Complications of chest wall around malignant tumors: differences based on reconstruction strategy.

BACKGROUND: Malignant chest wall tumors need to be excised with wide resection to ensure tumor free margins, and the reconstruction method should be selected according to the depth and dimensions of the tumor. Vascularized tissue is needed to cover the superficial soft tissue defect or bone tissue defect. This study evaluated differences in complications according to reconstruction strategy. METHODS: Forty-five patients with 52 operations for resection of malignant tumors in the chest wall were retrospectively reviewed. Patients were categorized as having superficial tumors, comprising Group A with simple closure for small soft tissue defects and Group B with flap coverage for wide soft tissue defects, or deep tumors, comprising Group C with full-thickness resection with or without mesh reconstruction and Group D with full-thickness resection covered by flap with or without polymethyl methacrylate. Complications were evaluated for the 52 operations based on reconstruction strategy then risk factors for surgical and respiratory complications were elucidated. RESULTS: Total local recurrence-free survival rates in 45 patients who received first operation were 83.9% at 5 years and 70.6% at 10 years. The surgical complication rate was 11.5% (6/52), occurring only in cases with deep tumors, predominantly from Group D. Operations needing chest wall reconstruction (p = 0.0016) and flap transfer (p = 0.0112) were significantly associated with the incidence of complications. Operations involving complications showed significantly larger tumors, wider areas of bony chest wall resection and greater volumes of bleeding (p < 0.005). Flap transfer was the only significant predictor identified from multivariate analysis (OR: 10.8, 95%CI: 1.05-111; p = 0.0456). The respiratory complication rate was 13.5% (7/52), occurring with superficial and deep tumors, particularly Groups B and D. Flap transfer was significantly associated with the incidence of respiratory complications (p < 0.0005). Cases in the group with respiratory complications were older, more frequently had a history of smoking, had lower FEV1.0% and had a wider area of skin resected compared to cases in the group without respiratory complications (p < 0.05). Preoperative FEV1.0% was the only significant predictor identified from multivariate analysis (OR: 0.814, 95%CI: 0.693-0.957; p = 0.0126). CONCLUSIONS: Surgical complications were more frequent in Group D and after operations involving flap transfer. Severe preoperative FEV1.0% was associated with respiratory complications even in cases of superficial tumors with flap transfer.

Progression of vertebral deformity of prevalent vertebral fractures in the elderly: a population-based study.

BACKGROUND: Little is known about the progression pattern of vertebral deformities in elderly patients with prevalent vertebral fractures. This population-based cohort study investigated the incidence, progression pattern, and risk factors of vertebral deformity in prevalent vertebral fractures over a finite period of four years in a population-based cohort study. METHODS: A total of 224 inhabitants of a typical mountain village underwent medical examinations every second year from 1997 to 2009, and each participant was followed up for four years. The extent (mild, moderate, severe) and type (wedge, biconcave, crush) of prevalent vertebral fractures on spinal radiographs were evaluated using the Genant semi-quantitative method. Of these participants, 116 with prevalent vertebral fractures at baseline (32 men and 84 women; mean age: 70.0 years) were included in this study. The progression patterns of the 187 vertebral fractures with mild and moderate deformities (except severe deformity) were evaluated. Logistic regression analysis was used to identify the risk factors associated with deformity progression. RESULTS: The progression of vertebral deformities was identified in 13.4% (25 vertebral fractures) of the total 187 prevalent (mild and moderate) vertebral fracture deformities over four years. Among the three deformity types, the prevalence of deformity progression was significantly lower in wedge-type vertebral fractures (P < 0.05). Age and number of prevalent vertebral fractures per participant were independent risk factors associated with the progression of prevalent vertebral deformities. CONCLUSION: This study clarified the natural history of the progression pattern of vertebral deformities in radiographic prevalent vertebral fractures in elderly individuals. Multiple vertebral fractures in the elderly present a risk for the progression of vertebral deformities.

Comparison of femoral bone remodeling after total hip arthroplasty with cementless short-tapered wedge stem and fully hydroxyapatite-coated stem.

INTRODUCTION: We aimed to compare periprosthetic femoral bone remodeling after cementless total hip arthroplasty (THA) using a short-tapered wedge stem and a fully hydroxyapatite (HA)-coated stem. MATERIALS AND METHODS: In this retrospective study, 24 primary cementless THA procedures with short-tapered wedge stem and 24 using a fully HA-coated stem were performed. The follow-up duration was 2 years for both groups. Clinical evaluation was performed using the Merle d'Aubigné and Postel scoring systems. Standardized anteroposterior radiographs of the pelvis and femur were obtained. Dual-energy X-ray absorptiometry was performed, and the bone mineral density (BMD) around the stem was assessed in each Gruen zone at the first postoperative week as a baseline value and at 6 weeks, 3 and 6 months, and 1 and 2 years postoperatively. RESULTS: The mean Merle d'Aubigné and Postel scores improved significantly postoperatively in both groups. None of the hips showed loosening in either group. Spot welds occurred in zones 1, 2, 6, and 7 in the short-tapered wedge group, and in all zones in the fully HA-coated group. Significant BMD loss occurred only in zone 4 in the short-tapered wedge group, and no significant bone loss occurred in any zone in the fully HA-coated stem group; a significant difference between the two groups was observed only in zone 4 at 2 years after THA. CONCLUSIONS: Clinical and radiographical outcomes in both groups were good, and both stems suppressed postoperative BMD loss at 2 years.

Accuracy of cup placement and pelvic motion in total hip arthroplasty in the lateral decubitus position using a new computed tomography-based navigation system with augmented reality technology.

INTRODUCTION: This study aimed to investigate the accuracy of cup position and assess the changes in pelvic tilt during primary total hip arthroplasty (THA) in the lateral decubitus position using a new computed tomography (CT)-based navigation system with augmented reality (AR) technology. MATERIALS AND METHODS: There were 37 cementless THAs performed using a CT-based navigation system with AR technology in the lateral decubitus position and 63 cementless THAs performed using manual implant techniques in the lateral decubitus position in this retrospective study. Postoperative cup radiographic inclination and anteversion were measured using postoperative CT, and the proportion of hips within Lewinnek's safe zone was analyzed and compared between the two groups. The mean absolute values of navigation error were assessed. Intraoperative pelvic tilt angles were also recorded using navigation system. RESULTS: The percentage of cups inside Lewinnek's safe zone was 100% in the navigation group and 35% in the control group (p < 0.001). The mean absolute values of navigation error in inclination and anteversion were 2.9° ± 2.1° and 3.3° ± 2.4°, respectively. The mean abduction angle of the pelvis was 5.1° ± 4.8° after placing the patients in the lateral decubitus position and 4.1° ± 6.0° after cup placement. The mean posterior tilt angle was 6.8° ± 5.1° after placing the patients in the lateral decubitus position and 9.3° ± 5.9° after cup placement. The mean internal rotation angle was 14.8° ± 7.4° after cup placement. There were no correlations between the navigation error in inclination or anteversion and the absolute values of changes of the pelvic tilt angle at any phase. CONCLUSIONS: Although progressive pelvic motion occurred in THA in the lateral decubitus position, especially during cup placement, the CT-based navigation system with AR technology improved cup placement accuracy.

Prevalence and risk factors of ankle osteoarthritis in a population-based study.

BACKGROUND: This study aimed to investigate the prevalence of radiographic ankle osteoarthritis (AOA) in Japan and identify its risk factors. METHODS: The analysis included data from the population-based cohort study, radiographs of the knees and ankles, ultrasonography of the ankle to examine chronic ankle instability (CAI), and questionnaires on ankle pain, job history, height, and body weight. A total of 597 individuals aged > 50 years were included in the study. The risk factors for AOA were calculated using multivariate logistic regression analysis. RESULTS: The study revealed a 13.9% prevalence of radiographic AOA among the participants, with 1.2% reporting painful AOA. Female sex, aging, history of ankle fractures, and CAI were identified as the risk factors associated with AOA. CONCLUSIONS: This cross-sectional study highlights the significant prevalence of radiographic AOA in a rural Japanese population, emphasizing the importance of considering ankle fractures and CAI as potential risk factors for AOA development. LEVELS OF EVIDENCE: Level II, prospective cohort study.

A Novel Approach to Reducing Lung Metastasis in Osteosarcoma: Increasing Cell Stiffness with Carbenoxolone.

AIM: Primary malignant bone tumor osteosarcoma can metastasize to the lung. Diminishing lung metastasis would positively affect the prognosis of patients. Our previous studies demonstrated that highly metastatic osteosarcoma cell lines are significantly softer than low-metastasis cell lines. We therefore hypothesized that increasing cell stiffness would suppress metastasis by reducing cell motility. In this study, we tested whether carbenoxolone (CBX) increases the stiffness of LM8 osteosarcoma cells and prevents lung metastasis in vivo. METHODS: We evaluated the actin cytoskeletal structure and polymerization of CBX-treated LM8 cells using actin staining. Cell stiffness was measured using atomic force microscopy. Metastasis-related cell functions were analyzed using cell proliferation, wound healing, invasion, and cell adhesion assays. Furthermore, lung metastasis was examined in LM8-bearing mice administered with CBX. RESULTS: Treatment with CBX significantly increased actin staining intensity and stiffness of LM8 cells compared with vehicle-treated LM8 cells (p < 0.01). In Young's modulus images, compared with the control group, rigid fibrillate structures were observed in the CBX treatment group. CBX suppressed cell migration, invasion, and adhesion but not cell proliferation. The number of LM8 lung metastases were significantly reduced in the CBX administration group compared with the control group (p < 0.01). CONCLUSION: In this study, we demonstrated that CBX increases tumor cell stiffness and significantly reduces lung metastasis. Our study is the first to provide evidence that reducing cell motility by increasing cell stiffness might be effective as a novel anti-metastasis approach in vivo.

Change in prevalence of vertebral fractures over two decades: a Japanese medical examination-based study.

INTRODUCTION: Although remarkable progress has been made in osteoporosis treatment over the last two decades, no study has reported the change in the prevalence of vertebral fractures (VFs) during this time. This study aimed to compare the prevalence and pattern of VFs at three time points from 1997 to 2019 in a Japanese medical examination-based study. MATERIALS AND METHODS: The participants of this study were inhabitants of a typical Japanese mountain village who participated in these surveys at three time points: 1997 (group A), 2009 or 2011 (group B), and 2019 (group C). The age- and sex-adjusted groups were defined as groups A', B', and C', respectively (39 men and 85 women; mean age 73.6-74.0 years old). The type and extent of deformities of the prevalent fractures from T4 to L4 on the lateral thoracic and lumbar spine radiographs were semiquantitatively evaluated. RESULTS: The prevalence of VFs has significantly decreased over the past two decades. In group A, the percentages of thoracic level, biconcave type, and severe deformity of VFs were significantly higher than expected. The bone mineral density of the participants increased significantly over time. The treatment rate for osteoporosis in participants with osteoporosis has improved over the past two decades. CONCLUSION: This study demonstrated that the prevalence of VFs has decreased, and the pattern of VFs has changed over the last two decades in a typical Japanese mountain village due to multifactorial improvements in skeletal fragility, including improvement in osteoporosis treatment rate.

Central sensitization as a predictive factor for the surgical outcome in patients with lumbar spinal stenosis: a multicenter prospective study.

PURPOSE: The impact of central sensitization (CS) on neurological symptoms and surgical outcomes in patients with lumbar spinal stenosis (LSS) remains unknown. This study aimed to investigate the influence of preoperative CS on the surgical outcomes of patients with LSS. METHODS: A total of 197 consecutive patients with LSS (mean age 69.3) who underwent posterior decompression surgery with or without fusion were included in this study. The participants completed the CS inventory (CSI) scores and the following clinical outcome assessments (COAs) preoperatively and 12 months postoperatively: the Japanese Orthopaedic Association (JOA) score for back pain, JOA back pain evaluation questionnaire, and Oswestry Disability Index (ODI). The association between preoperative CSI scores and preoperative and postoperative COAs was analyzed, and postoperative changes were statistically evaluated. RESULTS: The preoperative CSI score significantly decreased at 12 months postoperatively and was significantly correlated with all COAs preoperatively and 12 months postoperatively. Higher preoperative CSI showed worse postoperative COAs and inferior postoperative improvement rates in the JOA score, VAS score for neurological symptoms, and ODI. Multiple regression analysis demonstrated that preoperative CSI was significantly associated with postoperative low back pain (LBP), mental health, quality of life (QOL), and neurological symptoms at 12 months postoperatively. CONCLUSIONS: Preoperative CS evaluated by CSI had a significantly worse impact on surgical outcomes, including neurological symptoms, disability, and QOL, especially related to LBP and psychological factors. CSI can be used clinically as a patient-reported measure for predicting postoperative outcomes in patients with LSS.

Two- and three-dimensional measurements of leg length change using an accelerometer-based portable navigation system in total hip arthroplasty.

BACKGROUND: The aim of this study was examining the accuracy of accelerometer-based portable navigation systems (HipAlign) when measuring leg length changes using two-dimensional (2D) and three-dimensional (3D) methods. METHODS: Inclusion criteria were patients ≥ 20 years old with symptomatic hip disease who underwent primary total hip arthroplasty (THA) in the supine position using HipAlign between June 2019 and April 2020. The exclusion criteria were patients who underwent THA via a posterior approach. We examined correlations between the leg length change measurement with HipAlign and either 2D or 3D measurement. We performed a multivariate analysis to determine which factors may have influenced the absolute error results. RESULTS: This study included 34 patients. The absolute error in leg length change between the HipAlign and 3D measurement (4.0 mm) was greater than the HipAlign and 2D measurement (1.7 mm). There were positive correlations between leg length change with HipAlign and 2D and 3D measurements. Male patients had larger errors with 2D measurement. No significant factors were identified for 3D measurement. CONCLUSION: HipAlign provided acceptable measurement accuracy for leg length changes.

Long-term results of hemi-resurfacing and metal-on-metal hip resurfacing for osteonecrosis of the femoral head.

PURPOSE: Hemi-resurfacing arthroplasty (Hemi) and metal-on-metal hip resurfacing arthroplasty (HR) were proposed as alternatives to conventional total hip arthroplasty (THA) for patients with osteonecrosis of the femoral head (ONFH). Long-term results were evaluated. METHODS: Twenty-three hips with ONFH were treated, using Hemi in 12 and HR in 11. Mean follow-up was 15 years in the Hemi group and 10 years in the HR group. Long-term outcomes were reviewed retrospectively. RESULTS: In the Hemi group, 8 hips showed acetabular protrusion and were revised to THA. One of the 8 hips showed femoral loosening. In the HR group, pseudotumor was detected in 4 hips (36%), and 1 hip was revised due to symptomatic pseudotumor. No evidence of any femoral or acetabular loosening was seen in the HR group. Ten-year survival rates were 64.2% and 90.9% in the Hemi and HR groups, respectively. Survival rate in the Hemi group dropped to 22.9% at 15 years. CONCLUSIONS: Long-term results of Hemi for patients with ONFH were very poor, and Hemi should not continue to be used. Although HR had a concern of pseudotumor, it could offer attractive indications for 10 years.

High rates of outliers in computer-assisted high tibial osteotomy with excellent mid-term outcomes.

PURPOSE: The primary aim was to evaluate the accuracy of navigation in opening wedge high tibial osteotomy (HTO). The secondary aim was to examine mid-term outcomes after HTO. METHODS: Inclusion criteria were patients with medial compartment knee osteoarthritis who underwent computer-assisted HTOs. Mechanical axis (MA), percentage MA (%MA), and change in posterior tibial slope (ΔPTS) were displayed on the navigation screen. Radiographic examinations included hip-knee-ankle (HKA) angle, medial proximal tibial angle (MPTA), joint line convergence angle (JLCA), and PTS. Preoperative and 5 weeks postoperative standing radiographs of the whole lower extremity and knee were used. Clinical evaluations were performed using American Knee Society knee score and function score both preoperatively and at last follow-up. Radiographic evaluations were performed by orthopedic surgeons. Intraoperative navigation after osteotomy and postoperative standing radiograph were compared. MA (HKA), %MA, and ΔPTS were compared. Outliers were defined as > 3° in MA, > 10% in %MA, and > 10° in ΔPTS. Outlier and non-outlier groups were compared. The rate of conversion to arthroplasty was examined. RESULTS: This study involved 38 patients (44 knees) and last follow-up was at a mean of 5 years (range, 1-9 years). Mean American Knee Society knee score and function score improved significantly from 59 to 69 preoperatively to 95 and 85 at last follow-up, respectively. Absolute values of mean errors for MA, %MA, and ΔPTS were 2.1°, 9.3%, 1.2°, respectively. Outlier rates were 18% in MA, 39% in %MA, and 5% in ΔPTS. No significant factors were found in MA and ΔPTS. In %MA, preoperative JLCA was significantly higher in the outlier group compared to the non-outlier group. No knees underwent conversion to total knee arthroplasty. No differences in outcomes were found between outlier and non-outlier groups. CONCLUSION: Although rates of outlier values in computer-assisted opening wedge HTO were high, mid-term outcomes were excellent. LEVEL OF EVIDENCE: IV.

What is a useful marker for predicting survival in patients with high-grade soft tissue sarcoma who have non-inflammatory conditions?

BACKGROUND: The modified Glasgow prognostic score (mGPS) is a reliable system for identifying patients at high risk of death among patients with soft tissue sarcoma (STS). The scoring systems use a combination of C-reactive protein (CRP) and albumin levels. Although patients with high-grade STS are at risk of metastasis and death, even if their mGPS is 0, the prognostic indicators in these patients are unknown. Therefore, we investigated useful prognostic indicators for survival and the development of metastasis in patients with high-grade STS and an mGPS of 0. METHODS: One hundred and four patients with CRP and albumin levels of <1.0 mg/dl and >3.5 g/dl, respectively, indicating an mGPS of 0, were included. The mean follow-up period was 79 months. RESULTS: The 5-year disease-specific survival (DSS) rate was 79.2%. Cox proportional analysis showed that tumor size and absolute neutrophil count (ANC) were prognostic variables in multivariate analyses. Patients with higher ANC (ANC>3370/µl) had a worse DSS than those with lower ANC. The 5-year DSS was 74.7% vs. 91.7%, respectively (p = 0.0207). The 5-year metastasis-free survival was 67.2%. Tumor size and ANC remained significant variables for predicting the development of metastasis in the multivariate analysis. Patients with higher ANC had a worse metastasis-free survival than those with lower ANC. The 5-year metastasis-free survival was 59.5% vs. 87.3%, respectively (p = 0.00269). CONCLUSIONS: When patients with high-grade STS have an mGPS of 0, the ANC and tumor size should be carefully evaluated. A higher neutrophil count and larger tumor size may increase the risk of metastasis development.

Artifactual hypoglycaemia may be common in patients with soft tissue sarcoma who received pegfilgrastim-supported chemotherapy.

BACKGROUND: Recently, we identified artifactual hypoglycemia in patients with soft tissue sarcoma (STS) who received pegfilgrastim-supported chemotherapy. In the present study, we measured white blood cell count and fasting blood glucose levels after the administration of pegfilgrastim in patients with STS and showed the relationship between artifactual hypoglycemia and white blood cell count. PATIENTS: A total of 19 patients were included in this study. The mean age of the patients was 54 years. They received chemotherapy and administration of pegfilgrastim. Pegfilgrastim was injected subcutaneously 48 h after chemotherapy. No patient had a history of diabetes mellitus. RESULTS: Fifty-nine cycles were administered to 19 patients. One hundred and twenty-eight samples were obtained within one week after the of pegfilgrastim administration. Hypoglycemia was observed in 38 of the 13 patients. There were no symptoms of hypoglycemia in any patient. The white blood cell count in samples from patients with hypoglycemia was significantly higher than that in samples without hypoglycemia (p < 0.001). The median white blood cell count in samples with hypoglycemia was 29,415 and 3420 in samples without hypoglycemia. Age, sex, body mass index, performance status, and red blood cell count were not associated with hypoglycemia. White blood cell count was strongly negatively correlated with fasting blood glucose levels (Pearson's r: 0.786, 95% confidence interval: 0.844-0.709, p < 0.001). Of the 38 samples with hypoglycemia, 32 were measured within 2 days after pegfilgrastim administration. CONCLUSION: If a lack of symptoms due to hypoglycemia and leukocytes is confirmed, physicians should wait and identify the normalization of the level of glucose according to the neutrophil nadir following temporal leukocytes, which prevents further invasive examination for hypoglycemia.

Association between low back pain and psychological stress response in a Japanese population-based study.

BACKGROUND: Psychological stress response refers to the negative emotional states generated when an individual perceives that they do not have the resources to cope with or respond to a threat. Low back pain (LBP) is a complex condition with multiple contributors, including psychological factors. However, whether LBP is a stressor that causes a psychological stress response remains unknown. This study aimed to investigate the association between LBP and psychological stress response in a Japanese population-based cohort. METHODS: Participants aged >50 years were recruited from inhabitants of a mountain village in Japan. The participants completed the following patient-reported outcome measures. The extent of the psychological stress response was measured using the Stress response scale (SRS)-18, which includes the subscales "Depression/Anxiety", "Irritability/Anger", and "Helplessness". LBP intensity in several situations/positions was measured using a numerical rating scale (NRS). Quality of life (QOL) was measured using the Oswestry Disability Index, EuroQol 5-dimension, and EuroQol visual analog scales. The association between SRS-18 and each parameter was statistically evaluated. RESULTS: A total of 282 participants (72.1 years old) were analyzed in this study, and 29.1% had chronic LBP. The SRS-18 total score of all participants ranged from 0 to 43, and the average SRS-18 total score was 7.7 ± 8.8 (depression/anxiety: 2.3 ± 3.2, irritability/anger: 2.4 ± 3.3, helplessness: 2.9 ± 3.2). SRS-18 scores of participants with LBP were significantly higher than those of participants without LBP. SRS-18 scores were significantly correlated with QOL scores (P < 0.01, correlation coefficient = 0.22-0.46). Multiple regression analysis showed that the NRS score of LBP during morning awakening was significantly associated with the SRS-18 total, depression/anxiety, and helplessness scores. CONCLUSIONS: Psychological stress responses were associated with LBP and LBP-related QOL among residents of a Japanese mountain village.

Advances in Platelet-Rich Plasma Treatment for Spinal Diseases: A Systematic Review.

Spinal diseases are commonly associated with pain and neurological symptoms, which negatively impact patients' quality of life. Platelet-rich plasma (PRP) is an autologous source of multiple growth factors and cytokines, with the potential to promote tissue regeneration. Recently, PRP has been widely used for the treatment of musculoskeletal diseases, including spinal diseases, in clinics. Given the increasing popularity of PRP therapy, this article examines the current literature for basic research and emerging clinical applications of this therapy for treating spinal diseases. First, we review in vitro and in vivo studies, evaluating the potential of PRP in repairing intervertebral disc degeneration, promoting bone union in spinal fusion surgeries, and aiding in neurological recovery from spinal cord injury. Second, we address the clinical applications of PRP in treating degenerative spinal disease, including its analgesic effect on low back pain and radicular pain, as well as accelerating bone union during spinal fusion surgery. Basic research demonstrates the promising regenerative potential of PRP, and clinical studies have reported on the safety and efficacy of PRP therapy for treating several spinal diseases. Nevertheless, further high-quality randomized controlled trials would be required to establish clinical evidence of PRP therapy.

Expression of Glial-Cell-Line-Derived Neurotrophic Factor Family Ligands in Human Intervertebral Discs.

Glial-cell-line-derived neurotrophic factor (GDNF) family ligands (GFLs) contribute to the sensitization of primary afferents and are involved in the pathogenesis of inflammatory pain. The purpose of this preliminary study was to examine the expression of other GFLs (neurturin (NRTN), artemin (ARTN), persephin (PSPN)) and receptors in human IVD cells and tissues exhibiting early and advanced stages of degeneration. Human IVD cells were cultured as a monolayer after isolation from the nucleus pulposus (NP) and anulus fibrosus (AF) tissues. The mRNA expression of NRTN, ARTN, PSPN, and their receptors (GFRA2-GFRA4) was quantified using real-time PCR. Protein expression was evaluated using immunohistochemistry and Western blotting. The expression of NRTN, ARTN, PSPN, and their co-receptors (GFRA2-GFRA4) was identified in human IVD cells at both mRNA and protein levels. A trend was noted wherein the mRNA expression of ARTN, PSPN, and GFRA2 was upregulated by IL-1ß treatment in a dose-dependent manner. The percentages of immunopositive cells in the advanced degenerate stage of ARTN, PSPN, and GFRA2 were significantly higher than those in the early degenerate stage. Their expression was enhanced in advanced tissue degeneration, which suggests that GFLs (ARTN and PSPN) may be involved in the pathogenesis of discogenic pain.

Expression of GADD45G and CAPRIN1 in Human Nucleus Pulposus: Implications for Intervertebral Disc Degeneration.

Marked cellular changes occur in human intervertebral disc (IVD) degeneration during disc degeneration with biochemical changes. Genome-wide analysis of the DNA methylation profile has identified 220 differentially methylated loci associated with human IVD degeneration. Among these, two cell-cycle-associated genes, growth arrest and DNA damage 45 gamma (GADD45G) and cytoplasmic activation/proliferation-associated protein-1 (CAPRIN1), were focused on. The expression of GADD45G and CAPRIN1 in human IVDs remains unknown. We aimed to examine the expression of GADD45G and CAPRIN1 in human nucleus pulposus (NP) cells and evaluate those in human NP tissues in the early and advanced stages of degeneration according to Pfirrmann magnetic resonance imaging (MRI) and histological classifications. Human NP cells were cultured as monolayers after isolation from NP tissues by sequential enzyme digestion. Total RNA was isolated, and the mRNA expression of GADD45G and CAPRIN1 was quantified using real-time polymerase chain reaction. To examine the effects of pro-inflammatory cytokines on mRNA expression, human NP cells were cultured in the presence of IL-1ß. Protein expression was evaluated using Western blotting and immunohistochemistry. GADD45G and CAPRIN1 expression was identified in human NP cells at both mRNA and protein levels. The percentage of cells immunopositive for GADD45G and CAPRIN1 significantly increased according to the Pfirrmann grade. A significant correlation between the histological degeneration score and the percentage of GADD45G-immunopositive cells was identified, but not with that of CAPRIN1-immunopositive cells. The expression of cell-cycle-associated proteins (GADD45G and CAPRIN1) was enhanced in human NP cells at an advanced stage of degeneration, suggesting that it may be regulated during the progression of IVD degeneration to maintain the integrity of human NP tissues by controlling cell proliferation and apoptosis under epigenetic alteration.

Relationship between oral frailty and locomotive syndrome in working-age individuals: a cross-sectional survey of workers in Japan.

BACKGROUND: Although the relationship between oral and physical frailty in older adults has been investigated, few studies have focused on the working-age population. This study examined the relationships of the number of remaining teeth and masticatory ability, i.e., signs of oral frailty, with locomotive syndrome (LS) in the working-age population. METHODS: The number of remaining teeth, masticatory ability, and presence of LS in 501 participants from four companies were examined. The relationships between the number of remaining teeth groups (≥ 20 teeth or ≤ 19 teeth) and LS and between the masticatory ability groups (high or low) and LS were examined. A binomial logistic regression analysis was conducted using LS from the stand-up test as the objective variable and the two subgroups based on the number of remaining teeth and potential crossover factors as covariates. RESULTS: The analysis included 495 participants (354 males and 141 females; median age, 43 years). The median number of remaining teeth among the participants was 28, and 10 participants (2.0%) had ≤ 19 teeth. The mean masticatory ability values were 39.9 for males and 37.7 for females, and 31 participants (6.3%) had low masticatory ability. In the stand-up test, those with ≤ 19 teeth had a higher LS rate than those with ≥ 20 teeth. The odds ratio for LS in the group with ≤ 19 remaining teeth was 5.99, and the confidence interval was 1.44-24.95. CONCLUSIONS: The results confirmed signs of oral frailty in the working-age population. Further, the number of remaining teeth possibly affects standing movement. Thus, oral frailty is associated with LS in the working-age population.

Predicting outcomes after total knee arthroplasty using intraoperative knee kinematics measured by navigation.

OBJECTIVES: The objective of the study is to evaluate the relationship between clinical results following posterior-stabilized total knee arthroplasty (TKA) and intraoperative kinematic pattern determined from navigation. METHODS: Participants were patients with knee osteoarthritis and varus deformity who underwent primary posterior-stabilized TKA. Preoperative and post-implantation kinematic data were recorded, and all kinematic patterns were divided into two types: medial pivot (MP) or non-MP. Knees with MP and non-MP patterns after implantation were compared in terms of postoperative flexion angle, pain, patient satisfaction, expectations, and activity using the new Knee Society Score 2011 at 1 year postoperatively. RESULTS: This study involved 55 patients (12 men, 43 women) with a mean age of 73.1 years and mean body mass index of 26.5 kg/m2. Preoperative kinematic measurements showed MP in 23 knees and non-MP in 32 knees. After implantation, navigation showed MP in 25 knees and non-MP in 30 knees. No significant differences were found between kinematic patterns preoperatively and after implantation. Postoperative flexion angle, pain, patient satisfaction, expectations, and activity using Knee Society Score 2011 showed no differences between MP and non-MP knees. CONCLUSION: Intraoperative knee kinematics as measured by navigation could not predict postoperative outcomes of TKA.

Association of bisphosphonate with bone loss and pain-related behavior in an adjuvant-induced osteoporosis model.

OBJECTIVES: Osteoporosis animal models are used extensively to determine the mechanisms of disease pathology and identify potential biological targets. The study aimed to establish a bone loss model, identify pain-related behavior in neighboring joints using an adjuvant-induced osteoporosis (AO) model, and examine the therapeutic effect of bisphosphonates (BP). METHODS: Complete Freund's adjuvant (CFA) was injected subcutaneously into the back of the right foot of 8-week-old female ddY mice. Subsequently, pain, arthritis, and bone density in the right knee were monitored over time. RESULTS: Pain evaluation using von Frey filaments showed a significantly exacerbated knee pain threshold compared to the control group (saline administration) at 7-day and 14-day intervals after CFA administration, and bone density during the same period also significantly declined. The AO model was created similarly; alendronate (ALN) 40 µg/kg was subcutaneously injected twice and vehicle once from 7 to 14 days after onset. In the ALN administration group on the 14th day, significant improvements in bone density, arthritis, and pain threshold around the knee were observed compared to the untreated group. CONCLUSIONS: ALN may contribute to pain improvement through the simultaneous effects of bone mass improvement and suppression of osteoporotic pain.