Is Tranexamic Acid Beneficial in Open Spine Surgery? and its Effects Vary by Dosage, Age, Sites, and Locations: A Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: The role of tranexamic acid (TXA) in controlling blood loss during spine surgery remains unclear. With the publication of new randomized controlled trials (RCTs), we conducted a meta-analysis to determine the safety and efficacy of TXA in spine surgery. METHODS: PubMed, Embase, Web of Science, and Cochrane databases were searched for relevant studies through 2022. Only RCTs were eligible for this study. The extracted data were analyzed using RevMan 5.3 software for meta-analysis. RESULTS: Twenty RCTs including 1497 patients undergoing spine surgery were included in this systematic evaluation. Compared with the control group, TXA significantly reduced total blood loss (mean difference [MD] = - 218.96, 95% confidence interval [CI] = - 309.77 to - 128.14, P < 0.00001), perioperative blood loss (MD = - 90.54, 95% CI = - 139.33 to - 41.75, P = 0.0003), postoperative drainage (MD = - 102.60, 95% CI = - 139.51 to - 65.70, P < 0.00001)，reduced hospital stay (MD = - 1.42, 95% CI = - 2.71 to - 0.14, P = 0.03), reduced total blood transfusion volume (MD = - 551.06, 95% CI = - 755.90 to - 346.22, P < 0.00001), and international normalized ratio (MD = -0.03, 95% CI = -0.04 to -0.02, P < 0.00001). CONCLUSIONS: Based on the meta-analysis of 20 RCTs, we demonstrated that TXA reduces blood loss in open spine surgery, decreases transfusion rates, and shortens hospital stays. The TXA administration during the perioperative period does not increase the incidence of postoperative complications.

Predictive risk factors for recollapse of cemented vertebrae after percutaneous vertebroplasty: A meta-analysis.

BACKGROUND: As one of the most common complications of osteoporosis, osteoporotic vertebral compression fracture (OVCF) increases the risk of disability and mortality in elderly patients. Percutaneous vertebroplasty (PVP) is considered to be an effective, safe, and minimally invasive treatment for OVCFs. The recollapse of cemented vertebrae is one of the serious complications of PVP. However, the risk factors associated with recollapse after PVP remain controversial. AIM: To identify risk factors for the recollapse of cemented vertebrae after PVP in patients with OVCFs. METHODS: A systematic search in EMBASE, MEDLINE, the Cochrane Library, and PubMed was conducted for relevant studies from inception until March 2020. Studies investigating risk factors for the recollapse of cemented vertebrae after PVP without additional trauma were selected for analysis. Odds ratios (ORs) or standardized mean differences with 95% confidence interval (CI) were calculated and heterogeneity was assessed by both the chi-squared test and the I-squared test. The methodological quality of the included studies was assessed according to the Newcastle-Ottawa Scale. RESULTS: A total of nine case-control studies were included in our meta-analysis comprising 300 cases and 2674 controls. The significant risk factors for the recollapse of cemented vertebrae after PVP in OVCF patients were fractures located at the thoracolumbar junction (OR = 2.09; 95%CI: 1.30 to 3.38; P = 0.002), preoperative intravertebral cleft (OR = 2.97; 95%CI: 1.93 to 4.57; P < 0.00001), and solid lump distribution pattern of the cement (OR = 3.11; 95%CI: 1.91 to 5.07; P < 0.00001). The analysis did not support that age, gender, lumbar bone mineral density, preoperative visual analogue scale score, injected cement volume, intradiscal cement leakage, or vertebral height restoration could increase the risk for cemented vertebra recollapse after PVP in OVCFs. CONCLUSION: This meta-analysis suggests that thoracolumbar junction fractures, preoperative intravertebral cleft, and solid lump cement distribution pattern are associated with the recollapse of cemented vertebrae after PVP in OVCF patients.

Morphologic analysis of Chinese lumbar endplate by three-dimensional computed tomography reconstructions for helping design lumbar disc prosthesis.

ABSTRACT: Lumbar disc prostheses have been used increasingly in recent years. The successful design of lumbar disc prostheses depends on accurate morphometric parameters. However, the morphologic dimensions of lumbar endplate area have not been investigated in Chinese population.A total of 1800 lumbar endplates were retrospectively accessed in 150 Chinese adults. Eighteen parameters of each lumbar segment were measured by three-dimensional computed tomography reconstructions from T12/L1 to L5/S1. These obtained parameters were compared between genders, bilateral sides, vertebral segments, and different populations.Endplate length and width increased in general, and there was a significant decrease for length/width ratio from T12 to S1 (P = .03). The average concavity depth of the lower lumbar endplate (2.09 ±â€Š0.93 mm) was usually larger than that of the upper lumbar endplate (1.61 ±â€Š0.74 mm) (P = .02). The percentage of the most concave point of the upper and lower lumbar endplate was 50.01 ±â€Š10.76% and 56.41 ±â€Š9.93%, respectively. Anterior, medium, or posterior intervertebral endplate height was severally 10.01 ±â€Š1.98 mm, 10.46 ±â€Š2.03 mm, and 6.41 ±â€Š1.74 mm, and increased among vertebral segments (P = .01).The intervertebral endplate angle significantly increased from T12-L1 to L5-S1 (P = .01). Parameters displayed significant difference between genders. The morphometric parameters of different populations also showed differences.In conclusion, there is a morphologic discrepancy in dimensions of lumbar endplate regarding genders, vertebral segments, and different populations. It is essential to design the lumbar disc prosthesis suited for Chinese patients specially, for which the morphometric parameters in our study can be utilized.

Decoding epigenetic codes: new frontiers in exploring recovery from spinal cord injury.

Spinal cord injury that results in severe neurological disability is often incurable. The poor clinical outcome of spinal cord injury is mainly caused by the failure to reconstruct the injured neural circuits. Several intrinsic and extrinsic determinants contribute to this inability to reconnect. Epigenetic regulation acts as the driving force for multiple pathological and physiological processes in the central nervous system by modulating the expression of certain critical genes. Recent studies have demonstrated that post-SCI alteration of epigenetic landmarks is strongly associated with axon regeneration, glial activation and neurogenesis. These findings not only establish a theoretical foundation for further exploration of spinal cord injury, but also provide new avenues for the clinical treatment of spinal cord injury. This review focuses on the epigenetic regulation in axon regeneration and secondary spinal cord injury. Together, these discoveries are a selection of epigenetic-based prognosis biomarkers and attractive therapeutic targets in the treatment of spinal cord injury.

Catastrophic thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture: A CARE-compliant case report.

RATIONALE: Intraspinal anesthesia, the most common anesthesia type of orthopedic operation, is regarded as safe and simple. Despite of the rare incidence, puncture related complication of intraspinal anesthesia is catastrophic for spinal cord. Here we present an intradural hematoma case triggered by improper anesthesia puncture. The principal reason of this tragedy was rooted in the neglect of spine deformities diagnosis before anesthesia. To the best of our knowledge, there is no specific case report focusing on the intradural hematoma triggered by improper anesthesia puncture. PATIENT CONCERNS: Hereby a case of thoracolumbar spinal massive hematoma triggered by intraspinal anesthesia puncture was reported. The presenting complaint of the patient was little neurologic function improvement after surgery at 6-month follow-up. DIAGNOSES: Emergency MRI demonstrated that massive spindle-like intradural T2-weighted image hypointense signal masses from T12 to S2 badly compressed the dural sac ventrally, and his conus medullaris was at L3/4 intervertebral level with absence of L5 vertebral lamina. Hereby, the diagnoses were congenital spinal bifida, tethered cord syndrome, spine intradural hematoma, and paraplegia. INTERVENTIONS: Urgent surgical interventions including laminectomy, spinal canal exploration hematoma removal, and pedicle fixation were performed. The patient received both medication (mannitol, mecobalamin, and steroids) and rehabilitation (neuromuscular electric stimulation, hyperbaric oxygen). OUTCOMES: Postoperation, he had regained only hip and knee flexion at II grade strength. His neurologic function was unchanged until 3 weeks postoperation. Six-month follow-up showed just little neurologic function improvement, and the American Spinal Injury Association grade was C. LESSONS: By presenting an intradural hematoma case triggered by improper anesthesia puncture, we shared the treatment experience and discussed the potential mechanism of neurologic compromise. The principal reason for this tragedy is preanesthesia examination deficiency. Necessary radiology examinations must be performed to prevent misdiagnosis for spinal malformation.

Thoracolumbar traumatic nucleus pulposus sequestration combined with a slight flexion distraction fracture: A rare case report and literature review.

RATIONALE: Traumatic nucleus pulposus sequestration (TNPS) usually occurs concurrently with severe destruction of bone. TNPS combined with a slight thoracolumbar flexion- distraction fracture, triggering a disastrous nerve injury, has rarely been reported. Due to the atypical radiologic manifestations, such a patient can easily be overlooked. PATIENT CONCERNS: Hereby, we present a TNPS patient as well as a slight thoracolumbar flexion-distraction fracture and serious neurologic symptoms. DIAGNOSES: T12 spinous process fracture, L1 flexion distraction fracture, thoracolumbar traumatic nucleus pulposuse sequestration and lower limbs incomplete paralysis INTERVENTIONS:: To avoid further neurologic compromise, an urgent laminectomy and exploration of the spinal canal was performed. OUTCOMES: After decompression OR and 4 months rehabilitation, the patient's neurologic function improved remarkably. LESSONS: A slight flexion-distraction fracture following injury is liable to eclipse the concurrence of TPNS. For this patient, a high-resolution MRI was needed to make a definitive diagnosis and guide surgery. Once TPNS has been diagnosed, sufficient decompression and discectomy surgery should be performed without delay.

MSC-derived cytokines repair radiation-induced intra-villi microvascular injury.

Microvascular injury initiates the pathogenesis of radiation enteropathy. As previously demonstrated, the secretome from mesenchymal stem cells contains various angiogenic cytokines that exhibited therapeutic potential for ischemic lesions. As such, the present study aimed to investigate whether cytokines derived from mesenchymal stem cells can repair endothelial injuries from irradiated intestine. Here, serum-free medium was conditioned by human adipose-derived mesenchymal stem cells, and we found that there were several angiogenic cytokines in the medium, including IL-8, angiogenin, HGF and VEGF. This medium promoted the formation of tubules between human umbilical cord vein endothelial cells and protected these cells against radiation-induced apoptosis in vitro. Likewise, our in vivo results revealed that repeated injections of mesenchymal stem cell-conditioned medium could accelerate the recovery of irradiated mice by reducing the serum levels of pro-inflammatory cytokines, including IL-1α, IL-6 and TNF-α, and promoting intra-villi angiogenesis. Herein, intervention by conditioned medium could increase the number of circulating endothelial progenitors, whereas neutralizing SDF-1α and/or inhibiting PI3K would hamper the recruitment of endothelial progenitors to the injured sites. Such results suggested that SDF-1α and PI3K-mediated phosphorylation were required for intra-villi angiogenesis. To illustrate this, we found that conditioned medium enabled endothelial cells to increase intracellular levels of phosphorylated Akt Ser473, both under irradiated and steady state conditions, and to up-regulate the expression of the CXCR4 and CXCR7 genes. Collectively, the present results revealed the therapeutic effects of mesenchymal stem cell-derived cytokines on microvascular injury of irradiated intestine.

Minocycline Attenuates Kidney Injury in a Rat Model of Streptozotocin-Induced Diabetic Nephropathy.

The effects of minocycline on the development of diabetic nephropathy (DN) in streptozotocin (STZ) induced diabetic rats were evaluated in this study. The diabetes rats with DN were induced by STZ (55 mg/kg) injection. The experiment included 5 groups 1) normal, 2) normal plus minocycline for 16 weeks, 3) DN plus vehicle, 4) DN plus minocycline 16 weeks and 5) DN plus minocycline for 8 weeks. The pathological changes were analyzed by hematoxylin and eosin (H&E) staining and the apoptotic cells were stained by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining. The mRNA expression of caspase-3, Bax and Bcl-2 in the kidney tissues was detected by quantitative RT-PCR. The biochemical parameters of blood and urine were determined by biochemical analyzer. Treatment with minocycline reduced the urine volume, 24-h urine protein, serum creatinine (Scr), blood urea nitrogen (BUN) but not blood alanine aminotransferase (ALT) in the DN rats. Furthermore, treatment with minocycline improved the pathological score of STZ-injured kidney and reduced the numbers of apoptotic cells in the kidney of DN rats. Moreover, minocycline mitigated the expression of caspase-3 and Bax mRNA, but increased Bcl-2 expression in the kidney of DN rats. These data indicated that minocycline improved the STZ-induced kidney damages, at least partially by protection form long-term hyperglycemia-induced kidney cell apoptosis.

In vivo electroporation of adult mouse sensory neurons for studying peripheral axon regeneration.

Electroporation has been a widely used tool to introduce DNA plasmids or RNA oligos into cultured cells and recently in vivo into chick or mouse embryos. Here we report a rapid and efficient approach to transfect adult mouse dorsal root ganglion neurons in vivo with precise spatiotemporal control via electroporation. This approach will allow both gain- and loss-of-function experiments in vivo to study the function of adult sensory neurons, such as sensory axon regeneration.

Akt-independent GSK3 inactivation downstream of PI3K signaling regulates mammalian axon regeneration.

Inactivation of glycogen synthase kinase 3 (GSK3) has been shown to mediate axon growth during development and regeneration. Phosphorylation of GSK3 by the kinase Akt is well known to be the major mechanism by which GSK3 is inactivated. However, whether such regulatory mechanism of GSK3 inactivation is used in neurons to control axon growth has not been directly studied. Here by using GSK3 mutant mice, in which GSK3 is insensitive to Akt-mediated inactivation, we show that sensory axons regenerate normally in vitro and in vivo after peripheral axotomy. We also find that GSK3 in sensory neurons of the mutant mice is still inactivated in response to peripheral axotomy and such inactivation is required for sensory axon regeneration. Lastly, we provide evidence that GSK3 activity is negatively regulated by PI3K signaling in the mutant mice upon peripheral axotomy, and the PI3K-GSK3 pathway is functionally required for sensory axon regeneration. Together, these results indicate that in response to peripheral nerve injury GSK3 inactivation, regulated by an alternative mechanism independent of Akt-mediated phosphorylation, controls sensory axon regeneration.

Signaling pathways that regulate axon regeneration.

Neurons in the mammalian central nervous system (CNS) cannot regenerate axons after injury. in contrast, neurons in the mammalian peripheral nervous system and in some non-mammalian models, such as C. elegans and Drosophila, are able to regrow axons. Understanding the molecular mechanisms by which these neurons support axon regeneration will help us find ways to enhance mammalian CNS axon regeneration. Here, recent studies in which signaling pathways regulating naturally-occurring axon regeneration that have been identified are reviewed, focusing on how these pathways control gene expression and growth-cone function during axon regeneration.

MicroRNA-138 and SIRT1 form a mutual negative feedback loop to regulate mammalian axon regeneration.

Regulated gene expression determines the intrinsic ability of neurons to extend axons, and loss of such ability is the major reason for the failed axon regeneration in the mature mammalian CNS. MicroRNAs and histone modifications are key epigenetic regulators of gene expression, but their roles in mammalian axon regeneration are not well explored. Here we report microRNA-138 (miR-138) as a novel suppressor of axon regeneration and show that SIRT1, the NAD-dependent histone deacetylase, is the functional target of miR-138. Importantly, we provide the first evidence that miR-138 and SIRT1 regulate mammalian axon regeneration in vivo. Moreover, we found that SIRT1 also acts as a transcriptional repressor to suppress the expression of miR-138 in adult sensory neurons in response to peripheral nerve injury. Therefore, miR-138 and SIRT1 form a mutual negative feedback regulatory loop, which provides a novel mechanism for controlling intrinsic axon regeneration ability.