Intravoxel Incoherent Motion and Dynamic Contrast-Enhanced Magnetic Resonance Imaging Can Differentiate Between Atypical Cartilaginous Tumors and High-Grade Chondrosarcoma: Correlation With Histological Vessel Characteristics.

OBJECTIVE: To differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma of the major long bones using intravoxel incoherent motion (IVIM) and Dynamic Contrast-Enhanced magnetic resonance imaging (DCE-MRI), and explore the correlation of quantitative parameters with hypoxia inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF) and microvessel density (MVD). METHOD: Between September 2016 and March 2022, 35 patients (17 atypical cartilaginous tumors, 18 high-grade chondrosarcoma) underwent MRI examination and pathological confirmation at our hospital. First, IVIM-derived parameters ( D , D* , and f ), and DCE-MRI parameters ( Ktrans , Kep , and V e ) were measured, and intraclass correlation efficient (ICC) and Mann-Whitney U test were performed. Second, receiver-operating characteristic curve analysis was performed to evaluate the diagnostic performance. Finally, Spearman's correlation analysis was performed between the quantitative parameters of IVIM-DWI and DCE-MRI and the immunohistochemical factors HIF-1α, VEGF, and MVD in chondrosarcoma tissue. RESULTS: D in atypical cartilaginous tumors was significantly higher than that in high-grade chondrosarcoma ( P = 0.003), whereas D* , Ktrans , and K ep in atypical cartilaginous tumors were significantly lower than those in high-grade chondrosarcoma (all P < 0.001). Ktrans demonstrated the highest area under the curve (AUC) of 0.979. The D* , Ktrans , and K ep were positively correlated with HIF-1α, VEGF, and MVD (all P < 0.001), whereas D had no correlation with HIF-1α, VEGF, and MVD ( P = 0.113, 0.077, 0.058, respectively). CONCLUSION: The IVIM-DWI quantitative parameters ( D , D* ) and DCE-MRI quantitative parameters ( Ktrans , Kep ) are helpful to differentiate between atypical cartilaginous tumors and high-grade chondrosarcoma and could be imaging biomarkers to reflect the expressions of HIF-1α, VEGF, and angiogenesis of chondrosarcoma.

Prognostic Factors and Surgical Impact of Non-metastatic Conventional Chondrosarcoma of the Extremities.

OBJECTIVE: Chondrosarcoma is a common bone malignancy, and the main treatment method is surgery. Different surgeries lead to different survival outcomes. The aim of this study was to construct a new clinical predictive tool to accurately predict the overall survival (OS) and cause specific survival (CSS) of patients with chondrosarcoma receiving different treatments. METHODS: A total of 620 patients with chondrosarcoma registered between January 1, 2000 and December 31, 2016 were recruited as study targets. The missing values are filled by multiple imputation. Two continuous variables, age and tumor size, were divided into binary variables based on Kaplan-Meier curve. Univariate and multivariate analyses were used to explore predictors and establish nomograms. Propensity score matching (PSM) analysis was used to reduce the impact of potential confounders to determine whether different surgical modalities had any survival benefits in subgroups. RESULTS: In a multivariate cox regression, age, grade, tumor size, radiotherapy, chemotherapy, and surgical methods were identified as independent prognostic factors for chondrosarcoma. To construct 1-, 3-, and 5-year nomogram maps of OS and CSS with prognostic factors and verify the c index internally (OS, 0.807; CSS, 0.847) above American Joint Committee on Cancer (AJCC) (OS, 0.685; CSS, 0.732). CONCLUSION: This study found that the 5 year overall survival rate of patients with non-metastatic chondrosarcoma of the extremities was about 80%. Age, high malignancy, large tumor, prior chemoradiotherapy, and poor surgical selection were independent risk factors. Therefore, the nomogram established in this study will help to optimize clinicians' personalized decision making for patients.

MRI radiomics-based evaluation of tuberculous and brucella spondylitis.

OBJECTIVES: We analyzed magnetic resonance imaging (MRI) and radiomics labels from tuberculous spondylitis (TBS) and brucella spondylitis (BS) to build machine learning models that differentiate TBS from BS and culture-positive TBS (TBS(+)) from culture-negative TBS (TBS(-). METHODS: This retrospective study included 56 patients with BS, 63 patients with TBS(+) and 71 patients with TBS(-). Radiomics labels were extracted from T2-weighted fat-suppression images. MRI labels were analyzed via logistic regression (LR); radiomics labels were analyzed by t-tests, SelectKBest, and least absolute shrinkage and selection operator (LASSO). Random forest (RF) and support vector machine (SVM) models were established using radiomics or joint (radiomics+MRI) labels. Models were evaluated by receiver operating characteristic curves, areas under the curve (AUCs), decision curve analysis (DCA), and Hosmer-Lemeshow tests. RESULTS: When joint-label models were used to compare BS vs TBS(+) and BS vs TBS(-) groups, SVM AUCs were 0.904 and 0.944, respectively, whereas RF AUCs were 0.950 and 0.947, respectively; these were higher than the AUCs of the MRI label-based LR model. DCA showed that radiomics-based machine learning models had a greater net benefit; Hosmer-Lemeshow tests demonstrated good prediction consistency for all models. CONCLUSIONS: Radiomics can help distinguish TBS from BS and TBS(+) from TBS(-).

Genetic and functional analyses detect an EXT1 splicing pathogenic variant in a Chinese hereditary multiple exostosis (HME) family.

BACKGROUND: Hereditary multiple exostosis (HME) is an autosomal dominant skeletal disorder characterized by the development of multiple cartilage-covered tumors on the external surfaces of bones (osteochondromas). Most of HME cases result from heterozygous loss-of-function mutations in EXT1 or EXT2 gene. METHODS: Clinical examination was performed to diagnose the patients: Whole exome sequencing (WES) was used to identify pathogenic mutations in the proband, which is confirmed by Sanger sequencing and co-segregation analysis: qRT-PCR was performed to identify the mRNA expression level of EXT1 in patient peripheral blood samples: minigene splicing assay was performed to mimic the splicing process of EXT1 variants in vitro. RESULTS: We evaluated the pathogenicity of EXT1 c.1056 + 1G > T in a Chinese family with HME. The clinical, phenotypic, and genetic characterization of patients in this family were described. The variant was detected by whole-exome sequencing (WES) and confirmed by Sanger sequencing. Sequencing of the RT-PCR products from the patient's blood sample identified a large deletion (94 nucleotides), which is the whole exome 2 of the EXT1 cDNA. Splicing assay indicated that the mutated minigene produced alternatively spliced transcripts, which cause a frameshift resulting in an early termination of protein expression. CONCLUSIONS: Our study establishes the pathogenesis of the splicing mutation EXT1 c.1056 + 1G > T to HME and provides scientific foundation for accurate diagnosis and precise medical intervention for HME.

Evaluation of the Peripheral Rim Instability of the Discoid Meniscus in Children by Using Weight-Bearing Magnetic Resonance Imaging.

OBJECTIVE: The aim of the study was to assess the peripheral rim instability and the clinical value of discoid meniscus. METHODS: We retrospectively studied 79 magnetic resonance imaging (MRI) examinations of discoid meniscus from May 2017 to September 2019. The patient symptoms and physical findings were documented. The patients underwent "dedicated" 0.25 T supine and weight-bearing MRI examination. Finally, all patients underwent arthroscopy. RESULTS: Sound/clicking during motion (P = 0.009) and limited extension (P = 0.044) of subjective symptoms, clunk during motion (P = 0.035), and flexion contracture (P = 0.012) of physical findings were significant predictors of peripheral rim instability. The comparison of the weight-bearing MRI with the supine position MRI demonstrated that the disformed discoid meniscus was shifted significantly and that no shift was displaced centrally (P = 0.001). A correlation between discoid meniscal displacement and the presence of peripheral rim instability in arthroscopy was noted (P < 0.001) using weight-bearing MRI. CONCLUSIONS: The clinical symptoms of the patients combined with weight-bearing MRI can determine peripheral rim instability optimally.

Cooperativity effect involving drug-DNA/RNA intermolecular interaction: A B3LYP-D3 and MP2 theoretical investigation on ketoprofen⋯cytosine⋯H2O system.

In order to examine the origin of the drug action and design new DNA/RNA-targeted drugs, the cooperativity effect involving drug-DNA/RNA intermolecular interaction in ketoprofen⋯cytosine⋯H2O ternary system were investigated by the B3LYP, B3LYP-D3, and MP2 methods with the 6-311++G(2d,p) basis set. The thermodynamic cooperativity was also evaluated at 310.15 K. The N-H⋯O, O-H⋯O, O-H⋯N, C-H⋯N, and C-H⋯O H bonds coexist in ternary complexes. The intermolecular interactions obtained by B3LYP-D3 are close to those calculated by MP2. The steric effects and van der Waals interactions have little influence on the cooperativity effects. The anti-cooperativity effect in ket⋯cyt⋯H2O is far more notable than the cooperativity effect, and the stability of the cyclic structure with anti-cooperativity effect is higher than that of the linear structure with cooperativity effect, as is confirmed by the AIM (atoms in molecules) and RDG (reduced density gradient) analysis. Thus, it can be inferred that, in the presence of H2O, the anti-cooperativity effect plays a dominant role in the drug-DNA/RNA interaction, and the nature of the hydration in the binding of drugs to DNA/RNA bases is the H-bonding anti-cooperativity effect. Furthermore, the drug always links simultaneously with DNA/RNA base and H2O, and only in this way can the biological activity of drugs play a role. In most cases, the enthalpy change is the major factor driving the cooperativity, as is different from most of biomacromolecule complexes.

A Preliminary Study on a Novel Growth Guidance Rod System for Early-Onset Scoliosis in a Sheep Model.

STUDY DESIGN: An animal study with immature sheep to evaluate the effects of a multisegment growth guidance rod (MSGGR) on spine growth. OBJECTIVE: To determine whether the spine of the immature sheep can still grow after MSGGR fixation. SUMMARY OF BACKGROUND DATA: The disadvantages for current growing rod techniques are that they can partially correct only the spinal curve and have little control to the apex of the curve. The rigidity of the spine after a growing rod procedure may also interfere with the final correction. Current systems are complex and not always affordable, especially in the developing world. Newer, more inexpensive techniques that provide 3-dimensional deformity correction while allowing normal spinal growth without surgical lengthening are still desired. METHODS: The MSGGR is a rod consisting of segments. Spinal deformation in scoliosis is corrected and maintained by the rods without fusion. The system allows the growth of the fixed spinal segments. It is stable when twisted and bent but extendable when stretched. Rod extension occurs through sliding between the segments along the sockets in accordance to the growth of the spine. Ten 3-month-old immature sheep were used in this study. Dual MSGGRs were implanted to fix the lumber and low thoracic spine. Radiographs, magnetic resonance image, and computed tomographic scan of the spine were obtained to evaluate the fixation, rod extension, and spine health. RESULTS: All of the sheep spines grew with the implants in position. The spine segments within the instruments were 12.5 ± 0.8 cm and grew by 10.9% (range: 6%-18.4%) from their original length in 4 months. None of the implants failed. No MSGGR-related complications were observed. Magnetic resonance imaging showed normal disc within the instrumented segments. Motion of the instrumented spinal segments was conserved. CONCLUSION: Growth guidance with this novel MSGGR allowed for continued growth in this sheep model, and repeated surgical lengthening of the system is not needed. LEVEL OF EVIDENCE: N/A.

Preoperative evaluation of venous systems with computed tomography venography in parasagittal meningiomas.

OBJECTIVE: Parasagittal meningiomas (PSM) may pose a difficult surgical challenge because venous patency and collateral anastomoses have to be clearly defined for correct surgical planning. The aim of this study was to study the diagnostic accuracy of computed tomography venography (CTV) in assessing the superior sagittal sinus (SSS) obstruction and venous collaterals. METHODS: Twenty-four patients undergoing surgery for meningiomas located adjacent to the SSS were prospectively evaluated. All the patients underwent both conventional computed tomography examination and CTV. Computed tomography venography was evaluated by 2 expert neuroradiologists to assess (1) patency of the sinus (patent/occluded), (2) the extent of occlusion (in centimeters), and (3) the number of collateral anastomoses close to the insertion of the meningioma. Computed tomography venography assessment was compared with surgery. All patients were operated on, and intraoperative findings were taken as the criterion standard. RESULTS: Computed tomography venography showed the sinus to be occluded in 6 cases. Computed tomography venography data were confirmed by surgery, showing 6 patients to have have an occlusion of the SSS. The CTV sensitivity was thus 100%. Computed tomography venography depicted 83% of collateral venous anastomoses close to the meningioma as subsequently confirmed by surgery. CONCLUSIONS: In the preoperative planning for patients with meningiomas located close to the SSS, CTV can provide additional and more reliable information concerning venous infiltration and the presence of collateral anastomoses compared with noncontrast computed tomography.

The thin sectional anatomy of the temporal bone correlated with multislice spiral CT.

The aim of this study was to explore the method for obtaining the thin sectional anatomy data of the adult temporal bone and study the fine structures using this method. Three fresh adult cadaveric heads were scanned with multi-slice computer tomography (MSCT) centered on petrous bones. The CT images of 0.6 mm were obtained by multi-planar reformation (MPR). The slices of 0.1 mm were shaved off the specimen in the axial direction with the numerical control milling machine after being embedded and frozen, pictures of which were taken by the digital camera and saved in the computer. The thin axial sectional anatomic structures of the intra-temporal were investigated and correlated with MPR images. Via the comparison, fifty micro-anatomic structures of the temporal bone that can't be delineated clearly or missed in the thick sections were evaluated. The anatomical details of the temporal bone can be clearly delineated in MSCT in sub-millimeter and were identical to those in sectional anatomy images. This method can supply anatomical details that had been missed or overlooked for imaging diagnosis and surgical anatomy.