Impact of malnutrition on mortality and neurological recovery of older patients with spinal cord injury.

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.

Neurological recovery rate and predictive factors of incomplete AIS grade C spinal cord injury in the older aged population.

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.

Influence of the timing of surgery for cervical spinal cord injury without bone injury in the elderly: A retrospective multicenter study.

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.

Zinc deficiency impairs axonal regeneration and functional recovery after spinal cord injury by modulating macrophage polarization via NF-κB pathway.

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.

Prognosis of Cervical Diffuse Idiopathic Skeletal Hyperostosis-Related Spine Injuries in Elderly Patients: Analyses of Both Fracture and Spinal Cord Injury Without Fracture.

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.

Reduced Neuroinflammation Via Astrocytes and Neutrophils Promotes Regeneration After Spinal Cord Injury in Neonatal Mice.

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.

Macrophages play a leading role in determining the direction of astrocytic migration in spinal cord injury via ADP-P2Y1R axis.

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.

Prognostic impact of respiratory dysfunction in elderly patients with cervical spinal cord injury and/or fractures: a multicenter survey.

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.

Effects of Dementia on Outcomes after Cervical Spine Injuries in Elderly Patients: Evaluation of 1512 Cases in a Nationwide Multicenter Study in Japan.

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.

Delirium Risk Score in Elderly Patients with Cervical Spinal Cord Injury and/or Cervical Fracture.

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.

Bone marrow-derived fibroblast migration via periostin causes irreversible arthrogenic contracture after joint immobilization.

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.

Characteristics of the cervical spine and cervical cord injuries in older adults with cervical ossification of the posterior longitudinal ligament.

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.

Macrophages play a leading role in determining the direction of astrocytic migration in spinal cord injury via ADP-P2Y1R axis.

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.

Epidemiology of Cervical Fracture/Cervical Spinal Cord Injury and Changes in Surgical Treatment Modalities in Elderly Individuals During a 10-year Period: A Nationwide Multicenter Study in Japan.

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.

Risk Factors for Early Mortality in Older Patients with Traumatic Cervical Spine Injuries-A Multicenter Retrospective Study of 1512 Cases.

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.

Glial scar survives until the chronic phase by recruiting scar-forming astrocytes after spinal cord injury.

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.

Is Blood Loss Greater in Elderly Patients under Antiplatelet or Anticoagulant Medication for Cervical Spine Injury Surgery? A Japanese Multicenter Survey.

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.

Differences in clinical characteristics of cervical spine injuries in older adults by external causes: a multicenter study of 1512 cases.

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.

Zinc chelator treatment in crush syndrome model mice attenuates ischemia-reperfusion-induced muscle injury due to suppressing of neutrophil infiltration.

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.

Factors Affecting the Waiting Time from Injury to Surgery in Elderly Patients with a Cervical Spine Injury: A Japanese Multicenter Survey.

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.