Effects of Chemical Sterilization and Gamma Irradiation on the Biochemical and Biomechanical Properties of Human Tendon Allografts In Vitro Study.

OBJECTIVE: Pre-implantation sterilization procedures for tendons are important measures to reduce the risk of disease transmission, however these procedures may compromise tendon microarchitecture and biomechanical properties to varying degrees. We explore the effects of different sterilization procedures on the micro-histology, biomechanical strength and biochemical properties of human tendon allografts in vitro study. METHODS: The tendon allografts were harvested from cadaveric donors after the donors were serologically screened by antibody or nucleic acid testing of infectious agents. All samples were divided into five groups, which were fresh-frozen group (control group), 15 kGy gamma irradiation group, 25 kGy gamma irradiation group, 70% ethanol group, and peracetic acid-ethanol group. Each group included 10 tendons for testing. Histological staining and transmission electron microscopy were applied to observe the internal structure and arrangement of tendon collagen fibers, while the machine learning classifier was trained to distinguish the darker cross-sections of collagen fibers and brighter backgrounds of the electron micrograph to detect the distribution of diameters of tendon collagen fibers. The viscoelasticity, mechanical properties and material properties of tendon allografts were examined to detect the influence of different intervention factors on the biomechanical properties of tendons. RESULTS: Histological staining and transmission electron microscopy showed that the structure of fresh-frozen tendons was similar to the structures of other experimental groups, and no obvious fiber disorder or delamination was observed. In the uniaxial cyclic test, the cyclic creep of 25 kGy irradiation group (1.5%) and peracetic acid-ethanol group (1.5%) were significantly lower than that of the control group (3.6%, F = 1.52, P = 0.039) while in the load-to-failure test, the maximum elongation and maximum strain of the peracetic acid-ethanol group were significantly higher than those of the control group (F = 4.60, P = 0.010), and there was no significant difference in other biomechanical indicators. According to the experimental results of denatured collagen, it could be seen that no matter which disinfection procedure was used, the denaturation of the tendon sample would be promoted (F = 1.97, P = 0.186), and high-dose irradiation seemed to cause more damage to collagen fibers than the other two disinfection procedures (296.2 vs 171.1 vs 212.9 µg/g). CONCLUSION: Biomechanical experiments and collagen denaturation tests showed that 15 kGy gamma irradiation and 70% ethanol can preserve the biomechanical strength and biochemical properties of tendons to the greatest extent, and these two sterilization methods are worthy of further promotion.

Application of Controlled Hypotension During Surgery for Spinal Metastasis.

With advances in tumor treatment, metastasis to bone is increasing, and surgery has become the only choice for most terminal patients. However, spinal surgery has a high risk and is prone to heavy bleeding. Controlled hypotension during surgery has outstanding advantages in reducing intraoperative bleeding and ensuring a clear field of vision, thus avoiding damage to important nerves and vessels. Antihypertensive drugs should be carefully selected after considering the patient's age, different diseases, etc, and a single or combined regimen can be used. Hypotension also inevitably leads to a decrease in perfusion of important organs, so the threshold of hypotension and the maintenance time of hypotension should be strictly limited, and the monitoring of important organs during the operation is particularly important. Information such as blood perfusion, blood oxygen saturation, cardiac output, and neurophysiological conduction potential changes should be obtained in a timely fashion, which will help to reduce the risk of hypotension. In short, when applying controlled hypotension, it is necessary to choose an appropriate threshold and duration, and appropriate monitoring should be conducted during the operation to ensure the safety of the patient.

Separation Surgery in the Treatment of Spinal Metastasis.

The life expectancy of patients with advanced cancer has been prolonged with the development of systemic treatment technology. Spinal metastasis is one of the common ways of metastasis of advanced tumors, leading to spinal cord compression and compression fractures, which often lead to a significant reduction in patients' quality of life and physical function. Therefore, surgical treatment is still needed for functional recovery and local control. Separation surgery has been known since 2014 when it was purposed. Combined with radiotherapy, it can achieve an ideal goal of local control. This paper gives a brief introduction to separation surgery, hoping to increase the reader's understanding and consider this method in the course of treatment.

Peracetic Acid-Ethanol Processed Human Tendon Allograft: A Morphological, Biochemical, and Biomechanical Study In Vitro.

OBJECTIVE: To clarify the morphological, biochemical, and biomechanical effects of peracetic acid-ethanol sterilization processing to human hamstring tendon allografts for different time periods. METHODS: Thirty-two fresh-frozen human hamstring tendon allografts obtained from an allograft supplier were prepared and incubated in peracetic acid-ethanol solution (PES) containing 1% v/v peracetic acid and 24% v/v ethanol. Specimens were randomly classified into four groups according to the PES processing time (untreated as the control group, 30 min as the PES30 group, 120 min as the PES120 group, and 240 min as the PES240group). Light microscopy with hematoxylin-eosin and toluidine blue were performed, along with transmission electron microscopy (TEM) to measure the collagen fibril diameters and their distributions, from which the collagen fibril index (CFI) and mass average diameter (MAD) were calculated. The thermal stability and collagen denaturation were analyzed by differential scanning calorimetry (DSC) and collagen denaturation test by α-chymotrypsin. Cyclic loading and failure testing were applied on five tendons from each group, from which the cyclic creep strain, elastic modulus, maximum stress, maximum strain, and strain energy density were calculated. RESULTS: Tendons in the control, PES30, PES120 groups showed similar regularly aligned collagen fibers in light microscopy images, while the images from the PES240 group revealed relatively disordered and heterogeneous collagen bundles with larger interfiber spaces. TEM analysis showed that the mean diameter (F = 3.09, P = 0.04) was lower in the PES120 group (87.15 ± 4.76 nm) than it was in the control group (99.39 ± 9.19 nm) but not statistically (P = 0.05). Moreover, the CFI value in the PES30 group (65.37 ± 4.14%) was the lowest among groups (all P ≤ 0.01), while no variance existed in density and MAD among groups (F = 2.09, P = 0.13, and F = 0.27, P = 0.85, respectively). The onset temperature (H = 8.74, P = 0.03) and peak temperature (H = 9.97, P = 0.02) were decreased in the PES30 group compared to the control group (P = 0.02 and P = 0.01, respectively), but there were no differences in enthalpy of denaturation among groups (F = 2.20, P = 0.17). The collagen denaturation test revealed lower hydroxyproline concentrations in PES-treated specimens with no statistical differences among groups (H = 8.86, P = 0.07). The maximum stress showed variance (F = 10.52, P < 0.01) that it was higher in PES30 group (68.29 ± 10.86 MPa) compared to the PES120 and the PES240 group, while it was lower in the PES120 group (19.40 ± 4.94 MPa) compared to the control and the PES30 group (all P < 0.05). The strain energy density (F = 7.34, P < 0.01) was over 4 times higher in the PES30 group (7.39 ± 2.51 MPa) than it was in the PES120 group (1.56 ± 0.64 MPa, P < 0.01). CONCLUSION: PES treatment for 30 min has no adverse effect on the properties of human hamstring tendon allografts, longer processing time could not promise better properties preservation.

Nomogram for Predicting the Postoperative Venous Thromboembolism in Spinal Metastasis Tumor: A Multicenter Retrospective Study.

INTRODUCTION: Venous thromboembolism can be divided into deep vein thrombosis and pulmonary embolism. These diseases are a major factor affecting the clinical prognosis of patients and can lead to the death of these patients. Unfortunately, the literature on the risk factors of venous thromboembolism after surgery for spine metastatic bone lesions are rare, and no predictive model has been established. METHODS: We retrospectively analyzed 411 cancer patients who underwent metastatic spinal tumor surgery at our institution between 2009 and 2019. The outcome variable of the current study is venous thromboembolism that occurred within 90 days of surgery. In order to identify the risk factors for venous thromboembolism, a univariate logistic regression analysis was performed first, and then variables significant at the P value less than 0.2 were included in a multivariate logistic regression analysis. Finally, a nomogram model was established using the independent risk factors. RESULTS: In the multivariate logistic regression model, four independent risk factors for venous thromboembolism were further screened out, including preoperative Frankel score (OR=2.68, 95% CI 1.78-4.04, P=0.001), blood transfusion (OR=3.11, 95% CI 1.61-6.02, P=0.041), Charlson comorbidity index (OR=2.01, 95% CI 1.27-3.17, P=0.013; OR=2.29, 95% CI 1.25-4.20, P=0.017), and operative time (OR=1.36, 95% CI 1.14-1.63, P=0.001). On the basis of the four independent influencing factors screened out by multivariate logistic regression model, a nomogram prediction model was established. Both training sample and validation sample showed that the predicted probability of the nomogram had a strong correlation with the actual situation. CONCLUSION: The prediction model for postoperative VTE developed by our team provides clinicians with a simple method that can be used to calculate the VTE risk of patients at the bedside, and can help clinicians make evidence-based judgments on when to use intervention measures. In clinical practice, the simplicity of this predictive model has great practical value.

Picrosirius-Polarization Method for Collagen Fiber Detection in Tendons: A Mini-Review.

Although the structure and composition of collagen have been studied by polarized light microscopy since the early 19th century, many studies and reviews have paid little or no attention to the morphological problems of histopathological diagnosis. The morphology of collagen fibers is critical in guiding mechanical and biological properties in both normal and pathological tendons. Highlighting the organization and spatial distribution of tendon-containing collagen fibers can be very useful for visualizing a tendon's ultrastructure, biochemical and indirect mechanical properties, which benefits other researchers and clinicians. Picrosirius red (PSR) staining, relying on the birefringence of collagen fibers, is one of the best understood histochemical methods that can highly and specifically underline fibers better than other common staining techniques when combined with polarized light microscopy (PLM). Polarized light microscopy provides complementary information about collagen fibers, such as orientation, type and spatial distribution, which is important for a comprehensive assessment of collagen alteration in a tendon. Here, this brief review serves as a simplistic and important primer to research developments in which differential staining of collagen types by the Picrosirius-polarization method is increasing in diverse studies of the medical field, mainly in the assessment of the morphology, spatial distribution, and content of collagen in tendons.

Assessment of the Defatting Efficacy of Mechanical and Chemical Treatment for Allograft Cancellous Bone and Its Effects on Biomechanics Properties of Bone.

OBJECTIVE: To assess the defatting efficacy of high pressure washing and gradient alcohol and biomechanical properties of defatted bone. METHODS: Fresh cancellous bone was obtained from the femoral condyle and divided into six groups according to different defatting treatments, which were: high pressure washing for 10 s (10S group), 20 s (20S group), and 30 s (30S group), gradient alcohol immersion (Alcohol group), acetone immersion (Acetone group), and non-defatted (Fresh group). The appearance of six groups was observed, and the appearance of defatted bone and fresh bone was compared. The residual lipid content and infrared spectrum were used to compare the efficacy of defatting, the DNA content was used to compare the cell content after defatting, and the maximum stress and elastic modulus were used to compare the effects of defatting treatment on biomechanical properties. RESULTS: The fresh bone was yellow and the pores contained a lot of fat. The defatted bone was white and the porous network was clear. There was no difference in residual lipid content among the three groups with high pressure washing (1.45% ± 0.16%, 1.40% ± 0.13%, and 1.46% ± 0.11%, respectively) (P = 0.828). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (1.45% ± 0.16%, 1.28% ± 0.07%, and 1.13% ± 0.22%, respectively) (P = 0.125). Infrared spectra showed that the fat content of the five defatting groups was significantly lower than that of the fresh group. There was no difference in residual lipid content among the three groups with high pressure washing (4.53 ± 0.23 ug/mL, 4.61 ± 0.18 ug/mL, and 4.66 ± 0.25 ug/mL, respectively) (P = 0.645). There was no difference in residual lipid content among the 10S, alcohol, and acetone groups (4.53 ± 0.23 ug/mL, 4.29 ± 0.24 ug/mL, and 4.27 ± 0.29 ug/mL, respectively) (P = 0.247). The maximum stress of the bone decreased significantly with the increase of the washing time (9.95 ± 0.31 Mpa, 9.07 ± 0.45 Mpa, and 8.17 ± 0.35 Mpa, respectively) (P = 0.003). The elastic modulus of the bone decreased significantly with the increase of the washing time (116.40 ± 3.54 Mpa, 106.10 ± 5.29 Mpa, and 95.63 ± 4.08 Mpa, respectively) (P = 0.003). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group, and the acetone group (10.09 ± 0.67 Mpa, 9.95 ± 0.31 Mpa, 10.11 ± 0.07 Mpa, and 10.09 ± 0.39 Mpa, respectively) (P = 0.963). There was no statistical difference in the maximum stress between the fresh group, the 10S group, the alcohol group and the acetone group (119.93 ± 4.94 Mpa, 116.40 ± 3.54 Mpa, 118.27 ± 0.85 Mpa, 118.10 ± 4.52 Mpa, respectively) (P = 0.737). CONCLUSION: The defatting efficiency was satisfactory at a time of 10 s under high pressure washing. In terms of defatting efficiency and its effect on biomechanical properties of bone, high pressure washing and gradient alcohol were similar to conventional acetone solvent extraction defatting.

Percutaneous vertebral augmentation procedures in the management of spinal metastases.

Bone metastasis is a common complication of cancer, and bone is the third most common metastatic site following the lung and liver. Among the various bones, spine is the most common site of metastatic tumors. The treatment goals of patients with spinal metastases are mostly palliative, with the aim of reducing pain and improving quality of life. The treatment of spinal metastases has made significant progress over the past few decades. Each new technology has tried to solve the shortcomings of its predecessors. Currently, there are no mature algorithms or specific techniques that have proven to be the best for spinal metastases, and the treatment method often relies on operator and institutional preferences or biases in some cases. Percutaneous vertebral augmentation has unique value in the management of spinal metastases, understanding its indications, surgical techniques, uses, advantages and complications is critical to providing optimal patient care. We believe that the application of percutaneous vertebral augmentation alone or combined with other techniques can achieve optimal pain relief and functional improvement in the patients with spinal metastases.

Establishment and validation of a nomogram model for periprosthetic infection after megaprosthetic replacement around the knee following bone tumor resection: A retrospective analysis.

BACKGROUND: Due to the particularity of patients with bone tumors, the risk of periprosthetic infection following megaprosthetic replacement is much higher than that of traditional total knee arthroplasty. Unfortunately, few studies specifically reported the risk factors for periprosthetic infection following megaprosthetic replacement. The purposes of the study were to (1) establish a nomogram model, which can provide a reference for clinicians, and patients to reduce the occurrence of periprosthetic infection (2) explore the risk factors for deep infection of megaprosthesis. HYPOTHESIS: A prediction model can be established and has favorable predictive accuracy. PATIENTS AND METHODS: One hundred and seventy-seven megaprostheses were identified. There were 61 female patients and 116 male patients with a mean age of 35 years. The following risk factors were analyzed: tumor site, sex, age, material for prosthetic stem, tumor type, smoking, diabetes, length of bone resection, operation time, chemotherapy, BMI, malignant tumor staging and hematoma formation. Finally, based on the multivariate analysis, the independent risk factors were used to develop a nomogram model. RESULTS: Univariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were risk factors for periprosthetic infection. Multivariate Cox regression analysis showed that the chemotherapy, longer operation time and hematoma formation were significant risk factors for periprosthetic infection. The nomogram model was established using these significant risk factors, with a C-index of 0.766 and an acceptable consistency according to the internal validation, indicating that the prediction model had favorable predictive accuracy. DISCUSSION: This study has important implications for the future investigations of prevention of periprosthetic infection. The nomogram model identifies high-risk patients for whom attached prophylaxis measures are required. Future studies regarding reduction of incidence of periprosthetic infection should pay close attention to these high-risk patients. LEVEL OF EVIDENCE: IV, retrospective, cohort study.

Establishment and validation of a nomogram model for aseptic loosening after tumor prosthetic replacement around the knee: a retrospective analysis.

BACKGROUND: Aseptic loosening has become the main cause of prosthetic failure in medium- to long-term follow-up. The objective of this study was to establish and validate a nomogram model for aseptic loosening after tumor prosthetic replacement around knee. METHODS: We collected data on patients who underwent tumor prosthetic replacements. The following risk factors were analyzed: tumor site, stem length, resection length, prosthetic motion mode, sex, age, extra-cortical grafting, custom or modular, stem diameter, stem material, tumor type, activity intensity, and BMI. We used univariate and multivariate Cox regression for analysis. Finally, the significant risk factors were used to establish the nomogram model. RESULTS: The stem length, resection length, tumor site, and prosthetic motion mode showed a tendency to be related to aseptic loosening, according to the univariate analysis. Multivariate analysis showed that the tumor site, stem length, and prosthetic motion mode were independent risk factors. The internal validation indicated that the nomogram model had acceptable predictive accuracy. CONCLUSIONS: A nomogram model was developed for predicting the prosthetic survival rate without aseptic loosening. Patients with distal femoral tumors and those who are applied with fixed hinge and short-stem prostheses are more likely to be exposed to aseptic loosening.

Prognostic Discrepancy on Overall Survival Between Ambulatory and Nonambulatory Patients with Metastatic Spinal Cord Compression.

BACKGROUND: Contradictory results have been reported regarding the prognostic effect of ambulatory status in patients with metastatic spinal cord compression (MSCC). The aim of this study was to investigate whether ambulatory status is a significant predictor of overall survival in patients with MSCC and to distinguish the differences of predictors between patients who were ambulatory and those who were not ambulatory before operation. METHODS: Three clinical centers were retrospectively reviewed to identify patients operated on for MSCC between 2005 and 2015. Fourteen prognostic factors were analyzed using Kaplan-Meier survival curves, univariate log-rank test, and multivariate Cox hazard regression model for the whole cohort and the subgroups of ambulatory and nonambulatory patients. RESULTS: In all, 169 patients were consecutively enrolled. Their mean age was 59.6 ± 10.5 years (range, 18-84 years). The median survival time in the whole cohort was 7.0 ± 0.5 months, whereas it was 7.0 ± 0.8 months and 5.0 ± 1.3 months in ambulatory and nonambulatory patients, respectively. Multivariate Cox regression analysis showed that ambulatory status was not a significant predictor of overall survival (P = 0.266), but primary tumor type and Karnofsky performance status were independent predictors of overall survival for the whole cohort. Primary tumor and metastatic site were significantly associated with survival in ambulatory patients. Gender and Karnofsky performance status were associated with survival in nonambulatory patients. CONCLUSIONS: Ambulatory status was not shown to predict the prognosis of patients with MSCC. prognostic factors should be distinguished between ambulatory and nonambulatory patients when choosing a therapeutic modality.

Prognostic effect of factors involved in revised Tokuhashi score system for patients with spinal metastases: a systematic review and Meta-analysis.

BACKGROUND: Cancer patients' survival time has obviously improved, with the development of systemic treatment techniques. However, the probability of metastases to the vertebrae has also been increased which makes some adverse effects on patients' quality of life. The prediction of survival plays a key role in choosing therapeutic modality, and Tokuhashi Score was established as one of the most commonly used predictive systems for spinal metastases. Thus, this study was conducted to identify the prognostic effect of factors involved in revised Tokuhashi Score (RTS). METHODS: Two investigators independently retrieved relevant literature on platforms of PubMed, Embase and Cochrane Library. We identified eligible studies through title/abstract and full-text perusing. Data was extracted including general information of studies, participants' characteristics, therapeutic modality, overall survival and prognostic effect of factors. Hazard ratio (HR) for each factor was synthesized if available through fixed- or random-effect models as appropriate. RESULTS: A total of 63 eligible studies with 10,411 participants were identified. Overall, cases with thyroid cancer had the highest survival rate, while the ones with non-small cell lung cancer and hepatocellular carcinoma lived for the shorted survival time. Performance status, bone metastasis, number of involved vertebrae, visceral metastasis, primary tumor and neurological status were regarded as significant predictors in 71.4, 40.0, 18.2, 63.4, 73.1 and 44.7% of the involved studies respectively. Thirty-eight articles were included in meta-analysis, and prognostic effects of five factors (apart from primary tumor) were analyzed. Factors were all proved to be significant except comparisons between KPS (Karnofsky Performance Status) 10-40 VS. 50-70 and single VS. multiple spinal metastases. CONCLUSION: All factors of RTS were significant on prognosis predicting and should be considered when choosing therapeutic modality for spinal metastases. What's more, we believe that more accurate prognosis may be obtained after removal of the cut-offs for KPS 10-40 VS. 50-70 and single VS. multiple involved vertebrae.

Is Ambulatory Status a Prognostic Factor of Survival in Patients with Spinal Metastases? An Exploratory Meta-analysis.

This study was conducted to identify the influence of ambulatory status prior to treatment on survival of patients with spinal metastases. Two investigators independently retrieved relevant electronic literature in PubMed, Embase, and Cochrane Library databases, to identify eligible studies. Effect estimates for hazard risk (HR) were extracted and synthesized through fixed-effects or random-effects models as appropriate. A total of 17 eligible studies were identified, with an accumulated number of 3962 participants. HR from 14 studies regarding comparison between ambulatory versus non-ambulatory groups were pooled using a random-effects model, and statistical significance was presented for the pooled HR (HR = 1.96; 95% confidence interval [CI], 1.65-2.34). In subgroups of mixed primary tumor and lung cancer, ambulatory status was considered to be a significant prognostic factor (P < 0.05), while in the subgroup of prostate cancer it was not (HR = 1.72; 95% CI, 0.79-3.74). HR from 4 studies related to comparison between Frankel E versus Frankel C-D were pooled using a fixed-effects model, which revealed statistical significance (HR = 1.73; 95% CI, 1.27-2.36). Ambulatory status is a significant prognostic factor in patients with spinal metastases. However, in patients with primary prostate cancer, the prognostic effect of ambulatory status has not yet been confirmed to be significant.