Safety and feasibility of intravenous administration of a single dose of allogenic-Muse cells to treat human cervical traumatic spinal cord injury: a clinical trial.

INTRODUCTION: Spinal cord injury (SCI) is a devastating injury and remains one of the largest medical and social burdens because of its intractable nature. According to the recent advances in stem cell biology, the possibility of spinal cord regeneration and functional restoration has been suggested by introducing appropriate stem cells. Multilineage-differentiating stress enduring (Muse) cells are a type of nontumorigenic endogenous reparative stem cell. The positive results of Muse cell transplantation for SCI was shown previously. As a first step for clinical application in human SCI, we conducted a clinical trial aiming to confirm the safety and feasibility of intravenously injected donor-Muse cells. METHODS: The study design of the current trial was a prospective, multicenter, nonrandomized, nonblinded, single-arm study. The clinical trial registration number was JRCT1080224764. Patients with a cervical SCI with a neurological level of injury C4 to C7 with the severity of modified Frankel classification B1 and B2 were included. A primary endpoint was set for safety and feasibility. Our protocol was approved by the PMDA, and the trial was funded by the Life Science Institute, Tokyo, Japan. The present clinical trial recruited 10 participants (8 males and 2 females) with an average age of 49.3 ± 21.2 years old. All 10 participants received a single dose of allogenic CL2020 (a total of 15 × 106 cells, 2.1-2.7 × 105 cells/kg of body weight), which is a Muse cell-based product produced from human mesenchymal stem cells, by an intravenous drip. RESULTS: There were two reported severe adverse events, both of which were determined to have no causal relationship with Muse cell treatment. The change in the ISNCSCI motor score, the activity of daily living and quality of life scores showed statistically significant improvements compared to those data at the time of CL2020 administration. CONCLUSION: In the present trial, no safety concerns were identified, and Muse cell product transplantation demonstrated good tolerability. Future clinical trials with appropriate study designs incorporating a control arm will clarify the definitive efficacy of single-dose allogenic Muse cell treatment with intravenous administration to treat SCI. TRIAL REGISTRATION: jRCT, JRCT1080224764. Registered 03 July 2019, https://jrct.niph.go.jp/latest-detail/jRCT1080224764 .

Ten-Year Follow-up of Posterior Decompression and Fusion Surgery for Thoracic Ossification of the Posterior Longitudinal Ligament.

BACKGROUND: We evaluated the clinical, functional, and quality of life (QoL) outcomes of surgical treatment of thoracic ossification of the posterior longitudinal ligament (T-OPLL). METHODS: We retrospectively evaluated 51 patients followed for ≥10 years after posterior decompression and corrective fusion surgery for T-OPLL. The data collected included demographics, comorbidities, and pre- and postoperative symptoms. The Japanese Orthopaedic Association (JOA) score, numerical rating scale (NRS) for back and leg pain, and EuroQol-5 Dimension-5 Level (EQ-5D-5L) were used to assess neurological function, pain, and QoL. Imaging evaluations were conducted to assess changes in kyphotic angles and ossification progression. RESULTS: A significant improvement was observed in the JOA score from preoperatively (3.7) to 2 years postoperatively (7.9) (p < 0.05); the score remained stable thereafter. The mean EQ-5D-5L score improved from 0.53 preoperatively to 0.68 at 10 years postoperatively (p < 0.001). NRS scores for back and leg pain decreased from 5.4 to 3.5 and 4.0 to 3.0, respectively, from preoperatively to 10 years (p < 0.001 for both). Radiographic outcomes showed changes in kyphotic angles and ossification areas, with no significant progression after 2 years. Fourteen (27.5%) of the patients experienced postoperative complications. Of these, 8 (15.7%) required reoperation, 6 (11.8%) in the perioperative period and 2 (3.9%) later. Four (7.8%) of the patients underwent additional surgeries for conditions including lumbar spinal canal stenosis and cervical OPLL. Nonetheless, physical function in all cases with postoperative complications or additional surgery remained stable over the decade. CONCLUSIONS: Surgical treatment of T-OPLL is effective in improving neurological function, QoL, and pain management over an extended period. The long-term outcomes of T-OPLL surgery revealed that, although cervical and lumbar spinal lesions led to reoperations, they did not affect QoL, and relative improvement was maintained even after 10 years. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Multimodal Deep Learning-based Radiomics Approach for Predicting Surgical Outcomes in Patients with Cervical Ossification of the Posterior Longitudinal Ligament.

STUDY DESIGN: A retrospective analysis. OBJECTIVE: This research sought to develop a predictive model for surgical outcomes in patients with cervical ossification of the posterior longitudinal ligament (OPLL) using deep learning and machine learning (ML) techniques. SUMMARY OF BACKGROUND DATA: Determining surgical outcomes assists surgeons in communicating prognosis to patients and setting their expectations. Deep learning and ML are computational models that identify patterns from large datasets and make predictions. METHODS: Of the 482 patients, 288 patients were included in the analysis. A minimal clinically important difference (MCID) was defined as gain in Japanese Orthopaedic Association (JOA) score of 2.5 points or more. The predictive model for MCID achievement at 1 year post-surgery was constructed using patient background, clinical symptoms, and preoperative imaging features (x-ray, CT, MRI) analyzed via LightGBM and deep learning with RadImagenet. RESULTS: The median preoperative JOA score was 11.0 (IQR: 9.0-12.0), which significantly improved to 14.0 (IQR: 12.0-15.0) at 1 year after surgery (P < 0.001, Wilcoxon signed-rank test). The average improvement rate of the JOA score was 44.7%, and 60.1% of patients achieved the MCID. Our model exhibited an area under the receiver operating characteristic curve of 0.81 and the accuracy of 71.9% in predicting MCID at 1 year. Preoperative JOA score and certain preoperative imaging features were identified as the most significant factors in the predictive models. CONCLUSION: A predictive ML and deep learning model for surgical outcomes in OPLL patients is feasible, suggesting promising applications in spinal surgery. LEVEL OF EVIDENCE: 4.

Longitudinal impact of multi-segment spinal fixation surgery on mobility status and clinical outcomes in adult spinal deformity: a multicenter retrospective study.

PURPOSE: To investigate changes in postoperative mobility status in patients with ASD, and the determining factors that influence these changes and their impact on clinical outcomes, including the rate of home discharge and long-term mobility. METHODS: A total of 299 patients with ASD who underwent multi-segment posterior spinal fusion were registered in a multi-center database were investigated. Patient mobility status was assessed using walking aids and classified into five levels (1: independent, 2: cane, 3: walker, 4: assisted, and 5: wheelchair) preoperatively, at discharge, and after 2 years. We determined improvements or declines in the patient's mobility based on changes in the classification levels. The analysis focused on the factors contributing to the deterioration of postoperative mobility. RESULTS: Two years postoperatively, 87% of patients maintained or improved mobility. However, 27% showed decreased mobility status at discharge, associated with a lower rate of home discharge (49% vs. 80% in the maintained mobility group) and limited improvement in mobility status (35% vs. 5%) after 2 years. Notably, postoperative increases in thoracic kyphosis (7.0 ± 12.1 vs. 2.0 ± 12.4°, p = 0.002) and lower lumbar lordosis (4.2 ± 13.1 vs. 1.8 ± 12.6°, p = 0.050) were substantial factors in mobility decline. CONCLUSION: Postoperative mobility often temporarily decreases but generally improves after 2 years. However, an overcorrection in sagittal alignment, evidenced by increased TK, could detrimentally affect patients' mobility status. Transient mobility decline associated with overcorrection may require further rehabilitation or hospitalization. Further studies are required to determine the biomechanical effects of surgical correction on mobility.

Does global spinal alignment affect the use of walking aids after multi-segment spinal fixation for patients with ASD? A multicenter retrospective study.

PURPOSE: This study aimed to clarify the relation between global spinal alignment and the necessity of walking aid use in patients with adult spinal deformity (ASD) and to investigate the impact of spinal fixation on mobility status after surgery. METHODS: In total, 456 older patients with ASD who had multi-segment spinal fixation surgery and were registered in a multi-center database were investigated. Patients under 60 years of age and those unable to walk preoperatively were excluded. Patients were classified by their mobility status into the independent, cane, and walker groups. Comparison analysis was conducted using radiographic spinopelvic parameters and the previously reported global spine balance (GSB) classification. In addition, preoperative and 2 years postoperative mobility statuses were investigated. RESULTS: Of 261 patients analyzed, 66 used walking aids (canes, 46; walkers, 20). Analysis of preoperative radiographical parameters showed increased pelvic incidence and pelvic incidence-lumbar lordosis mismatch in the walker group and increased sagittal vertebral axis in the cane and walker groups versus the independent group. Analysis of GSB classification showed a higher percentage of walker use in those with severe imbalance (grade 3) in the sagittal classification but not in the coronal classification. While postoperative radiographical improvements were noted, there was no significant difference in the use of walking aids before and 2 years after surgery (P = 0.085). CONCLUSION: A significant correlation was found between "sagittal" spinal imbalance and increased reliance on walking aids, particularly walkers. However, the limitation of improvement in postoperative mobility status suggested that multiple factors influence the mobility ability of elderly patients with ASD.

Analysis of spinopelvic parameters in adult patients with lumbosacral transitional vertebrae.

PURPOSE: Spinopelvic sagittal alignment is crucial for assessing balance and determining treatment efficacy in patients with adult spinal deformity (ASD). Only a limited number of reports have addressed spinopelvic parameters and lumbosacral transitional vertebrae (LSTV). Our primary objective was to study spinopelvic sagittal parameter changes in patients with LSTV. A secondary objective was to investigate clinical symptoms and quality of life (QOL) in patients with LSTV. METHODS: In this study, we investigated 371 participants who had undergone medical check-ups for the spine. LSTV was evaluated using Castellvi's classification, and patients were divided into LSTV+ (type II-IV, L5 vertebra articulated or fused with the sacrum) and LSTV- groups. After propensity score matching for demographic data, we analyzed spinopelvic parameters, sacroiliac joint degeneration, clinical symptoms, and QOL for these two participant groups. Oswestry Disability Index (ODI) scores and EQ-5D (EuroQol 5 dimensions) indices were compared between the two groups. RESULTS: Forty-four patients each were analyzed in the LSTV + and LSTV- groups. The LSTV + group had significantly greater pelvic incidence (52.1 ± 11.2 vs. 47.8 ± 10.0 degrees, P = 0.031) and shorter pelvic thickness (10.2 ± 0.9 vs. 10.7 ± 0.8 cm, P = 0.018) compared to the LSTV- group. The "Sitting" domain of ODI (1.1 ± 0.9 vs. 0.6 ± 0.7, P = 0.011) and "Pain/Discomfort" domain of EQ-5D (2.0 ± 0.8 vs. 1.6 ± 0.7, P = 0.005) were larger in the LSTV + group. CONCLUSION: There was a robust association between LSTV and pelvic sagittal parameters. Clinical symptoms also differed between the two groups in some domains. Surgeons should be aware of the relationship between LSTV assessment, radiographic parameters and clinical symptoms.

Trabecular Bone Remodeling after Posterior Lumbar Interbody Fusion: Comparison of the Osseointegration in Three-Dimensional Porous Titanium Cages and Polyether-Ether-Ketone Cages.

STUDY DESIGN: Retrospective cohort study. OBJECTIVES: Imaging changes in the vertebral body after posterior lumbar interbody fusion (PLIF) are determined to be trabecular bone remodeling (TBR). This study aimed to investigate the influence of cage materials on TBR and segment stabilization in PLIF by studying image changes. METHODS: This was a retrospective study reviewing 101 cases who underwent one-level PLIF with three-dimensional porous titanium (3DTi) cages (53 patients) or polyether-ether-ketone (PEEK) cages (48 patients). Computed tomography images obtained 3 months, 1 year, and 2 years postoperatively were examined for TBR, vertebral endplate cyst formation as an instability sign, cage subsidence, and clear zone around pedicle screw (CZPS). RESULTS: No significant differences in the TBR-positivity rates were observed between the two cages at 3 months, 1 year, and 2 years postoperatively. However, all 3DTi cage segments that were TBR-positive at 3 months postoperatively showed no CZPS and fewer final instability segments than the TBR-negative segments (0% vs 9%). In contrast, although the PEEK cage segments that were TBR-positive at 3 months postoperatively were not associated with future segmental stabilization, those that were TBR-positive at 1 year postoperatively had fewer final instability segments than the TBR-negative segments (0% vs 33%). CONCLUSIONS: The 3DTi cage segments with TBR 3 months postoperatively showed significant final segmental stabilization, whereas TBR at 1 year rather than 3 months postoperatively was useful in determining final segmental stabilization for the PEEK cage segments. The timing of TBR, a new osseointegration assessment, were associated with the cage material.

Preoperative low Hounsfield units in the lumbar spine are associated with postoperative mechanical complications in adult spinal deformity.

PURPOSE: To determine the most valid bone health parameter to predict mechanical complications (MCs) following surgery for adult spinal deformity (ASD). METHODS: This multicenter study retrospectively examined the records of patients who had undergone fusion of three or more motion segments, including the pelvis, with a minimum two-year follow-up period. Patients with moderate and severe global alignment and proportion scores were included in the study and divided into two groups: those who developed MCs and those who did not. Bone mineral density (BMD) of the lumbar spine and femoral neck was measured using dual-energy X-ray absorptiometry, and Hounsfield units (HUs) were measured in the lumbar spine on computed tomography. Radiographic parameters were evaluated preoperatively, immediately after surgery, and at final follow-up. RESULTS: Of 108 patients, 30 (27.8%) developed MCs, including 26 cases of proximal junctional kyphosis/failure, 2 of distal junctional failure, 6 of rod fracture, and 11 reoperations. HUs were significantly lower in patients who experienced MCs (113.7 ± 41.1) than in those who did not (137.0 ± 46.8; P = 0.02). BMD did not differ significantly between the two groups. The preoperative and two-year postoperative global tilt, as well as the immediately postoperative sagittal vertical axis, were significantly greater in patients who developed MCs than in those who did not (P = 0.02, P < 0.01, and P = 0.01, respectively). CONCLUSION: Patients who experienced MCs following surgery for ASD had lower HUs than those who did not. HUs may therefore be more useful than BMD for predicting MCs following surgery for ASD.

A Longitudinal Study on the Effect of Exercise Habits on Locomotive Syndrome and Quality of Life during the Coronavirus Disease 2019 Pandemic.

During the COVID-19 pandemic, this study investigated the potential of exercise habits to improve quality of life (QOL) and prevent locomotive syndrome (LS) in residents of Yakumo-cho, Hokkaido, Japan. Participants from the 2018 health checkup were surveyed in February 2022, focusing on 200 respondents. These individuals were divided based on their 2018 exercise habits (at least 1 h per week): the exercise group (E group) and the non-exercise group (N group), further categorized in 2022 into the 2022E and 2022N groups. QOL was measured using the SF-36 (physical functioning, general health, physical role, physical pain, vitality, social functioning, emotional role, and mental health) and EuroQoL 5-dimension 5-level questionnaires (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression), and LS was assessed with the 25-question geriatric locomotive function scale. These showed no significant change in exercise habits from 2018 to 2022. In the non-LS group, the 2022E group had higher vitality and emotional role functioning scores compared to the 2022N group. For those with LS, the 2022E group reported less physical pain. Notably, the LS incidence was significantly lower in the 2022E group. This study concludes that consistent exercise habits positively impact QOL and reduce the LS risk, underscoring the importance of regular physical activity, especially during challenging times like a pandemic. These findings highlight the broader benefits of maintaining exercise routines for public health, particularly in periods of global health crises. Based on our findings, we recommend that people continue to exercise at least one hour per week to prevent LS.

Obesity Is Associated with Asymptomatic Vertebral Fractures: A Yakumo Study.

(1) Background: Patients with primary vertebral fracture (VF) are at high risk of re-fracture and mortality. However, approximately two-thirds of patients with VFs receive minimal clinical attention. (2) Methods: The current study aimed to investigate the factors associated with asymptomatic VFs in middle-aged and elderly individuals who underwent resident health examinations. (3) Results: The current study included 217 participants aged > 50 years. VFs were diagnosed based on lateral radiographic images using Genant's semiquantitative (SQ) method. The participants were divided into non-VF (N; SQ grade 0) and asymptomatic VF (F; SQ grades 1-3) groups. Data on body composition, blood tests, quality of life measures, and radiographic parameters were assessed. A total of 195 participants were included in the N group (mean age, 64.8 ± 7.8 years), and 22 were in the F group (mean age, 66.1 ± 7.9 years). The F group had a significantly higher body mass index (BMI), body fat percentage (BF%), and proportion of patients with knee osteoarthritis (KOA) than the N group. The F group had a significantly higher knee joint pain visual analog scale (VAS) score and painDETECT score than the N group. Logistic regression analysis showed that BF% was associated with asymptomatic VFs. (4) Conclusions: Middle-aged and elderly individuals with asymptomatic VF presented with high BMIs, BF%, and incidence of KOA.

Is spinopelvic compensation associated with unstable gait?: Analysis using whole spine X-rays and a two-point accelerometer during gait in healthy adults.

BACKGROUND: Pelvic incidence (PI)-lumbar lordosis (LL) mismatch has a significant destabilizing effect on the center of gravity sway in the static standing position. However, the association between spinopelvic alignment and balance during gait in healthy volunteers is poorly understood. RESEARCH QUESTION: The degree of PI-LL mismatch and trunk anterior tilt in the static standing posture influences dynamic balance during gait. METHODS: In this study, 131 healthy volunteers were divided into two groups: harmonious group (PI - LL ≤ 10°; n = 91) and unharmonious group (PI - LL > 10°; n = 40). A two-point accelerometer system was used for gait analysis; accelerometers were attached to the pelvis and upper trunk to measure acceleration in the forward-backward, right-left, and vertical directions so that sagittal (front-back) deviation width, coronal (right-left) width, and vertical width and their ratios were calculated. Measurements were compared between the two groups, and correlations between alignment and accelerometer data were examined. RESULTS: The harmonious group showed a negative correlation between pelvic sagittal width and PI - LL, pelvic tilt (PT), and sagittal vertical axis (SVA) (correlation coefficient ρ = -0.42, -0.38, and -0.4, respectively), and a positive correlation between sagittal ratio and PI - LL (ρ = 0.35). The unharmonious group showed a positive correlation between pelvic sagittal width and PI and PT (ρ = 0.43 and 0.33, respectively) and between sagittal ratio and SVA (ρ = 0.32). The unharmonious group showed a positive correlation between upper trunk sagittal width and PI - LL and PT (ρ = 0.38 and 0.36, respectively). SIGNIFICANCE: The association between spinal alignment and gait parameters differs depending on the presence or absence of PI-LL mismatch. The degree of pelvic compensation and trunk anterior tilt during static standing were associated with unstable gait balance.

Rod fracture after multiple-rod technique for adult spinal deformity: a case report.

Here we report the case of a 71-year-old woman who complained of lower back and left leg pain due to rod fracture following instrumented fusion using the lateral lumbar interbody fusion and multi-rod technique to treat adult spinal deformity. Radiographic images revealed bilateral rod fractures at L4-5 and pseudoarthrosis at L2-5; lower lumbar lordosis was minimal, but upper lumbar hyperlordosis was noted. The patient underwent revision surgery, which included posterior spinal instrument replacement, L3-4 and L4-5 lateral lumbar interbody fusion cage removal, and L4 vertebral body replacement via the anterior approach. This is a rare case of reoperation with the multi-rod technique. Revision surgery should be performed in consideration of the proportion of lumbar lordosis and anterior bony fusion as the posterior component is resected and bony fusion can only be achieved anteriorly.

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.

Do Postural and Walking Stabilities Change over a Decade by Aging? A Longitudinal Study.

BACKGROUND: Previous studies have demonstrated that the center of gravity (COG) is more unstable in the elderly than in young people. However, it is unclear whether aging itself destabilizes the COG. This study aimed to investigate changes in COG sway and gait kinematics over time by a longitudinal study of middle-aged and elderly adults. METHODS: This study included 198 healthy middle-aged and elderly people who underwent stabilometry at ten-year intervals. The participants' mean age at baseline was 62.9 ± 6.5 years, and 77 (39%) of them were male. The results of stabilometry (mean velocity, sway area, postural sway center in the medial-lateral direction [X center], and postural sway center in the anterior-posterior direction [Y center]), and results of exercise tests (the height-adjusted maximum stride length [HMSL] and the 10 m walk test [10MWT]) were analyzed. The destabilized group with 11 participants, whose mean velocity exceeded 3 cm/s after 10 years, was compared with the stable group with 187 participants, whose mean velocity did not exceed 3 cm/s. RESULTS: Mean velocity increased significantly over ten years (open-eye, from 1.53 ± 0.42 cm to 1.86 ± 0.67 cm, p < 0.001); however, the sway area did not change significantly. X center showed no significant change, whereas Y center showed a significant negative shift (open-eye, from -1.03 ± 1.28 cm to -1.60 ± 1.56 cm, p < 0.001). Although the results of 10MWT and initial HMSL did not differ significantly, the HMSL in the destabilized group at ten years was 0.64, which was significantly smaller than the 0.72 of others (p = 0.019). CONCLUSIONS: The ten-year changes in COG sway in middle-aged and elderly adults were characterized by a significant increase in mean velocity but no significant difference in sway area. Because the destabilized group had significantly smaller HMSL at ten years, instability at the onset of movement is likely to be affected by COG instability.

Cellular senescence is associated with osteonecrosis of the femoral head while mesenchymal stem cell conditioned medium inhibits bone collapse.

Osteonecrosis of the femoral head (ONFH) is a type of ischemic osteonecrosis that causes pain, loss of function, and femoral head collapse. Here, we analyzed samples of femoral heads excised from patients with ONFH to clarify the relationship between ischemic osteonecrosis and cellular senescence. X-gal staining was strong and p16INK4a-positive cells were abundant in the transitional region of ONFH. The ß-galactosidase-positive cells in the transitional region were also positive for nestin, periostin, or DMP-1. In contrast, no ß-galactosidase-positive cells were detected in the healthy region. The senescence-associated p16INK4a, p21, and p53 were upregulated in ONFH tissue. We also examined and analyzed a mouse ischemic femoral osteonecrosis model in vivo to verify the association between ONFH and cellular senescence. Human mesenchymal stem cell-conditioned medium (MSC-CM) was administered to determine its therapeutic efficacy against cellular senescence and bone collapse. MSC-CM reduced the number of senescent cells and downregulated the aforementioned senescence-related genes. It also decreased the number of empty lacunae 4 weeks after ischemia induction and promoted bone formation. At 6 weeks post-surgery, MSC-CM increased the trabecular bone volume, thereby suppressing bone collapse. We conclude that cellular senescence is associated with ONFH and that MSC-CM suppresses bone collapse in this disorder.

Early Versus Delayed Surgery for Elderly Traumatic Cervical Spinal Injury: A Nationwide Multicenter Study in Japan.

STUDY DESIGN: Retrospective multicenter study. OBJECTIVES: The effectiveness of early surgery for cervical spinal injury (CSI) has been demonstrated. However, whether early surgery improves outcomes in the elderly remains unclear. This study investigated whether early surgery for CSI in elderly affects complication rates and neurological outcomes. METHODS: This retrospective multicenter study included 462 patients. We included patients with traumatic acute cervical spinal cord injury aged ≥65 years who were treated surgically, whereas patients with American Spinal Injury Association (ASIA) Impairment Scale E, those with unknown operative procedures, and those waiting for surgery for >1 month were excluded. The minimum follow-up period was 6 months. Sixty-five patients (early group, 14.1%) underwent surgical treatment within 24 hours, whereas the remaining 397 patients (85.9%) underwent surgery on a standby basis (delayed group). The propensity score-matched cohorts of 63 cases were compared. RESULTS: Patients in the early group were significantly younger, had significantly more subaxial dislocations (and fractures), tetraplegia, significantly lower ASIA motor scores, and ambulatory abilities 6 months after injury. However, no significant differences in the rate of complications, ambulatory abilities, or ASIA Impairment Scale scores 6 months after injury were observed between the matched cohorts. At 6 months after injury, 61% of the patients in the early group (25% unsupported and 36% supported) and 53% of the patients in the delayed group (34% unsupported and 19% supported) were ambulatory. CONCLUSIONS: Early surgery is possible for CSI in elderly patients as the matched cohort reveals no significant difference in complication rates and neurological or ambulatory recovery between the early and delayed surgery groups.