Proteomics Analysis of Knee Subchondral Bone Identifies Differentially Expressed Proteins Associated with Osteoarthritis.

Osteoarthritis (OA) is a prevalent debilitating whole-joint disorder. Currently, a growing number of proteomic studies have been performed to evaluate molecular biomarkers in several tissues from OA patients; however, little is known about the protein profiles in subchondral bone of OA. In this study, proteomic analysis was performed on subchondral bone from patients with OA to identify differentially expressed proteins (DEPs). Bioinformatics tools were used to further investigate these DEPs. Thereafter, DEPs were validated in the samples from patients with OA, as well as in bilateral ovariectomy-induced OA (OVX-OA) rats using immunohistochemistry. A comprehensive subchondral bone proteome profile of patients with OA was constructed. Additionally, biological information analysis showed that a majority of DEPs participated in the dysregulation of the complement and coagulation cascades. The validation experiments suggested that SerpinA5, the protein involved in the complement and coagulation cascades, was significantly increased in severely damaged subchondral bone of patients with OA compared to the control group. Furthermore, the increase of SerpinA5 in OVX-OA rats compared to control rats was also confirmed. Our results indicated that the dysregulation of coagulation and complement pathways plays a role in the progression of OA, and it provides a promising therapeutic target of OA.

Age-related bone diseases: Role of inflammaging.

Bone aging is characterized by an imbalance in the physiological and pathological processes of osteogenesis, osteoclastogenesis, adipogenesis, and chondrogenesis, resulting in exacerbated bone loss and the development of age-related bone diseases, including osteoporosis, osteoarthritis, rheumatoid arthritis, and periodontitis. Inflammaging, a novel concept in the field of aging research, pertains to the persistent and gradual escalation of pro-inflammatory reactions during the aging process. This phenomenon is distinguished by its low intensity, systemic nature, absence of symptoms, and potential for management. The mechanisms by which inflammaging contribute to age-related chronic diseases, particularly in the context of age-related bone diseases, remain unclear. The precise manner in which systemic inflammation induces bone aging and consequently contributes to the development of age-related bone diseases has yet to be fully elucidated. This article primarily examines the mechanisms underlying inflammaging and its association with age-related bone diseases, to elucidate the potential mechanisms of inflammaging in age-related bone diseases and offer insights for developing preventive and therapeutic strategies for such conditions.

Effects of exosomes derived from platelet-rich plasma on osteogenic differentiation of dental pulp stem cells.

Platelet-rich plasma (PRP) can cause osteogenic differentiation of dental pulp stem cells (DPSCs). However, the effect of exosomes derived from PRP (PRP-Exos) on osteogenic differentiation of DPSCs remains unclear. Herein, we evaluated the impact of PRP-Exos on osteogenic differentiation of DPSCs. PRP-Exos were isolated and identified by transmission electron microscopy (TEM) and western blotting (WB). Immunofluorescence staining was performed to evaluate endocytosis of PRP-Exos by DPSCs. Alkaline phosphatase staining, alizarin red staining, western blot and qRT-PCR were carried out to evaluate the DPSCs osteogenic differentiation. The sequencing microRNA (miRNA) was conducted to determine the microRNA profile of PRP-Exos treated and untreated DPSCs. The results showed that endocytosis of PRP-Exos stimulated DPSCs odontogenic differentiation by elevated expression of ALP, DMP-1, OCN, and RUNX2. ALP activity and calcified nodules formation of PRP-Exos treated DPSCs were considerably elevated relative to that of the control group. MicroRNA sequencing revealed that 112 microRNAs considerably varied in PRP-Exos treated DPSCs, of which 84 were elevated and 28 were reduced. Pathway analysis suggested that genes targeted by differentially expressed (DE) miRNAs were contributed to many signaling cascades, such as the Wnt cascade. 65 genes targeted by 30 DE miRNA were contributed to Wnt signaling. Thus, it can be infered that PRP-Exos could enhance osteogenic differentiation and alter the miRNA expression profile of DPSCs.

A pig model of symptomatic spinal epidural hematoma.

PURPOSE: The purpose of this study was to establish an animal model capable of simulating the development and decompression process of symptomatic spinal epidural hematoma (SSEH). METHODS: A total of 16 male Bama miniature pigs were included in this study and randomly allocated into four groups: Group A (4 h 20 mmHg hematoma compression), Group B (4 h 24 mmHg hematoma compression), Group C (4 h 28 mmHg hematoma compression), and Group Sham (control). Real-time intra-wound hematoma compression values were obtained using the principle of connectors. Electrophysiological analyses, including the latency and amplitude of somatosensory evoked potentials (SSEP) and motor evoked potentials (MEP), along with behavioral observations (Tarlov score), were performed to assess this model. RESULTS: ANOVA tests demonstrated significant differences in the latency and relative amplitude of SSEP and MEP between Groups C and Sham after 4 h of hematoma compression and one month after surgery (P < 0.01). Behavioral assessments 8 h after surgery indicated that animals subjected to 28 mmHg hematoma compression suffered the most severe spinal cord injury. Pearson correlation coefficient test suggested a negative correlation between the epidural pressure and Tarlov score (r = -0.700, p < 0.001). With the progression of compression and the escalation of epidural pressure, the latency of SSEP and MEP gradually increased, while the relative amplitude gradually decreased. CONCLUSIONS: When the epidural pressure reaches approximately 24 mmHg, the spinal cord function occurs progressive dysfunction. Monitoring epidural pressure would be an effective approach to assist to identify the occurrence of postoperative SSEH.

Safety and risk analysis of total resection surgery for thoracic and lumbar spinal tumors: a decadal analysis of 103 cases.

STUDY DESIGN: Retrospective cohort study. PURPOSE: To explore the complications and risk factors for total resection (TR) of primary thoracic and lumbar spinal tumors over the past decade at our institution. METHODS: Patients meeting inclusion criteria (primary spinal tumors, thoracic or lumbar location, TR at our center) were included. Demographic characteristics, surgical data, perioperative complications and management results were reviewed. Patients were stratified by tumor site, the number of excised segments, and recurrence status to elucidate distinctive characteristics. RESULTS: The cohort comprised 103 patients, with a mean age of 35.8 years. On average, 1.83 vertebral segments were resected per patient. Perioperative complications were substantial, totaling 166 events, with 71 classified as major and 95 as minor, yielding an average of 1.61 complications per patient. No perioperative deaths occurred, but 79 patients (76.7%) experienced at least one complication. Multiple vertebral sections correlated with a higher complication rate (P = 0.031), and lumbar surgeries exhibited elevated risks of large vascular injury (P = 0.001), neurological deterioration, and cerebrospinal fluid leakage compared to thoracic cases. Conversely, thoracic spinal procedures showed a higher rate of pleural effusion (P = 0.004). Binary logistics stepwise regression identified multi-segmental resection as the independent risk factor for major perioperative complications. CONCLUSIONS: TR of primary spinal tumors is associated with a high perioperative complication rate, although most events have a favorable prognosis. Complication characteristics vary based on the surgical site, number of excised segments, and surgical history. A nuanced preoperative evaluating approach considering patient age, surgical segments, and extent of resection is crucial.

Complications and local recurrence of chondrosarcoma and chordoma treated by total tumor resection in thoracic and lumbar spine.

BACKGROUND: En bloc resection of spinal tumors is challenging and associated with a high incidence of complications; however, it offers the potential to reduce the risk of recurrence when a wide margin is achieved. This research aims to investigate the safety and efficacy of en bloc resection in treating thoracic and lumbar chondrosarcoma/chordoma. METHODS: Data from patients diagnosed with chondrosarcoma and chordoma in the thoracic or lumbar region, who underwent total en bloc or piecemeal resection at our institution over a 7-year period, were collected and regularly followed up. The study analyzed overall perioperative complications and compared differences in complications and local tumor recurrence between the two surgical methods. RESULTS: Seventeen patients were included, comprising 12 with chondrosarcoma and 5 with chordoma. Among them, 5 cases underwent intralesional piecemeal resection, while the remaining 12 underwent planned en bloc resection. The average surgical time was 684 min (sd = 287), and the mean estimated blood loss was 2300 ml (sd = 1599). Thirty-five complications were recorded, with an average of 2.06 perioperative complications per patient. 82% of patients (14/17) experienced at least one perioperative complication, and major complications occurred in 64.7% (11/17). Five patients had local recurrence during the follow-up, with a mean recurrence time of 16.2 months (sd = 7.2) and a median recurrence time of 20 months (IQR = 12.5). Hospital stays, operation time, blood loss, and complication rates did not significantly differ between the two surgical methods. The local recurrence rate after en bloc resection was lower than piecemeal resection, although not statistically significant (P = 0.067). CONCLUSIONS: The complication rates between the two surgical procedures were similar. Considering safety and local tumor control, en bloc resection is recommended as the primary choice for patients with chondrosarcoma/chordoma in the thoracic and lumbar regions who are eligible for this treatment.

Perioperative complications of en bloc resection and anterior column reconstruction for thoracic and lumbar spinal tumors.

PURPOSE: To evaluate the perioperative clinical outcomes of en bloc resection and anterior column reconstruction for thoracolumbar spinal tumors. METHODS: This study conducted a retrospective analysis of prospective data collection of 86 consecutive patients, including 40 males and 46 females, with an average age of 39 years (ranged from 10 to 71 years). There were 35 cases of a malignant primary tumor,42 cases of an aggressive benign tumor, and nine cases of metastases. The main lesions were located in 65 cases of thoracic spine, 17 cases of lumbar spine, and 4 cases of thoracolumbar spine. Tumors involved one level in 45 patients, two levels in 12 patients, three levels in 21 patients, four levels in five patients, five levels in two patients, and six levels in one patient. RESULTS: According to the Weinstein-Boriani-Biagini surgical staging system, all patients achieved en bloc resections, including 74 cases of total en bloc spondylectomy and 12 cases of sagittal resections. The mean surgical time was 559 min (210-1208 min), and the mean total blood loss was 1528 ml (260-5500 ml). A total of 122 complications were observed in 62(72.1%) patients, of which 18(20.9%) patients had 25 major complications and one patient (1.2%) died of complications. The combined approach (P = 0.002), total blood loss (P = 0.003), staged surgery (P = 0.004), previous surgical history (P = 0.045), the number of involved vertebrae (P = 0.021) and lumbar location (P = 0.012) were statistically significant risk factors for major complication. When all above risk factors were incorporated in multivariate analysis, only the combined approach (P = 0.052) still remained significant. CONCLUSIONS: En bloc resection and anterior column reconstruction is accompanied by a high incidence of complications, especially when a combined approach is necessary.

Would the one-stage combined approach lead to better long-term neurological outcomes than the posterior approach alone in multilevel degenerative cervical myelopathy patients with T2-Weighted increased signal intensity? An 8-year follow-up results and propensity score matching analysis.

BACKGROUND: T2-weighted increased signal intensity (ISI) is commonly recognized as a sign of more severe spinal cord lesions, usually accompanied by worse neurological deficits and possibly worse postoperative neurological recovery. The combined approach could achieve better decompression and better neurological recovery for multilevel degenerative cervical myelopathy (MDCM). The choice of surgical approach for MDCM with intramedullary T2-weighted ISI remains disputed. This study aimed to compare the neurological outcomes of posterior and one-stage combined posteroanterior approaches for MDCM with T2-weighted ISI. METHODS: A total of 83 consecutive MDCM patients with confirmed ISI with at least three intervertebral segments operated between 2012 and 2014 were retrospectively enrolled. Preoperative demographic, radiological and clinical condition variables were collected, and neurological conditions were evaluated by the Japanese Orthopedic Assessment score (JOA) and Neck Disability Index (NDI). Propensity score matching analysis was conducted to produce pairs of patients with comparable preoperative conditions from the posterior-alone and combined groups. Both short-term and mid-term surgical outcomes were evaluated, including the JOA recovery rate (JOARR), NDI improvements, complications, and reoperations. RESULTS: A total of 83 patients were enrolled, of which 38 and 45 patients underwent posterior surgery alone and one-stage posteroanterior surgery, respectively. After propensity score matching, 38 pairs of comparable patients from the posterior and combined groups were matched. The matched groups presented similar preoperative clinical and radiological features and the mean follow-up duration were 111.6 ± 8.9 months. The preoperative JOA scores of the posterior and combined groups were 11.5 ± 2.2 and 11.1 ± 2.3, respectively (p = 0.613). The combined group presented with prolonged surgery duration(108.8 ± 28.0 and 186.1 ± 47.3 min, p = 0.028) and greater blood loss(276.3 ± 139.1 and 382.1 ± 283.1 ml, p<0.001). At short-term follow-up, the combined group presented a higher JOARR than the posterior group (posterior group: 50.7%±46.6%, combined group: 70.4%±20.3%, p = 0.024), while no significant difference in JOARR was observed between the groups at long-term follow-up (posterior group: 49.2%±48.5%, combined group: 59.6%±47.6%, p = 0.136). No significant difference was found in the overall complication and reoperation rates. CONCLUSIONS: For MDCM patients with ISI, both posterior and one-stage posteroanterior approaches could achieve considerable neurological alleviations in short-term and long-term follow-up. With greater surgical trauma, the combined group presented better short-term JOARR but did not show higher efficacy in long-term neurological function preservation in patients with comparable preoperative conditions.

[Clinical outcomes of 3D-printing stand-alone artificial vertebral body in anterior cervical surgeries].

OBJECTIVE: To explore the short-term outcomes of 3D-printing stand-alone artificial vertebral body (AVB) in the surgical procedure of anterior cervical corpectomy and fusion (ACCF). METHODS: Following the proposal of IDEAL (idea, development, exploration, assessment, and long-term follow-up) framework, we designed and conducted this single-armed, retrospective cohort study. The patients with cervical spondylotic myelopathy were recruited, and these patients exclusively received the surgical procedure of single-level ACCF in our single center. After the process of corpectomy, the size was tailored using different trials and the most suitable stand-alone AVB was then implanted. This AVB was manufactured by the fashion of 3D-printing. Two pairs of screws were inserted in an inclined way into the adjacent vertebral bodies, to stabilize the AVB. The participants were regularly followed-up after the operation. Their clinical data were thoroughly reviewed. We assessed the neurological status according to Japanese Orthopedic Association (JOA) scale. We determined the fusion based on imaging examination six months after the operation. The recorded clinical data were analyzed using specific software and they presented in suitable styles. Paired t test was employed in comparison analysis. RESULTS: In total, there were eleven patients being recruited eventually. The patients were all followed up over six months after the operation. The mean age of the cohort was (57.2±10.2) years. The mean operation time was (76.1±23.1) min and the median bleeding volume was 150 (100, 200) mL. The postoperative course was uneventful for all the cases. Dysphagia, emergent hematoma, and deterioration of neurological function did not occur. Mean JOA scores were 13.2±2.2 before the operation and 16.3±0.8 at the final follow-up, which were significantly different (P < 0.001). The mean recovery rate of neurological function was 85.9%. By comparing the imaging examinations postoperatively and six months after the operation, we found that the average subsidence length was (1.2±1.1) mm, and that there was only one cases (9.1%) of the severe subsidence (>3 mm). We observed significant improvement of cervical lordosis after the operation (P=0.013). All the cases obtained solid fusion. CONCLUSION: 3D-printing stand-alone AVB presented favorable short-term outcome in one-level ACCF in this study. The fusion rate of this zero-profile prosthesis was satisfactory and the complication rate was relatively low.

Clinical and radiographic features of adult calcified thoracic disc herniation: a retrospective analysis of 31 cases.

PURPOSE: To analyze the clinical and radiographic characteristics of calcified thoracic disc herniation (CTDH) and explore the possible pathogeneses. METHODS: This is a retrospective clinical review of prospectively collected imaging data based at a single institute from 2004 to 2021. Clinical and radiographic parameters of CTDH patients were retrospectively collected and analyzed. RESULTS: All 31 patients included presented thoracic myelopathy with a 17.05-month preoperative disease duration. Three (9.7%) patients had a history of trauma, and the rest had insidious onset. The average spinal canal ventral-occupying ratio was 74.90 ± 15.16%. The most prominent radiographic feature was the calcification of the nucleus pulposus in the intervertebral disc and the calcified lesion contiguous with the disc space protruding into the spinal canal. Three main imaging forms of CTDH were found: calcium-ringed lesion (5), heterogeneous calcification lesion (19), and homogeneous calcification lesion (7). The radiographic manifestations, intraoperative findings, and postoperative pathologies of the three subtypes were different. The calcium-ringed lesion type was younger and had a shorter preoperative duration and significantly lower mJOA score. A special case was observed conservatively for five years, which suggested that a heterogeneous lesion could progress to a homogeneous lesion. CONCLUSIONS: Adult CTDH is a special thoracic disc disease with insidious onset, a long course, and a high spinal canal-occupying ratio. Calcium deposits in the spinal canal originate from the nucleus pulposus. The intraoperative findings and postoperative pathology of subtypes are different, which might indicate different pathological mechanisms.

Comparison of the prognostic factors of total en bloc spondylectomy and total piecemeal spondylectomy in patients with Enneking stage III giant cell tumor in the thoracic and lumbar spine.

PURPOSE: To compare total en bloc spondylectomy with marginal margins against piecemeal spondylectomy with intralesional margins in the surgical treatment of Enneking stage III spinal giant cell tumor (GCT) in terms of local recurrence. METHODS: A retrospective survival analysis of patients with Enneking stage III GCT who underwent TES with marginal margins or total piecemeal spondylectomy with intralesional margins was performed between January 2006 and April 2020. Local recurrence-free survival (LRFS) was the time between the date of surgery and recurrence. Factors with p-values < 0.05 in the univariate analysis were included in the multivariate analysis using proportional hazard analysis. RESULTS: Sixty patients (25 men and 35 women) with a mean age of 35.6 (range 11-71) years were included. The mean follow-up duration was 93 (range 24-198) months. Two patients were lost to follow-up 6 and 14 years after the procedure. Over a 10-year period, the recurrence rate was 13.3%. The 2-, 5-, and 10-year LRFS rates were 95%, 88%, and 78%, respectively. Univariate analysis identified total piecemeal spondylectomy and no adjuvant radiotherapy as prognostic factors for LRFS. Multivariate Cox-regression models showed a significant association between local recurrence and total piecemeal spondylectomy and no adjuvant radiotherapy. CONCLUSION: TES with marginal margins is better than total piecemeal spondylectomy with intralesional margins owing to its lower postoperative recurrence rate. Adjuvant radiotherapy should be administered to reduce postoperative recurrence rates.

Predicting post-laminoplasty kyphosis in cervical spondylotic myelopathy patients without preoperative kyphosis: a retrospective study.

BACKGROUND: This study aimed to determine potential risk factors for post-laminoplasty kyphosis and the effect of postoperative kyphosis on neurologic function recovery. METHODS: A total of 266 patients with cervical spondylotic myelopathy (CSM) underwent traditional cervical laminoplasty with a minimum of a 12-month follow-up period. The patients were divided into non-kyphosis (NK group) and kyphosis (K group) groups based on the postoperative C2-7 Cobb angle. Clinical and radiological measurements were collected preoperatively and at the final follow-up. RESULTS: Of the 266 patients, 26 (9.77%) developed postoperative kyphosis at the final follow-up. The postoperative Japanese Orthopedic Association score did not differ significantly between the NK and K groups (P > 0.05). The postoperative numeric rating scale (NRS) also showed no significant difference between the NK and K groups; however, postoperative NRS improved better than the preoperative values in the NK group (P < 0.001). Multivariate analysis revealed that the preoperative C2-7 extension Cobb angle and C2-7 Cobb angle were independent predictors of post-laminoplasty kyphosis. Cut-off values for predicting postoperative kyphosis were a C2-7 extension Cobb angle of 18.00° and a C2-7 Cobb angle of 9.30°. CONCLUSIONS: Low preoperative C2-7 extension Cobb angle and C2-7 Cobb angle may be associated with post-laminoplasty kyphosis in CSM patients without preoperative kyphosis. The cut-off value of the C2-7 extension Cobb angle and C2-7 Cobb angle were 18.00° and 9.30°, respectively.

Complications and prognosis of primary thoracic and lumbar giant cell tumors treated by total tumor resection.

BACKGROUND: Spinal giant cell tumor (SGCT) is a relatively rare primary tumor. En bloc resection is the preferred surgical procedure for it due to its aggressiveness, meanwhile leading to more complications. We reported the characteristics of perioperative complications and local control of total tumor resection including en bloc resection and piecemeal resection for primary thoracic and lumbar spinal giant cell tumors in a single center over 10 years. METHODS: This is a retrospective cross-sectional and cohort study. Forty-one consecutive patients with SGCTs who underwent total tumor resection from 2010 to 2020 at our institution and were followed up for at least 24 months were reviewed. Surgery data, complication characteristics and local tumor control were collected and compared by different surgical procedure. RESULTS: Forty-one patients were included, consisting of 18 males and 23 females, with a mean age of 34.2 years. Thirty-one had thoracic vertebra lesions, and 10 had lumbar vertebra lesions. Thirty-five patients were primary cases, and 6 patients were recurrent cases. Eighteen patients were treated by total en bloc spondylectomy (TES), 12 patients underwent en bloc resection according to WBB surgical system, and 11 patients underwent piecemeal resection. The average surgical time was 498 min, and the mean estimated blood loss was 2145 ml. A total of 58 complications were recorded, and 30 patients (73.2%) had at least one perioperative complication. All patients were followed up after surgery for at least 2 years. A total of 6 cases had postoperative internal fixation failure, and 4 cases presented local tumor recurrence (9.8%). CONCLUSIONS: Although the surgical technique is difficult and accompanied by a high rate of perioperative complications, en bloc resection can achieve favorable local control in SGCT. When it is too difficult to complete en bloc resection, thoroughly piecemeal resection without residual is also acceptable, given the relatively low recurrence rate.

Oral microbial changes and oral disease management before and after the treatment of hematological malignancies: a narrative review.

OBJECTIVES: Patients with hematological malignancies have dynamic changes in oral microbial communities before and after treatment. This narrative review describes the changes in oral microbial composition and diversity, and discusses an oral microbe-oriented strategy for oral disease management. MATERIALS AND METHODS: A literature search was performed in PubMed/Medline, Web of Science, and Embase for articles published between 1980 and 2022. Any articles on the changes in oral microbial communities in patients with hematological malignancies and their effects on disease progression and prognosis were included. RESULTS: Oral sample detection and oral microbial sequencing analysis of patients with hematological malignancies showed a correlation between changes in oral microbial composition and diversity and disease progression and prognosis. The possible pathogenic mechanism of oral microbial disorders is the impairment of mucosal barrier function and microbial translocation. Probiotic strategies, antibiotic strategies, and professional oral care strategies targeting the oral microbiota can effectively reduce the risk of oral complications and the grade of severity in patients with hematological malignancies. CLINICAL RELEVANCE: This review provides dentists and hematologists with a comprehensive understanding of the host-microbe associated with hematologic malignancies and oral disease management advice.

The Dilemma of Balance between Benefits and Losses for Chondromyxoid Fibroma-like Osteosarcoma in Thoracic Spine with Azygos Tumor Thrombosis: A Case Report.

Background: Chondromyxoid fibroma-like osteosarcoma (CMF-OS) is an extremely rare subtype of osteosarcoma, its clinical data are scarce, and our understanding of it is far from sufficient. As it has few typical imaging manifestations, it is not uncommonly misdiagnosed clinically. Azygos vein thrombosis is also a rare entity, and there is a big controversy over treatments for it. Case presentation: Herein, we report a case of CMF-OS that occurred in the spine, coincidently, azygos vein thrombosis was found. A young male patient came to our clinic because of continuous back pain, and a neoplastic lesion was suspected in the thoracolumbar vertebrae. The pathological results of the biopsy showed a low grade of osteosarcoma, and chondromyxoid fibroma-like osteosarcoma was the primary diagnosis. Since the tumor cannot be en-bloc resected, he received palliative decompression surgery, followed by radio and chemotherapy. Azygos vein tumor thrombosis was not treated and, unfortunately, he died of heart failure caused by the thrombus migrating from the azygos vein to the right atrium. Before the palliative decompression surgery, both the patient and the clinical team were trapped in the dilemma of how big a surgery should be carried out to maximize the benefits of this patient. Results and complications: CMF-OS is indeed more aggressive than its pathological sections suggest. Guidelines for osteosarcoma should be followed. Furthermore, it is important to recognize the danger of tumor thrombosis in the azygos vein. Preventive measures have to be performed in a timely manner to avoid catastrophic results.

Utility of Advanced DWI in the Detection of Spinal Cord Microstructural Alterations and Assessment of Neurologic Function in Cervical Spondylotic Myelopathy Patients.

BACKGROUND: Diffusion-weighted imaging (DWI) can quantify the microstructural changes in the spinal cord. It might be a substitute for T2 increased signal intensity (ISI) for cervical spondylotic myelopathy (CSM) evaluation and prognosis. PURPOSE: The purpose of the study is to investigate the relationship between DWI metrics and neurologic function of patients with CSM. STUDY TYPE: Retrospective. POPULATION: Forty-eight patients with CSM (18.8% females) and 36 healthy controls (HCs, 25.0% females). FIELD STRENGTH/SEQUENCE: 3 T; spin-echo echo-planar imaging-DWI; turbo spin-echo T1/T2; multi-echo gradient echo T2*. ASSESSMENT: For patients, conventional MRI indicators (presence and grades of T2 ISI), DWI indicators (neurite orientation dispersion and density imaging [NODDI]-derived isotropic volume fraction [ISOVF], intracellular volume fraction, and orientation dispersion index [ODI], diffusion tensor imaging [DTI]-derived fractional anisotropy [FA] and mean diffusivity [MD], and diffusion kurtosis imaging [DKI]-derived FA, MD, and mean kurtosis), clinical conditions, and modified Japanese Orthopaedic Association (mJOA) were recorded before the surgery. Neurologic function improvement was measured by the 3-month follow-up recovery rate (RR). For HCs, DWI, and mJOA were measured as baseline comparison. STATISTICAL TESTS: Continuous (categorical) variables were compared between patients and HCs using Student's t-tests or Mann-Whitney U tests (chi-square or Fisher exact tests). The relationships between DWI metrics/conventional MRI findings, and the pre-operative mJOA/RR were assessed using correlation and multivariate analysis. P < 0.05 was considered statistically significant. RESULTS: Among patients, grades of T2 ISI were not correlated with pre-surgical mJOA/RR (P = 0.717  and 0.175, respectively). NODDI ODI correlated with pre-operative mJOA (r = -0.31). DTI FA, DKI FA, and NODDI ISOVF were correlated with the recovery rate (r = 0.31, 0.41, and -0.34, respectively). In multivariate analysis, NODDI ODI (DTI FA, DKI FA, NODDI ISOVF) significantly contributed to the pre-operative mJOA (RR) after adjusting for age. DATA CONCLUSION: DTI FA, DKI FA, and NODDI ISOVF are predictors for prognosis in patients with CSM. NODDI ODI can be used to evaluate CSM severity. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY STAGE: 5.

A sheep model of chronic cervical compressive myelopathy via an implantable wireless compression device.

PURPOSE: This study aimed to establish an animal model in which we can precisely displace the spinal cord and therefore mimic the chronic spinal compression of cervical spondylotic myelopathy. METHODS: In vivo intervertebral compression devices (IVCDs) connected with subcutaneous control modules (SCCMs) were implanted into the C2-3 intervertebral disk spaces of sheep and connected by Bluetooth to an in vitro control system. Sixteen sheep were divided into four groups: (Group A) control; (Group B) 10-week progressive compression, then held; (Group C) 20-week progressive compression, then held; and (Group D) 20-week progressive compression, then decompression. Electrophysiological analysis (latency and amplitude of the N1-P1-N2 wave in somatosensory evoked potentials, SEP), behavioral changes (Tarlov score), imaging test (encroachment ratio (ER) of intraspinal invasion determined by X-ray and CT scan), and histological examinations (hematoxylin and eosin, Nissl, and TUNEL staining) were performed to assess the efficacy of our model. RESULTS: Tarlov scores gradually decreased as compression increased with time and partially recovered after decompression. The Pearson correlation coefficient between ER and time was r = 0.993 (p < 0.001) in Group B at 10 weeks and Groups C and D at 20 weeks. And ER was negatively correlated with the Tarlov score (r = -0.878, p < 0.001). As compression progressed, the SEP latency was significantly extended (p < 0.001), and the amplitude significantly decreased (p < 0.001), while they were both partially restored after decompression. The number of abnormal motor neurons and TUNEL-positive cells increased significantly (p < 0.001) with compression. CONCLUSION: Our implantable and wireless intervertebral compression model demonstrated outstanding controllability and reproducibility in simulating chronic cervical spinal cord compression in animals.

Repair of critical diaphyseal defects of lower limbs by 3D printed porous Ti6Al4V scaffolds without additional bone grafting: a prospective clinical study.

The repair of critical diaphyseal defects of lower weight-bearing limbs is an intractable problem in clinical practice. From December 2017, we prospectively applied 3D printed porous Ti6Al4V scaffolds to reconstruct this kind of bone defect. All patients experienced a two-stage surgical process, including thorough debridement and scaffold implantation. With an average follow-up of 23.0 months, ten patients with 11 parts of bone defects were enrolled in this study. The case series included three females and seven males, their defect reasons included seven parts of osteomyelitis and four parts of aseptic nonunion. The bone defects located at femur (five parts) and tibia (six parts), with an average defect distance of 12.2 cm. Serial postoperative radiologic follow-ups displayed a continuous process of new bone growing and remodeling around the scaffold. One patient suffered tibial varus deformity, and he underwent a revision surgery. The other nine patients achieved scaffold stability. No scaffold breakage occurred. In conclusion, the implantation of 3D printed Ti6Al4V scaffold was feasible and effective to reconstruct critical bone defects of lower limbs without additional bone grafting. Graphical abstract.

CMTM3 suppresses chordoma progress through EGFR/STAT3 regulated EMT and TP53 signaling pathway.

BACKGROUND: Chordomas are rare, slow-growing and locally aggressive bone sarcomas. At present, chordomas are difficult to manage due to their high recurrence rate, metastasis tendency and poor prognosis. The underlying mechanisms of chordoma tumorigenesis and progression urgently need to be explored to find the effective therapeutic targets. Our previous data demonstrates that EGFR plays important roles in chordoma development and CKLF-like MARVEL transmembrane domain containing (CMTM)3 suppresses gastric cancer metastasis by inhibiting the EGFR/STAT3/EMT signaling pathway. However, the roles and mechanism of CMTM3 in chordomas remain unknown. METHODS: Primary chordoma tissues and the paired adjacent non-tumor tissues were collected to examine the expression of CMTM3 by western blot. The expression of CMTM3 in chordoma cell lines was tested by Real-time PCR and western blot. CCK-8 and colony forming unit assay were performed to delineate the roles of CMTM3 in cell proliferation. Wound healing and Transwell assays were performed to assess cell migration and invasion abilities. A xenograft model in NSG mice was used to elucidate the function of CMTM3 in vivo. Signaling pathways were analyzed by western blot and IHC. RNA-seq was performed to further explore the mechanism regulated by CMTM3 in chordoma cells. RESULTS: CMTM3 expression was downregulated in chordoma tissues compared with paired normal tissues. CMTM3 suppressed proliferation, migration and invasion of chordoma cells in vitro and inhibited tumor growth in vivo. CMTM3 accelerated EGFR degradation, suppressed EGFR/STAT3/EMT signaling pathway, upregulated TP53 expression and enriched the TP53 signaling pathway in chordoma cells. CONCLUSIONS: CMTM3 inhibited tumorigenesis and development of chordomas through activating the TP53 signaling pathway and suppressing the EGFR/STAT3 signaling pathway, which suppressed EMT progression. CMTM3 might be a potential therapeutic target for chordomas.

Radiographic and clinical features of thoracic disk disease associated with myelopathy: a retrospective analysis of 257 cases.

PURPOSE: To analyze the clinical and radiographic characteristics of thoracic disk disease associated with myelopathy (TDM). METHODS: This is a retrospective clinical review of prospectively collected imaging data based at a single institute. Based on preoperative CT and MRI, we classified TDM as thoracic disk herniation (TDH), THD with ossification (THDO), TDH with posterior bony avulsions of the vertebrae (TDH with PBA), TDH with posterior vertebral osteophytes (TDH with PVO), giant thoracic osteophyte and calcific discitis with herniation (CDH). Patient characteristics and radiographic data were compared between different types of TDM. RESULTS: Among the 257 patients included, 12.06% of patients presented with symptoms after traumatic events. The most frequent complaint at onset and preoperative was back pain (29.2%) and subjective lower limb weakness (75.5%), respectively. All TDH with PBA is distributed at the lower thoracic segments, while CDH predominantly in the middle and lower thoracic segments. TDH with PBA was more frequent in men than TDH and CDH. Compared with TDH, TDHO, and TDH with PVO, TDH with PBA was younger in surgery age, and TDH and CDH had lower preoperative JOA scores than TDH with PBA. CDH had a larger ventral occupying ratio than TDH, TDHO, and TDH with PBA. CONCLUSIONS: The onset of TDM was generally insidious but may be triggered acutely by apparently trivial events. With a low prevalence, TDM varied clinical symptoms. Different types of TDM had various clinical features, which might indicate different pathological mechanisms.