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STUDY DESIGN: Retrospective cohort study. OBJECTIVES: To define the prognosis and predictive factors for neurological improvement in older patients with incomplete spinal cord injury (SCI) of American Spinal Injury Association Impairment Scale grade C (AIS-C). SETTINGS: Multi-institutions in Japan. METHODS: We included patients aged ≥65 years with traumatic SCI of AIS-C who were treated conservatively or surgically with >3 follow-up months. To identify factors related to neurological improvement, patients were divided into three groups according to their neurological status at the final follow-up, with univariate among-group comparisons of demographics, radiographic, and therapeutic factors. Significant variables were included in the multivariate logistic regression analysis. RESULTS: Overall, 296 older patients with SCI of AIS-C on admission were identified (average age: 75.2 years, average follow-up: 18.7 months). Among them, 190 (64.2%) patients improved to AIS-D and 21 (7.1%) patients improved to AIS-E at final follow-up. There were significant among-group differences in age (p = 0.026), body mass index (p = 0.007), status of pre-traumatic activities of daily living (ADL) (p = 0.037), and serum albumin concentrations (p = 0.011). Logistic regression analysis showed no significant differences in variables in the stratified group of patients who improved to AIS-D. Meanwhile, serum albumin was a significant variable in patients who improved to AIS-E (p = 0.026; OR: 6.20, pre-traumatic ADL was omitted due to data skewness). CONCLUSIONS: Most older patients with incomplete AIS-C SCI demonstrated at least 1 grade of neurological improvement. However, <10% of patients achieved complete recovery. Key predictors of complete recovery were high serum albumin levels on admission and independent pre-traumatic ADL. SPONSORSHIP: No funding was received for this study.
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Traumatismos de la Médula Espinal , Humanos , Persona de Mediana Edad , Anciano , Traumatismos de la Médula Espinal/diagnóstico , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/terapia , Estudios Retrospectivos , Actividades Cotidianas , Recuperación de la Función , Albúmina SéricaRESUMEN
BACKGROUND: Although previous studies have demonstrated the advantages of early surgery for traumatic spinal cord injury (SCI), the appropriate surgical timing for cervical SCIs (CSCIs) without bone injury remains controversial. Here, we investigated the influence of relatively early surgery within 48 h of injury on the neurological recovery of elderly patients with CSCI and no bone injury. METHODS: In this retrospective multicenter study, we reviewed data from 159 consecutive patients aged ≥65 years with CSCI without bone injury who underwent surgery in participating centers between 2010 and 2020. Patients were followed up for at least 6 months following CSCI. We divided patients into relatively early (≤48 h after CSCI, n = 24) and late surgery (>48 h after CSCI, n = 135) groups, and baseline characteristics and neurological outcomes were compared between them. Multivariate analysis was performed to identify factors associated with neurological recovery. RESULTS: The relatively early surgery group demonstrated a lower prevalence of cardiac disease, poorer baseline American Spinal Injury Association (ASIA) impairment scale grade, and lower baseline ASIA motor score (AMS) than those of the late surgery group (P < 0.030, P < 0.001, and P < 0.001, respectively). Although the AMS was lower in the relatively early surgery group at 6 months following injury (P = 0.001), greater improvement in this score from baseline to 6-months post injury was observed (P = 0.010). Multiple linear regression analysis revealed that relatively early surgery did not affect postoperative improvement in AMS, rather, lower baseline AMS was associated with better AMS improvement (P < 0.001). Delirium (P = 0.006), pneumonia (P = 0.030), and diabetes mellitus (P = 0.039) negatively influenced postoperative improvement. CONCLUSIONS: Although further validation by future studies is required, relatively early surgery did not show a positive influence on neurological recovery after CSCI without bone injury in the elderly.
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Médula Cervical , Traumatismos de los Tejidos Blandos , Traumatismos de la Médula Espinal , Anciano , Humanos , Resultado del Tratamiento , Médula Cervical/lesiones , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/cirugía , Estudios Retrospectivos , Vértebras Cervicales/cirugía , Vértebras Cervicales/lesiones , Estudios Multicéntricos como AsuntoRESUMEN
PURPOSE: To investigate the impact of early post-injury respiratory dysfunction for neurological and ambulatory ability recovery in patients with cervical spinal cord injury (SCI) and/or fractures. METHODS: We included 1,353 elderly patients with SCI and/or fractures from 78 institutions in Japan. Patients who required early tracheostomy and ventilator management and those who developed respiratory complications were included in the respiratory dysfunction group, which was further classified into mild and severe respiratory groups based on respiratory weaning management. Patient characteristics, laboratory data, neurological impairment scale scores, complications at injury, and surgical treatment were evaluated. We performed a propensity score-matched analysis to compare neurological outcomes and mobility between groups. RESULTS: Overall, 104 patients (7.8%) had impaired respiratory function. In propensity score-matched analysis, the respiratory dysfunction group had a lower home discharge and ambulation rates (p = 0.018, p = 0.001, respectively), and higher rate of severe paralysis (p < 0.001) at discharge. At the final follow-up, the respiratory dysfunction group had a lower ambulation rate (p = 0.004) and higher rate of severe paralysis (p < 0.001). Twenty-six patients with severe disability required respiratory management for up to 6 months post-injury and died of respiratory complications. The mild and severe respiratory dysfunction groups had a high percentage of severe paraplegic cases with low ambulatory ability; there was no significant difference between them. The severe respiratory dysfunction group tended to have a poorer prognosis. CONCLUSION: Respiratory dysfunction in elderly patients with SCI and/or cervical fracture in the early post-injury period reflects the severity of the condition and may be a useful prognostic predictor.
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Médula Cervical , Traumatismos del Cuello , Traumatismos de la Médula Espinal , Fracturas de la Columna Vertebral , Humanos , Anciano , Pronóstico , Médula Cervical/lesiones , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/cirugía , Fracturas de la Columna Vertebral/cirugía , Parálisis , Traumatismos del Cuello/complicaciones , Vértebras Cervicales/cirugíaRESUMEN
STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate the neurological outcomes of older individuals treated with surgery versus conservative treatment for cervical spinal cord injury (CSCI) without bone injury. SETTING: Thirty-three medical institutions in Japan. METHODS: This study included 317 consecutive persons aged ≥65 years with CSCI without bone injury in participating institutes between 2010 and 2020. The participants were followed up for at least 6 months after the injury. Individuals were divided into surgery (n = 114) and conservative treatment (n = 203) groups. To compare neurological outcomes and complications between the groups, propensity score matching of the baseline factors (characteristics, comorbidities, and neurological function) was performed. RESULTS: After propensity score matching, the surgery and conservative treatment groups comprised 89 individuals each. Surgery was performed at a median of 9.0 (3-17) days after CSCI. Baseline factors were comparable between groups, and the standardized difference in the covariates in the matched cohort was <10%. The American Spinal Injury Association (ASIA) impairment scale grade and ASIA motor score (AMS) 6 months after injury and changes in the AMS from baseline to 6 months after injury were not significantly different between groups (P = 0.63, P = 0.24, and P = 0.75, respectively). Few participants who underwent surgery demonstrated perioperative complications such as dural tear (1.1%), surgical site infection (2.2%), and C5 palsy (5.6%). CONCLUSION: Conservative treatment is suggested to be a more favorable option for older individuals with CSCI without bone injuries, but this finding requires further validation.
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Médula Cervical , Traumatismos de la Médula Espinal , Anciano , Médula Cervical/lesiones , Vértebras Cervicales/cirugía , Estudios de Cohortes , Humanos , Parálisis/complicaciones , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/cirugíaRESUMEN
BACKGROUND: The 1-year mortality and functional prognoses of patients who received surgery for cervical trauma in the elderly remains unclear. The aim of this study is to investigate the rates of, and factors associated with mortality and the deterioration in walking capacity occurring 1 year after spinal fusion surgery for cervical fractures in patients 65 years of age or older. METHODS: Three hundred thirteen patients aged 65 years or more with a traumatic cervical fracture who received spinal fusion surgery were enrolled. The patients were divided into a survival group and a mortality group, or a maintained walking capacity group and a deteriorated walking capacity group. We compared patients' backgrounds, trauma, and surgical parameters between the two groups. To identify factors associated with mortality or a deteriorated walking capacity 1 year postoperatively, a multivariate logistic regression analysis was conducted. RESULTS: One year postoperatively, the rate of mortality was 8%. A higher Charlson comorbidity index (CCI) score, a more severe the American Spinal Cord Injury Association impairment scale (AIS), and longer surgical time were identified as independent factors associated with an increase in 1-year mortality. The rate of deterioration in walking capacity between pre-trauma and 1 year postoperatively was 33%. A more severe AIS, lower albumin (Alb) and hemoglobin (Hb) values, and a larger number of fused segments were identified as independent factors associated with the increased risk of deteriorated walking capacity 1 year postoperatively. CONCLUSIONS: The 1-year rate of mortality after spinal fusion surgery for cervical fracture in patients 65 years of age or older was 8%, and its associated factors were a higher CCI score, a more severe AIS, and a longer surgical time. The rate of deterioration in walking capacity was 33%, and its associated factors were a more severe AIS, lower Alb, lower Hb values, and a larger number of fused segments.
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Fracturas Óseas , Traumatismos del Cuello , Traumatismos de la Médula Espinal , Fracturas de la Columna Vertebral , Fusión Vertebral , Anciano , Fracturas Óseas/complicaciones , Humanos , Estudios Retrospectivos , Traumatismos de la Médula Espinal/cirugía , Fracturas de la Columna Vertebral/complicaciones , Fracturas de la Columna Vertebral/cirugía , Fusión Vertebral/efectos adversos , CaminataRESUMEN
This retrospective cohort study established malnutrition's impact on mortality and neurological recovery of older patients with cervical spinal cord injury (SCI). It included patients aged ≥ 65 years with traumatic cervical SCI treated conservatively or surgically. The Geriatric Nutritional Risk Index was calculated to assess nutritional-related risk. Overall, 789 patients (mean follow-up: 20.1 months) were examined and 47 had major nutritional-related risks on admission. One-year mortality rate, median survival time, neurological recovery, and activities of daily living (ADL) at 1 year post-injury were compared between patients with major nutrition-related risk and matched controls selected using 1:2 propensity score matching to adjust for age, pre-traumatic neurological impairment, and activity. In the Kaplan-Meier analysis, the median survival times were 44.9 and 76.5 months for patients with major nutrition-related risk and matched controls, respectively (p = 0.015). Matched controls had more individuals with a neurological improvement of American Spinal Injury Association Impairment Scale ≥ 1 grade (p = 0.039) and independence in ADL at 1 year post-injury than patients with major nutrition-related risk (p < 0.05). In conclusion, 6% of older patients with cervical SCI had major nutrition-related risks; they showed a significantly higher 1 year mortality rate, shorter survival time, poorer neurological improvement, and lower ADL at 1 year post-injury than matched controls.
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Desnutrición , Traumatismos de la Médula Espinal , Humanos , Anciano , Actividades Cotidianas , Estudios Retrospectivos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Desnutrición/complicaciones , Estado Nutricional , Recuperación de la FunciónRESUMEN
STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: To investigate changes over a 10-years period in the profile of cervical spine and spinal cord injuries among the elderly in Japan. METHODS: The current multicenter study was a retrospective analysis of inpatients aged ≥65 years, suffering cervical fracture (CF) and/or cervical spinal cord injury (CSCI). We analyzed 1413 patients' epidemiology (from 2010 to 2019). Moreover, 727 patients who underwent surgical treatment were analyzed in 2 groups: the early (2010-2014) and late period (2015-2019). RESULTS: Both the number of patients and number of surgical patients showed a significant increasing trend (P < .001), while the mean age, the distribution of injury levels and paralysis severity, and the proportion of surgical indications remained the same. The number of surgical patients doubled from 228 to 499 from the early to late periods. Posterior surgery was the most common approach (90.4%), instrumentation surgery with screws increased significantly, and the range of fusion was significantly longer in the late period (2.1 vs 2.7 levels, P = .001). Significantly worsening neurological symptoms were recorded in the late period (1.3% vs 5.8%, P = .006), with C5 palsy being the major one. Otherwise, perioperative, major, and other complications, including mortality, did not differ significantly in incidence. CONCLUSIONS: Both the number of elderly CF and/or CSCI patients and number of patients undergoing surgery increased dramatically over the decade without any change in profile. Instrumentation surgeries with screws increased, without an increase in systemic complications.
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For older patients with decreased reserve function, traumatic cervical spine injuries frequently lead to early mortality. However, the prognostic factors for early mortality remain unclear. This study included patients aged ≥65 years and hospitalized for treatment of traumatic cervical spine injuries in 78 hospitals between 2010 and 2020. Early mortality was defined as death within 90 days after injury. We evaluated the relationship between early mortality and the following factors: age, sex, body mass index, history of drinking and smoking, injury mechanisms, presence of a cervical spine fracture and dislocation, cervical ossification of the posterior longitudinal ligament, diffuse idiopathic skeletal hyperostosis, American Spinal Injury Association Impairment Scale, concomitant injury, pre-existing comorbidities, steroid administration, and treatment plan. Overall, 1512 patients (mean age, 75.8 ± 6.9 years) were included in the study. The early mortality rate was 4.0%. Multivariate analysis identified older age (OR = 1.1, p < 0.001), male sex (OR = 3.7, p = 0.009), cervical spine fracture (OR = 4.2, p < 0.001), complete motor paralysis (OR = 8.4, p < 0.001), and chronic kidney disease (OR = 5.3, p < 0.001) as risk factors for early mortality. Older age, male sex, cervical spine fracture, complete motor paralysis, and chronic kidney disease are prognostic factors for early mortality in older patients with traumatic cervical spine injuries.
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We aimed to retrospectively investigate the demographic characteristics and short-term outcomes of traumatic cervical spine injuries in patients with dementia. We enrolled 1512 patients aged ≥ 65 years with traumatic cervical injuries registered in a multicenter study database. Patients were divided into two groups according to the presence of dementia, and 95 patients (6.3%) had dementia. Univariate analysis revealed that the dementia group comprised patients who were older and predominantly female and had lower body mass index, higher modified 5-item frailty index (mFI-5), lower pre-injury activities of daily living (ADLs), and a larger number of comorbidities than patients without dementia. Furthermore, 61 patient pairs were selected through propensity score matching with adjustments for age, sex, pre-injury ADLs, American Spinal Injury Association Impairment Scale score at the time of injury, and the administration of surgical treatment. In the univariate analysis of the matched groups, patients with dementia had significantly lower ADLs at 6 months and a higher incidence of dysphagia up to 6 months than patients without dementia. Kaplan-Meier analysis revealed that patients with dementia had a higher mortality than those without dementia until the last follow-up. Dementia was associated with poor ADLs and higher mortality rates after traumatic cervical spine injuries in elderly patients.
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Although the incidence of cervical spinal cord injury (CSCI) with ossification of the posterior longitudinal ligament (OPLL) has increased in older adults, its etiology and neurological outcomes remain unknown. We identified OPLL characteristics and determined whether they influence neurological severity and improvement of CSCI in older patients. This multicenter retrospective cohort study identified 1512 patients aged ≥ 65 years diagnosed with CSCI on admission during 2010-2020. We analyzed CSCI etiology in OPLL patients. We performed propensity score-adjusted analyses to compare neurological outcomes between patients with and without OPLL. Cases were matched based on variables influencing neurological prognosis. The primary neurological outcome was rated according to the American Spine Injury Association (ASIA) impairment scale (AIS) and ASIA motor score (AMS). In 332 OPLL patients, the male-to-female ratio was approximately 4:1. Half of all patients displayed low-energy trauma-induced injury and one-third had CSCI without a bony injury. Propensity score matching created 279 pairs. There was no significant difference in the AIS grade and AMS between patients with and without OPLL during hospitalization, 6 months, and 12 months following injury. OPLL patients tended to exhibit worse neurological findings during injury; nevertheless, OPLL was not associated with poor neurological improvement in older CSCI patients.
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Médula Cervical , Traumatismos del Cuello , Osificación del Ligamento Longitudinal Posterior , Traumatismos de los Tejidos Blandos , Traumatismos de la Médula Espinal , Humanos , Masculino , Femenino , Anciano , Ligamentos Longitudinales , Estudios Retrospectivos , Osteogénesis , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/epidemiología , Traumatismos de la Médula Espinal/diagnóstico , Osificación del Ligamento Longitudinal Posterior/complicaciones , Osificación del Ligamento Longitudinal Posterior/epidemiología , Vértebras Cervicales , Traumatismos de los Tejidos Blandos/complicaciones , Resultado del TratamientoRESUMEN
STUDY DESIGN: Retrospective multicenter study. OBJECTIVE: The purpose of this study was to compare the prognosis of elderly patients with injuries related to cervical diffuse idiopathic skeletal hyperostosis (cDISH) to matched control for each group, with and without fractures. METHODS: The current multicenter study was a retrospective analysis of 140 patients aged 65 years or older with cDISH-related cervical spine injuries; 106 fractures and 34 spinal cord injuries without fracture were identified. Propensity score-matched cohorts from 1363 patients without cDISH were generated and compared. Logistic regression analysis was performed to determine the risk of early mortality for patients with cDISH-related injury. RESULTS: Patients with cDISH-related injuries with fracture did not differ significantly in the incidence of each complication and ambulation or severity of paralysis compared to matched controls. In patients with cDISH-related injury without fracture, those who were nonambulatory at discharge comprised 55% vs 34% of controls, indicating significantly poorer ambulation in those with cDISH-related injuries (P = .023). There was no significant difference in the incidence of complications and ambulation or paralysis severity at 6 months as compared with controls. Fourteen patients died within 3 months. Logistic regression analysis identified complete paralysis (odds ratio [OR] 36.99) and age (OR 1.24) as significant risk factors for mortality. CONCLUSIONS: The current study showed no significant differences in the incidence of complications, ambulation outcomes between patients with cDISH-related injury with fracture and matched controls, and that the ambulation at discharge for patients with cDISH-related injury without fractures were significantly inferior to those of matched controls.
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The number of elderly patients with cervical trauma is increasing. Such patients are considered to be at high risk for delirium, which is an acute neuropsychological disorder that reduces the patient's capacity to interact with their environment due to impairments in cognition. This study aimed to establish a risk score that predicts delirium in elderly patients with cervical SCI and/or cervical fracture regardless of treatment type. This retrospective cohort study included 1512 patients aged ≥65 years with cervical SCI and/or cervical fracture. The risk factors for delirium according to treatment type (surgical or conservative) were calculated using multivariate logistic regression. A delirium risk score was established as the simple arithmetic sum of points assigned to variables that were significant in the multivariate analyses. Based on the statistical results, the delirium risk score was defined using six factors: old age (≥80 years), hypoalbuminemia, cervical fracture, major organ injury, dependence on pre-injury mobility, and comorbid diabetes. The score's area under the curve for the prediction of delirium was 0.66 (p < 0.001). Although the current scoring system must be validated with an independent dataset, the system remains beneficial because it can be used after screening examinations upon hospitalization and before deciding the treatment strategy.
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Although traumatic cervical spine injuries in older adults are commonly caused by minor traumas, such as ground-level falls, their prognosis is often unfavorable. Studies examining the clinical characteristics of cervical spine injuries in older adults according to the external cause of injury are lacking. This study included 1512 patients of ≥ 65 years of age with traumatic cervical spine injuries registered in a Japanese nationwide multicenter database. The relationship between the external causes and clinical characteristics, as well as factors causing unfavorable outcomes at the ground-level falls, were retrospectively reviewed and examined. When fall-induced cervical spine injuries were categorized and compared based on fall height, the patients' backgrounds and injury statuses differed significantly. Of note, patients injured from ground-level falls tended to have poorer pre-injury health conditions, such as medical comorbidities and frailty, compared with those who fell from higher heights. For ground-level falls, the mortality, walking independence, and home-discharge rates at 6 months post-injury were 9%, 67%, and 80%, respectively, with preexisting medical comorbidities and frailty associated with unfavorable outcomes, independent of age or severity of neurological impairment at the time of injury.
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Fragilidad , Traumatismos del Cuello , Traumatismos Vertebrales , Anciano , Vértebras Cervicales/lesiones , Humanos , Estudios Retrospectivos , Traumatismos Vertebrales/etiologíaRESUMEN
Introduction: In elderly patients with cervical spinal cord injury, comorbidities such as cardiovascular and cerebrovascular diseases are common, with frequent administration of antiplatelet/anticoagulant (APAC) drugs. Such patients may bleed easily or unexpectedly during surgery despite prior withdrawal of APAC medication. Few reports have examined the precise relationship between intraoperative blood loss and history of APAC use regarding surgery for cervical spine injury in the elderly. The present multicenter database survey aimed to answer the question of whether the use of APAC drugs affected the amount of intraoperative blood loss in elderly patients with cervical spinal cord trauma. Methods: The case histories of 1512 patients with cervical spine injury at 33 institutes were retrospectively reviewed. After excluding cases without spinal surgery or known blood loss volume, 797 patients were enrolled. Blood volume loss was the outcome of interest. We calculated propensity scores using the inverse probability of treatment weighting (IPTW) method. As an alternative sensitivity analysis, linear mixed model analyses were conducted as well. Results: Of the 776 patients (mean age: 75.1±6.4 years) eligible for IPTW calculation, 157 (20.2%) were taking APAC medications before the injury. After weighting, mean estimated blood loss was 204 mL for non-APAC patients and 215 mL for APAC patients. APAC use in elderly patients was not significantly associated with surgical blood loss according to the IPTW method with propensity scoring or linear mixed model analyses. Thus, it appeared possible to perform surgery expecting comparable blood loss in APAC and non-APAC cases. Conclusions: This multicenter study revealed no significant increase in surgical blood loss in elderly patients with cervical trauma taking APAC drugs. Surgeons may be able to prioritize patient background, complications, and preexisting conditions over APAC use before injury when examining the surgical indications for cervical spine trauma in the elderly.
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OBJECTIVE: The management of cervical spine injuries in the elderly is often complicated by the presence of multiple medical comorbidities, and it is not uncommon for preoperative testing to reveal other conditions that require the postponement of surgery. However, the factors that affect the waiting time from injury to surgery have not been clarified. The purpose of this multicenter database study was to analyze the clinical features and identify the factors affecting the number of days waited between injury and surgery in elderly patients with a cervical spine injury. METHODS: We retrospectively reviewed the case histories of 1512 Japanese patients with a cervical spinal injury, who were seen at 33 institutions. After excluding patients who were not initially receiving a surgery for cervical spinal injury, 694 patients were ultimately analyzed. Based on a multivariate mixed model, we determined the factors related to the number of days from injury to surgery. RESULTS: The mean time from injury to surgery was 12.3 days. Multivariate analysis revealed delays of 10.7 days for a renal disorder, 7.3 days for anticoagulant use, and 15.2 days for non-surgical thoracolumbar fracture as factors prolonging wait time. In contrast, a C3 or lower spine injury was significantly associated with a shortening of 9.5 days to surgery. CONCLUSIONS: This multicenter database study identified several factors influencing the time between injury and cervical spine surgery in elderly patients. While renal impairment, anticoagulant use, and non-surgical thoracolumbar fracture may increase the number of days to surgery, trauma to C3 or lower may expedite surgical treatment.
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Traumatismos del Cuello , Traumatismos Vertebrales , Anciano , Anticoagulantes , Vértebras Cervicales/lesiones , Vértebras Cervicales/cirugía , Humanos , Japón/epidemiología , Estudios Retrospectivos , Traumatismos Vertebrales/cirugía , Listas de EsperaRESUMEN
INTRODUCTION: The number of patients who suffered from osteoporotic vertebral fractures is increasing. Osteoporosis has been reported to affect the healing process using long bone models. However, few studies have reported using vertebrae. In this study, we created a bone defect in the anterior part of vertebral body in ovariectomized rat and evaluated the healing process. METHODS: Fifty-six 12-week old Sprague Dawley rats were divided into ovariectomy (OVX) and sham operation groups. A bone defect was created in the vertebral body 8 weeks after the first surgery. In both groups, the vertebral bodies were harvested immediately or at 4, 8, or 12 weeks after the second surgery ( n = 7 at each time point). Bone volume (BV, mm3), bone volume fraction (BV/TV, %), trabecular thickness (Tb.Th, mm), trabecular number (Tb.N, 1/mm), and trabecular separation (Tb.Sp, µm) were evaluated by micro-computed tomography to assess the new bone formation. Histological analysis was also performed. RESULTS: The BV and the BV/TV were significantly lower at 4 and 12 weeks in the OVX group compared with those in the sham group. The Tb.Th was significantly lower at 8 and 12 weeks in the OVX group. Histologically, at 12 weeks, in the OVX group, the bone had a thinner, layered structure on the surface of the defect, and the trabecular structure was less dense. CONCLUSION: This study demonstrated that bone mass formation was suppressed and the quality of repaired bone was poor in the healing process of vertebral body defect under osteoporotic conditions. These findings could be the key to understand the pathology of osteoporotic vertebral fracture and to develop its therapies.
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Curación de Fractura/fisiología , Vértebras Lumbares/lesiones , Fracturas Osteoporóticas/fisiopatología , Fracturas de la Columna Vertebral/fisiopatología , Animales , Densidad Ósea , Femenino , Fracturas Osteoporóticas/diagnóstico por imagen , Fracturas Osteoporóticas/etiología , Ovariectomía , Ratas , Ratas Sprague-Dawley , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/etiología , Microtomografía por Rayos XRESUMEN
The objective of the present study was to investigate the effect of platelet-rich plasma (PRP) combined with gelatin ß-tricalcium phosphate (ß-TCP) sponge on bone generation in a lumbar vertebral body defect of ovariectomized rat. After creating critical-size defects in the center of the anterior vertebral body, the defects were filled with the following materials: (1) no material (control group), (2) gelatin ß-TCP sponge with PRP (PRP sponge group), and (3) gelatin ß-TCP sponge with phosphate-buffered saline (PBS sponge group). Microcomputed tomography and histological evaluation were performed immediately after surgery and at 4, 8, and 12 weeks to assess bone regeneration. Biomechanical test was also performed at postoperative week 12. In the PRP sponge group, both imaging and histological examination showed that visible osteogenesis was first induced and additional growth of bone tissue was observed in the transplanted sponge, compared with the PBS sponge group. There was no negative effect of either PRP sponge or PBS sponge transplantation on bone tissue generation around the periphery of the defect. Biomechanical test showed increased stiffness of the affected vertebral bodies in the PRP sponge group. These results indicate that PRP-impregnated gelatin ß-TCP sponge is effective for facilitating bone regeneration in lumbar vertebral bone defect under osteoporotic condition. PRP combined with gelatin ß-TCP sponges could be potentially useful for developing a new approach to vertebroplasty for osteoporotic vertebral fracture.
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Regeneración Ósea/fisiología , Fosfatos de Calcio/química , Esponja de Gelatina Absorbible/análisis , Esponja de Gelatina Absorbible/uso terapéutico , Plasma Rico en Plaquetas , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/fisiología , Sistemas de Liberación de Medicamentos , Humanos , Ingeniería de Tejidos/métodosRESUMEN
The etiology of intervertebral disc (IVD) degeneration is closely related to apoptosis and extracellular matrix degradation in nucleus pulposus (NP) cells. These defects in NP cells are induced by excessive external stressors such as reactive oxygen species (ROS) and inflammatory cytokines. Recently, hepatocyte growth factor (HGF) has been shown to repair damage in various diseases through anti-apoptotic and anti-inflammatory activity. In this study, we investigated the effects of HGF on NP cell abnormality caused by ROS and inflammatory cytokines by using primary NP cells isolated from rabbit IVD. HGF significantly enhanced the proliferation of NP cells. Apoptosis of NP cells induced by H2 O2 or TNF-α was significantly inhibited by HGF. Induction of mRNA expression of the inflammation mediators cyclooxygenase-2 and matrix metalloproteinase-3 and -9 by TNF-α was significantly suppressed by HGF treatment. Expression of c-Met, a specific receptor for HGF, was confirmed in NP cells and was increased by TNF-α, suggesting that inflammatory cytokines increase sensitivity to HGF. These findings demonstrate that activation of HGF/c-Met signaling suppresses damage caused by ROS and inflammation in NP cells through multiple pathways. We further suggest the clinical potential of HGF for counteracting IVD degradation involved in NP cell abnormalities.
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Factor de Crecimiento de Hepatocito/uso terapéutico , Disco Intervertebral/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Ciclooxigenasa 2/metabolismo , Evaluación Preclínica de Medicamentos , Matriz Extracelular/metabolismo , Factor de Crecimiento de Hepatocito/metabolismo , Factor de Crecimiento de Hepatocito/farmacología , Disco Intervertebral/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Conejos , Especies Reactivas de Oxígeno , Factor de Necrosis Tumoral alfaRESUMEN
AIM: We investigated the expression pattern of Notch-1 in normal and hypertrophied plantaris muscle of mice. MAIN METHODS: We performed immunofluorescence of both Notch-1 and the Notch-1-linking molecules. KEY FINDINGS: Immunofluorescence labeling revealed Notch-1 protein in Pax7-positive satellite cells during days 2-6. We observed clear co-localization between Notch-1 and myogenin (4.9+/-1.3%) in the hypertrophied muscle at 4days. Several mononuclei (possibly satellite cells) possessed both Notch-1 and Foxo1 in the plantaris muscle subjected to mechanical overloading (4.1+/-1.2%). SIGNIFICANCE: Notch-1 may play an important role in the maintenance of quiescent satellite cells.