Effect of recombinant irisin on recombinant human bone morphogenetic protein-2 induced osteogenesis and osteoblast differentiation.

Osteoporotic fragility fractures substantially impact aging societies, necessitating long-term care and increasing healthcare costs. Myokine irisin, secreted by skeletal muscle, influences bone metabolism; however, a comprehensive understanding of the mechanisms by which irisin affects bone metabolism is still lacking. Therefore, this study aimed to explore the effects of irisin on osteogenesis and osteoblast differentiation triggered by bone morphogenetic protein-2 (BMP-2). We used 4-week-old male ICR mice and implanted polyethylene glycol pellets containing recombinant human BMP-2 (rh-BMP-2) into the left dorsal muscle pouch. Mice received weekly intraperitoneal injections of either phosphate-buffered saline or recombinant irisin (re-irisin). Ectopic bone formation was evaluated 3 weeks post-surgery using micro-computed tomography (µ-CT) and histological analysis. In vitro experiments, C2C12 cells were treated with or without rh-BMP-2 and re-irisin, and we assessed osteoblast differentiation markers, e.g., runt-related transcription factor 2, alkaline phosphatase, osteocalcin, and osteopontin, using real-time reverse transcription-polymerase chain reaction. The µ-CT analyses showed that re-irisin significantly increased bone mineral content and bone volume of ectopic bones newly formed by rh-BMP-2. The gene expressions of the osteoblast markers were significantly increased by rh-BMP-2 and further upregulated by re-irisin. The treatment of cyclic AMP response element-binding protein (CREB) small interfering RNA attenuated these effects, suggesting that CREB signaling pathway was involved in rh-BMP-2/re-irisin-induced osteoblastic differentiation. This study demonstrates the potential of irisin to enhance osteogenesis through BMP signaling, offering insights for osteoporosis treatment and highlighting irisin as a promising therapeutic target for improving bone health and extending a healthy lifespan.

Does cessation of combustible cigarette and heated tobacco product smoking immediately following a fracture benefit fracture healing? In vivo and in vitro validation.

Combustible cigarette and heated tobacco products (HTPs), the two most frequently used tobacco products, negatively affect bone healing. However, whether smoking cessation following fracture benefits bone healing is unclear. Therefore, this study investigated the effect of smoking cessation immediately after surgery on reduced fracture healing induced by smoking. Smoking combustible cigarettes and heated tobacco products generates cigarette smoking extracts (CSE) (extracts from combustible cigarettes [cCSE] and from HTPs [hCSE], respectively). In vivo, CSEs were injected intraperitoneally into rat models for 3 weeks before femoral midshaft osteotomy and fixation. The rats were then divided into CSE continuation and cessation groups postoperatively. Micro-computed tomography (µCT) and biomechanical analyses were performed 6 weeks postoperatively to assess bone union at the fracture site. In vivo study showed µCT assessment also revealed significantly higher cortical bone mineral density (p = 0.013) and content (p = 0.013), and a higher bone union score (p = 0.046) at the fracture site in the cCSE cessation group than in the cCSE continuation group. Biomechanical assessment revealed that elasticity at the fracture site was significantly higher in the cCSE cessation group than in the cCSE continuation group (p = 0.041). These findings provide that smoking cessation, particularly of combustible cigarette, immediately after a fracture accelerates bone fracture healing and increases mechanical strength at the fracture site.

Periostin increased by mechanical stress upregulates interleukin-6 expression in the ligamentum flavum.

Ligamentum flavum (LF) hypertrophy is a major cause of lumbar spinal canal stenosis. Although mechanical stress is thought to be a major factor involved in LF hypertrophy, the exact mechanism by which it causes hypertrophy has not yet been fully elucidated. Here, changes in gene expression due to long-term mechanical stress were analyzed using RNA-seq in a rabbit LF hypertrophy model. In combination with previously reported analysis results, periostin was identified as a molecule whose expression fluctuates due to mechanical stress. The expression and function of periostin were further investigated using human LF tissues and primary LF cell cultures. Periostin was abundantly expressed in human hypertrophied LF tissues, and periostin gene expression was significantly correlated with LF thickness. In vitro, mechanical stress increased gene expressions of periostin, transforming growth factor-ß1, α-smooth muscle actin, collagen type 1 alpha 1, and interleukin-6 (IL-6) in LF cells. Periostin blockade suppressed the mechanical stress-induced gene expression of IL-6 while periostin treatment increased IL-6 gene expression. Our results suggest that periostin is upregulated by mechanical stress and promotes inflammation by upregulating IL-6 expression, which leads to LF degeneration and hypertrophy. Periostin may be a pivotal molecule for LF hypertrophy and a promising therapeutic target for lumbar spinal stenosis.

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.

Impact of surgical treatment on patient reported outcome in patients with spinal metastases from prostate cancer.

OBJECTIVE: This study aimed to elucidate postoperative outcomes in patients with spinal metastases of prostate cancer, with a focus on patient-oriented assessments. METHODS: This was a prospective multicenter registry study involving 35 centers. A total of 413 patients enrolled in the Japanese Association for Spine Surgery and Oncology Multicenter Prospective Study of Surgery for Metastatic Spinal Tumors were evaluated for inclusion. The eligible patients were followed for at least 1 year after surgery. The Frankel Classification, Eastern Cooperative Oncology Group Performance Status, visual analog scale for pain, face scale, Barthel Index, vitality index, indications for oral pain medication, and the EQ-5D-5L questionnaire were used for evaluating functional status, activities of daily living, and patient motivation. RESULTS: Of the 413 eligible patients, 41 with primary prostate cancer were included in the study. The patient-oriented assessments indicated that the patients experienced postoperative improvements in quality of life and motivation in most items, with the improvements extending for up to 6 months. More than half of the patients with Frankel classifications B or C showed improved neurological function at 1 month after surgery, and most patients presented maintained or improved their classification at 6 months. CONCLUSION: Surgical intervention for spinal metastases of prostate cancer significantly improved neurological function, quality of life, and motivation of the patients. Consequently, our results support the validity of surgical intervention for improving the neurological function and overall well-being of patients with spinal metastases of prostate cancer.

Less-invasive decompression procedures can reduce risk of reoperation for lumbar spinal stenosis with diffuse idiopathic skeletal hyperostosis extended to the lumbar segment: analysis of two retrospective cohorts.

PURPOSE: Clinical outcomes after decompression procedures are reportedly worse for lumbar spinal stenosis (LSS) with diffuse idiopathic skeletal hyperostosis (DISH), especially DISH extended to the lumbar segment (L-DISH). However, no studies have compared the effect of less-invasive surgery versus conventional decompression techniques for LSS with DISH. The purpose of this study was to compare the long-term risk of reoperation after decompression surgery focusing on LSS with L-DISH. METHODS: This study compared open procedure cohort (open conventional fenestration) and less-invasive procedure cohort (bilateral decompression via a unilateral approach) with ≥ 5 years of follow-up. After stratified analysis by L-DISH, patients with L-DISH were propensity score-matched by age and sex. RESULTS: There were 57 patients with L-DISH among 489 patients in the open procedure cohort and 41 patients with L-DISH among 297 patients in the less-invasive procedure cohort. The reoperation rates in L-DISH were higher in the open than less-invasive procedure cohort for overall reoperations (25% and 7%, p = 0.026) and reoperations at index levels (18% and 5%, p = 0.059). Propensity score-matched analysis in L-DISH demonstrated that open procedures were significantly associated with increased overall reoperations (hazard ratio [HR], 6.18; 95% confidence interval [CI], 1.37-27.93) and reoperations at index levels (HR, 4.80; 95% CI, 1.04-22.23); there was no difference in reoperation at other lumbar levels. CONCLUSIONS: Less-invasive procedures had a lower risk of reoperation, especially at index levels for LSS with L-DISH. Preserving midline-lumbar posterior elements could be desirable as a decompression procedure for LSS with L-DISH.

Relationship between body mass index and spinal pathology in community-dwelling older adults.

PURPOSE: To clarify the relationship between body mass index (BMI) and spinal pathologies including spinal sagittal balance, back extensor strength (BES), paraspinal muscle mass, prevalent vertebral fracture, disc degeneration, Modic changes, low back pain, and quality of life (QOL) in community-dwelling older adults. METHODS: This study included 380 participants (age: ≥ 65 years, male/female: 152/228) from the Shiraniwa Study. Multivariate nonlinear regression analysis was used to investigate the relationship between BMI and sagittal vertical axis (SVA), BES, paraspinal muscle mass, visual analog scale (VAS) for low back pain, Oswestry Disability Index (ODI), and EuroQoL-5 Dimension (EQ5D) score after adjusting for sex, age, Hospital Anxiety and Depression Scale score, and Charlson Comorbidity Index. In addition, multiple logistic regression analysis was used to investigate the association between BMI and prevalent vertebral fracture, disc degeneration, and Modic changes. RESULTS: BMI was significantly correlated with SVA, BES, paraspinal muscle mass, VAS, ODI, and EQ5D score. The increase in BMI was associated with the deterioration of all outcomes, which accelerated when the BMI increased from approximately 22-23 kg/m2. Moreover, overweight/obesity was significantly correlated with disc degeneration and Modic changes. CONCLUSION: Increased BMI is significantly associated with spinal pathologies such as SVA, BES, paraspinal muscle mass, VAS, QOL, disc degeneration, and Modic changes. The findings suggest that measures for controlling overweight and obesity among older adults can play an important role in the prevention and treatment of spinal pathologies.

Machine-learning-based approach for nonunion prediction following osteoporotic vertebral fractures.

PURPOSE: An osteoporotic vertebral fracture (OVF) is a common disease that causes disabilities in elderly patients. In particular, patients with nonunion following an OVF often experience severe back pain and require surgical intervention. However, nonunion diagnosis generally takes more than six months. Although several studies have advocated the use of magnetic resonance imaging (MRI) observations as predictive factors, they exhibit insufficient accuracy. The purpose of this study was to create a predictive model for OVF nonunion using machine learning (ML). METHODS: We used datasets from two prospective cohort studies for OVF nonunion prediction based on conservative treatment. Among 573 patients with acute OVFs exceeding 65 years in age enrolled in this study, 505 were analyzed. The demographic data, fracture type, and MRI observations of both studies were analyzed using ML. The ML architecture utilized in this study included a logistic regression model, decision tree, extreme gradient boosting (XGBoost), and random forest (RF). The datasets were processed using Python. RESULTS: The two ML algorithms, XGBoost and RF, exhibited higher area under the receiver operating characteristic curves (AUCs) than the logistic regression and decision tree models (AUC = 0.860 and 0.845 for RF and XGBoost, respectively). The present study found that MRI findings, anterior height ratio, kyphotic angle, BMI, VAS, age, posterior wall injury, fracture level, and smoking habit ranked as important features in the ML algorithms. CONCLUSION: ML-based algorithms might be more effective than conventional methods for nonunion prediction following OVFs.

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.

Artificial intelligence model to identify elderly patients with locomotive syndrome: A cross-section study.

BACKGROUND: Identifying elderly individuals with locomotive syndrome is important to prevent disability in this population. Although screening tools for locomotive syndrome are available, these require time commitment and are limited by an individual's ability to complete questionnaires independently. To improve on this limitation, we developed a screening tool that uses information on the distribution of pressure on the plantar surface of the foot with an artificial intelligence (AI)-based decision system to identify patients with locomotor syndrome. Herein, we describe our AI-based system and evaluate its performance. METHODS: This was a cross-sectional study of 409 participants (mean age, 73.5 years). A foot scan pressure system was used to record the planter pressure distribution during gait. In the image processing step, we developed a convolutional neural network (CNN) to return the logit of the probability of locomotive syndrome based on foot pressure images. In the logistic regression step of the AI model, we estimated the predictor coefficients, including age, sex, height, weight, and the output of the CNN, based on foot pressure images. RESULTS: The AI model improved the identification of locomotive syndrome among elderly individuals compared to clinical data, with an area under curve of 0.84 (95% confidence interval, 0.79-0.88) for the AI model compared to 0.80 (95% confidence interval, 0.75-0.85) for the clinical model. Including the footprint force distribution image significantly improved the prediction algorithm (the net reclassification improvement was 0.675 [95% confidence interval, 0.45-0.90] P < 0.01; the integrated discrimination improvement was 0.059 [95% confidence interval, 0.039-0.088] P < 0.01). CONCLUSIONS: The AI system, which includes force distribution over the plantar surface of the foot during gait, is an effective tool to screen for locomotive syndrome.

Development of locomotive syndrome in elderly population after COVID-19 outbreak: A population-based cross-sectional study with over 12,000 participants.

BACKGROUND: Restrictions during the coronavirus disease 2019 (COVID-19) pandemic have decreased physical activity levels, which may result in locomotive syndrome. This study evaluated the change in locomotive syndrome prevalence and associated risk factors among an elderly population before and after a coronavirus outbreak. METHODS: This written self-administered cross-sectional survey was conducted in conjunction with the coronavirus disease vaccination program in Habikino City, Japan. Participants who were aged ≥65 years completed the five-question Geriatric Locomotive Function Scale before and during the pandemic. The diagnosis of locomotive syndrome and its stage was based on the Geriatric Locomotive Function Scale score: stage 1 (2-3 points), 2 (4-5 points), and 3 (≥6 points). Data on lifestyle changes, including regular exercise, during the pandemic were collected. RESULTS: This study included 12,197 participants (36.7% of the city's total elderly residents). The prevalence of locomotive syndrome increased from 41.3% to 47.1% after the outbreak. In total, 765 (6.3% of overall population) and 295 (9.5% of the participants who had stages 1-2 before the pandemic) participants developed locomotive syndrome and stage 3 locomotive syndrome, respectively. The multivariate logistic regression analysis indicated that a decrease in exercise was significantly associated with the onset of locomotive syndrome (all stages) (odds ratio = 2.5, p < 0.001) and locomotive syndrome stage 3 (odds ratio = 2.6, p < 0.001). CONCLUSIONS: Extrapolation of the study's findings to the entire population of Japan suggests that approximately 2 million elderly individuals might develop locomotive syndrome after the coronavirus outbreak. Additionally, 10% of the participants with mild-moderate locomotive syndrome before the pandemic may develop severe locomotive syndrome after the outbreak. The greatest risk factor for new-onset or worsening locomotive syndrome was a decrease in daily exercise. Thus, there is an urgent need for adequate exercise guidelines during the coronavirus pandemic, especially for the elderly population.

Decreased daily exercise since the COVID-19 pandemic and the deterioration of health-related quality of life in the elderly population: a population-based cross-sectional study.

BACKGROUNDS: The current prolonging state of the coronavirus disease (COVID-19), could affect many aspects of people's lives, especially the elderly population who experience a decrease in regular exercise. However, whether this decrease in regular exercise affects health-related quality of life (HRQOL) of the elderly population, remains unclear. METHODS: The current population-based cross-sectional survey aimed to identify the relationship between the decrease in regular exercise since the COVID-19 pandemic and any changes in the HRQOL in the general elderly Japanese population. This study was conducted as a part of the COVID-19 vaccination program in Habikino city in Japan, between June and July 2021 using printed questionnaires. The participants included residents of the city who were aged ≥ 65 years, and were being vaccinated for COVID-19 at the city's center. The EuroQoL 5-dimension 5-level (EQ-5D-5L) was assessed at two different time points (pre-pandemic and current). Data on lifestyle changes, including their regular exercise routine since the pandemic, were collected. RESULTS: Finally, 14,494 participants (45.3% of the city's total elderly residents) were enrolled. Among them, 4321 participants (29.8%) had experienced a decrease in regular exercise since the pandemic. These participants showed a significantly higher rate of deterioration in all the EQ-5D-5L domains than the participants who did not experience a decrease in regular exercise. In the multivariate logistic regression analysis, participants with a decrease in regular exercise were significantly related to the EQ-5D-5L index deterioration compared to those with an unchanged regular exercise routine (p < 0.001, adjusted odds ratio = 5.60) independent of age, sex, body mass index (BMI), and the existence of back pain, joint pain, and/or numbness of extremities. CONCLUSION: The current survey that included 45% of the elderly people living in a city revealed that up to 30% of them had experienced a decrease in the regular exercise since the COVID-19 pandemic. This decrease was significantly related to HRQOL deterioration independent of age, sex, BMI, baseline activities of daily living status, and musculoskeletal symptoms. Our data could be useful for understanding the current problem and provide a strong basis for the creation of exercise guidelines for the post-COVID-19 era.

Decreased muscle mass and strength affected spinal sagittal malalignment.

PURPOSE: Correction surgeries for spinal malalignment showed good clinical outcomes; however, there were concerns including increased invasiveness, complications, and impact on medico-economics. Ideally, an early intervention is needed. To better understand the patho-mechanism and natural course of spinal alignment, the effect of factors such as muscle mass and strength on spinal sagittal imbalance were determined in a multicenter cross-sectional study. METHODS: After excluding metal implant recipients, 1823 of 2551 patients (mean age: 69.2 ± 13.8 years; men 768, women 1055) were enrolled. Age, sex, past medical history (Charlson comorbidity index), body mass index (BMI), grip strength (GS), and trunk muscle mass (TM) were reviewed. Spinal sagittal imbalance was determined by the SRS-Schwab classification. Multiple comparison analysis among four groups (Normal, Mild, Moderate, Severe) and multinomial logistic regression analysis were performed. RESULTS: On multiple comparison analysis, with progressing spinal malalignment, age in both sexes tended to be higher; further, TM in women and GS in both sexes tended to be low. On multinomial logistic regression analysis, age and BMI were positively associated with spinal sagittal malalignment in Mild, Moderate, and Severe groups. TM in Moderate and Severe groups and GS in the Moderate group were negatively associated with spinal sagittal malalignment. CONCLUSION: Aging, obesity, low TM, and low GS are potential risk factors for spinal sagittal malalignment. Especially, low TM and low GS are potentially associated with more progressed spinal sagittal malalignment. Thus, early intervention for muscles, such as exercise therapy, is needed, while the spinal sagittal alignment is normal or mildly affected.

Does surgery improve neurological outcomes in older individuals with cervical spinal cord injury without bone injury? A multicenter study.

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.

A multicenter study of 1-year mortality and walking capacity after spinal fusion surgery for cervical fracture in elderly patients.

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.

Expression and function of fibroblast growth factor 1 in the hypertrophied ligamentum flavum of lumbar spinal stenosis.

BACKGROUND: Fibrosis is one of the main pathologies caused by hypertrophy of the ligamentum flavum (LF), which leads to lumbar spinal stenosis (LSS). The fibroblast growth factor (FGF) family is a key mediator of fibrosis. However, acidic fibroblast growth factor (FGF-1) expression and function are not well understood in LF. This study sought to evaluate FGF-1 expression in the hypertrophied and non-hypertrophied human LF, and to investigate its function using primary human LF cell cultures. METHODS: We obtained hypertrophied lumbar LF from LSS patients and non-hypertrophied lumbar LF from control patients during surgery. Immunohistochemistry and qPCR were performed to evaluate FGF-1 expression in LF tissue. The function of FGF-1 and transforming growth factor beta 1 (TGF-ß1) was also investigated using primary LF cell culture. The effects on cell morphology and cell proliferation were examined using a crystal violet staining assay and MTT assay, respectively. Immunocytochemistry, western blotting, and qPCR were performed to evaluate the effect of FGF-1 on TGF-ß1-induced myofibroblast differentiation and fibrosis. RESULTS: Immunohistochemistry and qPCR showed higher FGF-1 expression in hypertrophied LF compared to control LF. Crystal violet staining and MTT assay revealed that FGF-1 decreases LF cell size and inhibits their proliferation in a dose-dependent manner, whereas TGF-ß1 increases cell size and promotes proliferation. Immunocytochemistry and western blotting further demonstrated that TGF-ß1 increases, while FGF-1 decreases, α-SMA expression in LF cells. Moreover, FGF-1 also caused downregulation of collagen type 1 and type 3 expression in LF cells. CONCLUSION: FGF-1 is highly upregulated in the LF of LSS patients. Meanwhile, in vitro, FGF-1 exhibits antagonistic effects to TGF-ß1 by inhibiting cell proliferation and decreasing LF cell size as well as the expression of fibrosis markers. These results suggest that FGF-1 has an anti-fibrotic role in the pathophysiology of LF hypertrophy.

The health-related quality of life of patients with musculoskeletal disorders after the COVID-19 pandemic.

PURPOSE: To verify changes in the health-related quality of life (HRQOL) of patients with musculoskeletal disorders after the coronavirus disease 2019 (COVID-19) pandemic and to assess the relationship between the patients' change in several activities of daily living and in the HRQOL to discover factors related to the deterioration in HRQOL. METHODS: A multi-centre cross-sectional questionnaire survey was administered between November 1, 2020, and December 31, 2020, in Japan. The participants included those who visited the orthopaedics clinic within the survey period and had experienced the first and second waves of COVID-19 in Japan and the first stay-at-home order issued by the government. Patients' HRQOL at the two different time points (pre-outbreak and post-second wave of COVID-19) was assessed with the EuroQoL-5 dimensions 5-level (EQ-5D). RESULTS: The survey was completed by 1254 patients (average age: 52.5 ± 21.9 years; 644 women). Among them, 431 patients (34.3%) reported a decrease in the EQ-5D index after the pandemic. The largest decrease was in the pain domain followed by the mobility domain. Multivariate logistic regression analysis revealed that the patients with decreased regular exercise habits were significantly related to deterioration in HRQOL compared with those with stable regular exercise (adjusted odds ratio = 1.76, p < 0.001) independently from age, sex, and change of symptoms. CONCLUSIONS: Up to 35% of patients with musculoskeletal disorders reported deterioration of HRQOL after the COVID-19 pandemic. Pain and mobility rather than anxiety were the two leading factors of the HRQOL decrease. The decrease in regular exercise was related to the HRQOL decrease.

Classification and prognostic factors of residual symptoms after minimally invasive lumbar decompression surgery using a cluster analysis: a 5-year follow-up cohort study.

PURPOSE: Residual symptoms indicating incomplete remission of lower leg numbness or low back pain may occur after spine surgery. The purpose was to elucidate the pattern of residual symptoms 5 years after minimally invasive lumbar decompression surgery using a cluster analysis. METHODS: The study comprised 193 patients with lumbar spinal stenosis (LSS) (108 men, 85 women) ranging in age from 40 to 86 years (mean, 67.9 years). Each patient underwent 5-year follow-up. The Japanese Orthopedic Association score and visual analog scale scores for low back pain, leg pain, and leg numbness at 5 years were entered into the cluster analysis to characterize postoperative residual symptoms. Other clinical data were analyzed to detect the factors significantly related to each cluster. RESULTS: The analysis yielded four clusters representing different patterns of residual symptoms. Patients in cluster 1 (57.0%) were substantially improved and had few residual symptoms of LSS. Patients in cluster 2 (11.4%) were poorly improved and had major residual symptoms. Patients in cluster 3 (17.6%) were greatly improved but had mild residual low back pain. Patients in cluster 4 (14.0%) were improved but had severe residual leg numbness. Prognostic factors of cluster 2 were a short maximum walking distance, motor weakness, resting lower leg numbness, cofounding scoliosis, and high sagittal vertical axis. CONCLUSIONS: This is the first study to identify specific patterns of residual symptoms of LSS after decompression surgery. Our results will contribute to acquisition of preoperative informed consent and identification of patients with the best chance of postoperative improvement.

Characteristics and Short-Term Surgical Outcomes of Patients with Recurrent Lumbar Disc Herniation after Percutaneous Laser Disc Decompression.

Background and Objectives: Although percutaneous laser disc decompression (PLDD) is one of the common treatment methods for patients with lumbar disc herniation (LDH), the recurrence of LDH after PLDD is estimated at 4-5%. This study compares the preoperative clinical data and clinical outcomes of patients who underwent primary microendoscopic discectomy (MED) or MED following PLDD. Materials and Methods: We retrospectively analyzed 2678 patients who underwent MED for LDH. The PLDD group included patients with previous PLDD history at the same level of LDH, and a matched control group was created using propensity score matching for age, sex, and body mass index. Preoperative data, preoperative radiographic findings, and surgical data of the groups were compared. To compare postoperative changes in clinical scores between the groups, a mixed-effect model was used. Results: As a result, 42 patients (1.6%) had previously undergone PLDD, and a control group with 42 patients were created. The disc degeneration severity was not significantly different between the groups. However, Modic changes were more frequent in the PLDD group than in the matched control group (p = 0.028). There were no significant differences in dural adhesion rate or surgery-related complications including dural injury, length of stay, and recurrence rate of LDH after surgery. In addition, the improvement of clinical scores did not significantly differ between the two groups (p = 0.112, 0.913, respectively). Conclusions: We concluded that patients with recurrent LDH after PLDD have advanced endplate degeneration, which may reflect endplate injury from a previous PLDD. However, a previous history of PLDD does not have a negative impact on the clinical result of MED.