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Cervical spondylosis is the most common degenerative spinal disorder in modern societies. Patients require a great deal of medical knowledge, and large language models (LLMs) offer patients a novel and convenient tool for accessing medical advice. In this study, we collected the most frequently asked questions by patients with cervical spondylosis in clinical work and internet consultations. The accuracy of the answers provided by LLMs was evaluated and graded by 3 experienced spinal surgeons. Comparative analysis of responses showed that all LLMs could provide satisfactory results, and that among them, GPT-4 had the highest accuracy rate. Variation across each section in all LLMs revealed their ability boundaries and the development direction of artificial intelligence.
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Chordoma is a rare bone tumor that frequently recurs after surgery, and the prognosis is poor with current treatments. This study aimed to identify potential novel immunotherapeutic targets for chordomas by identifying target proteins in clinical samples as well as tumor microenvironmental factors to enhance efficacy. Fourteen chordoma samples were analyzed by single-cell RNA sequencing, and B7-H3 and IL-7 were identified as potential targets and potentiators, respectively. B7-H3-targeted chimeric antigen receptor T (CAR-T) cells and B7-H3 CAR-T cells expressing IL-7 were synthesized and their anti-tumor activity evaluated in vitro, including in primary chordoma organoid models. The B7-H3 CAR-T/IL-7 therapy showed enhanced cytotoxicity and prolonged duration of action against tumor cells. Additionally, IL-7 modulated favorable subpopulations of cultured CAR-T cells, diminished immune checkpoint expression on T-cell surfaces, and enhanced T-cell functionality. The incorporation of IL-7 molecules into the B7-H3 CAR structure augmented CAR-T-cell function and improved CAR-T-cell efficacy, thus providing a novel dual therapeutic strategy for chordoma treatment.
Subject(s)
B7 Antigens , Chordoma , Immunotherapy, Adoptive , Interleukin-7 , Receptors, Chimeric Antigen , Chordoma/immunology , Chordoma/therapy , Chordoma/pathology , Chordoma/metabolism , Chordoma/genetics , Humans , Interleukin-7/metabolism , Immunotherapy, Adoptive/methods , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/metabolism , Receptors, Chimeric Antigen/genetics , B7 Antigens/metabolism , B7 Antigens/genetics , T-Lymphocytes/immunology , T-Lymphocytes/metabolism , Female , Male , Middle Aged , Tumor Microenvironment/immunology , Cell Survival , Cell Line, Tumor , AdultABSTRACT
BACKGROUND: This study aims to evaluate the effect of various background reference regions on spinal 18F-FET PET imaging, with a focus on distinguishing between spinal tumors and myelitis. To enhance diagnostic accuracy, we investigated the pons and several other spinal cord area as potential references, given the challenges in interpreting spinal PET results. RESULTS: A retrospective analysis was conducted on 30 patients, 15 with cervical myelitis and 15 with cervical tumors, who underwent O-(2-[18F]-fluoroethyl)-L-tyrosine (FET) PET/MR imaging. The stability of uptake across four regions, including the pons, C2, C2-C7, and T1-T3, was compared. The standardized uptake value ratio (SUVR) was then evaluated using various background regions, and their effectiveness in differentiating between spinal tumors and myelitis was compared. Additionally, we correlated the SUVR values derived from these regions with the Ki-67 proliferation index in tumor patients. The study found no significant difference in SUVmax (U = 110, p = 0.93) and SUVmean (U = 89, p = 0.35) values at lesion sites between myelitis and tumor patients. The pons had the highest average uptake (p < 0.001) compared to the other three regions. However, its coefficient of variation (CV) was significantly lower than that of the C2-C7 (p < 0.0001) and T1-T3 segments (p < 0.05). The SUVRmax values, calculated using the regions of pons, C2-C7 and T1-T3, were found to significantly differentiate between tumors and myelitis (p < 0.05). However, only the pons-based SUVRmean was able to significantly distinguish between the two groups (p < 0.05). Additionally, the pons-based SUVRmax (r = 0.63, p = 0.013) and SUVRmean (r = 0.67, p = 0.007) demonstrated a significant positive correlation with the Ki-67 index. CONCLUSIONS: This study suggests that the pons may be considered a suitable reference region for spinal 18F-FET PET imaging, which can improve the differentiation between spinal tumors and myelitis. The significant correlation between pons-based SUVR values and the Ki-67 index further highlights the potential of this approach in assessing tumor cell proliferation.
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Objective: This study aimed to compare the diagnostic efficacy of O-(2-18F-fluoroethyl)-l-tyrosine (18F-FET) PET and 2-deoxy-2-[18F]fluoro-d-deoxyglucose (18F-FDG) PET for spinal cord lesions. Materials and methods: Paired preoperative 18F-FDG PET/MRI and 18F-FET PET/MRI scans were conducted on patients with suspected spinal cord tumors. Clinical manifestations and PET performance, including SUVmean, SUVmax, TBRmean, TBRmax, metabolic tumor volume (MTV), and total lesion metabolism (TLM), and tumor volume, were compared using group analysis and receiver operating characteristic (ROC) curves. Results: Thirty-five patients were categorized into three groups based on their pathological diagnosis: high-grade tumors (HGTs, n = 6), low-grade tumors (LGTs, n = 19), and non-tumor diseases (NTDs, n = 10). The background SUVmean of 18F-FET PET was significantly lower than that of 18F-FDG PET (p < 0.0001), while the delineated tumor volumes showed no significant difference (p > 0.05). The mass SUVmean, SUVmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET were statistically different between HGTs and LGTs (p < 0.05). Similarly, the mass SUVmax, TBRmax, MTV, and TLM values of both 18F-FDG PET and 18F-FET PET, as well as the mass SUVmean of 18F-FET PET, exhibited statistical differences between HGTs and NTDs (p < 0.05). But none were able to distinguish LGTs and NTDs (p > 0.05). Notably, 18F-FET PET provided valuable supporting diagnostic evidence in 1 case of mixed neuronal-glial tumor (MNGT) and 2 cases of intramedullary inflammatory lesions. Optimal cut-off values of all measured parameters for distinguishing tumors and NTDs were determined through ROC analysis. Conclusion: 18F-FET PET presented comparable diagnostic performance to 18F-FDG PET in differentiating HGTs, LGTs, and NTDs, but exhibited particular utility in MNGT and inflammatory lesions.
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OBJECTIVE: Intraspinal cysts are uncommon, and the success rate of complete resection is still low for spinal neurenteric cysts (NCs). The aim of this study was to evaluate the efficacies of an anterior microscopic surgical approach in the treatment of ventral and ventrolateral subaxial cervical NCs (SCNCs). METHODS: Between 2019 and 2022, 9 patients with NCs of the subaxial spine underwent an anterior microsurgical approach. Their clinical presentations, radiological features, operative findings, and follow-up data were retrospectively reviewed and analyzed. RESULTS: All spinal cysts were intradural and extramedullary in origin. Five patients were first-time cases while 4 patients with recurrence underwent revision surgery. The most common clinical manifestation was pain (77.78%). One patient was found to have a concomitant disorder of Klippel-Feil syndrome. Microscopically confirmed gross-total resection was achieved in 8 patients (88.89%) based on clinical comparisons between pre- and postoperative MRI and intraoperative video. One patient had symptom recurrence 1 year after subtotal resection, while there was no evidence of recurrence during follow-up for the other patients. Dense adhesions within the spinal cord were observed in 8 patients (88.89%) intraoperatively. Most importantly, the surgical outcome was significantly improved in all patients, and the mean (± SE) Japanese Orthopaedic Association score increased from 11.33 ± 0.91 preoperatively to 16.22 ± 0.32 postoperatively (p = 0.008). CONCLUSIONS: An anterior surgical approach was proven to be both safe and effective in treating the ventral or ventrolateral SCNCs. The authors believe that an anterior microsurgical approach should be considered as a useful approach especially in patients with ventral recurrent SCNCs. Its clinical efficacy compared with a posterior approach in ventral spinal cyst may be better as most of the neurenteric cysts are ventrally or ventrolaterally located.
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BACKGROUND: Diffusion tensor imaging (DTI) has been increasingly recognized for its capability to study microstructural changes in the neuropathology of brain diseases. However, the optimal DTI metric and its diagnostic utility for a variety of spinal cord diseases are still under investigation. PURPOSE: To evaluate the diagnostic efficacy of DTI metrics for differentiating between cervical spondylosis, myelitis, and spinal tumors. METHODS: This retrospective study analyzed DTI scans from 68 patients (22 with cervical spondylosis, 23 with myelitis, and 23 with spinal tumors). DTI indicators, including fractional anisotropy (FA), mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD), were calculated. The Kruskal-Wallis test was used to compare these indicators, followed by Receiver Operating Characteristic (ROC) curve analysis, to evaluate the diagnostic efficacy of each indicator across disease pairs. Additionally, we explored the correlations of DTI indicators with specific clinical measurements. RESULTS: FA values were significantly lower in tumor patients compared to those with cervical spondylosis (p < 0.0001) and myelitis (p < 0.05). Additionally, tumor patients exhibited significantly elevated MD and RD values relative to the spondylosis and myelitis groups. ROC curve analysis underscored FA's superior discriminative performance, with an area under the curve (AUC) of 0.902 for differentiating tumors from cervical spondylosis, and an AUC of 0.748 for distinguishing cervical myelitis from spondylosis. Furthermore, a significant negative correlation was observed between FA values and Expanded Disability Status Scores (EDSSs) in myelitis patients (r = -0.62, p = 0.002), as well as between FA values and Ki-67 scores in tumor patients (r = -0.71, p = 0.0002). CONCLUSION: DTI indicators, especially FA, have the potential in distinguishing spondylosis, myelitis, and spinal cord tumors. The significant correlation between FA values and clinical indicators highlights the value of FA in the clinical assessment and prognosis of spinal diseases and may be applied in diagnostic protocols in the future.
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Extra-axial cavernous hemangiomas (ECHs) are complex vascular lesions mainly found in the spine and cavernous sinus. Their removal poses significant risk due to their vascularity and diffuse nature, and their genetic underpinnings remain incompletely understood. Our approach involved genetic analyses on 31 tissue samples of ECHs employing whole-exome sequencing and targeted deep sequencing. We explored downstream signaling pathways, gene expression changes, and resultant phenotypic shifts induced by these mutations, both in vitro and in vivo. In our cohort, 77.4% of samples had somatic missense variants in GNA14, GNAQ, or GJA4. Transcriptomic analysis highlighted significant pathway upregulation, with the GNAQ c.626A>G (p.Gln209Arg) mutation elevating PI3K-AKT-mTOR and angiogenesis-related pathways, while GNA14 c.614A>T (p.Gln205Leu) mutation led to MAPK and angiogenesis-related pathway upregulation. Using a mouse xenograft model, we observed enlarged vessels from these mutations. Additionally, we initiated rapamycin treatment in a 14-year-old individual harboring the GNAQ c.626A>G (p.Gln209Arg) variant, resulting in gradual regression of cutaneous cavernous hemangiomas and improved motor strength, with minimal side effects. Understanding these mutations and their pathways provides a foundation for developing therapies for ECHs resistant to current therapies. Indeed, the administration of rapamycin in an individual within this study highlights the promise of targeted treatments in treating these complex lesions.
Subject(s)
GTP-Binding Protein alpha Subunits, Gq-G11 , GTP-Binding Protein alpha Subunits , Humans , GTP-Binding Protein alpha Subunits, Gq-G11/genetics , Animals , Mice , Female , Male , GTP-Binding Protein alpha Subunits/genetics , Mutation , Adult , Middle Aged , Signal Transduction , Hemangioma, Cavernous/genetics , Hemangioma, Cavernous/pathology , Adolescent , Exome Sequencing , Sirolimus/pharmacology , Sirolimus/therapeutic use , TOR Serine-Threonine Kinases/metabolism , TOR Serine-Threonine Kinases/geneticsABSTRACT
OBJECTIVE: The optimal choice for fusion strategy in Anterior Cervical Discectomy and Fusion (ACDF) remains an unresolved issue. This study aims to perform a network meta-analysis and systematic review of fusion rate and complication rate of various fusion strategies used in ACDF. METHODS: This study followed Prisma guidelines, and we searched PubMed, Embase, Cochrane Library, and Web of Science from inception to November 11, 2022, for Randomized Controlled trials comparing the efficacy and safety of fusion modalities in ACDF. The primary outcome was the fusion rate and complication rate. The PROSPERO number is CRD42022374440. RESULTS: This meta-analysis identified 26 Randomized Controlled trial studies with 1789 patients across 15 fusion methods. The cage with autograft + plating showed the highest fusion rate, surpassing other methods like iliac crest bone graft (ICBG) and artificial bone graft (AFG). The stand-alone cage with autograft (SATG) had the second highest fusion rate. Regarding complication rate, the cage with AFG (CAFG) had the highest rate, more than other methods. The ICBG had a higher complication rate compared to ICBG + P, AFG, stand-alone cage with artificial bone graft, SATG, and CALG. The SATG performed well in both fusion and complication rate. CONCLUSIONS: In this study, we conducted the first network meta-analysis to compare the efficacy and safety of various fusion methods in ACDF. Our findings suggest that SATG, with superior performance in fusion rate and complication rate, may be the optimal choice for ACDF. However, the results should be interpreted cautiously until additional research provides further evidence.
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OBJECTIVE: To develop and validate a computed tomography (CT)-based scoring system for evaluating the risk of dural defects (DDs) in anterior surgery for cervical ossification of the posterior longitudinal ligament (OPLL). METHODS: We retrospectively analyzed CT imaging features of 114 OPLL patients in our institute who received anterior decompression surgery. Intraoperative DDs were found in 16 patients. A multivariable logistic regression was used to evaluate the predictors. According to the odd ratio of the included risk factors, we developed a CT scoring system for evaluating the risk of DDs in anterior OPLL surgery. The system was further validated in an independent group of 39 OPLL patients. RESULTS: We developed a CT scoring system as follows: hook sign (2 points), K-line (-) (1 point) and broad base (1 point). Thus, the system comprised 4 total points, and patients were at high risks of dural defects when the score ≥3 points. The operating characteristics of a score ≥3 for predicting DDs in the validation group were: sensitivity of 0.83, specificity of 0.94, LR positive of 13.75, LR negative of 0.18 and AUC of 0.886. The discriminatory ability of the proposed score could be demonstrated in the validation cohort. CONCLUSIONS: The relatively simple and easy-to-use scoring system we propose integrates the 3 most reliable spinal CT findings observed in patients with OPLL and a DD. The likelihood to identify the underlying risks of spinal CSF leaks may be useful to triage patients who may benefit from indirect decompression techniques.
Subject(s)
Cervical Vertebrae , Decompression, Surgical , Dura Mater , Ossification of Posterior Longitudinal Ligament , Tomography, X-Ray Computed , Humans , Ossification of Posterior Longitudinal Ligament/surgery , Ossification of Posterior Longitudinal Ligament/diagnostic imaging , Male , Female , Middle Aged , Aged , Tomography, X-Ray Computed/methods , Dura Mater/surgery , Dura Mater/diagnostic imaging , Decompression, Surgical/methods , Retrospective Studies , Cervical Vertebrae/surgery , Cervical Vertebrae/diagnostic imaging , Adult , Risk FactorsABSTRACT
BACKGROUND: Chordomas are rare osseous neoplasms with a dismal prognosis when they recur. Here we identified cell surface proteins that could potentially serve as novel immunotherapeutic targets in patients with chordoma. METHODS: Fourteen chordoma samples from patients attending Xuanwu Hospital Capital Medical University were subjected to single-cell RNA sequencing. Target molecules were identified on chordoma cells and cancer metastasis-related signalling pathways characterised. VEGFR-targeting CAR-T cells and VEGFR CAR-T cells with an additional TGF-ß scFv were synthesised and their in vitro antitumor activities were evaluated, including in a primary chordoma organoid model. RESULTS: Single-cell transcriptome sequencing identified the chordoma-specific antigen VEGFR and TGF-ß as therapeutic targets. VRGFR CAR-T cells and VEGFR/TGF-ß scFv CAR-T cells recognised antigen-positive cells and exhibited significant antitumor effects through CAR-T cell activation and cytokine secretion. Furthermore, VEGFR/TGF-ß scFv CAR-T cells showed enhanced and sustained cytotoxicity of chordoma cell lines in vitro compared with VRGFR CAR-T cells. CONCLUSIONS: This study provides a comprehensive single-cell landscape of human chordoma and highlights its heterogeneity and the role played by TGF-ß in chordoma progression. Our findings substantiate the potential of VEGFR as a target for CAR-T cell therapies in chordoma which, together with modulated TGF-ß signalling, may augment the efficacy of CAR-T cells.
Subject(s)
Chordoma , Immunotherapy, Adoptive , Single-Cell Analysis , Humans , Chordoma/therapy , Chordoma/genetics , Chordoma/pathology , Chordoma/immunology , Immunotherapy, Adoptive/methods , Female , Male , Transforming Growth Factor beta/metabolism , Cell Line, Tumor , Receptors, Chimeric Antigen/immunology , Receptors, Chimeric Antigen/genetics , Middle Aged , Adult , Bone Neoplasms/therapy , Bone Neoplasms/pathology , Bone Neoplasms/genetics , Bone Neoplasms/immunologyABSTRACT
BACKGROUND AND OBJECTIVES: Venous hypertensive myelopathy (VHM), mainly induced by the spinal dural arteriovenous fistula, is a congestive spinal cord injury that currently has no appropriate animal model available in preclinical research. METHODS: Sprague Dawley rats (280-320 g) were used. The rats were divided into 3 groups: (1) Group 1, which underwent renal artery-dorsal spinal venous bypass (AVB group); (2) Group 2, which underwent renal artery-dorsal spinal venous bypass and drainage vein stenosis (AVB/VS group); and (3) Control group, with T13 dorsal vein ligation. The success of the model was assessed using Doppler ultrasound and 7.0-T magnetic resonance imaging. Transmission electron microscopy, histochemistry, proteomics, and western blot analysis were used to evaluate ultrastructural, pathological, and molecular features in the spinal cord and cerebrospinal fluid (CSF). RESULTS: The success rate of the arteriovenous bypass was 100% at 5 days and 83% at 2 weeks. The locomotor assessment showed decreased lower extremity strength in the AVB/VS group ( P = .0067), whereas unremarkable changes were found in the AVB and Control groups. Histochemical staining suggested a 2-fold expansion of the dorsal spinal vein in the AVB/VS group, which was lower than that in the AVB group ( P < .05); however, the former displayed greater myelin and neuronal damage ( P < .05) and slight dilatation of the central canal ( P > .05). Proteomics analysis revealed that the complement and coagulation cascade pathways were upregulated in the CSF of AVB/VS rats, whereas the C3 level was elevated both in the CSF and bilateral spinal cord. Furthermore, overexpression of C3, ITGB2, and CD9 in the spinal cord was confirmed by immunoblotting. CONCLUSION: These findings suggest that the AVB/VS model can effectively mimic the clinical and molecular characteristics of VHM. Furthermore, they suggest that impaired deep intramedullary venous drainage is the key reason for the VHM.
Subject(s)
Disease Models, Animal , Rats, Sprague-Dawley , Animals , Rats , Male , Spinal Cord Diseases/surgery , Spinal Cord Diseases/etiology , Spinal Cord Diseases/diagnostic imaging , Spinal Cord/metabolism , Spinal Cord/pathology , Spinal Cord/diagnostic imaging , Constriction, Pathologic , Arteriovenous Shunt, Surgical , HypertensionABSTRACT
OBJECTIVE: Recent years have witnessed a rapidly growing interest in CVJ bony abnormalities, and a qualitative and quantitative analysis of relevant literatures is necessary. This study aims to identify and summarize the published articles related to craniovertebral junction bony abnormalities, to analyze and visualize the current research trends and major contributors. METHODS: We collected data from Web of Science, excluding certain article types. Two researchers screened articles for relevance. Data were organized with EndnoteX9, and analyzed using VOSviewer and CiteSpace for co-authorship, co-occurrence, keyword burst, and co-citation analyses to identify research trends and collaborations. RESULTS: A total of 2,776 articles were included, revealing an increasing trend in annual publications of CVJ bony abnormalities. The USA was the leading country. King Edward Memorial Hospital was the most prolific institution, and Seth GS Medical College had the most citations. The Spine is the most popular journal with the highest number of publications and citations. Professor Goel Atul from India emerged as the most influential pioneer in this field. Keyword analysis highlighted surgical techniques, diagnosis, and anatomy as the primary research hotspots and Fixation, Placement, and Basilar invagination gradually become the new research trend. However, there is a relative weakness in basic research and epidemiology. CONCLUSIONS: This study provides valuable insights into the current research trends and critical contributors in CVJ bony abnormalities, guiding evidence-based decisions and fostering international collaborations to advance knowledge in this field.
Subject(s)
Bibliometrics , Humans , Atlanto-Occipital Joint/abnormalities , Atlanto-Axial Joint/abnormalitiesABSTRACT
PURPOSE: Surgical treatment for atlantoaxial instability in pediatric patients is challenging. We report our experience with posterior intra-articular distraction technique in treating this disorder. METHODS: This is a retrospective descriptive study which included 15 patients of atlantoaxial instability whose age was less than 16 years at the time of clinical presentation. All patients underwent anterior soft tissue released through a posterior-only approach, followed by intra-facet cage implantation, cantilever correction, and instrumentation. Clinical results were measured using the Japanese Orthopedic Association (JOA) scale and radiographic measurements including the atlantodental interval (ADI), posterior atlantodental interval (pADI), the distance of odontoid tip above Chamberlain's line, clivuscanal angle (CCA), and triangular area (TA) of craniovertebral junction. RESULTS: The follow-up period ranged from 18 to 72 months, with an average of 41.2 ± 15.2 months. The JOA score increased from 13.6 ± 2.3 to 16.6 ± 0.8. ADI decreased from 4.31 ± 2.37 to 1.85 ± 1.09 mm, and TA decreased from 261.96 ± 107.99 to 197.12 ± 72.37 mm2. pADI increased from 12.89 ± 3.52 to 18.25 ± 3.89 mm, and CCA improved from 132.19 ± 16.34 to 144.35 ± 13.91°. All changes in measurements showed statistically significant. There were no evidence of surgery-related complications or iatrogenic secondary cervical deformity during follow-up. Radiological evaluation showed satisfactory corrections and bony fusions of C1-2 facet joint in all cases. CONCLUSION: Posterior intra-articular distraction followed by cage implantation and cantilever correction can be one of the safe and effective ways to solve atlantoaxial instability in pediatric patients.
Subject(s)
Atlanto-Axial Joint , Joint Instability , Humans , Atlanto-Axial Joint/surgery , Atlanto-Axial Joint/diagnostic imaging , Joint Instability/surgery , Joint Instability/diagnostic imaging , Female , Male , Child , Adolescent , Retrospective Studies , Treatment Outcome , Spinal Fusion/methods , Child, PreschoolABSTRACT
OBJECTIVE: Surgical procedures for patients with posttraumatic syringomyelia (PTS) remain controversial. Until now, there have been no effective quantitative evaluation methods to assist in selecting appropriate surgical plans before surgery. METHODS: We consecutively enrolled PTS patients (arachnoid lysis group, n = 42; shunting group, n = 14) from 2003 to 2023. Additionally, 19 intrathecal anesthesia patients were included in the control group. All patients with PTS underwent physical and neurological examinations and spinal magnetic resonance imaging preoperatively, 3-12 months postoperatively and during the last follow-up. Preoperative lumbar puncture was performed and blood-spinal cord barrier disruption was detected by quotient of albumin (Qalb, cerebrospinal fluid/serum). RESULTS: The ages (p = 0.324) and sex (p = 0.065) of the PTS and control groups did not differ significantly. There were also no significant differences in age (p = 0.216), routine blood data and prognosis (p = 0.399) between the arachnoid lysis and shunting groups. But the QAlb level of PTS patients was significantly higher than that of the control group (p < 0.001), and the shunting group had a significantly higher QAlb (p < 0.001) than the arachnoid lysis group. A high preoperative QAlb (odds ratio, 1.091; 95% confidence interval, 1.004-1.187; p = 0.041) was identified as the predictive factor for the shunting procedure, with the receiver operating characteristic curve showing 100% specificity and 80.95% sensitivity for patients with a QAlb > 12.67. CONCLUSION: Preoperative QAlb is a significant predictive factor for the types of surgery. For PTS patients with a QAlb > 12.67, shunting represents the final recourse, necessitating the exploration and development of novel treatments for these patients.
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BACKGROUND: The spinal inflammatory signal often spreads to distant segments, accompanied by widespread pain symptom under neuropathological conditions. Multiple cytokines are released into the cerebrospinal fluid (CSF), potentially inducing the activation of an inflammatory cascade at remote segments through CSF flow. However, the detailed alteration of CSF in neuropathic pain and its specific role in widespread pain remain obscure. METHODS: A chronic constriction injury of the infraorbital nerve (CCI-ION) model was constructed, and pain-related behavior was observed on the 7th, 14th, 21st, and 28th days post surgery, in both vibrissa pads and hind paws. CSF from CCI-ION rats was transplanted to naïve rats through intracisternal injection, and thermal and mechanical allodynia were measured in hind paws. The alteration of inflammatory cytokines in CCI-ION's CSF was detected using an antibody array and bioinformatic analysis. Pharmacological intervention targeting the changed cytokine in the CSF and downstream signaling was performed to evaluate its role in widespread pain. RESULTS: CCI-ION induced local pain in vibrissa pads together with widespread pain in hind paws. CCI-ION's CSF transplantation, compared with sham CSF, contributed to vibrissa pad pain and hind paw pain in recipient rats. Among the measured cytokines, interleukin-6 (IL-6) and leptin were increased in CCI-ION's CSF, while interleukin-13 (IL-13) was significantly reduced. Furthermore, the concentration of CSF IL-6 was correlated with nerve injury extent, which gated the occurrence of widespread pain. Both astrocytes and microglia were increased in remote segments of the CCI-ION model, while the inhibition of astrocytes in remote segments, but not microglia, significantly alleviated widespread pain. Mechanically, astroglial signal transducer and activator of transcription 3 (STAT3) in remote segments were activated by CSF IL-6, the inhibition of which significantly mitigated widespread pain in CCI-ION. CONCLUSION: IL-6 was induced in the CSF of the CCI-ION model, triggering widespread pain via activating astrocyte STAT3 signal in remote segments. Therapies targeting IL-6/STAT3 signaling might serve as a promising strategy for the widespread pain symptom under neuropathological conditions.
Subject(s)
Interleukin-6 , Neuralgia , Rats , Animals , Interleukin-6/metabolism , Rats, Sprague-Dawley , STAT3 Transcription Factor/metabolism , Gliosis/complications , Constriction , Hyperalgesia/etiology , Hyperalgesia/drug therapy , Neuralgia/drug therapy , CytokinesABSTRACT
Spinal cord injury (SCI) results in neurological deficits below the level of injury, causing motor dysfunction and various severe multisystem complications. Rehabilitative training plays a crucial role in the recovery of individuals with SCI, and exoskeleton serves as an emerging and promising tool for rehabilitation, especially in promoting neuroplasticity and alleviating SCI-related complications. This article reviews the classifications and research progresses of medical exoskeletons designed for SCI patients and describes their performances in practical application separately. Meanwhile, we discuss their mechanisms for enhancing neuroplasticity and functional remodeling, as well as their palliative impacts on secondary complications. The potential trends in exoskeleton design are raised according to current progress and requirements on SCI rehabilitation.