The effect of phosphorylation on the conformational dynamics and allostery of the association of death-associated protein kinase with calmodulin.

Protein phosphorylation plays an important role in the signal transduction and is capable of regulation of cell activity. The death-associated protein kinase 1 (DAPK1), as a Ser/Thr kinase, interacts with calmodulin (CaM) to regulate apoptotic and autophagic signaling. Autophosphorylation of DAPK1 at Ser308 located at the autoregulatory domain (ARD) blocks CaM binding and inhibits kinase catalytic activity. However, the mechanism underlying the influence of Ser308 phosphorylation (pS308) on the DAPK1 activity remains unclear. Here, we performed multiple, microsecond length molecular dynamics (MD) simulations, the molecular mechanics generalized Born/surface area (MM-GBSA) binding free energy calculations, principal component analysis, and dynamic cross-correlation analysis to unravel the conformational dynamics and allostery of the DAPK1 - CaM interaction triggered by the pS308 at the ARD. MD simulations showed that pS308 affected the conformational stability of the DAPK1 - CaM complex. Further energetic and structural exploration revealed that pS308 weakened the association of the phosphorylated DAPK1 to CaM, which lowered the susceptibility of DAPK1 to be activated by CaM. This result can provide mechanistic insights into the molecular underpinning through which the DAPK1 kinase activity is modulated by the auto-phosphorylation.Communicated by Ramaswamy H. Sarma.

Clinical outcomes of short rod technique in posterior lumbar interbody fusion surgery: a minimum of 2-year follow-up.

PURPOSE: We present for the first time a novel entry point of pedicle screws (Short Rod Technique, SRT), which can avoid superior facet violation and has been verified as a safe screw placement method. The purpose of this study is to determine the clinical outcomes of SRT in posterior lumbar interbody fusion (PLIF) surgery. METHODS: We retrospectively analyzed the clinical outcomes of 89 patients who received SRT and 109 patients who received PLIF surgery with regular entry points of pedicle screws with a minimum of 2 years of follow-ups. Patients were divided into three groups according to the number of fusion segments, and the clinical outcomes of the three groups were compared. RESULTS: The length of the wound and the length of rods were significantly shorter in the each SRT group. Less intraoperative blood loss was observed in the SRT group in patients with a single segment and two segments fusions, but not in three segments fusions. Fewer degenerations of the upper adjacent segment were observed in the SRT group in patients with a single segment and three segments fusions. In addition, less postoperative wound pain related to PLIF surgery was observed in the SRT group in patients with two and three segments fusions. CONCLUSION: SRT has been validated as an effective technique with good clinical outcomes, especially for reducing the occurrence of upper ASD in PLIF surgery with a single segment and three segments. The present study provides spinal surgeons with a novel method for performing PLIF surgery.

Can a Nomogram Predict Survival After Treatment for an Ankylosing Spondylitis Cervical Fracture in a Patient With Neurologic Impairment? A National, Multicenter Study.

BACKGROUND: Ankylosing spondylitis-related cervical spine fracture with neurologic impairment (ASCF-NI) is a rare but often lethal injury. Factors independently associated with survival after treatment remain poorly defined, and identifying patients who are likely to survive the injury remains challenging. QUESTIONS/PURPOSES: (1) What factors are independently associated with survival after treatment among patients with ASCF-NI? (2) Can a nomogram be developed that is sufficiently simple for clinicians to use that can identify patients who are the most likely to survive after injury? METHODS: This retrospective study was conducted based on a multi-institutional group of patients admitted and treated at one of 29 tertiary hospitals in China between March 1, 2003, and July 31, 2019. A total of 363 patients with a mean age of 53 ± 12 years were eventually included, 343 of whom were male. According to the National Household Registration Management System, 17% (61 of 363) died within 5 years of injury. Patients were treated using nonsurgical treatment or surgery, including procedures using the anterior approach, posterior approach, or combined anterior and posterior approaches. Indications for surgery included three-column injury, unstable fracture displacement, neurologic impairment or continuous progress, and intervertebral disc incarceration. By contrast, patients generally received nonsurgical treatment when they had a relatively stable fracture or medical conditions that did not tolerate surgery. Demographic, clinical, and treatment data were collected. The primary study goal was to identify which factors are independently associated with death within 5 years of injury, and the secondary goal was the development of a clinically applicable nomogram. We developed a multivariable Cox hazards regression model, and independent risk factors were defined by backward stepwise selection with the Akaike information criterion. We used these factors to create a nomogram using a multivariate Cox proportional hazards regression analysis. RESULTS: After controlling for potentially confounding variables, we found the following factors were independently associated with a lower likelihood of survival after injury: lower fracture site, more-severe peri-injury complications, poorer American Spinal Injury Association (ASIA) Impairment Scale, and treatment methods. We found that a C5 to C7 or T1 fracture (ref: C1 to C4 and 5; hazard ratio 1.7 [95% confidence interval 0.9 to 3.5]; p = 0.12), moderate peri-injury complications (ref: absence of or mild complications; HR 6.0 [95% CI 2.3 to 16.0]; p < 0.001), severe peri-injury complications (ref: absence of or mild complications; HR 30.0 [95% CI 11.5 to 78.3]; p < 0.001), ASIA Grade A (ref: ASIA Grade D; HR 2.8 [95% CI 1.1 to 7.0]; p = 0.03), anterior approach (ref: nonsurgical treatment; HR 0.5 [95% CI 0.2 to 1.0]; p = 0.04), posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.8]; p = 0.006), and combined anterior and posterior approach (ref: nonsurgical treatment; HR 0.4 [95% CI 0.2 to 0.9]; p = 0.02) were associated with survival. Based on these factors, a nomogram was developed to predict the survival of patients with ASCF-NI after treatment. Tests revealed that the developed nomogram had good performance (C statistic of 0.91). CONCLUSION: The nomogram developed in this study will allow us to classify patients with different mortality risk levels into groups. This, coupled with the factors we identified, was independently associated with survival, and can be used to guide more appropriate treatment and care strategies for patients with ASCF-NI. LEVEL OF EVIDENCE: Level III, therapeutic study.

Instantaneous death risk, conditional survival and optimal surgery timing in cervical fracture patients with ankylosing spondylitis: A national multicentre retrospective study.

Background: The mortality rate in patients with ankylosing spondylitis (AS) and cervical fracture is relatively high. Objectives: This study aimed to investigate the instantaneous death risk and conditional survival (CS) in patients with AS and cervical fracture. We also studied the relationship between surgical timing and the incidence of complications. Methods: This national multicentre retrospective study included 459 patients with AS and cervical fractures between 2003 and 2019. The hazard function was used to determine the risk of instantaneous death. The five-year CS was calculated to show the dynamic changes in prognosis. Results: The instantaneous death risk was relatively high in the first 6 months and gradually decreased over time in patients with AS and cervical fracture. For patients who did not undergo surgery, the instantaneous risk of death was relatively high in the first 15 months and gradually decreased over time. For patients with American Spinal Injury Association impairment scale (ASIA) A and B, the 5-year CS was 55.3% at baseline, and improved steadily to 88.4% at 2 years. Odds ratios (ORs) for pneumonia, electrolyte disturbance, respiratory insufficiency, and phlebothrombosis decreased as the surgery timing increased. Conclusion: Deaths occurred mainly in the first 6 months after injury and gradually decreased over time. Our study highlights the need for continued surveillance and care in patients with AS with cervical fractures and provides useful survival estimates for both surgeons and patients. We also observed that early surgery can significantly increase functional recovery, and decrease the incidence of complications and rehospitalisation.

Sagittal imaging study of the lumbar spine with the short rod technique.

PURPOSE: The short rod technique (SRT) is a novel method for lumbar pedicle screw placement to reduce surgical trauma and avoid damage to the facet joint and articular surface. The core concept is to change the entry point and angle of the screw on the vertebrae at both ends in the sagittal plane to shorten the length of the longitudinal rods. The purpose of this study is to determine the sagittal screw angle (SSA) and its safe Maximum (MAX) value on each lumbar vertebra for the SRT and to observe the shortening effect on the longitudinal rods. METHODS: A total of 152 healthy adults were investigated by measuring the lumbar spine lateral view images. The SSA and MAX-SSA were measured with SRT as reference to the conventional placement technique method. The distance between the entry points of the proximal and distal vertebrae was measured to compare the changes in the length of the longitudinal rods using the two screw placement techniques. RESULTS: + SSA increased from L1 to L4, and -SSA increased from L2 to L5, in which the -SSA of L2, L3, and L4 were significantly greater than those of + SSA (P < 0.05). + MAX-SSA at L1-L4 was 23.26 ± 3.54°, 23.68 ± 3.37°, 24.12 ± 3.29°, and 24.26 ± 3.42°, respectively. -MAX-SSA at L2-L5 was 36.25 ± 3.26°, 38.26 ± 3.73°, 38.62 ± 3.63° and 37.33 ± 3.31°, respectively. Theoretical reductions by calculation for the 2-segment lumbar pedicles were: L1-2: 9 mm, L2-3: 9.29 mm, L3-4: 6.23 mm, and L4-5: 7.08 mm; And the 3-segment lumbar pedicles were: L1-3: 16.97 mm, L2-4: 16.73 mm, L3-5, and 18.24 mm, respectively. CONCLUSIONS: The application of the SRT to lumbar pedicles is a safe screw placement method that can significantly shorten the length of the used longitudinal rods.

Biomechanical evaluation of a short-rod technique for lumbar fixation surgery.

Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique. Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4-L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement. Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending. Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.

Mechanistic insights into the role of calcium in the allosteric regulation of the calmodulin-regulated death-associated protein kinase.

Calcium (Ca2+) signaling plays an important role in the regulation of many cellular functions. Ca2+-binding protein calmodulin (CaM) serves as a primary effector of calcium function. Ca2+/CaM binds to the death-associated protein kinase 1 (DAPK1) to regulate intracellular signaling pathways. However, the mechanism underlying the influence of Ca2+ on the conformational dynamics of the DAPK1-CaM interactions is still unclear. Here, we performed large-scale molecular dynamics (MD) simulations of the DAPK1-CaM complex in the Ca2+-bound and-unbound states to reveal the importance of Ca2+. MD simulations revealed that removal of Ca2+ increased the anti-correlated inter-domain motions between DAPK1 and CaM, which weakened the DAPK1-CaM interactions. Binding free energy calculations validated the decreased DAPK1-CaM interactions in the Ca2+-unbound state. Structural analysis further revealed that Ca2+ removal caused the significant conformational changes at the DAPK1-CaM interface, especially the helices α1, α2, α4, α6, and α7 from the CaM and the basic loop and the phosphate-binding loop from the DAPK1. These results may be useful to understand the biological role of Ca2+ in physiological processes.

Involvement of circRNA_0007059 in the regulation of postmenopausal osteoporosis by promoting the microRNA-378/BMP-2 axis.

Increasing evidence suggests that postmenopausal osteoporosis (PMO), a severe disturbance, imposes heavy physical, psychosocial, and financial burdens and dramatically influences the quality of life of postmenopausal women. Circular RNAs (circRNAs) and microRNAs (miRs) play important roles in the occurrence and development of PMO. However, the roles of circRNAs and miRs in osteoporosis regulation still need to be further investigated. circRNAs with different expression levels in patients with PMO were screened via RNA-seq and bioinformatics analysis. We found that circ_0007059 was upregulated in patients with PMO and during osteoclastogenesis of human bone marrow stromal cells (hBMSCs). Next, we investigated the effect of circ_0007059 overexpression during osteoclastogenesis of hBMSCs. circ_0007059 overexpression attenuated hBMSC differentiation into osteoclasts in vitro. This was demonstrated by downregulated bone morphogenetic protein 2 (BMP-2) expression, upregulated osteoclast-specific gene expression, and TRAP staining. circ_0007059 was demonstrated to directly target miR-378, which in turn targeted BMP-2 via bioinformatics analysis and the dual-luciferase reporter assay. Transfection of the miR-378 mimic reversed the effect of circ_0007059 on the osteoclastogenesis of hBMSCs. These results suggest that circ_0007059 plays an important role in osteoclastogenesis via the miR-378/BMP-2 signaling pathway. Targeting the circ_0007059/miR-378/BMP-2 axis is possibly a novel idea in osteoporosis treatment.

Comparison of a minimally invasive surgical technique with open surgery for transverse patella fractures.

The current study aimed to compare a minimally invasive surgical technique with open surgery for the treatment of transverse patella fractures. A total of 38 patients with displaced transverse fractures of the patella were included in the current prospective study. A total 21 of them were treated with a minimally invasive surgical (MIS) technique and the other 17 patients had open surgery (OS) when using the Cable Pin System. Postoperative comparisons were based on radiographs, the visual analog scale (VAS) of pain, their ranges of motion and the Bostman grading scale. Compared with the OS group, the VAS score for pain was significantly lower and the angle of active flexion was better in the MIS group at 4 and 8 weeks. The angle of active extension at 4 weeks and the Bostman score at 8 weeks after surgery were better in the MIS group, although the differences became non-significant at 8 weeks and 12 months. In conclusion, the MIS technique for transverse patella fractures provided better clinical results and the knees functioned with less pain when compared with the OS group in the early period following surgery. MIS could be an adequate alternative in the treatment of transverse patella fractures.

Computational investigation of a ternary model of SnoN-SMAD3-SMAD4 complex.

The transforming growth factor ß (TGFß) plays an essential role in the regulation of cellular processes such as cell proliferation, migration, differentiation, and apoptosis by association with SMAD transcriptional factors that are regulated by the transcriptional regulator SnoN. The crystal structure of SnoN-SMAD4 reveals that SnoN can adopt two binding modes, the open and closed forms, at the interfaces of SMAD4 subunits. Accumulating evidence indicates that SnoN can interact with both SMAD3 and SMAD4 to form a ternary SnoN-SMAD3-SMAD4 complex in the TGFß signaling pathway. However, how the interaction of SnoN with the SMAD3 and SMAD4 remains unclear. Here, molecular dynamics (MD) simulations and molecular modeling methods were performed to figure out this issue. The simulations reveal that SnoNopen exists in two, open and semi-closed, conformations. Molecular modeling and MD simulation studies suggest that the SnoNclosed form interferes with the SMAD3-SMAD4 protein; in contract, the SnoNopen can form a stable SnoN-SMAD3-SMAD4 complex. These mechanistic mechanisms may help elucidate the detailed engagement of SnoN with two SMAD3 and SMAD4 transcriptional factors in the regulation of TGFß signaling pathway.

Which Combination Treatment Is Better for Spinal Metastasis: Percutaneous Vertebroplasty With Radiofrequency Ablation, 125I Seed, Zoledronic Acid, or Radiotherapy?

BACKGROUND: Percutaneous vertebroplasty (PVP) can not only alleviate pain but also restore mechanical stability with injection of bone cement, whereas it exhibits a poor effect on antitumor activity. But through combinations with other therapies, it may be possible to achieve the maximum effect in clinical treatment. Thus, this study is designed to assess the clinical efficacy of PVP separately combined with 4 ways for spinal metastasis (SM) treatment. STUDY QUESTION: Which combination treatment is better for spinal metastasis, percutaneous vertebroplasty with radiofrequency ablation, I seed, zoledronic acid or radiotherapy? STUDY DESIGN: A total of 169 patients with SM were retrospectively recruited and randomly assigned to 4 groups to receive 4 different ways separately: 49 patients (group A) received PVP plus I seed, 51 (group B) received PVP plus radiofrequency ablation (RFA), 38 (group C) underwent PVP plus zoledronic acid (ZA), and 31 (group D) underwent PVP plus radiotherapy (RT). MEASURES AND OUTCOMES: All of them underwent routine examinations before operation. Visual analog scale (VAS), World Health Organization (WHO) Pain Relief, and ODI were applied to evaluate pain relief and motor function. RESULTS: PVP plus RT achieved the best efficacy in relieving pains, with the highest WHO Pain Relief (P < 0.05). The PVP plus RFA exhibited lowest ODI, suggesting the best outcome after treatment (P < 0.05). The PVP plus I showed the lowest VAS score, but it was the worst to improve the routine exercise ability and relieve pains from patients. The PVP plus ZA presented higher VAS and ODI (P < 0.05). CONCLUSIONS: PVP combined with I seed exhibited the best clinical efficacy in terms of VAS, PVP combined with RT was the best choice in terms of WHO Pain Relief, and PVP combined with RFA showed the best effect in terms of ODI for the treatment of SM.

Allicin protects against H2O2-induced apoptosis of PC12 cells via the mitochondrial pathway.

Allicin is a major bioactive ingredient of garlic and has a broad range of biological activities. Allicin has been reported to protect against cell apoptosis induced by H2O2 in human umbilical vein endothelial cells. The present study evaluated the neuroprotective effect of allicin on the H2O2-induced apoptosis of rat pheochromocytoma PC12 cells in vitro and explored the underlying mechanism involved. PC12 cells were incubated with increasing concentrations of allicin and the toxic effect of allicin was measured by MTT assay. The cells were pretreated for 24 h with low dose (L-), medium dose (M-) and high dose (H-) of allicin, followed by exposure to 200 µM H2O2 for 2 h, and the cell viability was examined by MTT assay. In addition, cell apoptosis rate was analyzed by Annexin V-FITC/PI assay, while intracellular reactive oxygen species (ROS) and mitochondrial transmembrane potential (∆ψm) were measured by flow cytometry. Bcl-2, Bax, cleaved-caspase-3 and cytochrome c (Cyt C) in the mitochondria were also examined by western blotting. The results demonstrated that 0.01 µg/ml (L-allicin), 0.1 µg/ml (M-allicin) and 1 µg/ml (H-allicin) were non-toxic doses of allicin. Furthermore, H2O2 reduced cell viability, promoted cell apoptosis, induced ROS production and decreased ∆ψm. However, allicin treatment reversed the effect of H2O2 in a dose-dependent manner. It was also observed that H2O2 exposure significantly decreased Bcl-2 and mitochondrial Cyt C, while it increased Bax and cleaved-caspase-3, which were attenuated by allicin pretreatment. The results revealed that allicin protected PC12 cells from H2O2-induced cell apoptosis via the mitochondrial pathway, suggesting the potential neuroprotective effect of allicin against neurological diseases.

Celastrol inhibits chondrosarcoma proliferation, migration and invasion through suppression CIP2A/c-MYC signaling pathway.

Chondrosarcomas (CS) is the second most frequent tumors of cartilage origin. A small compound extracted from Thunder God Vine (Tripterygium wilfordii Hook. F.) called celastrol can directly bound CIP2A protein and effectively inhibit cell proliferation and induce apoptosis in several cancer cells. However, little knowledge is concern about the important role of CIP2A in CS patients and the therapeutic value of celastrol on CS. Our results showed that CIP2A and c-MYC were verified to be oncoproteins by detecting their mRNA and protein expression in 10 human CS tissues by qRT-PCR and Western blots. After treatment of celastrol, the proliferation, migration and invasion were significantly inhibited; whereas the apoptosis was largely induced in human CS cell lines. In addition, celastrol inhibited the expression of CIP2A, c-MYC, and suppressed apoptotic proteins BAX and caspase-8 in human CS cells, on the other hand, it induced the expression of antiapoptotic protein Bcl-2. Finally, knockdown of CIP2A also inhibited the migration and invasion and induced apoptosis of human CS cells. To sum up, we found that celastrol had effects on inhibiting proliferation, migration, invasion and inducing apoptosis through suppression CIP2A/c-MYC signaling pathway in vitro, which may provide a new therapeutic regimen for CS.

Study of Double-level Degeneration of Lower Lumbar Spines by Finite Element Model.

BACKGROUND: Degeneration of intervertebral disks in the lower lumbar spine is associated with significant structural alterations. Finite element model has been widely used in the study of spinal mechanical behaviors. Our study used this technique to characterize the motional influence to the double-level (L4-5 and L5-S) degeneration. METHODS AND RESULTS: Three grades of disk degeneration were modeled with the changes in geometry and material properties. In the extension and flexion of range of motion (ROM), single segment degeneration in L4-5 or L5-S resulted in a decreased angle in itself and increased angle in the other segment. Double-level degeneration resulted in a decreased rotation in both segments. Bending resulted in a decreased ROM in all 3 grades of degeneration in the double-level degeneration. In torsion loading, mild and moderate single degeneration in L4-5 and L5-S increased the rotation angle. In double-level degeneration, mild and moderate L4-5 degeneration increased the L4-5 rotation angle by 14%-19%. In contrast, severe L4-5 decreased L4-5 rotation angle. Concurrently, mild and moderate L5-S degeneration increased the rotation angle, respectively, by 15% and 6%, and severe degeneration decreased the rotation angle by 29%. CONCLUSIONS: Different loading motions in double-level degeneration had differing effects on the ROM. These changes are important to understand the biomechanics of the progression of disk degeneration in the lower lumbar spine. Our results provide insights for the clinical intervention of double-level intervertebral disks.

Neuroprotective effect of allicin in a rat model of acute spinal cord injury.

AIMS: This study aims to investigate the effect of allicin on motor functions and histopathologic changes after spinal cord injury and the mechanism underlying its neuroprotective effects. MAIN METHODS: The motor function of rats was evaluated with the Basso, Beattie, and Bresna test. Histopathologic changes were evaluated by hematoxylin and eosin and Nissl staining. Spinal cord oxidative stress markers were determined by measuring glutathione and malondialdehyde content and superoxide dismutase activity using commercial kits. Inflammatory factors were determined by measuring tumor necrosis factor-α, interleukin-1ß and interleukin-6 using ELISA assay. Apoptosis was examined using TUNEL staining. The effect of allicin on Nrf2 protein levels and localization was assessed using immunofluorescence staining and Western blotting analysis. KEY FINDINGS: Results demonstrated that allicin accelerated the motor functional recovery and protected neuron damage against spinal cord injury (SCI). SCI-induced oxidative stress, inflammatory response and cell apoptosis in the spinal cord were also prevented by allicin. In addition, we observed that SCI increased Nrf2 nuclear expression, and allicin treatment further increased Nrf2 nuclear translocation in neurons and astrocytes. siRNA-mediated Nrf2 gene knockdown completely blocked the effect of allicin on spinal cord tissue. SIGNIFICANCE: Our finding suggests that allicin promotes the recovery of motor function after SCI in rats, and this effect may be related to its anti-oxidant, anti-inflammatory and anti-apoptotic effects. Allicin mediated Nrf2 nuclear translocation may be involved in the protective effect as well.

MicroRNA-375 functions as a tumor suppressor in osteosarcoma by targeting PIK3CA.

Osteosarcoma has become one of the most common primary malignant bone tumors in childhood and adult. Numerous studies have demonstrated that aberrant microRNA (miRNA) expression is involved in human disease including cancer. To date, the potential miRNAs regulating osteosarcoma growth and progression are not fully identified yet. Herein, we showed that miR-375 was frequently downregulated in osteosarcoma tissue and cell lines compared to normal human colon tissues. Overexpression of miR-375 resulted in decreased expression of PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit alpha) at both mRNA and protein levels. We found that miR-375 overexpression markedly suppressed cell proliferation in vitro. And inhibition of miR-375 promotes osteosarcoma growth. Mechanistic studies showed that PIK3CA was a potential target of miR-375 and it mediated reduction of PIK3CA resulted in suppression of PI3K/Akt pathway. Taken together, our results demonstrate that miR-375 functions as a growth-suppressive miRNA and plays an important role in inhibiting the tumorigenesis through targeting PIK3CA in osteosarcoma.

A Comparison of Anterior Cervical Corpectomy and Fusion Combined With Artificial Disc Replacement and Cage Fusion in Patients With Multilevel Cervical Spondylotic Myelopathy.

STUDY DESIGN: A retrospective study. OBJECTIVE: The aim of this study was to compare clinical and radiological outcomes of anterior cervical corpectomy and fusion (ACCF) combined with artificial disc replacement (C-ADR) and ACCF combined with anterior cervical discectomy and fusion (ACDF) in patients with consecutive 3-level cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: The optimal surgical strategy for multilevel CSM (MCSM) remains undefined. C-ADR maintains motion at the level of the surgical procedure and decreases strain on the adjacent segments. The clinical results of multilevel C-ADR have not yet been elucidated. ACCF combined with 1-level C-ADR for the treatment of consecutive 3-level CSM may be a reasonable alternative to 3-level fusion. METHODS: We retrospectively reviewed the histories of patients who underwent surgery for consecutive 3-level CSM between C3-4 and C6-7 from June 2007 to August 2011. A total of 42 patients were divided into 2 groups. Group A (n = 19) underwent ACCF combined with 1-level C-ADR; group B (n = 23) underwent ACCF combined with 1-level ACDF. We compared perioperative parameters, clinical parameters, and radiological parameters. RESULTS: There were no significant differences in the average age, sex ratio, the preoperative heights of the disc space or average blood loss between the 2 groups. Group A had longer operation times than group B (P < 0.05). During the follow-up period, group A showed a better Neck Dysfunction Index recovery (P < 0.05) at 24 months postoperatively, and less visual analogue scale scores at 12 and 24 months postoperatively (P < 0.05 and P < 0.001, respectively). Moreover, group A exhibited better C2-C7 range of motion recovery at 6, 12, and 24 months postoperatively (P < 0.05, respectively). CONCLUSION: Group A was superior to Group B in terms of better Neck Dysfunction Index recovery, less intermediate term pain, and better C2-C7 ROM recovery. ACCF hybrid 1-level C-ADR may be a suitable choice for the management of 3-level CSM in appropriate patients. LEVEL OF EVIDENCE: 3.

Anterior discectomy/corpectomy and fusion with internal fixation for the treatment of unstable hangman's fractures: a retrospective study of 38 cases.

OBJECT: The object of this study was to describe the authors' method of anterior discectomy/corpectomy and fusion combined with internal fixation for the treatment of unstable hangman's fractures and to evaluate the clinical and radiological outcomes. METHODS: This study included 38 consecutive patients who underwent surgery for unstable hangman's fractures between July 2002 and October 2011 and were followed up for more than 2 years. The patients were 18 women and 20 men with a mean age of 42.8 years (range 20-69 years). The fracture resulted from a fall in 9 patients, a motor vehicle accident in 21 patients, and a motorcycle accident in 8 patients. The Levine-Edwards classification was Type II in 13 patients, Type IIA in 20 patients, and Type III in 5 patients. All patients underwent anterior C2-3 intervertebral disc excision or C-3 corpectomy, decompression and reduction, interbody implantation of an autologous iliac bone graft, and internal fixation with a titanium plate. Pain was assessed before and after surgery using a visual analog scale (VAS). Myelopathy was graded using the Japanese Orthopaedic Association (JOA) score. Patient satisfaction with the surgery was assessed using Odom's grading system. Anteroposterior, lateral, and dynamic (flexion/extension) radiographs were obtained during the follow-up period. Two-dimensional CT studies with sagittal and coronal reconstructions were routinely performed. RESULTS: The mean follow-up period was 49.2 months (range 24-132 months). There was a significant decrease between the preoperative and final follow-up VAS scores (mean [SD] 7.56 ± 1.52 vs 2.36 ± 1.25, p < 0.05) and a significant increase between the preoperative and final follow-up JOA scores (12.58 ± 1.34 vs 16.13 ± 1.17, p < 0.05). Postoperative radiographs showed satisfactory reduction of the fracture in all cases. Postoperative complications included transient neurological deficits (3 cases), hematoma (2 cases), temporary dysphagia (5 cases), temporary hoarseness (2 cases), prolonged pain at the iliac crest donor site (4 cases), and wound infection at the iliac crest donor site (2 cases). Solid fusion was achieved in 94.7% of patients at the final follow-up. CONCLUSIONS: Anterior discectomy/corpectomy and fusion combined with internal fixation is a safe and effective procedure for the treatment of unstable hangman's fractures.

Surgical treatment of calcaneal fractures of Sanders type II and III by a minimally invasive technique using a locking plate.

The aim of the present study was to investigate the outcomes of surgical treatment of calcaneal fractures of Sanders type II and III using a minimally invasive technique and a locking plate. We reviewed 33 feet in 33 consecutive patients with Sanders type II and III calcaneal fractures who had undergone a minimally invasive technique using percutaneous reduction and locking plates. All operations were performed by the same surgeons. The postoperative evaluation included radiographs, determination of restoration of Böhler's angle and Gissane's angle, and administration of the American Orthopaedic Foot and Ankle Society ankle-hind foot scale, Maryland Foot Score, and visual analog scale of pain. The mean visual analog scale score was 1.6 ± 1.4 when radiographic fracture healing was observed. The median functional score of the 33 patients (33 feet) reached 82 (interquartile range 80 to 99) at the last follow-up evaluation according to the American Orthopaedic Foot and Ankle Society ankle-hind foot scale and 89 (interquartile range 80 to 99) according to Maryland Foot Score. All cases achieved restoration of a normal Böhler's angle and Gissane's angle. Postoperative superficial infections occurred in 2 patients, subtalar arthritis developed in 2, and no soft tissue necrosis was observed. For Sanders type II and III fractures of the calcaneus bone, treatment with a minimally invasive technique combining percutaneous reduction and locking plate fixation provided satisfactory clinical results, with a lower incidence of complications. However, longer term studies with a larger sample size and more randomized controlled trials are required to define the superiority of our minimally invasive technique compared with conventional surgical treatment of calcaneal fractures.

Effect of lordosis angle change after lumbar/lumbosacral fusion on sacrum angular displacement: a finite element study.

PURPOSE: To assess and characterize the sacrum angular displacements in response to lumbar lordosis after lumbar/lumbosacral fusion. METHODS: A finite element model of the lower lumbar spine-pelvis was established and used to simulate the posterior fusion at L3-L5 and L4-S1. The lordosis angle in the fusion segments was set to five different conditions with respect to the intact model: 10° less than intact, 5° less than intact, same as intact, 5° more than intact, and 10° more than intact. Variations of the sacrum angular displacements with lordosis changes were analyzed under loading setting of axial compression, flexion, extension, lateral bending, and axial rotation. RESULTS: Compared with the intact lordosis, both increased and decreased lumbar lordosis angles caused the sacrum angular displacements to be increased. The lordosis angle increased by 10° induced the most substantial increase in sacrum angular displacements. In addition, the sacrum angular displacements of the L4-S1 fusion model at different lordosis angles were higher than those of the L3-L5 fusion model. CONCLUSION: The sacrum angular displacements occur as a result of the fusion surgery (L4-S1) and the changes in lumbar lordosis.