Construct a Magnetic Pt/Ru Alloy Peroxidase Mimic As a Reusable and Cost-Effective "Signal-Off" Sensing Platform for Sensitive and Wide-Linear-Range Assay.

"Signal-off" nanozyme sensing platforms are usually employed to detect analytes (e.g., ascorbic acid (AA) and alkaline phosphatase (ALP)), which are mostly based on oxidase (OXD) nanozymes. However, their drawbacks, like dissolved oxygen-dependent catalysis capability, relatively low enzyme activity, limited amount, and kind, may not favor sensing platforms' optimization. Meanwhile, with the need for sustainable development, a reusable "signal-off" sensing platform is essential for cutting down the cost of the assay, but it is rarely developed in previous studies. Magnetic peroxidase (POD) nanozymes potentially make up the deficiencies and become reusable and better "signal-off" sensing platforms. As a proof of concept, we first construct Fe3O4@polydopamine-supported Pt/Ru alloy nanoparticles (IOP@Pt/Ru) without stabilizers. IOP@Pt/Ru shows high POD activity with Vmax of 83.24 × 10-8 M·s-1 for 3,3',5,5'-Tetramethylbenzidine (TMB) oxidation. Meanwhile, its oxidation rate for TMB is slower than the reduction of oxidized TMB by reducers, favorable for a more significant detection signal. On the other hand, IOP@Pt/Ru possesses great magnet-responsive capability, making itself be recycled and reused for at least 15-round catalysis. When applying IOP@Pt/Ru for AA (ALP) detection, it performs better detectable adaptability, with a linear range of 0.01-0.2 mM (0.1-100 U/L) and a limit of detection of 0.01 mM (0.05 U/L), superior to most of OXD nanozyme-based ALP sensing platform. Finally, IOP@Pt/Ru's reusable assay was demonstrated in real blood samples for ALP assay, which has never been explored in previous studies. Overall, this study develops a reusable "signal-off" nanozyme sensing platform with superior assay capabilities than traditional OXD nanozymes, paves a new way to optimize nanozyme-based "signal-off" sensing platforms, and provides an idea for constructing inexpensive and sustainable sensing platforms.

Myeloid zinc finger 1 knockdown promotes osteoclastogenesis and bone loss in part by regulating RANKL-induced ferroptosis of osteoclasts through Nrf2/GPX4 signaling pathway.

The overactivation of the osteoclasts is a crucial pathological factor in the development of osteoporosis. MZF1, belonging to the scan-zinc finger family, plays a significant role in various processes associated with tumor malignant progression and acts as an essential transcription factor regulating osteoblast expression. However, the exact role of MZF1 in osteoclasts has not been determined. In this study, the purpose of our study was to elucidate the role of MZF1 in osteoclastogenesis. First, we established MZF1-deficient female mice and evaluated the femur bone phenotype by micro-computed tomography and histological staining. Our findings indicate that MZF1-/- mice exhibited a low bone mass osteoporosis phenotype. RANKL could independently induce the differentiation of RAW264.7 cells into osteoclasts, and we found that the expression level of MZF1 protein decreased gradually. Then, the CRISPR/Cas 9 gene-editing technique was used to build a RAW264.7 cell model with MZF1 knockout, and RANKL was used to independently induce MZF1-/- and wild-type cells to differentiate into mature osteoclasts. Tartrate-resistant acid phosphatase staining and F-actin fluorescence results showed that the MZF1-/- group produced more tartrate-resistant acid phosphatase-positive mature osteoclasts and larger actin rings. The expression of osteoclast-associated genes (including tartrate-resistant acid phosphatase, CTSK, c-Fos, and NFATc1) was evaluated by reverse transcription quantitative polymerase chain reaction and Western blot. The expression of key genes of osteoclast differentiation in the MZF1-/- group was significantly increased. Furthermore, we found that cell viability was increased in the early stages of RANKL-induced cell differentiation in the MZF1-/- group cells. We examined some prevalent ferroptosis markers, including malondialdehyde, glutathione, and intracellular Fe, the active form of iron in the cytoplasm during the early stages of osteoclastogenesis. The results suggest that MZF1 may be involved in osteoclast differentiation by regulating RANKL-induced ferroptosis of osteoclasts. Collectively, our findings shed light on the essential involvement of MZF1 in the regulation of osteoclastogenesis in osteoporosis and provide insights into its potential underlying mechanism.

Low Body Fat Percentage and Menstrual Cycle Disorders in Female Elite Adolescent Dancers.

Introduction: The menstrual cycle is an important indicator of health in female athletes. Female elite adolescent dancers are expected to control their weight while also training intensely, which can lead to menstrual disorders. This study aimed to investigate the relationship between body composition and menstrual status in female elite adolescent dancers. Methods: In total, 131 female elite adolescent dancers (age: 15.9 ± 1.5 years) were enrolled in this study. We measured the height, weight, and body fat percentage (BFP) for each participant and calculated their body mass index (BMI). We gathered information on individual menstruation patterns and the participants' menstrual cycles over the previous year using recall methods. We then compared the differences between dancers with menstrual cycle disorders and those without. Primary amenorrhea was defined as menarche occurring after the age of 15, while secondary amenorrhe was defined as experiencing fewer than 5 or no menstrual periods for at least 3 of the previous 12 months. We conducted a reliability test using the same questionnaire 2 weeks later. Statistical significance was defined as P < .05, and we calculated the effect sizes (d) and 95% confidence intervals (95% CI). Results: The average BMI and BFP were 22.6 ± 3.0% and 19.4 ± 2.2 kg/m2, respectively. Low BFP and low BMI were observed in 51 (38.6%) and 47 (35.6%) participants, respectively. Primary amenorrhea in 3 participants (2.3%) and 29 (22.1%) reported experiencing secondary amenorrhea; they had lower BFP than the dancers who did not experience amenorrhea (P = .041, 95% CI, -2.51 to -0.05). Conclusion: Female elite adolescent dancers in China may have lower BFP and menstrual problems. Given that lower BFP may contribute to the occurrence of menstruation disorders, it is essential to pay an attention to both BFP and the menstruation status in female elite adolescent dancers.

The Potential of Natural Compounds Regulating Autophagy in the Treatment of Osteoporosis.

The maintenance of bone homeostasis is dynamically regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. Abnormal differentiation of osteoclast and insufficient osteoblast production can cause bone diseases such as osteoporosis. As one of the highly conserved catabolic pathways in eukaryotic cells, autophagy plays an important role in maintaining cell homeostasis, stress injury repair, proliferation and differentiation. Numerous studies have found that autophagy activity is essential for the survival, differentiation and function of bone cells, and that regulation of autophagy can affect the metabolism of osteoblasts and osteoclasts, thus affecting bone homeostasis. Therefore, using autophagy as a theme, this review outlines the basic process of autophagy, the relationship between autophagy and osteoblasts and osteoclasts, and summarizes the latest research progress of common autophagic signaling pathways in osteoblasts and osteoclasts. The regulatory effects of protein molecules and natural compounds on the autophagy pathway of osteoblasts and osteoclasts discovered in current research are summarized and discussed. This will help to further clarify the mechanism of osteoporosis, understand the relationship between autophagy and osteoporosis, and propose new therapeutic strategies and new ideas for anti-osteoporosis.

The Therapeutic Effect of Natural Compounds on Osteoporosis through Ferroptosis.

Ferroptosis is a newly discovered non-apoptotic cell death whose key is lipid peroxidation. It has been reported that ferroptosis is involved in the occurrence and development of tumors and nervous system and musculoskeletal diseases. Cellular ferroptosis contributes to the imbalance of bone homeostasis and is involved in the development of osteoporosis; however, the detailed mechanism of which is still unclear though it may provide a new direction for anti-osteoporosis. The current drugs used in the treatment of osteoporosis, such as bisphosphonates and teriparatide, have many side effects, increasing people's search for natural compounds to treat osteoporosis. This review paper briefly summarizes the current research regarding the mechanisms of ferroptosis and natural anti-osteoporosis compounds targeting its pathway.

Molecular Subtype Classification of Postmenopausal Osteoporosis and Immune Infiltration Microenvironment Based on Bioinformatics Analysis of Osteoclast-Regulatory Genes.

Osteoporosis is common in postmenopausal women but is often asymptomatic until a fracture occurs, highlighting the importance of early screening and preventive interventions. This study aimed to develop molecular subtype risk stratification of postmenopausal osteoporosis and analyze the immune infiltration microenvironment. Microarray data for osteoporosis were downloaded and analyzed. Logistic and least absolute shrinkage and selection operator (LASSO) regression analyses were used to construct the molecular risk model. Circulating blood samples were collected from 10 enrolled participants to validate the key differentially expressed genes, and consistent clustering based on the expression profiles of candidate genes was performed to obtain molecular subtypes. Three key genes, CTNNB1, MITF, and TNFSF11, were obtained as variables and used to construct the risk model. External experimental validation showed substantial differences in the three key genes between patients with osteoporosis and the controls (p < 0.05). Three subtypes were obtained based on dimensionality reduction clustering results. Cluster 3 had significantly more patients with low bone mineral density (BMD), whereas Cluster 2 had significantly more patients with high BMD (p < 0.05). This study introduced a novel molecular risk model and subtype classification system, which is an evidence-based screening strategy that will guide the active prevention, early diagnosis, and treatment of osteoporosis in high-risk postmenopausal women.

ER Stress, the Unfolded Protein Response and Osteoclastogenesis: A Review.

Endoplasmic reticulum (ER) stress and its adaptive mechanism, the unfolded protein response (UPR), are triggered by the accumulation of unfolded and misfolded proteins. During osteoclastogenesis, a large number of active proteins are synthesized. When an imbalance in the protein folding process occurs, it causes osteoclasts to trigger the UPR. This close association has led to the role of the UPR in osteoclastogenesis being increasingly explored. In recent years, several studies have reported the role of ER stress and UPR in osteoclastogenesis and bone resorption. Here, we reviewed the relevant literature and discussed the UPR signaling cascade response, osteoclastogenesis-related signaling pathways, and the role of UPR in osteoclastogenesis and bone resorption in detail. It was found that the UPR signal (PERK, CHOP, and IRE1-XBP1) promoted the expression of the receptor activator of the nuclear factor-kappa B ligand (RANKL) in osteoblasts and indirectly enhanced osteoclastogenesis. IRE1 promoted osteoclastogenesis via promoting NF-κB, MAPK signaling, or the release of pro-inflammatory factors (IL-6, IL-1ß, and TNFα). CREBH promoted osteoclast differentiation by promoting NFATc1 expression. The PERK signaling pathway also promoted osteoclastogenesis through NF-κB and MAPK signaling pathways, autophagy, and RANKL secretion from osteoblasts. However, salubrinal (an inhibitor of eIF2α dephosphorylation that upregulated p-eIF2α expression) directly inhibited osteoclastogenesis by suppressing NFATc1 expression and indirectly promoted osteoclastogenesis by promoting RANKL secretion from osteoblasts. Therefore, the specific effects and mechanisms of p-PERK and its downstream signaling on osteoclastogenesis still need further experiments to confirm. In addition, the exact role of ATF6 and BiP in osteoclastogenesis also required further exploration. In conclusion, our detailed and systematic review provides some references for the next step to fully elucidate the relationship between UPR and osteoclastogenesis, intending to provide new insights for the treatment of diseases caused by osteoclast over-differentiation, such as osteoporosis.

Advances in the Metabolic Mechanism and Functional Characteristics of Equol.

Equol is the most potent soy isoflavone metabolite and is produced by specific intestinal microorganisms of mammals. It has promising application possibilities for preventing chronic diseases such as cardiovascular disease, breast cancer, and prostate cancer due to its high antioxidant activity and hormone-like activity. Thus, it is of great significance to systematically study the efficient preparation method of equol and its functional activity. This paper elaborates on the metabolic mechanism of equol in humans; focuses on the biological characteristics, synthesis methods, and the currently isolated equol-producing bacteria; and looks forward to its future development and application direction, aiming to provide guidance for the application and promotion of equol in the field of food and health products.

Hypoxia-inducible factor 1α enhances RANKL-induced osteoclast differentiation by upregulating the MAPK pathway.

Background: Hypoxia (low-oxygen tension) and excessive osteoclast activation are common conditions in many bone loss diseases, such as osteoporosis, rheumatoid arthritis (RA), and pathologic fractures. Hypoxia-inducible factor 1 alpha (HIF1α) regulates cellular responses to hypoxic conditions. However, it is not yet known how HIF1α directly affects osteoclast differentiation and activation. This study sought to. explore the effects of HIF1α on osteoclast differentiation and it's molecular mechanisms. Methods: L-mimosine, a prolyl hydroxylase (PHDs) domain inhibitor, was used to stabilize HIF1α in normoxia. In the presence of receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL), RAW264.7 cells were cultured and stimulated by treatment with L-mimosine at several doses to maintain various levels of intracellular HIF1α. The multi-nucleated cells were assessed by a tartrate-resistant acid phosphatase (TRAP) and F-actin ring staining assays. The osteoclast-specific genes, such as Cathepsin K, ß3-Integrin, TRAP, c-Fos, nuclear factor of activated T cells, cytoplasmic 1 (NFATc1), and matrix metallo-proteinase 9 (MMP9), were analyzed by real time-polymerase chain reaction (RT-PCR). The expression of relevant proteins was analyzed by Western blot. Results: L-mimosine increased the content of intracellular HIF1α in a dose-dependent manner, which in turn promoted RANKL-induced osteoclast formation and relevant protein expression by upregulating the mitogen-activated protein kinase (MAPK) pathways. Conclusions: Our findings suggest that HIF1α directly increases the osteoclast differentiation of RANKL-mediated RAW264.7 cells in vitro by upregulating the MAPK pathways.

Predictive Factors for Bone Cement Displacement following Percutaneous Vertebral Augmentation in Kümmell's Disease.

Objective: To investigate the independent influencing factors of bone cement displacement following percutaneous vertebral augmentation (PVA) in patients with stage I and stage II Kümmell's disease. Methods: We retrospectively reviewed the records of 824 patients with stage Ⅰ and stage Ⅱ Kümmell's disease treated with percutaneous vertebroplasty (PVP) or percutaneous vertebroplasty (PKP) from January 2016 to June 2022. Patients were divided into the postoperative bone cement displacement group (n = 150) and the bone cement non-displacement group (n = 674) according to the radiographic inspection results. The following data were collected: age, gender, body mass index (BMI), underlying disease, bone mineral density (BMD), involved vertebral segment, Kümmell's disease staging, anterior height, local Cobb angle, the integrity of anterior vertebral cortex, the integrity of endplate in surgical vertebrae, surgical method, surgical approach, the volume of cement, distribution of cement, the viscosity of cement, cement leakage, and postoperative anti-osteoporosis treatment. Binary logistic regression analysis was performed to determine the independent influencing factors of bone cement displacement. The discrimination ability was evaluated using the area under the curve (AUC) of the receiver operating characteristic (ROC). Results: The results of logistic regression analysis revealed that thoracolumbar junction (odds ratio (OR) = 3.23, 95% confidence interval (CI) 2.12−4.50, p = 0.011), Kümmell's disease staging (OR = 2.23, 95% CI 1.81−3.41, p < 0.001), anterior cortex defect (OR = 5.34, 95% CI 3.53−7.21, p < 0.001), vertebral endplates defect (OR = 0.54, 95% CI 0.35−0.71, p < 0.001), cement distribution (OR = 2.86, 95% CI 2.03−3.52, p = 0.002), cement leakage (OR = 4.59, 95% CI 3.85−5.72, p < 0.001), restoration of local Cobb angle (OR = 3.17, 95% CI 2.40−5.73, p = 0.024), and postoperative anti-osteoporosis treatment (OR = 0.48, 95% CI 0.18−0.72, p = 0.025) were independently associated with the bone cement displacement. The results of the ROC curve analysis showed that the AUC was 0.816 (95% CI 0.747−0.885), the sensitivity was 0.717, and the specificity was 0.793. Conclusion: Thoracolumbar fracture, stage Ⅱ Kümmell's disease, anterior cortex defect, uneven cement distribution, cement leakage, and high restoration of the local Cobb angle were risk factors for cement displacement after PVA in Kümmell's disease, while vertebral endplates defect and postoperative anti-osteoporosis treatment are protective factors.

Receptor activator of nuclear factor-κB ligand-mediated osteoclastogenesis signaling pathway and related therapeutic natural compounds.

Osteoclast is a hematopoietic precursor cell derived from the mononuclear macrophage cell line, which is the only cell with bone resorption function. Its abnormal activation can cause serious osteolysis related diseases such as rheumatoid arthritis, Paget's disease and osteoporosis. In recent years, the adverse effects caused by anabolic anti-osteolytic drugs have increased the interest of researchers in the potential therapeutic and preventive effects of natural plant derivatives and natural compounds against osteolytic diseases caused by osteoclasts. Natural plant derivatives and natural compounds have become major research hotspots for the treatment of osteolysis-related diseases due to their good safety profile and ability to improve bone. This paper provides an overview of recent advances in the molecular mechanisms of RANKL and downstream signaling pathways in osteoclast differentiation, and briefly outlines potential natural compounds with antiosteoclast activity and molecular mechanisms.

Hydrogel-based delivery system applied in the local anti-osteoporotic bone defects.

Osteoporosis is an age-related systemic skeletal disease leading to bone mass loss and microarchitectural deterioration. It affects a large number of patients, thereby economically burdening healthcare systems worldwide. The low bioavailability and complications, associated with systemic drug consumption, limit the efficacy of anti-osteoporosis drugs currently available. Thus, a combination of therapies, including local treatment and systemic intervention, may be more beneficial over a singular pharmacological treatment. Hydrogels are attractive materials as fillers for bone injuries with irregular shapes and as carriers for local therapeutic treatments. They exhibit low cytotoxicity, excellent biocompatibility, and biodegradability, and some with excellent mechanical and swelling properties, and a controlled degradation rate. This review reports the advantages of hydrogels for adjuvants loading, including nature-based, synthetic, and composite hydrogels. In addition, we discuss functional adjuvants loaded with hydrogels, primarily focusing on drugs and cells that inhibit osteoclast and promote osteoblast. Selecting appropriate hydrogels and adjuvants is the key to successful treatment. We hope this review serves as a reference for subsequent research and clinical application of hydrogel-based delivery systems in osteoporosis therapy.

Factors for Predicting Instant Neurological Recovery of Patients with Motor Complete Traumatic Spinal Cord Injury.

The objective of this study was to analyze the factors affecting the instant recovery of neurological function in patients with motor complete traumatic spinal cord injury (TSCI) treated in hospital. Methods: A retrospective analysis of 1053 patients with TSCI classified according to the American Spinal Cord Injury Association (ASIA) as grades A and B at 59 tertiary hospitals from 1 January 2018 to 31 December 2018 was performed. All patients were classified into motor complete injury (ASIA A or B) and motor incomplete injury (ASIA C or D) groups, according to the ASIA upon discharge. The injury level, fracture segment, fracture type, ASIA score at admission and discharge, treatment protocol, and complications were recorded. Univariate and multivariate analyses were performed to evaluate the relationship between various factors and the recovery of neurological function. Results: The results of multiple logistic regression analysis revealed that the ASIA score on admission (p < 0.001, odds ratio (OR) = 5.722, 95% confidence interval (CI): 4.147−7.895), fracture or dislocation (p = 0.001, OR = 0.523, 95% CI: 0.357−0.767), treatment protocol (p < 0.001; OR = 2.664, 95% CI: 1.689−4.203), and inpatient rehabilitation (p < 0.001, OR = 2.089, 95% CI: 1.501−2.909) were independently associated with the recovery of neurological function. Conclusion: The recovery of neurological function is dependent on the ASIA score on admission, fracture or dislocation, treatment protocol, and inpatient rehabilitation.

A New Scale for Predicting the Risk of In-hospital Mortality in Patients With Traumatic Spinal Cord Injury.

Purpose: To analyze the relative factors influencing in-hospital mortality in patients with traumatic spinal cord injury (TSCI), and develop a score scale for predicting the risk of in-hospital mortality. Method: We reviewed the medical records from 59 spine centers in mainland China from 1 January 2018 to 31 December 2018. The inclusion criteria were (1) confirmed diagnosis of TSCI, (2) hospitalization within 7 days of injury, and (3) affecting neurological level from C1 to L1. The exclusion criteria were (1) readmission, and (2) incomplete data. Included patients were classified into the survival and non-survival groups according to their status at discharge. Univariate and multivariate logistic regressions were performed to identify the factors related to in-hospital mortality in patients with TSCI. A new scale was developed, and the mortality rate in each risk group was calculated. Results: Of the 3,176 participants, 23 (0.7%) died in the hospital, and most of them died from respiratory diseases (17/23, 73.9%). After univariate and multivariate logistic regression analysis, cervical spinal cord injury [odds ratio (OR) = 0.264, 95% confidence interval (CI): 0.076-0.917, P = 0.036], abdominal visceral injury (OR = 3.778, 95% CI: 1.038-13.755, P = 0.044), the American Spinal Injury Association (ASIA) score on admission (A: reference; B:OR = 0.326, 95% CI: 0.093-1.146, P = 0.081; C:OR = 0.070, 95% CI: 0.016-0.308, P < 0.001; D:OR = 0.069, 95% CI: 0.019-0.246, P < 0.001), and surgery (OR = 0.341, 95% CI: 0.146-0.796, P = 0.013) were significantly associated with in-hospital mortality. Scores for each of the four factors were derived according to mortality rates. The sum of the scores from all four factors was included in the scoring system and represented the risk of in-hospital mortality. The in-hospital mortality risk of the low-risk (0-3 points), moderate-risk (4-5 points), and high-risk groups (6-8 points) was 0.3, 2.7, and 9.7%, respectively (P < 0.001). Conclusions: Cervical spinal cord injury, abdominal visceral injury, ASIA score on admission, and surgery were significantly associated with in-hospital mortality in patients with TSCI and stable condition. The scale system may be beneficial for clinical decision-making and for communicating relevant information to patients and their families.

Relationship between degenerative scoliosis and lower extremity mechanical parameters based on EOS imaging system.

OBJECTIVE: This study aimed to assess the correlation between coronal imbalance and lower-limb physiological parameters in degenerative scoliosis using the biplanar whole body imaging system (EOS). MATERIALS AND METHODS: A total of 101 successive EOS images were selected between January 2018 and December 2021. Of the selected images, 63 patients were in the degenerative scoliosis group (DSG) and 38 patients were in the control group (CG). Two independent observers performed measurements of the parameters and compared the two groups. RESULTS: Among parameters examined, significant inter-group differences were found for coronal pelvic tilt angle (CPT), bilateral femoral length difference (ΔFL), and bilateral total lower limb length (ΔTL) difference. Additionally, the knee and ankle joints had more severe degeneration on the main curved side in patients with degenerative scoliosis. In the left curved group, 18 (42.86%) and 24 (57.1%) patients had more severe degeneration in the left knee and left ankle, respectively. In the right lateral bending group, 13 (61.9%) and 14 (66.7%) patients had more severe degeneration in the right knee and right ankle, respectively. Statistical differences were found in the degree of degeneration in both knee and ankle joints bilaterally. CONCLUSION: This study showed that biomechanical parameters of the lower limbs are affected in cases of degenerative scoliosis with altered coronal balance. The lower limb on the main curve side became shorter compared to its counterpart, and joint degeneration of the knee and ankle joints became more severe.

Novel method for diagnosing lateral patellar compression syndrome using X-ray: a retrospective case-control study.

BACKGROUND: A well-established reference is lacking for diagnosing lateral patellar compression syndrome (LPCS), and this diagnosis currently depends on clinicians' subjective judgment and several examination results. X-rays are primarily used to diagnose LPCS, but they have low detection rates of patellar tilt using the congruence angle (CA) and patellar tilting angle (PTA). METHODS: We enrolled 87 patients (31 men and 56 women; mean age: 42.11±15.33 years) between 2016 and 2019 and divided them as per diagnosis into three groups of 29 each: LPCS, patellar dislocation (PD, control), and meniscus tear (MT, negative control) groups. A senior radiologist and the chief physician of sports medicine examined their patellar axial radiographs of the knee in 30° flexion using a computer imaging system, measuring LPCA, CA and PTA. Univariate analysis of variance and Kruskal-Wallis H test were used to compare measurement data with normal distribution and non-normal distribution, respectively. Bonferroni correction was used to analyze different indicators for different groups. The area under the curve (AUC) was calculated to verify the value of LPCA in the initial diagnosis of LPCS. RESULTS: LPCA (19.88±7.49) was significantly higher in LPCS group than in MT (13.68±4.69) and PD groups (10.16±4.43) (P<0.01) and was also significantly higher on affected side than on healthy side (16.44±5.00) (P=0.04). LPCA >13.9° had sensitivity and specificity of 89.66% and 68.97%, respectively, for LPCS diagnosis (AUC: 0.82, 95% confidence interval: 0.719-0.891, P<0.001). CONCLUSIONS: We demonstrated that LPCA measured using an axial patellar radiograph of the knee in 30° flexion is high in patients with LPCS, and it may be used for diagnosing LPCS.

Delayed postoperative radiotherapy increases the incidence of radiographic local tumor progression before radiotherapy and leads to poor prognosis in spinal metastases.

BACKGROUND: Most previous studies focused on the minimum interval between surgery and radiotherapy in spinal metastases, leaving the maximum interval under-investigated. However, in real world, limited radiotherapist and equipment cannot meet the needs of a large patient population to obtain timely radiotherapy after the index spine surgery in developing countries. This study aimed to estimate the clinical risks of delayed radiotherapy after surgery in patients with spinal metastases in developing country. METHODS: Data from 89 patients who underwent surgery and postoperative radiotherapy at a single site in a developing country were retrospectively reviewed. Patients were divided into the progression before radiotherapy (PBR) and no progression before radiotherapy (NPBR) groups. Kaplan-Meier analysis and log-rank tests were used to compare the local control (LC) and overall survival (OS) between groups. RESULTS: Within 1 month after surgery, only 20.2% of patients underwent radiotherapy. Risk of local progression before radiotherapy at 1, 3, and 6 months was 1.2%, 24.1%, and 45.1%, respectively. The LC rate at 1 year was lower in the PBR group than in the NPBR group (53.3% vs. 76.3%, P = 0.040). The OS rate at 1 year was 61.9% and 79.6% in the PBR and NPBR groups, respectively (P = 0.001). The Karnofsky performance status significantly improved only in the NPBR group (52.5 ± 17.6 vs. 66.8 ± 26.3, P < 0.001). The sphincter dysfunction significantly improved in the NPBR group (0.3 ± 0.5 vs. 0.1 ± 0.3, P = 0.007) but it tended to be deteriorated in the PBR group (0.1 ± 0.4 vs. 0.3 ± 0.5, P = 0.500). CONCLUSIONS: In real world, about 80% of patients had delayed radiotherapy 1 month after spine surgery for metastases in our developing country. Patients had a higher risk for radiographic local progression before radiotherapy and poorer LC, OS, and quality of life as time to radiotherapy increased.

What Predicts the Prognosis of Spinal Metastases in Separation Surgery Procedures?

BACKGROUND: Separation surgery is performed to provide a safe gap between the epidural tumor and spinal cord for postoperative stereotactic body radiotherapy (SBRT) in cases of spinal metastases. However, there is a gap in evidence regarding sufficient tumor resection in separation surgery. We describe the prognoses according to the extent of resection in separation surgery. METHODS: This retrospective study included 36 consecutive patients who underwent separation surgery and postoperative SBRT between December 2016 and December 2019 at a single center. Local control (LC), overall survival (OS), distance of separation (DS), and quality-of-life parameters were analyzed. P values <0.05 were considered statistically significant. RESULTS: Patients were assigned to the aggressive resection group (ARG, n = 18) or moderate resection group (MRG, n = 18), with estimated LC and OS at 1 year of 79.0% and 75.9%, respectively. There were no significant differences between ARG and MRG in estimated LC (85.9% vs. 72.2%; P = 0.317) or OS (69.3% vs. 80.9%, P = 0.953) at 1 year. All 5 patients in MRG who developed local progression had less satisfactory tumor resection with DS <3 mm. A borderline significant difference in estimated LC at 1 year was noted between individuals with DS <3 mm and those with DS ≥3 mm (51.9% vs. 100.0%; P = 0.053) in MRG. There was no statistical difference between ARG and MRG in quality-of-life parameters. CONCLUSIONS: Moderate resection of ventral dural mass did not significantly reduce patients' prognosis in separation surgery. However, the minimal distance between the postoperative residual epidural tumor and spinal cord should be ≥3 mm.

Only Tumors Angiographically Identified as Hypervascular Exhibit Lower Intraoperative Blood Loss Upon Selective Preoperative Embolization of Spinal Metastases: Systematic Review and Meta-Analysis.

BACKGROUND: The role of preoperative embolization (PE) in reducing intraoperative blood loss (IBL) during surgical treatment of spinal metastases remains controversial. METHODS: A systematic search was conducted for retrospective studies and randomized controlled trials (RCTs) comparing the IBL between an embolization group (EG) and non-embolization group (NEG) for spinal metastases. IBL data of both groups were synthesized and analyzed for all tumor types, hypervascular tumor types, and non-hypervascular tumor types. RESULTS: In total, 839 patients in 11 studies (one RCT and 10 retrospective studies) were included in the analysis. For all tumor types, the average IBL did not differ significantly between the EG and NEG in the RCT (P = 0.270), and there was no significant difference between the two groups in the retrospective studies (P = 0.05, standardized mean difference [SMD] = -0.51, 95% confidence interval [CI]: -1.03 to 0.00). For hypervascular tumors determined as such by consensus (n = 542), there was no significant difference between the two groups (P = 0.52, SMD = -0.25, 95% CI: -1.01 to 0.52). For those determined as such using angiographic evidence, the IBL was significantly lower in the EG than in the NEG group, in the RCT (P = 0.041) and in the retrospective studies (P = 0.004, SMD = -0.93, 95% CI: -1.55 to -.30). For IBL of non-hypervascular tumor types, both the retrospective study (P = 0.215) and RCT (P = 0.947) demonstrated no statistically significant differences in IBL between the groups. CONCLUSIONS: Only tumors angiographically identified as hypervascular exhibited lower IBL upon PE in this study. Further exploration of non-invasive methods to identify the vascularity of tumors is warranted.

Efficacy and safety of different fractions in stereotactic body radiotherapy for spinal metastases: A systematic review.

BACKGROUND: In the treatment of spinal metastases, stereotactic body radiotherapy (SBRT) delivers precise, high-dose radiation to the target region while sparing the spinal cord. A range of doses and fractions had been reported; however, the optimal prescribed scheme remains unclear. METHODS: Two reviewers performed independent literature searches of the PubMed, EMBASE, Cochrane Database, and Web of Science databases. Articles were divided into one to five fractions groups. The Methodological Index for Non-randomized Studies (MINORS) was used to assess the quality of studies. Local control (LC) and overall survival (OS) were presented for the included studies and a pooled value was calculated by the weighted average. RESULTS: The 38 included studies comprised 3,754 patients with 4,731 lesions. The average 1-year LCs for the one to five fractions were 92.7%, 84.6%, 86.8%, 82.6%, and 80.6%, respectively. The average 1-year OS for the one to five fractions were 53.0%, 70.4%, 60.1%, 48%, and 80%, respectively. The 24 Gy/single fraction scheme had a higher 1-year LC (98.1%) than those of 24 Gy/two fractions (85.4%), 27 Gy/three fractions (84.9%), and 24 Gy/three fractions (89.0%). The incidence of vertebral compression fracture was 10.3%, with 10.7% in the single-fraction group and 10.1% in the multi-fraction group. The incidence of radiation-induced myelopathy was 0.19%; three and two patients were treated with single-fraction and multi-fraction SBRT, respectively. The incidence of radiculopathy was 0.30% and all but one patient were treated with multi-fraction SBRT. CONCLUSIONS: SBRT provided satisfactory efficacy and acceptable safety for spinal metastases. Single-fraction SBRT demonstrated a higher local control rate than those of the other factions, especially the 24 Gy dose. The risk of vertebral compression fracture (VCF) was slightly higher in single-fraction SBRT and more patients developed radiculopathy after multi-fraction SBRT.