Risk factors of instrumentation failure after laminectomy and posterior cervical fusions (PCF).

BACKGROUND: For patients with multilevel degenerative cervical myelopathy, laminectomy and posterior cervical fusions (PCF) with instrumentation are widely accepted techniques for symptom relief. However, hardware failure is not rare and results in neck pain or even permanent neurological lesions. There are no in-depth studies of hardware-related complications following laminectomy and PCF with instrumentation. METHODS: The present study was a retrospective, single centre, observational study. Patients who underwent laminectomy and PCF with instrumentation in a single institution between January 2019 and January 2021 were included. Patients were divided into hardware failure and no hardware failure group according to whether there was a hardware failure. Data, including sex, age, screw density, end vertebra (C7 or T1), cervical sagittal alignment parameters (C2-C7 cervical lordosis, C2-C7 sagittal vertical axis, T1 slope, Cervical lordosis correction), regional Hounsfield units (HU) of the screw trajectory and osteoporosis status, were collected and compared between the two groups. RESULTS: We analysed the clinical data of 56 patients in total. The mean overall follow-up duration was 20.6 months (range, 12-30 months). Patients were divided into the hardware failure group (n = 14) and no hardware failure group (n = 42). There were no significant differences in the general information (age, sex, follow-up period) of patients between the two groups. The differences in fusion rate, fixation levels, and screw density between the two groups were not statistically significant (p > 0.05). The failure rate of fixation ending at T1 was lower than that at C7 (9% vs. 36.3%) (p = 0.019). The regional HU values of the pedicle screw (PS) and lateral mass screw (LMS) in the failure group were lower than those in the no failure group (PS: 267 ± 45 vs. 368 ± 43, p = 0.001; LMS: 308 ± 53 vs. 412 ± 41, p = 0.001). The sagittal alignment parameters did not show significant differences between the two groups before surgery or at the final follow-up (p > 0.05). The hardware failure rate in patients without osteoporosis was lower than that in patients with osteoporosis (14.3% vs. 57.1%) (p = 0.001). CONCLUSIONS: Osteoporosis, fixation ending at C7, and low regional HU value of the screw trajectory were the independent risk factors of hardware failure after laminectomy and PCF. Future studies should illuminate if preventive measures targeting these factors can help reduce hardware failure and identified more risk factors, and perform long-term follow-up.

Integrating single-cell and spatial transcriptomics reveals endoplasmic reticulum stress-related CAF subpopulations associated with chordoma progression.

BACKGROUND: With cancer-associated fibroblasts (CAFs) as the main cell type, the rich myxoid stromal components in chordoma tissues may likely contribute to its development and progression. METHODS: Single-cell RNA sequencing (scRNA-seq), spatial transcriptomics, bulk RNA-seq, and multiplexed quantitative immunofluorescence (QIF) were used to dissect the heterogeneity, spatial distribution, and clinical implication of CAFs in chordoma. RESULTS: We sequenced here 72 097 single cells from 3 primary and 3 recurrent tumor samples, as well as 3 nucleus pulposus samples as controls using scRNA-seq. We identified a unique cluster of CAF in recurrent tumors that highly expressed hypoxic genes and was functionally enriched in endoplasmic reticulum stress (ERS). Pseudotime trajectory and cell communication analyses showed that this ERS-CAF subpopulation originated from normal fibroblasts and widely interacted with tumoral and immune cells. Analyzing the bulk RNA-seq data from 126 patients, we found that the ERS-CAF signature score was associated with the invasion and poor prognosis of chordoma. By integrating the results of scRNA-seq with spatial transcriptomics, we demonstrated the existence of ERS-CAF in chordoma tissues and revealed that this CAF subtype displayed the most proximity to its surrounding tumor cells. In subsequent QIF validation involving 105 additional patients, we confirmed that ERS-CAF was abundant in the chordoma microenvironment and located close to tumor cells. Furthermore, both ERS-CAF density and its distance to tumor cells were correlated with tumor malignant phenotype and adverse patient outcomes. CONCLUSIONS: These findings depict the CAF landscape for chordoma and may provide insights into the development of novel treatment approaches.

EGFR/MAPK signaling pathway acts as a potential therapeutic target for sulforaphane-rescued heart tube malformation induced by various concentrations of PhIP exposure.

BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyrimidine (PhIP) is a known carcinogen generated mainly from cooking meat and environmental pollutants. It is worth exploring the potential of natural small-molecule drugs to protect against adverse effects on embryonic development. PURPOSE: In this study, we investigated the potential toxicological effects of PhIP on embryonic heart tube formation and the effect of Sulforaphane (SFN) administration on the anti-toxicological effects of PhIP on embryonic cardiogenesis. STUDY DESIGN AND METHODS: First, the chicken embryo model was used to investigate the different phenotypes of embryonic heart tubes induced by various concentrations of PhIP exposure. We also proved that SFN rescues PhIP-induced embryonic heart tube malformation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR) and flow cytometry experiments were employed to explore the mechanisms by which SFN protects cardiac cells from oxidative damage in the presence of PhIP. We used RNA-seq analysis, molecular docking, in situ hybridization, cellular thermal shift assay and solution nuclear magnetic resonance spectroscopy to explore whether SFN protects cardiogenesis through the EGFR/MAPK signaling pathway. RESULTS: The study showed that PhIP might dose-dependently interfere with the C-looping heart tube (mild) or the fusion of a pair of bilateral endocardial tubes (severe) in chick embryos, while SFN administration prevented cardiac cells from oxidative damage in the presence of high-level PhIP. Furthermore, we found that excessive reactive oxygen species (ROS) production and subsequent apoptosis were not the principal mechanisms by which low-level PhIP induced malformation of heart tubes. This is due to PhIP-disturbed Mitogen-activated protein kinase (MAPK) signaling pathway could be corrected by SFN administration. CONCLUSIONS: This study provided novel insight that PhIP exposure could increase the risk of abnormalities in early cardiogenesis and that SFN could partially rescue various concentrations of PhIP-induced abnormal heart tube formation by targeting EGFR and mediating EGFR/MAPK signaling pathways.

Relationships between lumbar lordosis correction and the change in global tilt (GT) in adult spinal deformity.

PURPOSE: This study aimed to explore the relationships between lumbar lordosis (LL) correction and improvement of postoperative global sagittal alignment and to establish corresponding linear regressions to predict the change in global tilt (GT) based on the corrected LL following adult spinal deformity (ASD) surgery. METHODS: A total of 240 ASD patients who underwent lumbar correction were enrolled in this multicentre study. The following sagittal parameters were measured pre- and postoperatively: thoracic kyphosis (TK), LL, upper and lower LL (ULL and LLL), pelvic tilt (PT), sagittal vertical axis (SVA) and GT. The correlations among the changes in GT (△GT), SVA (△SVA), PT (△PT), TK (△TK), LL (△LL), ULL (△ULL) and LLL (△LLL) were assessed, and linear regressions were conducted to predict △GT, △SVA, △PT and △TK from △LL, △ULL and △LLL. RESULTS: △LL was statistically correlated with △GT (r = 0.798, P < 0.001), △SVA (r = 0.678, P < 0.001), △PT (r = 0.662, P < 0.001) and △TK (r = - 0.545, P < 0.001), and the outcomes of the linear regressions are: △GT = 3.18 + 0.69 × â–³LL (R2 = 0.636), △SVA = 4.78 + 2.57 × â–³LL (R2 = 0.459), △PT = 2.57 + 0.34 × â–³LL (R2 = 0.439), △TK = 7.06-0.43 × â–³LL (R2 = 0.297). In addition, △LLL had more correlations with △GT, △SVA and △PT, while △ULL had more correlations with △TK. CONCLUSION: Surgical correction of LL could contribute to the restoration of global sagittal morphology following ASD surgery. These models were established to predict the changes in sagittal parameters, in particular △GT, determined by △LL, which has not been previously done and may help to customize a more precise correction plan for ASD patients.

Predicting thoracic kyphosis morphology and the thoracolumbar inflection point determined by individual lumbar lordosis in asymptomatic adults.

PURPOSE: The aims of this study were to explore the correlations between thoracic kyphosis (TK) and lumbar lordosis (LL) parameters and to build corresponding linear regressions to predict TK morphology and the thoracolumbar inflection point (IP) determined by individual LL parameters in asymptomatic adults. METHODS: A total of 280 adult healthy volunteers were recruited, and full-spine X-rays were performed for each subject in a standing posture. The following sagittal parameters were measured: cumulative TK, LL, proximal LL (PLL), the apices of TK (TKA) and LL (LLA), the IP and the distance from the plumb line of the thoracic apex (TAPL) and the lumbar apex (LAPL) to the gravity line. The correlations between TK and LL parameters were analyzed, and the corresponding linear regressions were conducted. RESULTS: Extensive variations existed in TK alignment, including angular and morphological parameters. In addition, there were statistical correlations of all cumulative TK angles with LL (r values from - 0.173 to - 0.708) and PLL (r values from - 0.206 to - 0.803), TKA and IP with LLA (rs = 0.359 and 0.582, respectively) and TAPL with LAPL (rs = 0.335). The common predictive formulas employed in ASD surgery could include T10-L1 = - 3.6-0.2*LL (R2 = 0.201), T4-L1 = 3.4-0.5*LL (R2 = 0.457), TKA = - 10.3 + 1.1*LLA (R2 = 0.180) and IP = - 12.7 + 1.6*LLA (R2 = 0.330). CONCLUSION: There were intimate associations between TK and LL parameters in asymptomatic adults. Moreover, predictive models for thoracic alignment, particularly cumulative TK, based on LL parameters were proposed, which could better delineate anatomical relationships, guide thoracic construction during adult spinal deformity surgery and may help preventing proximal junctional failure.

Corrigendum: Coexpression of HHLA2 and PD-L1 on tumor cells independently predicts the survival of spinal chordoma patients.

[This corrects the article DOI: 10.3389/fimmu.2021.797407.].

Clinicopathological and Prognostic Characteristics in Spinal Chondroblastomas: A Pooled Analysis of Individual Patient Data From a Single Institute and 27 Studies.

STUDY DESIGN: Retrospective pooled analysis of individual patient data. OBJECTIVES: Spinal chondroblastoma (CB) is a very rare pathology and its clinicopathological and prognostic features remain unclear. Here, we sought to characterize the clinicopathological data of a large spinal CB cohort and determine factors affecting the local recurrence-free survival (LRFS) and overall survival (OS) of patients. METHODS: Electronic searches using Medline, Embase, Google Scholar and Wanfang databases were performed to identify eligible studies per predefined criteria. A retrospective review was also conducted to include additional patients at our center. RESULTS: Twenty-seven studies from the literature and 8 patients from our local institute were identified, yielding a total of 61 patients for analysis. Overall, there were no differences in clinicopathological characteristics between the local and literature cohorts, except for absence or presence of spinal canal invasion by tumor on imagings and chicken-wire calcification in tumor tissues. Univariate Kaplan-Meier analysis revealed that previous treatment, preoperative or postoperative neurological deficits, type of tumor resection, secondary aneurysmal bone cyst (ABC), chicken-wire calcification and radiotherapy correlated closely with LRFS, though only type of tumor resection, chicken-wire calcification and radiotherapy were predictive of outcome based on multivariate Cox analysis. Analyzing OS, we found that a history of preoperative treatment, concurrent ABC, chicken-wire calcification, type of tumor resection and adjuvant radiotherapy had a significant association with survival, whereas only type of tumor resection remained statistically significant after adjusting for other covariables. CONCLUSION: These data may be helpful in prognostic risk stratification and individualized therapy decision making for patients.

Posterior instrumentation combined with anterior debridement and reconstruction using allogenic strut bone for the treatment of children with multilevel lumbar spinal tuberculosis: minimum 5-year follow-up.

OBJECTIVES: To evaluate the clinical outcomes of one-stage posterior instrumentation combined with anterior debridement and reconstruction using allogenic strut bone for the surgical treatment of multilevel lumbar spinal tuberculosis in children younger than 10 years of age with at least 5 years of follow-up. METHODS: A total of 16 children with multilevel lumbar spinal tuberculosis who underwent one-stage posterior instrumentation combined with anterior debridement and reconstruction using allogenic strut bone were enrolled from January 2003 to January 2017. Among them, 6 were females and 10 were males with an average age of 6.9 ± 2.2 years (range 3-10 years). Patients' clinical outcomes, including C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), kyphosis angle, and neurologic function, were assessed before and after surgery. P < 0.05 was considered statistically significant. RESULTS: The average follow-up was 7.8 ± 2.4 years. CRP and ESR of all patients returned to the normal range within 1 year. Compared with preoperative neurological deficits, postoperative and final follow-up neurological deficits improved significantly by grades 0.9 and 1.6, respectively. No instrumentation failure occurred, and all patients achieved solid bone fusion. The preoperative kyphosis angle was 29.9 ± 8.1°, which decreased significantly to 5.9 ± 2.6° postoperatively. There was a mild loss (2.5°) and the kyphosis angle was 8.4 ± 2.9° at final follow-up, with an overall correction rate of 71.3%. CONCLUSION: One-stage posterior instrumentation combined with anterior debridement and reconstruction using allogenic strut bone is a safe and effective procedure for children with multilevel lumbar spinal tuberculosis. This approach facilitates the removal of lesions and decompression of the spinal cord and is effective in restoring spinal stability, correcting kyphosis, and preventing deterioration of the deformity.

Corrigendum: Risk factors for tuberculous or nontuberculous spondylitis after percutaneous vertebroplasty or kyphoplasty in patients with osteoporotic vertebral compression fracture: A case-control study.

[This corrects the article DOI: 10.3389/fsurg.2022.962425.].

Risk factors for tuberculous or nontuberculous spondylitis after percutaneous vertebroplasty or kyphoplasty in patients with osteoporotic vertebral compression fracture: A case-control study.

Objectives: The contributing factors for spondylitis after percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) remain unclear. Here, we sought to investigate the factors affecting spondylitis occurrence after PVP/PKP. We also compared the clinical characteristics between patients with tuberculous spondylitis (TS) and nontuberculous spondylitis (NTS) following vertebral augmentation. Methods: Literature searches (from January 1, 1982 to October 16, 2020) using MEDLINE, EMBASE, Google Scholar and Web of science databases were conducted to identify eligible studies according to predefined criteria. The local database was also retrospectively reviewed to include additional TS and NTS patients at our center. Results: Thirty studies from the literature and 11 patients from our local institute were identified, yielding a total of 23 TS patients and 50 NTS patients for analysis. Compared with NTS group, patients in the TS group were more likely to have a history of trauma before PVP/PKP treatment. Univariate analyses of risk factors revealed pulmonary tuberculosis and diabetes were significant factors for TS after PVP/PKP. Analyzing NTS, we found obesity, a history of preoperative trauma, urinary tract infection, diabetes and multiple surgical segments (≥2) were significantly associated with its occurrence following PVP/PKP treatment. Multivariate logistic analyses showed a history of pulmonary tuberculosis and diabetes were independent risk factors for TS after PVP/PKP, while diabetes and the number of surgically treated segments independently influenced NTS development. Conclusions: A history of pulmonary tuberculosis and diabetes were independent risk factors for TS. For NTS, diabetes and the number of surgically treated segments significantly influenced the occurrence of postoperative spinal infection. These data may be helpful for guiding risk stratification and preoperative prevention for patients, thereby reducing the incidence of vertebral osteomyelitis after PVP/PKP.

Effect Analysis of Preoperative Intravenous Tranexamic Acid Combined With Intraoperative Immersion in Reducing Perioperative Blood Loss of One Stage Posterior Thoracolumbar Tuberculosis.

Background: To investigate the efficacy and safety of preoperative intravenous tranexamic acid (TXA) combined with intraoperative immersion in reducing perioperative blood loss in one-stage posterior thoracolumbar tuberculosis. Methods: All patients were divided into four groups: Group A received an intravenous drip of TXA before surgery, group B received multiple local immersions during the operation, group C received an intravenous drip combined with multiple local immersions, and the control group (group CG) were not treated with TXA during the same period. The total blood loss (TBL), intraoperative blood loss (IBL), hidden blood loss (HBL), postoperative drainage volume, maximum hemoglobin drop value (max Hb drop), liver and kidney function, coagulation indexes, blood transfusion rate, hospital stay and incidence of complications were compared among the four groups. Results: TBL, IBL, HBL, max Hb drop, POD1 drainage, and POD2 drainage in group A, group B, and group C were significantly lower than those in group CG. TBL, IBL, HBL and max Hb drop were group C < group A < group B < group CG. The drainage volume of group C was significantly lower than that of the other groups. There was no significant difference in blood coagulation index (PT, D-D) or liver and kidney function (ALT, Cr) among the four groups. There was no difference in postoperative hospital stay between group A and group B, but it was significantly lower in group C than in the other three groups. All patients achieved satisfactory bone graft fusion at the last follow-up. Conclusion: Preoperative intravenous drip of TXA combined with intraoperative multiple immersion can effectively reduce perioperative blood loss while not increasing the risk of thrombosis without affecting liver and kidney function, coagulation function or tuberculosis prognosis.

Incidence and Risk Factors for Cerebrovascular-Specific Mortality in Patients with Colorectal Cancer: A Registry-Based Cohort Study Involving 563,298 Patients.

BACKGROUND: Colorectal cancer (CRC) is one of the most prevalent diseases and the second leading cause of death worldwide. However, the relationship between CRC and cerebrovascular-specific mortality (CVSM) remains elusive, and less is known about the influencing factors associated with CVSM in CRC. Here, we aimed to analyze the incidence as well as the risk factors of CVSM in CRC. METHODS: Patients with a primary CRC diagnosed between 1973 and 2015 were identified from the Surveillance Epidemiology and End Results database, with follow-up data available until 31 December 2016. Conditional standardized mortality ratios were calculated to compare the incidence of CVSM between CRC patients and the general U.S. POPULATION: Univariate and multivariate survival analyses with a competing risk model were used to interrogate the risk factors for CVSM. RESULTS: A total of 563,298 CRC individuals were included. The CVSM in CRC patients was significantly higher than the general population in all age subgroups. Among the competing causes of death in patients, the cumulative mortality caused by cerebrovascular-specific diseases steadily increased during the study period. While age, surgery, other/unknown race and tumors located at the transverse colon positively influenced CVSM on both univariate and multivariate analyses, male patients and those who had radiotherapy, chemotherapy, a more recent year (2001-2015) of diagnosis, a grade II or III CRC, rectal cancer, or multiple primary or distant tumors experienced a lower risk of CVSM. INTERPRETATION: Our data suggest a potential role for CRC in the incidence of CVSM and also identify several significant predictors of CVSM that may be helpful for risk stratification and the therapeutic optimization of cerebrovascular-specific diseases in CRC patients.

Learning Curve and Initial Outcomes of Full-Endoscopic Posterior Lumbar Interbody Fusion.

Study Design: This was a retrospective cohort study. Objective: We evaluated the feasibility, safety, and accuracy of full-endoscopic posterior lumbar interbody fusion (FE-PLIF) by assessing the learning curve and initial clinical outcomes. Summary of Background Data: Low back pain is one of the crucial medical conditions worldwide. FE-PLIF has been reported to be a minimally invasive method to treat mechanical low back pain, but there lacks a thorough evaluation on this new technique. Methods: The patients were divided into three groups in the order of operating date, implying that Group A consisted of the initial 12 cases, Group B the subsequent 12 cases, and Group C the last 12 cases. The data of patients were reviewed for gender, age, preoperative symptoms, satisfaction, as well as clinical outcomes demonstrated by visual analog scale (VAS). The operative time and intraoperative fluoroscopy were recorded to demonstrate the learning curve and the extent of radiographic exposure. Statistical significance was set at a p < 0.05 (two-sided). Results: The patients enrolled in this study were followed up at an average of 1.41 ± 0.24 years. Overall, patients were satisfied with the surgery. The average number of intraoperative fluoroscopy was 6.97 ± 0.74. A significant improvement was observed in the VAS of both lumbar pain and leg pain. The overall fusion rate was 77.7%. Complications were reported in two patients in Group A, one in Group B, and none in Group C. The average operative time showed a trend of gradual decline. The learning curve was characterized using a cubic regression analysis as y = -27.07x + 1.42x2-0.24x3 + 521.84 (R 2 = 0.617, p = 0.000). Conclusions: FE-PLIF is an effective and safe method for treating low back pain caused by short-segmental degenerative diseases. The learning curve of this technique is steep at the initial stage but acceptable and shows great potential for improvement.

Distally Based Peroneal Artery Perforator-Plus Fasciocutaneous Flap to Reconstruct Soft Tissue Defect Combined With Chronic Osteomyelitis in the Lateral Malleolus.

Distally based peroneal artery perforator-plus fasciocutaneous (DPAPF) flaps are widely used to reconstruct soft tissue defects of the lower extremity. Treatment for soft tissue defect combined with chronic osteomyelitis in the lateral malleolus has rarely been reported. The aim of this study was to elaborate the superiority of the DPAPF flap and provide referential experience for using the DPAPF flap in this situation. Between June 2010 and December 2017, soft tissue defects in the setting of chronic osteomyelitis in the lateral malleolus were reconstructed with DPAPF flaps in 17 patients. After thorough debridement, the defect was repaired with the DPAPF flap, and patients subsequently followed an antibiotic regimen for 6 weeks. Follow-up periods for all patients were at least 24 months. The reconstruction outcomes and the satisfaction of the 17 patients were evaluated. Of the 17 flaps, 16 survived uneventfully, except one occurrence of partial necrosis. No infection occurred in the follow-up period. In the study, 17 patients except one were satisfied with flap appearance. All the patients were satisfied with the reconstruction outcomes. In a one-stage procedure, the use of DPAPF flaps is ideal for reconstructing soft tissue defects in the setting of chronic osteomyelitis in the lateral malleolus.

Secondary-structure switch regulates the substrate binding of a YopJ family acetyltransferase.

The Yersinia outer protein J (YopJ) family effectors are widely deployed through the type III secretion system by both plant and animal pathogens. As non-canonical acetyltransferases, the enzymatic activities of YopJ family effectors are allosterically activated by the eukaryote-specific ligand inositol hexaphosphate (InsP6). However, the underpinning molecular mechanism remains undefined. Here we present the crystal structure of apo-PopP2, a YopJ family member secreted by the plant pathogen Ralstonia solanacearum. Structural comparison of apo-PopP2 with the InsP6-bound PopP2 reveals a substantial conformational readjustment centered in the substrate-binding site. Combining biochemical and computational analyses, we further identify a mechanism by which the association of InsP6 with PopP2 induces an α-helix-to-ß-strand transition in the catalytic core, resulting in stabilization of the substrate recognition helix in the target protein binding site. Together, our study uncovers the molecular basis governing InsP6-mediated allosteric regulation of YopJ family acetyltransferases and further expands the paradigm of fold-switching proteins.

Clinicopathological and Prognostic Characteristics in Dedifferentiated/Poorly Differentiated Chordomas: A Pooled Analysis of Individual Patient Data From 58 Studies and Comparison With Conventional Chordomas.

BACKGROUND: Currently, the clinicopathological and prognostic characteristics of dedifferentiated chordoma (DC) and poorly differentiated chordoma (PDC) remain poorly understood. In this study, we sought to characterize clinicopathological parameters in a large PDC/DC cohort and determine their correlations with progression-free survival (PFS) and overall survival (OS) of patients. We also attempted to compare clinical features between PDC/DC and conventional chordoma (CC). METHODS: Literature searches (from inception to June 01, 2020) using Medline, Embase, Google Scholar and Wanfang databases were conducted to identify eligible studies according to predefined criteria. The local database at our center was also retrospectively reviewed to include CC patients for comparative analysis. RESULTS: Fifty-eight studies from the literature and 90 CC patients from our local institute were identified; in total, 54 PDC patients and 96 DC patients were analyzed. Overall, PDC or DC had distinct characteristics from CC, while PDC and DC shared similar clinical features. Adjuvant radiotherapy and chemotherapy were associated with both PFS and OS in PDC patients in the univariate and/or multivariate analyses. In the DC cohort, tumor resection type, adjuvant chemotherapy and tumor dedifferentiation components significantly affected PFS, whereas none of them were predictive of outcome in the multivariate analysis. By analyzing OS, we found that surgery, resection type and the time to dedifferentiation predicted the survival of DC patients; however, only surgery remained significant after adjusting for other covariables. CONCLUSIONS: These data may offer useful information to better understand the clinical characteristics of PDC/DC and may be helpful in improving the outcome prediction of patients.

Prognostic Significance of Tumor-Associated Macrophages in Chondroblastoma and Their Association with Response to Adjuvant Radiotherapy.

OBJECTIVE: Chondroblastoma (CB) is a rare and locally growing cartilage-derived tumor. Currently, clinical implications of tumor-associated macrophages (TAMs) in CB remain unclear. In this study, we sought to analyze the relationship between TAM parameters (including densities of CD68+ and CD163+ cells as well as the CD163+/CD68+ ratio) and clinicopathological characteristics and survival of patients. METHODS: Immunohistochemistry was used to assess TAM subtypes for CD68 and CD163, as well as the expression levels of p53, CD34, and Ki-67 on tumor cells in 132 tissue specimens retrieved between July 2002 and April 2020. Then, TAM parameters were retrospectively analyzed for their associations with patient outcomes (local recurrence-free survival [LRFS] and overall survival [OS]) and clinicopathological features. RESULTS: TAM densities were significantly higher in axial chondroblastoma tissue than in extra-axial chondroblastoma tissue. Moreover, the number of CD163+ TAMs was positively correlated with tumor invasion of surrounding tissues and high expression of CD34 and Ki-67 on tumor cells, whereas CD163+ cell density and the CD163/CD68 ratio were negatively associated with patient response to adjuvant radiotherapy. Univariate Kaplan-Meier analysis revealed that the number of CD68+ and CD163+ lymphocytes was significantly associated with both LRFS and OS. Multivariate Cox regression analysis showed that CD163+ and CD68+ cell levels were independent prognostic factors of LRFS, while TAM data independently predicted OS. More importantly, in subgroup analysis based on three significant factors in univariate survival analysis (including tumor location, adjuvant radiotherapy, and surrounding tissue invasion by tumors), the TAM parameters still displayed good prognostic performance. CONCLUSION: These data suggest that TAM may significantly affect the biological behavior of CB. We hypothesize that modulating the TAM level or polarization status in the microenvironment may be an effective approach for CB treatment.

Utilisation of distally based sural fasciocutaneous flaps in lower extremity reconstruction: a single-centre experience with 88 paediatric patients.

BACKGROUND: No large series have analysed distally based sural fasciocutaneous (DBSF) flaps in paediatric patients. The aims of this study were to assess the reliability and analyse the potential risk factors for these flaps and to describe complications in the donor site and the functional follow-up results. METHODS: Between June 2002 and November 2017, 88 DBSF flaps were used to reconstruct soft tissue defects in paediatric patients. Potential risk factors, reconstruction outcomes, and complications in the donor site of the flaps were analysed. RESULTS: Among the 88 flaps, partial necrosis developed in 8 flaps (9.1%). The partial necrosis rate was significantly higher in flaps with the top edge located in the 9th zone (26.1%), with a length-width ratio (LWR) ≥ 5:1 (28.6%), and with a dimension of the skin island ≥ 100 cm2 (22.7%). Partial necrosis did not occur in flaps with a dimension of the skin island < 80.0 cm2 or with a skin-island width < 7.0 cm. The reconstruction outcomes in most paediatric patients were evaluated as "excellent" or "good". The incidence of obvious scarring was higher in the donor site. CONCLUSIONS: Partial necrosis of DBSF flaps will significantly increase when the top edge of the flap is located in the 9th zone, when the LWR of the flap is ≥ 5:1, or when the dimension of the skin island is ≥ 100.0 cm2. Flaps with a skin-island width < 7.0 cm or with a dimension of the skin island < 80 cm2 are relatively safe and reliable.

Coexpression of HHLA2 and PD-L1 on Tumor Cells Independently Predicts the Survival of Spinal Chordoma Patients.

Background: Immunotherapy only achieves efficacy in some cancer patients, and less is known about other immune checkpoint molecules in chordoma. Here, we aimed to determine the expression of PD-L1, HHLA2, B7H3, IDO-1 and Galectin-9 in spinal chordoma and evaluated their association with tumor infiltrating lymphocytes (TILs), clinicopathological characteristics and survival of patients. Methods: Using multiplexed quantitative immunofluorescence (QIF), we simultaneously measured the levels of five different immune checkpoint molecules and major TIL subsets in 92 human spinal chordoma samples. Results: Tumor HHLA2 and PD-L1 were positive in 80.0% and 86.0% of cases, respectively. However, B7H3, IDO-1 and Galectin-9 positivity on tumor cells were only seen in 21.0% of cases, despite all showing predominantly stromal expression. Coexpression of these QIF markers in the tumor compartment was scarcely detected except for PD-L1 and HHLA2, which was observed in 69.6% of cases. While tumoral HHLA2 and stromal B7H3 expressions were associated with an aggressive tumor phenotype, suppressive immune response (specifically including elevated PD-1+ TILs level and decreased CD8+ TIL density) and poor prognosis, stromal levels of PD-L1 and Galectin-9 predicted the opposite outcomes. Importantly, HHLA2 and PD-L1 coexpression on tumor cells independently predicted both worse local recurrence-free survival and overall survival. Conclusion: These data provide a better understanding of the immunosuppressive mechanism in chordoma and may be useful for the development of combination or novel immunotherapy approaches aiming to improve therapeutic efficacy and survival.