95% CI, 174.99 to 354.16]; I 2:95.61%) and length of hospital stay (MD, 2.85; [95% CI, 1.60 to 4.10]; I 2:99.49%) were higher with fusion. Interpretation: Clinical effectiveness of decompression alone was comparable to that of decompression with fusion for degenerative lumbar spondylolisthesis. Decompression alone is recommended for patients with degenerative lumbar spondylolisthesis. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81871818), Tangdu Hospital Seed Talent Program (Fei-Long Wei), Natural Science Basic Research Plan in Shaanxi Province of China (No.2019JM-265) and Social Talent Fund of Tangdu Hospital (No.2021SHRC034).

Oblique Lateral Interbody Fusion vs. Minimally Invasive Transforaminal Lumbar Interbody Fusion for Lumbar Spinal Stenosis: A Retrospective Cohort Study.

Background: Minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is an effective surgical option for lumbar spinal stenosis (LSS) with spondylolisthesis. However, few studies have discussed oblique lateral interbody fusion (OLIF) with MIS-TLIF. Objective: To evaluate postoperative improvements, complications, and reoperation rates between patients with LSS undergoing OLIF or MIS-TLIF. Methods: We retrospectively studied 113 LLS patients who underwent OLIF (53) or MIS-TLIF (60) with percutaneous pedicle screw fixation between January 2016 and December 2018. We measured estimated blood loss, operative time, hospital stay, reoperation, and complication incidence, visual analog scale (VAS), Oswestry Disability Index (ODI), Japanese Orthopedic Association (JOA), and Short Form-36 (SF-36) scores, discal and foraminal height and lumbar lordotic angle. Results: The mean age was 58.81 ± 0.9 years. The TLIF group had increased operation time, blood loss, and hospital stays (p = 0.007, 0.001, and 0.016, respectively). Postoperatively, VAS and ODI scores significantly decreased while JOA and SF-36 scores significantly increased. The postoperative differences in main outcomes between the groups were insignificant (all p > 0.05). The OLIF group had the lowest rates of overall (9.8% OLIF vs. 12.9% MIS-TLIF), intraoperative (3.9% OLIF vs. 4.8% MIS-TLIF), and postoperative complications (5.9% OLIF vs. 8.1% MIS-TLIF), but the differences were insignificant (p = 0.607, 0.813, and 0.653, respectively). The reoperation rate did not differ significantly (3.8% OLIF vs. 3.3% MIS-TLIF) (p = 0.842). OLIF restored disc height (74.4 vs. 32.0%), foraminal height (27.4 vs. 18.2%), and lumbar lordotic angle (3.5 vs. 1.1%) with greater success than did MIS-TLIF. Conclusion: Patients undergoing OLIF with LSS improved similarly to MIS-TLIF patients. OLIF restored disc height, foraminal height and lumbar lordotic angle more successfully than did MIS-TLIF.

Association of robot-assisted techniques with the accuracy rates of pedicle screw placement: A network pooling analysis.

Background: Traditional paired meta-analyses have yielded inconsistent results for the safety and effectiveness of robotic-assisted pedicle screw placement due to the high heterogeneity within studies. This study evaluated the clinical effectiveness and safety of robotic-assisted pedicle screw placement. Methods: The Embase, PubMed, and Cochrane Library databases were searched with no language limitations from inception to Jan 4, 2022. Odds ratio (OR), mean difference (MD), and 95% confidence interval (CI) were used to report results. The main outcomes were accuracy of pedicle screw placement, proximal facet joint violation, and complications. The study protocol was published in PROSPERO (CRD42022301417). Findings: 26 trials including 2046 participants evaluating robotic-assisted pedicle screw placement were included in this study. Our pooled results showed that Renaissance (OR 2.86; [95% CI 1.79 to 4.57]) and TiRobot (OR 3.10; [95% CI 2.19 to 4.40]) yielded higher rates of perfect pedicle screw insertion (Grades A) than the conventional freehand technique. Renaissance (OR 2.82; [95% CI 1.51 to 5.25]) and TiRobot (OR 4.58; [95% CI 2.65 to 7.89]) yielded higher rates of clinically acceptable pedicle screw insertion (Grades A+B). However, ROSA, SpineAssist, and Orthobot were not associated with higher perfect pedicle screw insertion and clinically acceptable pedicle screw insertion rates. Robot-assisted techniques were associated with low rates of proximal facet joint violation (OR 0.18; [95% CI 0.10 to 0.32]; I2:9.55%) and overall complications (OR 0.38; [95% CI 0.23 to 0.63]; I2:27.05%). Moreover, robot-assisted techniques were associated with lower radiation doses (MD -14.38; [95% CI -25.62 to -3.13]; I2:100.00%). Interpretation: Our findings suggest that only Renaissance and TiRobot systems are associated with high accuracy rates of pedicle screw placement. Robotic-assisted techniques hold great promise in spinal surgery due to their safety and effectiveness. Funding: This work was supported by grants from the National Natural Science Foundation of China (No. 81871818), Tangdu Hospital Seed Talent Program (Fei-Long Wei) and Natural Science Basic Research Plan in Shaanxi Province of China (No.2019JM-265).

Exploring the Pharmacological Potential of Metformin for Neurodegenerative Diseases.

Metformin, one of the first-line of hypoglycemic drugs, has cardioprotective, anti-inflammatory and anticancer activities, in addition to its proven hypoglycemic effects. Furthermore, the preventive and therapeutic potential of metformin for neurodegenerative diseases has become a topic of concern. Increasing research suggests that metformin can prevent the progression of neurodegenerative diseases. In recent years, many studies have investigated the neuroprotective effect of metformin in the treatment of neurodegenerative diseases. It has been revealed that metformin can play a neuroprotective role by regulating energy metabolism, oxidative stress, inflammatory response and protein deposition of cells, and avoiding neuronal dysfunction and neuronal death. On the contrary, some have hypothesized that metformin has a two-sided effect which may accelerate the progression of neurodegenerative diseases. In this review, the results of animal experiments and clinical studies are reviewed to discuss the application prospects of metformin in neurodegenerative diseases.

Genome-wide CRISPR screen identified Rad18 as a determinant of doxorubicin sensitivity in osteosarcoma.

BACKGROUND: Osteosarcoma (OS) is a malignant bone tumor mostly occurring in children and adolescents, while chemotherapy resistance often develops and the mechanisms involved remain challenging to be fully investigated. METHODS: Genome-wide CRISPR screening combined with transcriptomic sequencing were used to identify the critical genes of doxorubicin resistance. Analysis of clinical samples and datasets, and in vitro and in vivo experiments (including CCK-8, apoptosis, western blot, qRT-PCR and mouse models) were applied to confirm the function of these genes. The bioinformatics and IP-MS assays were utilized to further verify the downstream pathway. RGD peptide-directed and exosome-delivered siRNA were developed for the novel therapy strategy. RESULTS: We identified that E3 ubiquitin-protein ligase Rad18 (Rad18) contributed to doxorubicin-resistance in OS. Further exploration revealed that Rad18 interact with meiotic recombination 11 (MRE11) to promote the formation of the MRE11-RAD50-NBS1 (MRN) complex, facilitating the activation of the homologous recombination (HR) pathway, which ultimately mediated DNA damage tolerance and leaded to a poor prognosis and chemotherapy response in patients with OS. Rad18-knockout effectively restored the chemotherapy response in vitro and in vivo. Also, RGD-exosome loading chemically modified siRad18 combined with doxorubicin, where exosome and chemical modification guaranteed the stability of siRad18 and the RGD peptide provided prominent targetability, had significantly improved antitumor activity of doxorubicin. CONCLUSIONS: Collectively, our study identifies Rad18 as a driver of OS doxorubicin resistance that promotes the HR pathway and indicates that targeting Rad18 is an effective approach to overcome chemotherapy resistance in OS.

Association of Use of Tourniquets During Total Knee Arthroplasty in the Elderly Patients With Post-operative Pain and Return to Function.

Objective: During total knee arthroplasty (TKA), tourniquet may negatively impact post-operative functional recovery. This study aimed at investigating the effects of tourniquet on pain and return to function. Methods: Pubmed, Embase, and Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15th, 2020. Search terms included; total knee arthroplasty, tourniquet, and randomized controlled trial. RCTs evaluating the efficacies of tourniquet during and after operation were selected. Two reviewers independently extracted the data. Effect estimates with 95% CIs were pooled using the random-effects model. Dichotomous data were calculated as relative risks (RR) with 95% confidence intervals (CI). Mean differences (MD) with 95% CI were used to measure the impact of consecutive results. Primary outcomes were the range of motion (ROM) and visual analog scale (VAS) pain scores. Results: Thirty-three RCTs involving a total of 2,393 patients were included in this study. The mean age is 65.58 years old. Compared to no tourniquet group, the use of a tourniquet resulted in suppressed ROM on the 3rd post-operative day [MD, -4.67; (95% CI, -8.00 to -1.35)] and the 1st post-operative month [MD, -3.18; (95% CI, -5.92 to -0.44)]. Pain increased significantly when using tourniquets on the third day after surgery [MD, 0.39; (95% CI, -0.19 to 0.59)]. Moreover, tourniquets can reduce intra-operative blood loss [MD, -127.67; (95% CI, -186.83 to -68.50)], shorter operation time [MD, -3.73; (95% CI, -5.98 to -1.48)], lower transfusion rate [RR, 0.85; (95% CI, 0.73-1.00)], higher superficial wound infection rates RR, 2.43; [(5% CI, 1.04-5.67)] and higher all complication rates [RR, 1.98; (95% CI, 1.22-3.22)]. Conclusion: Moderate certainty evidence shows that the use of a tourniquet was associated with an increased risk of higher superficial wound infection rates and all complication rates. Therefore, the findings did not support the routine use of a tourniquet during TKA.

A retrospective study of spine injuries in electric bicycles related collisions.

BACKGROUND: Electric bicycles related collisions could lead to severe consequences in spine injuries, while no study had comprehensively investigated the epidemiology and demography of spine injuries in electric bicycles related collisions. QUESTIONS/PURPOSES: The aim of this study is to (1) describe the epidemiological characteristics of spine injuries in electric bicycles related collisions, (2) develop clinical guideline of spine injuries in electric bicycles related collisions and (3) support the new road safety policy for electric bicycle riders. METHODS: A retrospective review of spine injuries in electric bicycle related collisions was performed from 86 patients in an urban trauma center between 2018 and 2020. The variables including gender, age, radiographic findings, associated injuries, neurologic injuries, treatment, average length of stay were fully collected. Chi-square test and paired sample mean t-test were used to test for statistically significant differences. All statistical analyses were performed using Statistical Product and Service Solutions 20.0.0 software. A P<0.001 was considered as significant. RESULTS: A total of 86 cases were involved in electric bicycles related collisions lead to spine injuries. The spine injuries victims were predominantly male (79.07%) and middle-aged (41-60years, 44.19%). The most common spine injuries were L1 fractures (10.48%). The most common fracture type was AO Fracture Classification type A (71.40%). Age and multivertebral fractures had significant difference between patients who suffered from an ASOI and from those who did not (P-value: 0.005, 0.005). There was significant difference between patients who suffered from neurologic injuries and from those who did not in AO Classification, multivertebral fractures and ASOI (P-value: 0.0001, 0.001, 0.032). Age, AO Classification, multivertebral fractures, ASOI and neurologic injuries had significant difference to influence patients' ISS and ALOS. CONCLUSIONS: Spine injuries in electric bicycles related collisions may make patients suffer from severe consequences including their potential permanent disability, economic cost, or even life safety. Patients with spine injuries in electric bicycles related collisions should be paid close attention to avoid missed diagnosis and misdiagnosis. Helmet, protective clothing or other safety gear should be required to use to provide greater protection for electric bicycle riders.

Sestrin2-Mediated Autophagy Contributes to Drug Resistance via Endoplasmic Reticulum Stress in Human Osteosarcoma.

One contributor to the high mortality of osteosarcoma is its reduced sensitivity to chemotherapy, but the mechanism involved is unclear. Improving the sensitivity of osteosarcoma to chemotherapy is urgently needed to improve patient survival. We found that chemotherapy triggered apoptosis of human osteosarcoma cells in vitro and in vivo; this was accompanied by increased Sestrin2 expression. Importantly, autophagy was also enhanced with increased Sestrin2 expression. Based on this observation, we explored the potential role of Sestrin2 in autophagy of osteosarcoma. We found that Sestrin2 inhibited osteosarcoma cell apoptosis by promoting autophagy via inhibition of endoplasmic reticulum stress, and this process is closely related to the PERK-eIF2α-CHOP pathway. In addition, our study showed that low Sestrin2 expression can effectively reduce autophagy of human osteosarcoma cells after chemotherapy, increase p-mTOR expression, decrease Bcl-2 expression, promote osteosarcoma cell apoptosis, and slow down tumour progression in NU/NU mice. Sestrin2 activates autophagy by inhibiting mTOR via the PERK-eIF2α-CHOP pathway and inhibits apoptosis via Bcl-2. Therefore, our results explain one underlying mechanism of increasing the sensitivity of osteosarcoma to chemotherapy and suggest that Sestrin2 is a promising gene target.

Eight Surgical Interventions for Lumbar Disc Herniation: A Network Meta-Analysis on Complications.

Objective: Therapeutic options for lumbar disc surgery (LDH) have been rapidly evolved worldwide. Conventional pair meta-analysis has shown inconsistent results of the safety of different surgical interventions for LDH. A network pooling evaluation of randomized controlled trials (RCT) was conducted to compare eight surgical interventions on complications for patients with LDH. Methods: PubMed, Embase, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched for RCT from inception to June 2020, with registration in PROSPERO (CRD42020176821). This study is conducted in accordance with Cochrane guidelines. Primary outcomes include intraoperative, post-operative, and overall complications, reoperation, operation time, and blood loss. Results: A total of 27 RCT with 2,948 participants and eight interventions, including automated percutaneous lumbar discectomy (APLD), chemonucleolysis (CN), microdiscectomy (MD), micro-endoscopic discectomy (MED), open discectomy (OD), percutaneous endoscopic lumbar discectomy (PELD), percutaneous laser disc decompression (PLDD), and tubular discectomy (TD) were enrolled. The pooling results suggested that PELD and PLDD are with lower intraoperative and post-operative complication rates, respectively. TD, PELD, PLDD, and MED were the safest procedures for LDH according to complications, reoperation, operation time, and blood loss. Conclusion: The results of this study provided evidence that PELD and PLDD were with lower intraoperative and post-operative complication rates, respectively. TD, PELD, PLDD, and MED were the safest procedures for LDH according to complications, reoperation, operation time, and blood loss. Systematic Review Registration: PROSPERO, identifier CRD42020176821.

Therapeutic Effect of Large Channel Endoscopic Decompression in Lumbar Spinal Stenosis.

Background: Percutaneous endoscopic decompression (PED) is a minimally invasive surgical technique that is now used for not only disc herniation but also lumbar spinal stenosis (LSS). However, few studies have reported endoscopic surgery for LSS. Therefore, we conducted this study to evaluate the outcomes and safety of large channel endoscopic decompression. Methods: Forty-one patients diagnosed with LSS who underwent PED surgery were included in the study. The estimated blood loss, operative time, length of hospital stay, hospital costs, reoperations, complications, visual analogue scale (VAS) score, Oswestry Disability Index (ODI) score, Japanese Orthopaedic Association (JOA) score and SF-36 physical-component summary scores were assessed. Preoperative and postoperative continuous data were compared through paired-samples t-tests. The significance level for all analyses was defined as p < 0.05. Results: A total of 41 consecutive patients underwent PED, including 21 (51.2%) males and 20 (48.8%) females. The VAS and ODI scores decreased from preoperatively to postoperatively, but the JOA and SF-36 physical component summary scores significantly increased. The VAS (lumbar) score decreased from 5.05 ± 2.33 to 0.45 ± 0.71 (P = 0.000); the VAS (leg) score decreased from 5.51 ± 2.82 to 0.53 ± 0.72 (P = 0.000); the ODI score decreased from 52.80 ± 20.41 to 4.84 ± 3.98 (P = 0.000), and the JOA score increased from 11.73 ± 4.99 to 25.32 ± 2.12 (P = 0.000). Only 1 patient experienced an intraoperative complication (2.4%; dural tear), and 1 patient required reoperation (2.4%). Conclusions: Surgical treatment for LSS is to sufficiently decompress and minimize the trauma and complications caused by surgery. This study did not reveal any obvious shortcomings of PED and suggested PED is a safe and effective treatment for LSS.

Comparison of Different Operative Approaches for Lumbar Disc Herniation: A Network Meta-Analysis and Systematic Review.

BACKGROUND: New approaches and technologies can be beneficial for patients but also bring corresponding complications. Traditional pairwise meta-analyses cannot be used to comprehensively rank all surgical approaches. OBJECTIVES: The purpose of this systematic review and network meta-analysis (NMA) was to compare the outcomes of different surgical approaches for lumbar disc herniation (LDH). STUDY DESIGN: NMA of randomized controlled trials (RCTs) for multiple treatment comparisons of LDH. METHODS: The PubMed, Embase, MEDLINE, Ovid, and Cochrane Library databases were searched for RCTs comparing different surgical approaches for patients with LDH from inception to February 10, 2020. The Markov chain Monte Carlo methods were used to perform a hierarchical Bayesian NMA in WinBUGS version 1.4.3 using a random effects consistency model. The primary outcomes were disability and pain intensity. The secondary outcomes were complications and reoperation. The PROSPERO number was CRD42020179406. RESULTS: A total of 22 trials including 2529 patients and all 5 different approaches (open discectomy or microdiscectomy [OD/MD], microendoscopic discectomy [MED], percutaneous endoscopic discectomy [PED], percutaneous discectomy [PD], and tubular discectomy [TD]) were retrospectively retrieved. PED had the best efficacy in improving patients' dysfunction with no statistical significance (probability = 50%). PD was significantly worse than OD/MD, MED, and PED in relieving patients' pain (standardized mean differences: 0.87 [0.03, 1.76], 0.94 [0.06, 1.88], and 1.02 [0.13, 1.94], respectively). There was no statistically significant difference between any 2 surgical approaches in dural tear; intraoperative, postoperative, and overall complications; or reoperation rate. PED had the lowest dural tear rate and the lowest intraoperative and overall complication rates (probability = 51%, 67%, and 33%, respectively). TD had the lowest postoperative complication and reoperation rates (probability = 35% and 39%, respectively). LIMITATIONS: The limitations of this NMA include the inconsistent follow-up times, the criteria for complications, and the reasons for reoperation. CONCLUSIONS: Compared with other approaches used to treat LDH, PED had the best safety and efficacy in general, and TD had the lowest reoperation rate. Finally, we recommended PED for LDH.