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OBJECTIVE: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments. METHODS: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation. RESULTS: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months. CONCLUSION: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer.
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STUDY DESIGN: Multicenter, prospective registry study. OBJECTIVE: To clarify minimal clinically important differences (MCIDs) for surgical interventions for spinal metastases, thereby enhancing patient care by integrating quality of life (QoL) assessments with clinical outcomes. SUMMARY OF BACKGROUND DATA: Despite its proven usefulness in degenerative spinal diseases and deformities, the MCID remains unexplored regarding surgery for spinal metastases. METHODS: This study included 171 (out of 413) patients from the multicenter "Prospective Registration Study on Surgery for Metastatic Spinal Tumors" by the Japan Association of Spine Surgeons. These were evaluated preoperatively and at 6 months postoperatively using the Face scale, EuroQol-5 Dimensions-5 Levels (EQ-5D-5L), including the visual analog scale (VAS), and performance status. The MCIDs were calculated using an anchor-based method, classifying participants into the improved, unchanged, and deteriorated groups based on the Face scale scores. Focusing on the improved and unchanged groups, the change in the EQ-5D-5L values from before to after treatment was analyzed, and the cutoff value with the highest sensitivity and specificity was determined as the MCID through receiver operating characteristic curve analysis. The validity of the MCIDs was evaluated using a distribution-based calculation method for patient-reported outcomes. RESULTS: The improved, unchanged, and deteriorated groups comprised 121, 28, and 22 participants, respectively. The anchor-based MCIDs for the EQ-5D-5L index, EQ-VAS, and domains of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression were 0.21, 15.50, 1.50, 0.50, 0.50, 0.50, and 0.50, respectively; the corresponding distribution-based MCIDs were 0.17, 15,99, 0.77, 0.80, 0.78, 0.60, and 0.70, respectively. CONCLUSION: We identified MCIDs for surgical treatment of spinal metastases, providing benchmarks for future clinical research. By retrospectively examining whether the MCIDs are achieved, factors favoring their achievement and risks affecting them can be explored. This could aid in decisions on surgical candidacy and patient counseling.
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Background: Spinal metastases can impair mobility, worsening the Karnofsky Performance Status (KPS). Surgery for spinal metastases has the potential to improve KPS and extend prognosis, but it is crucial to recognize the elevated risk of perioperative complications. Therefore, the development of a new scoring system to accurately predict perioperative complications in spinal metastatic surgery is essential. Methods: We conducted a retrospective observational study with 86 patients who underwent surgical intervention for spinal metastases. Patients were divided into two groups based on the presence or absence of perioperative complications within 14 days after surgery. Various factors related to perioperative complications were assessed through univariate and multivariate analyses. We established a clinical prognostic scoring system called the Perioperative Complications following Metastatic Spinal Surgery (PERCOM) score and evaluated its precision using receiver operating characteristic (ROC) analysis. Results: Five variables (age, KPS, primary prostate cancer, Albumin, and Hemoglobin) identified in the univariate analysis were assigned binary values of 0 or 1. The PERCOM score was then calculated for each patient by summing the individual points, ranging from 0 to 5. The optimal threshold determined by ROC curve analysis for the PERCOM score was 2 points, with a sensitivity of 86 % and a specificity of 56 %. Conclusions: The composite PERCOM score effectively predicted perioperative complications in spinal metastasis surgery. To further validate its precision, a prospective multicenter study is needed.
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BACKGROUND: In patients with cervical spinal cord injury (SCI), we need to make accurate prognostic predictions in the acute phase for more effective rehabilitation. We hypothesized that a multivariate prognosis would be useful for patients with cervical SCI. METHODS: We made two predictive models using Multiple Linear Regression (MLR) and Artificial Neural Networks (ANNs). We adopted MLR as a conventional predictive model. Both models were created using the same 20 clinical parameters of the acute phase data at the time of admission. The prediction results were classified by the ASIA Impairment Scale. The training data consisted of 60 cases, and prognosis prediction was performed for 20 future cases (test cohort). All patients were treated in the Spinal Injuries Center (SIC) in Fukuoka, Japan. RESULTS: A total of 16 out of 20 cases were predictable. The correct answer rate of MLR was 31.3%, while the rate of ANNs was 75.0% (number of correct answers: 12). CONCLUSION: We were able to predict the prognosis of patients with cervical SCI from acute clinical data using ANNs. Performing effective rehabilitation based on this prediction will improve the patient's quality of life after discharge. Although there is room for improvement, ANNs are useful as a prognostic tool for patients with cervical SCI.
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STUDY DESIGN: Retrospective study. OBJECTIVE: To investigate the characteristics of newly developing Modic changes following discectomy and their impact on residual low back pain (LBP) in the early postoperative stage of lumbar disc herniation. METHODS: We included 96 patients who underwent microscopic discectomy. Through MRI, we assessed new developments of Modic changes and the progression of disc degeneration at the surgical level. The presence of cartilaginous endplates was evaluated using resected specimens, and the main outcome was assessed using the visual analog scale (VAS). Further, the prevalence and time course of Modic changes, and their effects on clinical outcomes in the early postoperative period were examined. RESULTS: A new development of Modic changes was detected in 28% of cartilaginous herniations at 6 months. Modic changes were observed more frequently in patients with cartilaginous herniation than in those without cartilaginous herniation postoperatively (P < .001). The VAS scores for LBP up to 6 months were greater in patients with Modic changes (P < .001) than those without; however, no significant differences were identified in the presence or absence of Modic changes over the year follow-up. The development of Modic changes was closely associated with residual LBP at 6 months (ß:0.511, P < .001). CONCLUSIONS: Modic changes develop predominantly in patients with avulsion-type herniation than in those with annular rupture at an earlier phase after discectomy. Furthermore, disc herniation with cartilaginous endplates may be associated with a slower decrease in LBP for up to 6 months, supporting the notion that newly developing endplate changes may cause residual LBP.
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In osteoclastogenesis, the metabolism of metal ions plays an essential role in controlling reactive oxygen species (ROS) production, mitochondrial biogenesis, and survival, and differentiation. However, the mechanism regulating metal ions during osteoclast differentiation remains unclear. The metal-binding protein metallothionein (MT) detoxifies heavy metals, maintains metal ion homeostasis, especially zinc, and manages cellular redox levels. We carried out tests using murine osteoclast precursors to examine the function of MT in osteoclastogenesis and evaluated their potential as targets for future osteoporosis treatments. MT genes were significantly upregulated upon differentiation from osteoclast precursors to mature osteoclasts in response to receptor activators of nuclear factor-κB (NF-κB) ligand (RANKL) stimulation, and MT3 expression was particularly pronounced in mature osteoclasts among MT genes. The knockdown of MT3 in osteoclast precursors demonstrated a remarkable inhibition of differentiation into mature osteoclasts. In preosteoclasts, MT3 knockdown suppressed the activity of mitogen-activated protein kinase (MAPK) and NF-κB signaling pathways upon RANKL stimulation, leading to affect cell survival through elevated cleaved Caspase 3 and poly (ADP-ribose) polymerase (PARP) levels. Additionally, ROS levels were decreased, and nuclear factor erythroid 2-related factor 2 (NRF2) (a suppressor of ROS) and the downstream antioxidant proteins, such as catalase (CAT) and heme oxygenase 1 (HO-1), were more highly expressed in the MT3 preosteoclast knockdowns. mitochondrial ROS, which is involved in mitochondrial biogenesis and the production of reactive oxygen species, were similarly decreased because cAMP response element-binding (CREB) and peroxisome proliferator-activated receptor γ coactivator 1ß (PGC-1ß) were less activated due to MT3 depletion. Thus, by modulating ROS through the NRF2 pathway, MT3 plays a crucial role in regulating osteoclast differentiation and survival, acting as a metabolic modulator of intracellular zinc ions.
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Background: Spinal cord injury (SCI) is a devastating disease that results in permanent paralysis. Currently, there is no effective treatment for SCI, and it is important to identify factors that can provide therapeutic intervention during the course of the disease. Zinc, an essential trace element, has attracted attention as a regulator of inflammatory responses. In this study, we investigated the effect of zinc status on the SCI pathology and whether or not zinc could be a potential therapeutic target. Methods: We created experimental mouse models with three different serum zinc concentration by changing the zinc content of the diet. After inducing contusion injury to the spinal cord of three mouse models, we assessed inflammation, apoptosis, demyelination, axonal regeneration, and the number of nuclear translocations of NF-κB in macrophages by using qPCR and immunostaining. In addition, macrophages in the injured spinal cord of these mouse models were isolated by flow cytometry, and their intracellular zinc concentration level and gene expression were examined. Functional recovery was assessed using the open field motor score, a foot print analysis, and a grid walk test. Statistical analysis was performed using Wilcoxon rank-sum test and ANOVA with the Tukey-Kramer test. Results: In macrophages after SCI, zinc deficiency promoted nuclear translocation of NF-κB, polarization to pro-inflammatory like phenotype and expression of pro-inflammatory cytokines. The inflammatory response exacerbated by zinc deficiency led to worsening motor function by inducing more apoptosis of oligodendrocytes and demyelination and inhibiting axonal regeneration in the lesion site compared to the normal zinc condition. Furthermore, zinc supplementation after SCI attenuated these zinc-deficiency-induced series of responses and improved motor function. Conclusion: We demonstrated that zinc affected axonal regeneration and motor functional recovery after SCI by negatively regulating NF-κB activity and the subsequent inflammatory response in macrophages. Our findings suggest that zinc supplementation after SCI may be a novel therapeutic strategy for SCI.
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Doenças Desmielinizantes , Traumatismos da Medula Espinal , Camundongos , Animais , NF-kappa B/metabolismo , Traumatismos da Medula Espinal/patologia , Macrófagos/metabolismo , Modelos Animais de Doenças , Minerais/uso terapêutico , Zinco/metabolismo , Doenças Desmielinizantes/metabolismoRESUMO
After spinal cord injury (SCI), inflammatory cells such as macrophages infiltrate the injured area, and astrocytes migrate, forming a glial scar around macrophages. The glial scar inhibits axonal regeneration, resulting in significant permanent disability. However, the mechanism through which glial scar-forming astrocytes migrate to the injury site has not been clarified. Here we show that migrating macrophages attract reactive astrocytes toward the center of the lesion after SCI. Chimeric mice with bone marrow lacking IRF8, which controls macrophage centripetal migration after SCI, showed widely scattered macrophages in the injured spinal cord with the formation of a huge glial scar around the macrophages. To determine whether astrocytes or macrophages play a leading role in determining the directions of migration, we generated chimeric mice with reactive astrocyte-specific Socs3-/- mice, which showed enhanced astrocyte migration, and bone marrow from IRF8-/- mice. In this mouse model, macrophages were widely scattered, and a huge glial scar was formed around the macrophages as in wild-type mice that were transplanted with IRF8-/- bone marrow. In addition, we revealed that macrophage-secreted ATP-derived ADP attracts astrocytes via the P2Y1 receptor. Our findings revealed a mechanism through which migrating macrophages attract astrocytes and affect the pathophysiology and outcome after SCI.
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Gliose , Traumatismos da Medula Espinal , Animais , Camundongos , Fatores Reguladores de Interferon , MacrófagosRESUMO
Neonatal spinal cord injury (SCI) shows better functional outcomes than adult SCI. Although the regenerative capability in the neonatal spinal cord may have cues in the treatment of adult SCI, the mechanism underlying neonatal spinal cord regeneration after SCI is unclear. We previously reported age-dependent variation in the pathogenesis of inflammation after SCI. Therefore, we explored differences in the pathogenesis of inflammation after SCI between neonatal and adult mice and their effect on axon regeneration and functional outcome. We established two-day-old spinal cord crush mice as a model of neonatal SCI. Immunohistochemistry of the spinal cord revealed that the nuclear translocation of NF-κB, which promotes the expression of chemokines, was significantly lower in the astrocytes of neonates than in those of adults. Flow cytometry revealed that neonatal astrocytes secrete low levels of chemokines to recruit circulating neutrophils (e.g., Cxcl1 and Cxcl2) after SCI in comparison with adults. We also found that the expression of a chemokine receptor (CXCR2) and an adhesion molecule (ß2 integrin) quantified by flow cytometry was lower in neonatal circulating neutrophils than in adult neutrophils. Strikingly, these neonate-specific cellular properties seemed to be associated with no neutrophil infiltration into the injured spinal cord, followed by significantly lower expression of inflammatory cytokines (Il-1ß, Il-6 and TNF-α) after SCI in the spinal cords of neonates than in those of adults. At the same time, significantly fewer apoptotic neurons and greater axonal regeneration were observed in neonates in comparison with adults, which led to a marked recovery of locomotor function. This neonate-specific mechanism of inflammation regulation may have potential therapeutic applications in controlling inflammation after adult SCI.
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Traumatismos da Medula Espinal , Regeneração da Medula Espinal , Camundongos , Animais , Neutrófilos/metabolismo , Animais Recém-Nascidos , Doenças Neuroinflamatórias , Axônios/patologia , Astrócitos/metabolismo , Medula Espinal/metabolismo , Inflamação/etiologia , QuimiocinasRESUMO
Joint contracture causes distressing permanent mobility disorder due to trauma, arthritis, and aging, with no effective treatment available. A principal and irreversible cause of joint contracture has been regarded as the development of joint capsule fibrosis. However, the molecular mechanisms underlying contracture remain unclear. We established a mouse model of knee joint contracture, revealing that fibrosis in joint capsules causes irreversible contracture. RNA-sequencing of contracture capsules demonstrated a marked enrichment of the genes involved in the extracellular region, particularly periostin (Postn). Three-dimensional magnetic resonance imaging and immunohistological analysis of contracture patients revealed posterior joint capsule thickening with abundant type I collagen (Col1a2) and POSTN in humans. Col1a2-GFPTG ; Postn-/- mice and chimeric mice with Col1a2-GFPTG ; tdTomatoTG bone marrow showed fibrosis in joint capsules caused by bone marrow-derived fibroblasts, and POSTN promoted the migration of bone marrow-derived fibroblasts, contributing to fibrosis and contracture. Conversely, POSTN-neutralizing antibody attenuated contracture exacerbation. Our findings identified POSTN as a key inducer of fibroblast migration that exacerbates capsule fibrosis, providing a potential therapeutic strategy for joint contracture.
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Medula Óssea , Contratura , Humanos , Camundongos , Animais , Medula Óssea/patologia , Amplitude de Movimento Articular , Contratura/genética , Contratura/tratamento farmacológico , Fibrose , Fibroblastos/patologiaRESUMO
After spinal cord injury (SCI), inflammatory cells such as macrophages infiltrate the injured area, and astrocytes migrate, forming a glial scar around macrophages. The glial scar inhibits axonal regeneration, resulting in significant permanent disability. However, the mechanism by which glial scar-forming astrocytes migrate to the injury site has not been clarified. Here we show that migrating macrophages attract reactive astrocytes toward the center of the lesion after SCI. Chimeric mice with bone marrow lacking IRF8, which controls macrophage centripetal migration after SCI, showed widely scattered macrophages in injured spinal cord with the formation of a huge glial scar around the macrophages. To determine whether astrocytes or macrophages play a leading role in determining the directions of migration, we generated chimeric mice with reactive astrocyte-specific Socs3 -/- mice, which showed enhanced astrocyte migration, and bone marrow from IRF8 -/- mice. In this mouse model, macrophages were widely scattered, and a huge glial scar was formed around the macrophages as in wild-type mice that were transplanted with IRF8 -/ bone marrow. In addition, we revealed that macrophage-secreted ATP-derived ADP attracts astrocytes via the P2Y1 receptor. Our findings revealed a mechanism in which migrating macrophages attracted astrocytes and affected the pathophysiology and outcome after SCI.
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Objective: To investigate the usefulness of the combination of neurological findings and magnetic resonance imaging (MRI) as a prognostic predictor in patients with motor complete cervical spinal cord injury (CSCI) in the acute phase.Design: A cross-sectional analysisSetting: Department of Orthopaedic Surgery, Spinal Injuries CenterParticipants/Methods: Forty-two patients with an initial diagnosis of motor complete CSCI (AIS A, n = 29; AIS B, n = 13) within 72â h after injury were classified into the recovery group (Group R) and the non-recovery group (Group N), based on the presence or absence of motor recovery (conversion from AIS A/B to C/D) at three months after injury, respectively. The Neurological Level of Injury (NLI) at the initial diagnosis was investigated and the presumptive primary injured segment of the spinal cord was inferred from MRI performed at the initial diagnosis. We investigated whether or not the difference between the presumptive primary injured segment and the NLI exceeded one segment. The presence of a difference between the presumptive primary injured segment and the NLI was compared between Groups R and N.Results: The number of cases with the differences between the presumptive primary injured segment and the NLI was significantly higher in Group N than in Group R.Conclusion: The presence of differences between the presumptive primary injured segment and the NLI might be a poor improving prognostic predictor for motor complete CSCI. The NLI may be useful for predicting the recovery potential of patients with motor complete CSCI when combined with the MRI findings.
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Medula Cervical , Lesões do Pescoço , Traumatismos da Medula Espinal , Humanos , Prognóstico , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico por imagem , Medula Cervical/lesões , Estudos Transversais , Estudos Retrospectivos , Vértebras Cervicais/lesõesRESUMO
OBJECTIVES: To elucidate the incidence and risk factors for pneumonia after acute traumatic cervical spinal cord injury (CSCI). DESIGN: Retrospective cohort study.Setting: Spinal injuries center in Japan.Participants: Of 184 individuals who were admitted within 2 weeks after acute traumatic cervical spinal injuries, 167 individuals who met the criteria were included in this study.Interventions: The occurrence of pneumonia, degree of dysphagia using the Dysphagia Severity Scale, patient age, history of smoking, presence of tracheostomy, vital capacity, level of injury, and the American Spinal Injury Association Impairment Scale (AIS) 2 weeks after injury were assessed.Outcomes: Incidence of pneumonia were analyzed. Moreover, the risk factors of pneumonia were evaluated using logistic regression analysis. RESULTS: From the 167 individuals who met the criteria, 30 individuals (18%) had pneumonia; in 26 (87%) of these individuals, pneumonia was aspiration related, defined as Dysphagia Severity Scale ≤ 4. The median occurrence of aspiration pneumonia was 11.5 days after injury. A logistic regression analysis revealed that severe AIS and severe Dysphagia Severity Scale scores were significant risk factors of pneumonia after CSCI. CONCLUSIONS: It was highly likely that the pneumonias following CSCI were related to aspiration based on the Dysphagia Severity Scale. In addition, most of the patients developed aspiration pneumonia within 1 month after injury. Aspiration and severe paralysis were significant risk factors for pneumonia. The treatment of dysphagia in the acute phase should be considered an important indicator to prevent pneumonia.
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Medula Cervical , Transtornos de Deglutição , Lesões do Pescoço , Pneumonia Aspirativa , Pneumonia , Traumatismos da Medula Espinal , Traumatismos da Coluna Vertebral , Humanos , Recém-Nascido , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/epidemiologia , Estudos Retrospectivos , Incidência , Transtornos de Deglutição/epidemiologia , Transtornos de Deglutição/etiologia , Medula Cervical/lesões , Vértebras Cervicais/lesões , Pneumonia/epidemiologia , Pneumonia/etiologia , Lesões do Pescoço/complicações , Fatores de Risco , Pneumonia Aspirativa/complicaçõesRESUMO
Spinal cord injury (SCI) causes reactive astrogliosis, the sequential phenotypic change of astrocytes in which naïve astrocytes (NAs) transform into reactive astrocytes (RAs) and subsequently become scar-forming astrocytes (SAs), resulting in glial scar formation around the lesion site and thereby limiting axonal regeneration and motor/sensory functional recovery. Inhibiting the transformation of RAs into SAs in the acute phase attenuates the reactive astrogliosis and promotes regeneration. However, whether or not SAs once formed can revert to RAs or SAs is unclear. We performed selective isolation of astrocytes from glial scars at different time points for a gene expression analysis and found that the expression of Sox9, an important transcriptional factor for glial cell differentiation, was significantly increased in chronic phase astrocytes (CAs) compared to SAs in the sub-acute phase. Furthermore, CAs showed a significantly lower expression of chondroitin sulfate proteoglycan (CSPG)-related genes than SAs. These results indicated that SAs changed their phenotypes according to the surrounding environment of the injured spinal cord over time. Even though the integrin-N-cadherin pathway is critical for glial scar formation, collagen-I-grown scar-forming astrocytes (Col-I-SAs) did not change their phenotype after depleting the effect of integrin or N-cadherin. In addition, we found that Col-I-SAs transplanted into a naïve spinal cord formed glial scar again by maintaining a high expression of genes involved in the integrin-N-cadherin pathway and a low expression of CSPG-related genes. Interestingly, the transplanted Col-I-SAs changed NAs into SAs, and anti-ß1-integrin antibody blocked the recruitment of SAs while reducing the volume of glial scar in the chronic phase. Our findings indicate that while the characteristics of glial scars change over time after SCI, SAs have a cell-autonomous function to form and maintain a glial scar, highlighting the basic mechanism underlying the persistence of glial scars after central nervous system injury until the chronic phase, which may be a therapeutic target.
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Gliose , Traumatismos da Medula Espinal , Humanos , Gliose/patologia , Astrócitos/metabolismo , Cicatriz/patologia , Traumatismos da Medula Espinal/patologia , Medula Espinal/patologia , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Integrina beta1/metabolismo , Caderinas/metabolismo , Integrinas/metabolismo , Integrinas/uso terapêutico , Inflamação/metabolismoRESUMO
In crush syndrome, massive muscle breakdown resulting from ischemia-reperfusion muscle injury can be a life-threatening condition that requires urgent treatment. Blood reperfusion into the ischemic muscle triggers an immediate inflammatory response, and neutrophils are the first to infiltrate and exacerbate the muscle damage. Since free zinc ion play a critical role in the immune system and the function of neutrophils is impaired by zinc depletion, we hypothesized that the administration of a zinc chelator would be effective for suppressing the inflammatory reaction at the site of ischemia-reperfusion injury and for improving of the pathology of crush syndrome. A crush syndrome model was created by using a rubber tourniquet to compress the bilateral hind limbs of mice at 8 weeks. A zinc chelator N,N,N',N'-tetrakis-(2-pyridylmethyl)-ethylenediamine (TPEN) was administered immediately after reperfusion in order to assess the anti-inflammatory effect of the chelator for neutrophils. Histopathological evaluation showed significantly less muscle breakdown and fewer neutrophil infiltration in TPEN administration group compared with control group. In addition, the expression levels of inflammatory cytokine and chemokine such as IL-6, TNFα, CXCL1, CXCL2, CXCR2, CCL2 in ischemia-reperfusion injured muscle were significantly suppressed with TPEN treatment. Less dilatation of renal tubules in histological evaluation in renal tissue and significantly better survival rate were demonstrated in TPEN treatment for ischemia-reperfusion injury in crush syndrome. The findings of our study suggest that zinc chelators contributed to the resolution of exacerbation of the inflammatory response and attenuation of muscle breakdown in the acute phase after crush syndrome. In addition, our strategy of attenuation of the acute inflammatory reaction by zinc chelators may provide a promising therapeutic strategy not only for crush syndrome, but also for other diseases driven by inflammatory reactions.
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Quelantes , Síndrome de Esmagamento , Infiltração de Neutrófilos , Traumatismo por Reperfusão , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Quelantes/uso terapêutico , Quimiocinas , Síndrome de Esmagamento/tratamento farmacológico , Citocinas , Etilenodiaminas , Inflamação/tratamento farmacológico , Interleucina-6/uso terapêutico , Isquemia/tratamento farmacológico , Camundongos , Músculos/patologia , Infiltração de Neutrófilos/efeitos dos fármacos , Reperfusão , Traumatismo por Reperfusão/complicações , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Borracha , Fator de Necrose Tumoral alfa/uso terapêutico , Zinco/farmacologiaRESUMO
STUDY DESIGN: Basic science study. OBJECTIVE: The aim of this study was to examine whether epidural fat tissue (EFT) transplantation can prevent epidural adhesion after laminectomy more efficiently than subcutaneous fat tissue (SFT) transplantation. SUMMARY OF BACKGROUND DATA: Epidural adhesion is almost inevitable after laminectomy. Although many materials have been used to prevent adhesion, none has been widely accepted. As EFT is an ectopic fat tissue located on the dura mater and there is no adhesion between EFT and the dura mater, we focused on the efficacy of EFT for adhesion prevention. METHODS: We examined the differences in histology and gene expression between EFT and SFT of mice. We performed laminectomy at the 10th thoracic level and immediately transplanted EFT or SFT to the dura mater in mice. At 6âweeks after transplantation, we performed histological and gene expression analyses and evaluated the adhesion tenacity. In addition, we examined the characteristic differences between human EFT and SFT. RESULTS: The adipocytes of EFT were significantly smaller than those of SFT in mice and humans. The gene expression of inflammatory cytokine and fibrosis-related factors was significantly higher in SFT than in EFT. At 6âweeks after transplantation, the percentage of the remaining fat area over the dura mater was significantly greater in the EFT group than in SFT group, and the adhesion tenacity score was significantly lower in the EFT group than that in the SFT group. An RNA sequencing analysis revealed 1921 differentially expressed genes (DEGs) between human EFT and SFT, and a Gene Ontology term associated with the inflammatory response was most highly enriched in SFT. CONCLUSION: EFT has different molecular and histological profiles from SFT and EFT grafting is more effective for epidural adhesion prevention than conventional SFT transplantation after laminectomy in a mouse model.Level of Evidence: N/A.
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Cicatriz , Laminectomia , Animais , Cicatriz/patologia , Cicatriz/prevenção & controle , Modelos Animais de Doenças , Dura-Máter/patologia , Dura-Máter/cirurgia , Espaço Epidural/patologia , Espaço Epidural/cirurgia , Fibrose , Humanos , Laminectomia/efeitos adversos , Camundongos , Gordura Subcutânea , Aderências Teciduais/genética , Aderências Teciduais/patologia , Aderências Teciduais/prevenção & controleRESUMO
Spinal meningioma is a common benign intradural spinal tumor. It has been reported that the local recurrence rate after surgical resection increases with longer follow-up duration. Simpson grade 1 resection could reduce the risk of recurrence, but this procedure needs dural reconstruction, which would cause cerebrospinal fluid (CSF) leakage or iatrogenic spinal cord injury. Saito et al. reported dura preservation technique to reduce the risk of CSF leakage, in which the meningioma together with the inner layer of the dura is removed and the outer layer is preserved for simple dural closure. The long-term outcomes with this technique have never been investigated. In this study, we retrospectively analyzed the data of 38 surgically treated patients (dura preservation technique, 12 patients; Simpson grade 2 resection, 26 patients) to assess the long-term recurrence rate (mean, 121.5 months; range, 60-228 months). The local recurrence rate in the dura preservation group was 8.3% (1 of 12 cases), which was similar to that in Simpson grade 2 resection group (2 of 26 cases [7.7%]). Although this case series did not indicate the significant difference in the recurrence rates between the dura preservation group and Simpson grade 2 group, we consider that this technique still has advantages for surgically less invasiveness in terms of dural reconstruction which is necessary for Simpson grade 1 and higher possibility of complete resection of tumors compared with Simpson grade 2 resection.
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Dura-Máter/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Procedimentos Neurocirúrgicos/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos , Neoplasias da Medula Espinal/cirurgia , TempoRESUMO
STUDY DESIGN: Retrospective chart audits. OBJECTIVE: To investigate the optimal timing at which permanent complete cervical spinal cord injury (CSCI) can be confirmed when evaluating paralysis caused by traumatic CSCI. SETTING: Department of Orthopedic Surgery, Spinal Injuries Center, Japan. METHODS: Two-hundred and three patients with CSCI that was classified with an American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade A (AIS A) within 72 h of the initial diagnosis of traumatic CSCI were included in the present study. Neurological data from the time of the initial diagnosis to 1 year after the injury were extracted. The number of those with recovery from AIS A and changes of AIS in the recovery were examined. RESULTS: Thirty-five of 203 (17%) patients whose injuries were initially classified with an AIS A showed recovery from AIS A. Thirty-four of 35 (97%) patients showed recovery from AIS A within 8 weeks after injury. CONCLUSION: If CSCI patients with AIS A have not recovered by 8 weeks, the likelihood that they will recover from AIS A is marginal. However, this conversely means that we must consider the possibility that a patient with a traumatic CSCI classified with an AIS A may still show recovery from AIS A within the first 8 weeks after injury.
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Medula Cervical/lesões , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/reabilitação , Adolescente , Adulto , Idoso , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Adulto JovemRESUMO
OBJECTIVE: Compression of the spinal cord by thoracic ossification of the posterior longitudinal ligament (T-OPLL) often causes severe thoracic myelopathy. Although surgery is the most effective treatment for T-OPLL, problems associated with surgical intervention require resolution because surgical outcomes are not always favorable, and a small number of patients experience deterioration of their neurological status after surgery. The aim of the present study was to examine the surgery-related risk factors contributing to poor clinical outcomes for myelopathy caused by T-OPLL. METHODS: Data were extracted from the records of 55 patients with thoracic myelopathy due to T-OPLL at institutions in the Fukuoka Spine Group. The mean follow-up period was 5.3 years. Surgical outcomes were assessed using the Japanese Orthopaedic Association (JOA) scale. To investigate the definitive factors associated with surgical outcomes, univariate and multivariate regression analyses were performed with several patient-related and surgery-related factors, including preoperative comorbidities, radiological findings, JOA score, surgical methods, surgical outcomes, and complications. RESULTS: Neurological status improved in 33 patients (60.0%) and deteriorated in 10 patients (18.2%) after surgery. The use of instrumentation was significantly associated with an improved outcome. In the comparison of surgical approaches, posterior decompression and fusion resulted in a significantly higher neurological recovery rate than did anterior decompression via a posterior approach and fusion or decompression alone. It was also found that postoperative neurological status was significantly poorer when there were fewer instrumented spinal levels than decompression levels. CSF leakage was a predictable risk factor for deterioration following surgery. CONCLUSIONS: It is important to identify preventable risk factors for poor surgical outcomes for T-OPLL. The findings of the present study suggest that intraoperative CSF leakage and a lower number of instrumented spinal fusion levels than decompression levels were exacerbating factors for the neurological improvement in T-OPLL surgery.
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Traumatic spinal cord injury (SCI) brings numerous inflammatory cells, including macrophages, from the circulating blood to lesions, but pathophysiological impact resulting from spatiotemporal dynamics of macrophages is unknown. Here, we show that macrophages centripetally migrate toward the lesion epicenter after infiltrating into the wide range of spinal cord, depending on the gradient of chemoattractant C5a. However, macrophages lacking interferon regulatory factor 8 (IRF8) cannot migrate toward the epicenter and remain widely scattered in the injured cord with profound axonal loss and little remyelination, resulting in a poor functional outcome after SCI. Time-lapse imaging and P2X/YRs blockade revealed that macrophage migration via IRF8 was caused by purinergic receptors involved in the C5a-directed migration. Conversely, pharmacological promotion of IRF8 activation facilitated macrophage centripetal movement, thereby improving the SCI recovery. Our findings reveal the importance of macrophage centripetal migration via IRF8, providing a novel therapeutic target for central nervous system injury.