Osteosarcoma-targeted Cu and Ce based oxide nanoplatform for NIR II fluorescence/magnetic resonance dual-mode imaging and ros cascade amplification along with immunotherapy.

BACKGROUND: As the lethal bone tumor, osteosarcoma often frequently occurs in children and adolescents with locally destructive and high metastasis. Distinctive kinds of nanoplatform with high therapeutical effect and precise diagnosis for osteosarcoma are urgently required. Multimodal optical imaging and programmed treatment, including synergistic photothermal-chemodynamic therapy (PTT-CDT) elicits immunogenetic cell death (ICD) is a promising strategy that possesses high bio-imaging sensitivity for accurate osteosarcoma delineating as well as appreciable therapeutic efficacy with ignorable side-effects. METHODS AND RESULTS: In this study, mesoporous Cu and Ce based oxide nanoplatform with Arg-Gly-Asp (RGD) anchoring is designed and successfully constructed. After loading with indocyanine green, this nanoplatform can be utilized for precisely targeting and efficaciously ablating against osteosarcoma via PTT boosted CDT and the closely following ICD stimulation both in vitro and in vivo. Besides, it provides off-peak fluorescence bio-imaging in the second window of near-infrared region (NIR II, 1000-1700 nm) and Magnetic resonance signal, serves as the dual-mode contrast agents for osteosarcoma tissue discrimination. CONCLUSION: Tumor targeted Cu&Ce based mesoporous nanoplatform permits efficient osteosarcoma suppression and dual-mode bio-imaging that opens new possibility for effectively diagnosing and inhibiting the clinical malignant osteosarcoma.

Biomechanical Comparison of Anterior Cervical Corpectomy Decompression and Fusion, Anterior Cervical Discectomy and Fusion, and Anterior Controllable Antedisplacement and Fusion in the Surgical Treatment of Multilevel Cervical Spondylotic Myelopathy: A Finite Element Analysis.

PURPOSE: Multilevel cervical spondylotic myelopathy poses significant challenges in selecting optimal surgical approaches, warranting a comprehensive understanding of their biomechanical impacts. Given the lack of consensus regarding the most effective technique, this study aims to fill this critical knowledge gap by rigorously assessing and comparing the biomechanical properties of three distinct surgical interventions, including anterior controllable antedisplacement and fusion (ACAF), anterior cervical corpectomy decompression and fusion (ACCF), and anterior cervical discectomy and fusion (ACDF). The study offers pivotal insights to enhance treatment precision and patient outcomes. METHODS: The construction of the cervical spine model involved a detailed process using CT data, specialized software (Mimics, Geomagic Studio, and Hypermesh) and material properties obtained from prior studies. Surgical instruments were modeled (titanium mesh, anterior cervical plate, interbody cage, and self-tapping screws) to simulate three surgical approaches: ACAF, ACCF, and ACDF, each with specific procedures replicating clinical protocols. A 75-N follower load with 2 Nm was applied to simulate biomechanical effects. RESULTS: The range of motion decreased more after surgery for ACAF and ACDF than for ACCF, especially in flexion and lateral bending. ACCF have higher stress peaks in the fixation system than those of ACAF and ACDF, especially in flexion. The maximum von Mises stresses of the bone-screw interfaces at C3 of ACCF were higher than those of ACAF and ACDF. The maximum von Mises stresses of the bone-screw interfaces at C6 of ACDF were much higher than those of ACAF and ACCF. The maximum von Mises stresses of the grafts of ACCF and ACAF were much higher than those of ACDF. The maximum von Mises stresses of the endplate of ACCF were much higher than those of ACAF and ACDF. CONCLUSION: The ACAF and ACDF models demonstrated superior cervical reconstruction stability over the ACCF model. ACAF exhibited lower risks of internal fixation failure and cage subsidence compared to ACCF, making it a promising approach. However, while ACAF revealed improved stability over ACCF, higher rates of subsidence and internal fixation failure persisted compared to ACDF, suggesting the need for further exploration of ACAF's long-term efficacy and potential improvements in clinical outcomes.

Lupenone improves motor dysfunction in spinal cord injury mice through inhibiting the inflammasome activation and pyroptosis in microglia via the nuclear factor kappa B pathway.

JOURNAL/nrgr/04.03/01300535-202408000-00034/figure1/v/2023-12-16T180322Z/r/image-tiff Spinal cord injury-induced motor dysfunction is associated with neuroinflammation. Studies have shown that the triterpenoid lupenone, a natural product found in various plants, has a remarkable anti-inflammatory effect in the context of chronic inflammation. However, the effects of lupenone on acute inflammation induced by spinal cord injury remain unknown. In this study, we established an impact-induced mouse model of spinal cord injury, and then treated the injured mice with lupenone (8 mg/kg, twice a day) by intraperitoneal injection. We also treated BV2 cells with lipopolysaccharide and adenosine 5'-triphosphate to simulate the inflammatory response after spinal cord injury. Our results showed that lupenone reduced IκBα activation and p65 nuclear translocation, inhibited NLRP3 inflammasome function by modulating nuclear factor kappa B, and enhanced the conversion of proinflammatory M1 microglial cells into anti-inflammatory M2 microglial cells. Furthermore, lupenone decreased NLRP3 inflammasome activation, NLRP3-induced microglial cell polarization, and microglia pyroptosis by inhibiting the nuclear factor kappa B pathway. These findings suggest that lupenone protects against spinal cord injury by inhibiting inflammasomes.

Valproic acid ameliorates cauda equina injury by suppressing HDAC2-mediated ferroptosis.

INTRODUCTION: Persistent neuroinflammatory response after cauda equina injury (CEI) lowers nociceptor firing thresholds, accompanied by pathological pain and decreasing extremity dysfunction. Histone deacetylation has been considered a key regulator of immunity, inflammation, and neurological dysfunction. Our previous study suggested that valproic acid (VPA), a histone deacetylase inhibitor, exhibited neuroprotective effects in rat models of CEI, although the underlying mechanism remains elusive. METHODS: The cauda equina compression surgery was performed to establish the CEI model. The Basso, Beattie, Bresnahan score, and the von Frey filament test were carried out to measure the animal behavior. Immunofluorescence staining of myelin basic protein and GPX4 was carried out. In addition, transmission electron microscope analysis was used to assess the effect of VPA on the morphological changes of mitochondria. RNA-sequencing was conducted to clarify the underlying mechanism of VPA on CEI protection. RESULTS: In this current study, we revealed that the expression level of HDAC1 and HDAC2 was elevated after cauda equina compression model but was reversed by VPA treatment. Meanwhile, HDAC2 knockdown resulted in the improvement of motor functions and pathologic pain, similar to treatment with VPA. Histology analysis also showed that knockdown of histone deacetylase (HDAC)-2, but not HDAC1, remarkably alleviated cauda equina injury and demyelinating lesions. The potential mechanism may be related to lowering oxidative stress and inflammatory response in the injured region. Notably, the transcriptome sequencing indicated that the therapeutic effect of VPA may depend on HDAC2-mediated ferroptosis. Ferroptosis-related genes were analyzed in vivo and DRG cells further validated the reliability of RNA-sequencing results, suggesting HDAC2-H4K12ac axis participated in epigenetic modulation of ferroptosis-related genes. CONCLUSION: HDAC2 is critically involved in the ferroptosis and neuroinflammation in cauda equina injury, and VPA ameliorated cauda equina injury by suppressing HDAC2-mediated ferroptosis.

Small Object Detection via Pixel Level Balancing With Applications to Blood Cell Detection.

Object detection technology has been widely used in medical field, such as detecting the images of blood cell to count the changes and distribution for assisting the diagnosis of diseases. However, detecting small objects is one of the most challenging and important problems especially in medical scenarios. Most of the objects in medical images are very small but influential. Improving the detection performance of small objects is a very meaningful topic for medical detection. Current researches mainly focus on the extraction of small object features and data augmentation for small object samples, all of these researches focus on extracting the feature space of small objects better. However, in the training process of a detection model, objects of different sizes are mixed together, which may interfere with each other and affect the performance of small object detection. In this paper, we propose a method called pixel level balancing (PLB), which takes into account the number of pixels contained in the detection box as an impact factor to characterize the size of the inspected objects, and uses this as an impact factor. The training loss of each object of different size is adjusted by a weight dynamically, so as to improve the accuracy of small object detection. Finally, through experiments, we demonstrate that the size of objects in object detection interfere with each other. So that we can improve the accuracy of small object detection through PLB operation. This method can perform well with blood cell detection in our experiments.

New anterior controllable antedisplacement and fusion surgery for cervical ossification of the posterior longitudinal ligament: a biomechanical study.

OBJECTIVE: The traditional anterior approach for multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) is demanding and risky. Recently, a novel surgical procedure-anterior controllable antedisplacement and fusion (ACAF)-was introduced by the authors to deal with these problems and achieve better clinical outcomes. However, to the authors' knowledge, the immediate and long-term biomechanical stability obtained after this procedure has never been evaluated. Therefore, the authors compared the postoperative biomechanical stability of ACAF with those of more traditional approaches: anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF). METHODS: To determine and assess pre- and postsurgical range of motion (ROM) (2 Nm torque) in flexion-extension, lateral bending, and axial rotation in the cervical spine, the authors collected cervical areas (C1-T1) from 18 cadaveric spines. The cyclic fatigue loading test was set up with a 3-Nm cycled load (2 Hz, 3000 cycles). All samples used in this study were randomly divided into three groups according to surgical procedures: ACDF, ACAF, and ACCF. The spines were tested under the following conditions: 1) intact state flexibility test; 2) postoperative model (ACDF, ACAF, ACCF) flexibility test; 3) cyclic loading (n = 3000); and 4) fatigue model flexibility test. RESULTS: After operations were performed on the cadaveric spines, the segmental and total postoperative ROM values in all directions showed significant reductions for all groups. Then, the ROMs tended to increase during the fatigue test. No significant crossover effect was detected between evaluation time and operation method. Therefore, segmental and total ROM change trends were parallel among the three groups. However, the postoperative and fatigue ROMs in the ACCF group tended to be larger in all directions. No significant differences between these ROMs were detected in the ACDF and ACAF groups. CONCLUSIONS: This in vitro biomechanical study demonstrated that the biomechanical stability levels for ACAF and ACDF were similar and were both significantly greater than that of ACCF. The clinical superiority of ACAF combined with our current results showed that this procedure is likely to be an acceptable alternative method for multilevel cervical OPLL treatment.

Anatomical Evaluation of Spinal Nerve and Cervical Intervertebral Foramina in Anterior Controllable Antedisplacement and Fusion Surgery: A Cadaveric and Radiologic Study.

OBJECTIVE: To achieve the anatomical evaluation of spinal nerve and cervical intervertebral foramina in anterior controllable antedisplacement and fusion (ACAF) surgery, a novel surgical technique with the wider decompression, through a cadaveric and radiologic study. METHODS: Radiographic data of consecutive 47 patients (21 by ACAF and 26 by anterior cervical corpectomy and fusion [ACCF]) who have accepted surgery for treatment of cervical ossification of the posterior longitudinal ligament(OPLL) and stenosis from March 2017 to March 2018 were retrospectively reviewed and compared between an ACAF group and ACCF group. Three postoperative radiographic parameters were evaluated: the decompression width and the satisfaction rate of decompression at the entrance zone of intervertebral foramina on computed tomography (CT), and the transverse diameter of spinal cord in the decompression levels on magnetic resonance imaging (MRI). In the anatomic study, three fresh cadaveric spines (death within 3 months) undergoing ACAF surgery were also studied. Four anatomic parameters were evaluated: the width of groove, the distance between the bilateral origins of ventral rootlets, the length of ventral rootlet from their origin to the intervertebral foramina, the descending angle of ventral rootlet. RESULTS: The groove created in ACAF surgery included the bilateral origins of ventral rootlets. The rootlets tended to be vertical from the rostral to the caudal direction as their takeoff points from the central thecal sac became higher and farther away from their corresponding intervertebral foramina gradually. No differences were identified between left and right in terms of the length of ventral rootlet from the origin to the intervertebral foramina and the descending angle of ventral rootlet. The decompression width was significantly greater in ACAF group (19.2 ± 1.2 vs 14.7 ± 1.2, 21.3 ± 2.2 vs 15.4 ± 0.9, 21.5 ± 2.1 vs 15.7 ± 1.0, 21.9 ± 1.6 vs 15.9 ± 0.8, from C3 to C6 ). The satisfactory rate of decompression at the entrance zone of intervertebral foramina tended to be better in the left side in ACAF group (significant differences were identified in the left side at C3/4 , C4/5 , C6/7 level, and in the right side at C4/5 level when compared with ACCF). And decompression width was significantly greater than the transverse diameter of spinal cord in ACAF group. Comparatively, there existed no significant difference in the ACCF group besides the C5 level. CONCLUSION: ACAF can decompress the entrance zone of intervertebral foramina effectively and its decompression width includes the origins and massive running part of bilateral ventral rootlets. Due to its wider decompression range, ACAF can be used as a revision strategy for the patients with failed ACCF.

Anterior Controllable Antedisplacement and Fusion (ACAF) vs Posterior Laminoplasty for Multilevel Severe Cervical Ossification of the Posterior Longitudinal Ligament: Retrospective Study Based on a Two-Year Follow-up.

OBJECTIVES: To compare the clinical outcomes of anterior controllable antedisplacement fusion (ACAF), a new surgical technique, with laminoplasty for the treatment of multilevel severe cervical ossification of the posterior longitudinal ligament (OPLL) based on a 2-year follow-up. METHODS: Clinical data of 53 patients (21 by ACAF and 32 by laminoplasty) who have accepted surgery for treatment of cervical myelopathy caused by multilevel severe OPLL (occupying rate ≥ 50%) from March 2015 to March 2017 were retrospectively reviewed and compared between ACAF group and laminoplasty group. Operative time, blood loss, and complications of the two groups were recorded. Radiographic parameters were evaluated pre- and postoperatively: cervical lordosis on X-ray, space available for the cord (SAC) and the occupying ratio (OR) on computed tomography (CT), and the anteroposterior (AP) diameter of the spinal cord at the narrowest level and the spinal cord curvature on magnetic resonance imaging (MRI). Japanese Orthopaedic Association (JOA) scoring was used to evaluate neurologic recovery. Statistical analysis was conducted to analyze the differences between two groups. The Mann-Whitney U test and chi square test were used to compare categorical variables. unpaired t test was used to compare continuous data. RESULTS: All patients were followed up for at least 24 months. The operative time was longer in ACAF group (286.5 vs 178.2 min, P < 0.05). The blood loss showed no significant difference (291.6 vs 318.3 mL, P > 0.05). Less complications were observed in ACAF group than in laminoplasty group (one case [4.7%] of C5 palsy and one case [4.7%] of cerebrospinal fluid [CSF] leakage in ACAF group; four cases [12.5%] of C5 palsy, two cases [6.3%] of CSF leakage, and four cases [12.5%] of axial symptoms in laminoplasty group). The mean JOA score at last follow-up (14.6 vs 12.8, P < 0.05) and the improvement rate (IR) (63.8% vs 47.8%, P < 0.05) in ACAF group were superior to those in laminoplasty group significantly. The postoperative OR (16.7% vs 40.9%, P < 0.05), SAC (150.8 vs 110.5 mm2 , P < 0.05), AP spinal cord diameter (5.5 vs 4.2 mm, P < 0.05), and cervical lordosis (12.7° vs 4.7°, P < 0.05) were improved more considerably in ACAF group, with significant differences between two groups. Notably, the spinal cord on MRI showed a better curvature in ACAF group. CONCLUSIONS: This study showed that ACAF is considered superior to laminoplasty for the treatment of multilevel severe OPLL as anterior direct decompression and better curvature of the spinal cord led to satisfactory neurologic outcomes and low complication rate.

Snake-Eye Screwing: A Novel Free-Hand Technique of Pedicle Screw Placement in Cervicothoracic Spine and Preliminary Clinical Results.

OBJECTIVE: To propose a novel technique of free-hand pedicle screw placement in cervicothoracic spine (snake-eye method) and evaluate the preliminary effects and safety in clinical practice. METHODS: This is a retrospective study and we defined the period of this study as from December 2017 to April 2019 in our institution. Forty patients were included in this study who underwent cervicothoracic internal fixation in our hospital, and all patients undergoing implantation of 200 pedicle screws were divided into two groups. Twenty-two patients (108 screws) had screw placement using traditional method, while 18 patients (92 screws) had screw placement using snake-eye method. To reduce the possible selection bias, the patients we recruited in this study was originally performed on by one radiological doctor who was blind to the objective of this study. Patient demographics, including patient age, sex, obesity, smoking, and hypertension, were evaluated to figure out baseline differences between groups. Medical information was recorded including time, accuracy, and immediate (within 30 days after surgery) postoperative complications of pedicle screw placement (including pulmonary embolism or other thromboembolic events, surgical site infection, neurovascular injury, and mortality). RESULTS: There were 24 males and 16 females, with an average age of 52.2 years (range, 24-77). Finally, a total of 200 screws were successfully inserted in these patients, including fifteen patients with four pedicle screws, four patients with six screws, three patients with eight screws in traditional method group, and 12 patients with four pedicle screws, two patients with six screws, four patients with eight screws in snake-eye method group. Patient demographic and comparison of two surgery methods are shown in Tables 1 and 2. The data baselines of the two groups were comparable because no impact of the two groups on population characteristics was demonstrated in the presented experiment. Also, we noticed that time and accuracy of the two groups were different with statistical significance at the level of P = 0.05. We observed that immediate (within 30 days after surgery) postoperative complications, including pulmonary embolism (PE), surgical site infection (SSI), neurovascular injury (NI), and mortality, in the two groups did not differ. CONCLUSION: This study highlights a safe and effective technique for pedicle screw placement in cervicothoracic spine named snake-eye method, and this technique may be particularly useful in emergency conditions with limited resources.

Consensus statement on diagnosis and treatment of cervical ossification of posterior longitudinal ligament from Asia Pacific Spine Society (APSS) 2020.

PURPOSE: The study aimed to develop an evidence-based expert consensus statement on diagnosis and treatment of cervical ossification posterior longitudinal ligament (OPLL). METHOD: Delphi method was used to perform such survey, and the panel members from Asia Pacific Spine Society (APSS) 2020 were invited to answer the open-ended questions in rounds 1 and 2. Then the results were summarized and developed into a Likert-style questionnaire for voting in round 3, and the level of agreement was defined as 80%. In the whole process, we conducted a systematic literature search on evidence for each statement. RESULTS: Cervical OPLL can cause various degrees of neurological symptoms, an it's thought to be more common in Asia population. CT reconstruction is an important imaging examination to assist diagnosis and guide surgical choice. Segmental, continuous, mixed, and focal type is the most widely used classification system. The non-surgical treatment is recommended for patients with no or mild clinical symptoms, or irreversible neurological damage, or failed surgical decompression, or condition cannot tolerant surgery, or refusing surgery. As OPLL may continue to develop gradually, surgical treatment would be considered in their course inevitably. The surgical choice should depend on various conditions, such as involved levels, thickness, and type of OPLL, skill-experiences of surgeons, which are listed and discussed in the article. CONCLUSION: In this statement, we describe the clinical features, classifications, and diagnostic criteria of cervical OPLL, and review various surgical methods (such as their indications, complications), and provide a guideline on their choice strategy.

Expression of Nogo-A in dorsal root ganglion in rats with cauda equina injury.

OBJECTIVE: To investigate the expression of Nogo-A in dorsal root ganglion (DRG) in rats with cauda equina injury and the therapeutic effects of blocking Nogo-A and its receptor. METHODS AND MATERIALS: Fifty-eight male Sprague-Dawley rats were divided randomly into either the sham operation group (n = 24) or the cauda equina compression (CEC) control group (n = 34). Behavioral, histological, and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) analyses were conducted to assess the establishment of the model. The dynamic expression change of Nogo-A was evaluated using real time-qPCR. Immunofluorescence was used to evaluate the expression of Nogo-A in the DRG and cauda equina. Furthermore, 20 male Sprague-Dawley rats were equally divided into 4 groups, including the sham group, the CEC group, the NEP1-40 (the NgR antagonist peptide) treatment group, and the JTE-013 (the S1PR2 antagonist) treatment group. Behavioral assessments and western blotting were used to evaluate the therapeutic effect of cauda equina injury via blocking Nogo-A and its receptor. RESULTS: Tactile allodynia and heat hyperalgesia in the CEC model developed as soon as 1 day after surgery and recovered to normal at 7 days, which was followed by the downregulation of Nogo-A in DRG neurons. However, the locomotor function impairment in the CEC model showed a different prognosis from the sensory function, which was consistent with the expression change of Nogo-A in the spinal cord. Immunofluorescence results also demonstrated that Nogo A-positive/NF200-negative neurons and axons increased in the DRG and cauda equina 7 days after surgery. Surprisingly, Schwann cells, which myelinate axons in the PNS, also expressed considerable amounts of Nogo-A. Then, after blocking the Nogo-A/NgR signaling pathway by NEP1-40, significant improvement of mechanical allodynia was identified in the first 2 days after the surgery. Western blotting suggested the NEP1-40 treatment group had lower expression of cleaved caspase-3 than the CEC and JTE-013 treatment group. CONCLUSION: Neuronal Nogo-A in the DRG may be involved in regeneration and play a protective role in the CEC model. Whereas Nogo-A, released from the injured axons or expressed by Schwann cells, may act as an inhibiting factor in the process of CEC repairment. Thus, blocking the Nogo-A/NgR signaling pathway can alleviate mechanical allodynia by apoptosis inhibition.

The Emerging Role of lncRNAs in Spinal Cord Injury.

Spinal cord injury (SCI) is a highly debilitating disease and is increasingly being recognized as an important global health priority. However, the mechanisms underlying SCI have not yet been fully elucidated, and effective therapies for SCI are lacking. Long noncoding RNAs (lncRNAs), which form a major class of noncoding RNAs, have emerged as novel targets for regulating several physiological functions and mediating numerous neurological diseases. Notably, gene expression profile analyses have demonstrated aberrant changes in lncRNA expression in rats or mice after traumatic or nontraumatic SCI. LncRNAs have been shown to be associated with multiple pathophysiological processes following SCI including inflammation, neural apoptosis, and oxidative stress. They also play a crucial role in the complications associated with SCI, such as neuropathic pain. At the same time, some lncRNAs have been found to be therapeutic targets for neural stem cell transplantation and hydrogen sulfide treatment aimed at alleviating SCI. Therefore, lncRNAs could be promising biomarkers for the diagnosis, treatment, and prognosis of SCI. However, further researches are required to clarify the therapeutic effects of lncRNAs on SCI and the mechanisms underlying these effects. In this study, we reviewed the current progress of the studies on the involvement of lncRNAs in SCI, with the aim of drawing attention towards their roles in this debilitating condition.

Risk assessment of vertebral artery injury in anterior controllable antedisplacement and fusion (ACAF) surgery: a cadaveric and radiologic study.

PURPOSE: We have introduced a novel surgery technique named anterior controllable antedisplacement and fusion (ACAF) for the treatment of ossification of the posterior longitudinal ligament. As reported, the satisfactory postoperative outcome can be attributed to the larger decompression width. However, it may associate with high prevalence of vertebral artery injury (VAI) theoretically. Thus, assessment of the vulnerability of vertebral artery in ACAF is of great importance. METHODS: Computed tomographic scan data of 28 patients were retrospectively studied. Seven radiographic parameters were evaluated: uncinate process (UP) tips distance, transverse foramen (TF)-UP tips distance, TF-LWL (the ipsilateral limited wedging line) distance, the limited distance of lateral decompression, the maximum oblique angle of LWL, TF-LWG (the lateral wall of groove) distance, and width of groove. Eleven fresh cadaveric spines undergoing ACAF surgery were also studied. Two anatomic parameters were evaluated: width of groove and LWG-TF distance. RESULTS: The UP tips distance increased from C3 to C6 and tended to be larger in males. The UP tip-TF distance and LWL-TF distance were smallest at C4, but both were larger than 2 mm. Maximum oblique angle decreased from C3 to C6. Postoperatively, both radiographic and cadaveric measurements showed the width of groove was larger than UP tips distance, but LWG-TF distance was larger than 2 mm in all levels. CONCLUSION: UP can be used as anatomical landmarks to avoid VAI during ACAF surgery. Radiographic and cadaveric measurements verified the safety of ACAF surgery, even for those cases with wedging and lateral slotting.

How to Avoid Postoperative Remaining Ossification Mass in Anterior Controllable Antedisplacement and Fusion Surgery.

OBJECTIVES: To retrospectively review the cases with ossification of the posterior longitudinal ligament (OPLL) treated with anterior controllable antedisplacement and fusion (ACAF). Patients with postoperative remaining ossification mass (PROM) are analyzed to figure out the causes and preventions of this problem. METHODS: A total of 115 patients were included. PROM was identified as remaining OPLL existed in the spinal canal other than included in the vertebral-OPLL complex on postoperative computed tomography. The Japanese Orthopaedic Association scoring system was used to evaluate the neurologic status. Surgery-related complications such as cerebrospinal fluid (CSF) leakage and spinal cord or nerve injury were all recorded. The patients with the PROM group and those without the PROM group were compared. RESULTS: There were 14 patients with wide-base OPLL (12.2%) and 10 patients (8.7%) with PROM among the 115 patients with OPLL. The 10 patients with PROM were all with wide-base OPLL. The average improvement rate of Japanese Orthopaedic Association score in patients without PROM was significantly larger than that in patients with PROM (69.5 ± 22.6% vs. 36.7 ± 22.0, P < 0.01). Incidence rate of postoperative CSF leakage and neural deterioration were significantly higher in patients with PROM than that in patients without PROM (CSF leakage, 40.0% vs. 5.9%; neural deterioration, 50.0% vs. 3.0%). No other complications were observed. CONCLUSIONS: The occurrence of PROM might cause complications and poor neural function recovery in patients treated with ACAF. Surgical techniques should be noted to avoid PROM in ACAF surgery.

A Preliminary Attempt of Nonintervention in the Treatment of Patients with Intervertebral Disc Calcification Combined with Ossification of the Posterior Longitudinal Ligament.

BACKGROUND: Calcification of intervertebral disc is a common impairment, which has been considered as the degenerative condition of the spine. In clinical practice, we note that the onset of intervertebral disc calcification (IDC) and ossification of the posterior longitudinal ligament (OPLL) can exist simultaneously in some cases, especially in younger children. However, only 8 cases have been reported in detail previously. In addition, controversy remains in terms of the best way to treat this condition. CASE DESCRIPTION: An 8-year-old female child was referred to our department in March 2018 complaining of severe back pain and neck pain with a sign of neurologic dysfunction. Computed tomography and magnetic resonance imaging revealed the calcified intervertebral disc and OPLL at the C5-C6 level and spinal cord compression. We performed a noninterventional strategy for the patient. The patient's symptom recovered significantly in approximately 1 month. At 6 months of follow-up, the patient felt no discomfort, and computed tomography revealed the complete resorption of ossified lesion. Magnetic resonance imaging also showed no sign of compression on the spinal cord and nerve root at the involved segment. CONCLUSIONS: Pediatric IDC accompanied with OPLL is much less frequent, but we must be aware of this disease. Since the distribution of this disease is age-specific and sex-specific, further research is necessary. Treatment for IDC combined with OPLL needs to follow the treatment principles as described in the text.

Theory of Bowstring Disease: Diagnosis and Treatment Bowstring Disease.

Bowstring disease (BSD) is a new classification of spine disease caused by axial stretched lesion on nerve roots and the spinal cord, which is differentiated from disc herniation and canal stenosis in that it is caused by nerve compression lesions. BSD could be caused by mismatched growth rates between the spine and nerve roots (the juvenile type), or by imbalanced degenerative rates between the spine column and nerve roots (degenerative type). Here, we propose that there are several self-adjust mechanisms to relieve axial nerve tension: (i) nerve growth; (ii) posture adjustment and low back pain; (iii) autogenous degeneration of intervertebral disc; and (iv) idiopathic and degenerative scoliosis. Iatrogenic lesions could also result in BSD, which could be presented as adjacent segment degeneration, leading to adding-on effects and other neurological symptoms. The diagnosis criteria are proposed based on symptoms, physical examination, and radiological presentations. To remove axial tension on nerve roots, lumbar surgery should aim to restore the coordination of spine and cord units. Capsule surgery, shortening the spine column, could decompress cord and nerve roots 3-dimensionally.

Computer-assisted virtual operation planning in anterior controllable anterior-displacement and fusion surgery for ossification of the posterior longitudinal ligament based on actual computed tomography data.

OBJECTIVES: To investigate the effect of computer-assisted virtual operation planning (CAVOP) on anterior controllable anterior-displacement and fusion (ACAF) surgery for ossification of the posterior longitudinal ligament (OPLL). PATIENTS AND METHODS: A total of 25 patients with OPLL were enrolled in the study from September 2017 to December 2017. Preoperative Computed tomography (CT) scanning data were input into Mimics software to reconstruct three-dimensional (3D) models of actual cervical OPLL.Preoperative simulation of each surgical procedure and measurement of main parameters for intraoperative decision were conducted. Postoperative CT were used to test the clinical value of the preoperative planning. Width of vertebrae-OPLL complex (VOC), thickness of resected vertebral body (VB), height of intervertebral spacer, and length of screws and anterior plate were analyzed. RESULTS: There were no significant differences between the length of screws, width of VOC, and thickness of anterior resection of vertebrae in preoperative CT and postoperative CT. Statistical differences were found between preoperative and postoperative height of intervertebral space and length of anterior plate. CONCLUSION: A virtual ACAF surgical procedure for OPLL is feasible and useful clinically in surgical planning. It may provide a valuable tool for surgeons in formulating an appropriate surgical plan.

Anterior Controllable Antedisplacement and Fusion as Revision Surgery After Posterior Decompression Surgery in Patients with Ossification of the Posterior Longitudinal Ligament.

OBJECTIVE: The aim of the present study was to evaluate the surgical outcomes of anterior controllable antedisplacement and fusion (ACAF) as a revision surgery after posterior decompression surgery (PDS) in patients with ossification of the posterior longitudinal ligament (OPLL). METHODS: From June 2016 to May 2017, 15 patients (7 men; 8 women) had undergone ACAF as revision after PDS. The Japanese Orthopaedic Association (JOA) score was used to evaluate the pre- and postoperative neurological function. The kappa line and complications were also evaluated. RESULTS: The 15 patients were followed up for 15.1 ± 1.8 months (range, 12-18). The mean interval between the initial PDS and revision ACAF was 40.3 ± 11.3 months (range, 24-62). The JOA score improved from 8.9 ± 1.6 (range, 5-11) before revision ACAF to 13.9 ± 1.6 (range, 11-16) at the final follow-up evaluation (P < 0.05). The JOA recovery rate was 61.9% ± 15.8% (range, 37.5%-90.9%). The kappa line of 7 patients improved from negative values to positive values after ACAF. Five complications (33.3%) developed in 5 patients. No instrument failure or neurological deterioration was observed during the follow-up period. CONCLUSION: In the present study, the outcomes of ACAF for revision surgery for OPLL were satisfactory. ACAF could improve neurological function significantly and is an alternative surgical procedure for revision of PDS for OPLL.

ACVR1-knockout promotes osteogenic differentiation by activating the Wnt signaling pathway in mice.

Osteogenic differentiation refers to the process of bone formation and remodeling, which is controlled by complex molecular mechanisms. Activin A receptor type I (ACVR1) is reported to be associated with osteogenic differentiation. However, the underlying molecular mechanism remains elusive. Therefore, this study evaluates the function of ACVR1 in osteogenic differentiation through the Wnt signaling pathway. The expression of osteocalcin (Oc) and osterix together with osteogenic differentiation and mineralization was examined in ACVR1-knockout (KO) mouse. Furthermore, the Wnt signaling pathway was inhibited in bone marrow stromal cells (BMSCs) of mice to explore the role of the Wnt signaling pathway in osteogenic differentiation by means of alkaline phosphatase (ALP) activity detection and evaluation of mineralized nodules and calcium content. Subsequently, the effect of ACVR1 on the Wnt signaling pathway was assessed by determining the expression of ACVR1, ß-catenin, glycogen synthase kinase 3 ß (GSK3ß), dickkopf-related protein 1 (DKK1), and frizzled class receptor 1 (FZD1). Both their effects on osteogenic differentiation were further evaluated by determination of Oc, osterix, and Runx2 expression. AVCR1 KO mice exhibited increased Oc and osterix expression and promoted bone resorption and formation. ACVR1-knockout was observed to activate the Wnt signaling pathway with an increase of ß-catenin and reductions in GSK3ß, DKK1, and FZD1. With the inhibited Wnt signaling pathway expression of Oc, osterix, and Runx2 was decreased, and ALP activity, mineralized nodule, and calcium content in cellular matrix were decreased as well, indicating that inactivation of the Wnt signaling pathway reduced the differentiation of BMSCs into osteoclasts. These findings indicate that ACVR1-knockout promotes osteogenic differentiation by activating the Wnt signaling pathway in mice.

Quantitative Anterior Enlargement of the Spinal Canal by Anterior Controllable Antedisplacement and Fusion for the Treatment of Cervical Ossification of the Posterior Longitudinal Ligament with Myelopathy.

PURPOSE: This retrospective study aimed to investigate the effect of quantitative enlargement of spinal canal by anterior controllable antedisplacement and fusion (ACAF) for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: Forty-three patients with OPLL who underwent ACAF were enrolled. According to the use of a curvature ruler (CR), patients were divided into group A (CR used, n = 21) and group B (CR not used, n = 22). The average follow-up was 9.5 months. The occupation rate (OR) of the spinal canal and the curvature of the cervical plate were recorded. The Japanese Orthopedic Association (JOA) scores were analyzed, and the recovery rate (RR) was calculated. Surgical complications were also investigated. RESULTS: The OR of the spinal canal in group A decreased from 66.7% ± 12.8% to 19.1% ± 10.9% after surgery (P < 0.05). In group B, the preoperative and postoperative OR was 63.9% ± 11.7% and 21.2% ± 8.7%, respectively (P < 0.05). Patients in group A had higher agreement of the curvature of the cervical plate between preoperative planning and postoperative measurement. The RR of JOA scores in group A was 73.7% ± 19.7%, higher than in group B (70.9% ± 7.3%, P > 0.05). Further comparison between the 2 groups, excluding those patients with OR <50%, showed that both JOA score and RR in group A were higher than in group B at the final follow-up (P < 0.05). CONCLUSIONS: The quantitative enlargement of the spinal canal by ACAF may provide a positive and favorable effect on enlarging the spinal canal and achieving better neurologic recovery for the treatment of cervical OPLL with myelopathy. CR can facilitate the achievement of better and more quantitative spinal canal enlargement.