Optimal body mass index for protecting middle-aged and elderly patients with fatty liver from future fractures.

OBJECTIVE: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes. METHODS: This retrospective cohort study from 2011 to 2019 enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (DXA, for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes, and the effect of different ranges of BMI (18.5-24, 24-27, and ≥27 kg/m2 in women; 18.5-24, 24-27, 27-30 and ≥30 kg/m2 in men) on the risk of future fractures in FL patients. RESULTS: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors for osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24-27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5-24 kg/m2. CONCLUSION: The protective effect of a higher BMI against future fractures in middle-aged and elderly women and men with FL is not uniform and decreases beyond certain BMI ranges.

Safety and Tolerability of Intra-Articular Injection of Adipose-Derived Mesenchymal Stem Cells GXCPC1 in 11 Subjects With Knee Osteoarthritis: A Nonrandomized Pilot Study Without a Control Arm.

The current study aimed to determine the safety profile of intra-articular-injected allogeneic adipose-derived mesenchymal stem cells (ADSCs) GXCPC1 in subjects with knee osteoarthritis (OA) and its preliminary efficacy outcome. The 3 + 3 phase I study was designed with two dose-escalation cohorts: low dose (6.7 × 106 GXCPC1, N = 5) and high dose (4 × 107 GXCPC1, N = 6). The primary endpoint was safety, which was evaluated by recording adverse events throughout the trial; the secondary endpoints included total, pain, stiffness, and function subscales of the Western Ontario and McMaster Universities Arthritis Index (WOMAC), Visual Analogue Scale (VAS) for pain, and 12-Item Short Form (SF-12) health survey questionnaire. The GXCPC1 treatment was found to be safe after 1 year of follow-up with no treatment-related severe adverse events observed. When compared to baseline, subjects in both the low- and high-dose cohorts demonstrated improving trends in pain and knee function after receiving GXCPC1 treatment. Generally, the net change in pain (95% confidence interval (CI) = -7.773 to -2.561t at 12 weeks compared to baseline) and knee function (95% CI = -24.297 to -10.036t at 12 weeks compared to baseline) was better in subjects receiving high-dose GXCPC1. Although this study included a limited number of subjects without a placebo arm, it showed that the intra-articular injection of ADSCs was safe and well-tolerated in subjects with therapeutic alternatives to treat knee OA. However, a larger scale study with an appropriate control would be necessary for clinical efficacy in the following study.

The correlation between hip alpha angle and acetabular labral tear location and size: A cross-sectional study.

BACKGROUND: Explore the correlation between hip morphology and labral tear location/size. METHODS: This retrospective study analyzed patients with hip pain who received magnetic resonance (MR) arthrography at our institution, between January 2017 and December 2020. Imaging analysis includes labral tear location and size, and hip morphology measurement with alpha angle, lateral center-edge (CE) angle, anterior CE angle, and femoral neck version. The correlation between hip morphology angles and labral tear location/size was evaluated using multiple regression, followed by stratification analysis with Chi-square test to investigate interactions between the variables. RESULTS: A total of 103 patients (105 hips) with hip pain who received MR arthrography (mean age, 50 years ± 15 [SD]) were included, with mean alpha angle of 57.7° ± 9.9° [SD], mean lateral CE angle of 32.6° ± 6.8° [SD], mean anterior CE angle of 58.2° ± 8.1° [SD], mean femoral neck version of 17.1° ± 8.2° [SD]. Large alpha angle (>57°) and older age were both correlated with superior and posterosuperior labral tear incidence ( p < 0.05) and larger tear size ( p < 0.05). Furthermore, alpha angle is significantly correlated with superior labral tear incidence in young-age subgroup (age <45 years) ( p < 0.05), also significantly correlated with posterosuperior labral tear incidence and larger tear size in middle-age subgroup (45 ≤ age ≤ 60 years) ( p < 0.05). CONCLUSION: A large alpha angle (>57°) is significantly correlated with increased incidence of superior and posterosuperior labral tear, and larger tear size in patients with hip pain, and the relationships depend on age.

Classifying Temporomandibular Disorder with Artificial Intelligent Architecture Using Magnetic Resonance Imaging.

This study proposes a new diagnostic tool for automatically extracting discriminative features and detecting temporomandibular joint disc displacement (TMJDD) accurately with artificial intelligence. We analyzed the structural magnetic resonance imaging (MRI) images of 52 patients with TMJDD and 32 healthy controls. The data were split into training and test sets, and only the training sets were used for model construction. U-net was trained with 100 sagittal MRI images of the TMJ to detect the joint cavity between the temporal bone and the mandibular condyle, which was used as the region of interest, and classify the images into binary categories using four convolutional neural networks: InceptionResNetV2, InceptionV3, DenseNet169, and VGG16. The best models were InceptionV3 and DenseNet169; the results of InceptionV3 for recall, precision, accuracy, and F1 score were 1, 0.81, 0.85, and 0.9, respectively, and the corresponding results of DenseNet169 were 0.92, 0.86, 0.85, and 0.89, respectively. Automated detection of TMJDD from sagittal MRI images is a promising technique that involves using deep learning neural networks. It can be used to support clinicians in diagnosing patients as having TMJDD.

Validity of the Osteoarthritis Research Society International (OARSI) recommended performance-based tests of physical function in individuals with symptomatic Kellgren and Lawrence grade 0-2 knee osteoarthritis.

BACKGROUND: Performance-based physical tests have been widely used as objective assessments for individuals with knee osteoarthritis (KOA), and the core set of tests recommended by the Osteoarthritis Research Society International (OARSI) aims to provide reliable, valid, feasible and standardized measures for clinical application. However, few studies have documented their validity in roentgenographically mild KOA. Our goal was to test the validity of five performance-based tests in symptomatic KOA patients with X-ray findings of Kellgren and Lawrence (K-L) grade 0-2. METHODS: We recruited a convenience sample of thirty KOA patients from outpatient clinics and 30 age- and sex-matched asymptomatic controls from the community. They performed five OARSI-recommended physical tests and the KOA group answered the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index. The tests included the 9-step stair-climbing test (9 s-SCT), timed up and go (TUG) test, 30-second chair-stand test (30sCST), 40-m fast walking-test (40MFPW) and 6-minute walking test (6MWT). The discriminant validity of these physical tests were assessed by comparisons between the KOA and control groups, receiver operating curve and multivariate logistic regression analysis. The convergent/divergent validity was assessed by correlation between the physical tests results and the three subscale scores of the WOMAC in the KOA group. RESULTS: The KOA group had significantly worse performance than the control group. The percentage of difference was the largest in the 9 s-SCT (57.2%) and TUG tests (38.4%). Meanwhile, Cohen's d was above 1.2 for the TUG test and 6MWT (1.2 ~ 2.0), and between 0.8 and 1.2 for the other tests. The areas under the curve to discriminate the two groups were mostly excellent to outstanding, except for the 30sCST. Convergent validity was documented with a moderate correlation between the 9 s-SCT and the physical function (WOMAC-PF) subscale scores (Spearman's ρ = 0.60). CONCLUSIONS: The OARSI recommended core set was generally highly discriminative between people with K-L grade 0-2 KOA and their controls, but convergent/divergent validity was observed only in the 9 s-SCT. Further studies are required to evaluate the responsiveness of these tests and understand the discordance of physical performance and self-reported measures.

Preparation of curcumin-loaded liposome with high bioavailability by a novel method of high pressure processing.

Curcumin has been incorporated for the development of new products with applicability in food, pharmaceutical and cosmetic fields in Asia, due to the traits of anti-oxidation and anti-inflammatory. In the application of food engineering, high-pressure processing (HPP) can destroy non-covalent bonds and use as a method to inactivate bacteria for extending the perseveration of food. Thus, this study focuses on a novel approach for the microencapsulation of curcumin by the combination of ethanol injection and HPP at the room temperature for stabilizing pure curcumin in aqueous solutions and in liposome. The results revealed that the most optimal curcumin-liposome was prepared by HPP at operational pressure of 200 MPa within 5 mins holding time to obtain the minimum particle size of 281.9 nm, encapsulation efficiency of 87.25% and polydispersity index (PDI) of 0.23. Particle size could reduce to nanoscale (70.65 nm) after 0.5% addition of Tween 80, but the encapsulation efficiency spontaneously decreased to 45.05%. It is an option to produce liposome with nanosize and uniform distribution for the consideration of high drug delivery. Conclusively, HPP process could not only effectively decrease particle size and PDI of liposome but also efficiently sterilize bacteria around concentration of 103 CFU/g.

Ground truth generalizability affects performance of the artificial intelligence model in automated vertebral fracture detection on plain lateral radiographs of the spine.

BACKGROUND CONTEXT: Computer-aided diagnosis with artificial intelligence (AI) has been used clinically, and ground truth generalizability is important for AI performance in medical image analyses. The AI model was trained on one specific group of older adults (aged≧60) has not yet been shown to work equally well in a younger adult group (aged 18-59). PURPOSE: To compare the performance of the developed AI model with ensemble method trained with the ground truth for those aged 60 years or older in identifying vertebral fractures (VFs) on plain lateral radiographs of spine (PLRS) between younger and older adult populations. STUDY DESIGN/SETTING: Retrospective analysis of PLRS in a single medical institution. OUTCOME MEASURES: Accuracy, sensitivity, specificity, and interobserver reliability (kappa value) were used to compare diagnostic performance of the AI model and subspecialists' consensus between the two groups. METHODS: Between January 2016 and December 2018, the ground truth of 941 patients (one PLRS per person) aged 60 years and older with 1101 VFs and 6358 normal vertebrae was used to set up the AI model. The framework of the developed AI model includes: object detection with You Only Look Once Version 3 (YOLOv3) at T0-L5 levels in the PLRS, data pre-preprocessing with image-size and quality processing, and AI ensemble model (ResNet34, DenseNet121, and DenseNet201) for identifying or grading VFs. The reported overall accuracy, sensitivity and specificity were 92%, 91% and 93%, respectively, and external validation was also performed. Thereafter, patients diagnosed as VFs and treated in our institution during October 2019 to August 2020 were the study group regardless of age. In total, 258 patients (339 VFs and 1725 normal vertebrae) in the older adult population (mean age 78±10.4; range, 60-106) were enrolled. In the younger adult population (mean age 36±9.43; range, 20-49), 106 patients (120 VFs and 728 normal vertebrae) were enrolled. After identification and grading of VFs based on the Genant method with consensus between two subspecialists', VFs in each PLRS with human labels were defined as the testing dataset. The corresponding CT or MRI scan was used for labeling in the PLRS. The bootstrap method was applied to the testing dataset. RESULTS: The model for clinical application, Digital Imaging and Communications in Medicine (DICOM) format, is uploaded directly (available at: http://140.113.114.104/vght_demo/svf-model (grading) and http://140.113.114.104/vght demo/svf-model2 (labeling). Overall accuracy, sensitivity and specificity in the older adult population were 93.36% (95% CI 93.34%-93.38%), 88.97% (95% CI 88.59%-88.99%) and 94.26% (95% CI 94.23%-94.29%), respectively. Overall accuracy, sensitivity and specificity in the younger adult population were 93.75% (95% CI 93.7%-93.8%), 65.00% (95% CI 64.33%-65.67%) and 98.49% (95% CI 98.45%-98.52%), respectively. Accuracy reached 100% in VFs grading once the VFs were labeled accurately. The unique pattern of limbus-like VFs, 43 (35.8%) were investigated only in the younger adult population. If limbus-like VFs from the dataset were not included, the accuracy increased from 93.75% (95% CI 93.70%-93.80%) to 95.78% (95% CI 95.73%-95.82%), sensitivity increased from 65.00% (95% CI 64.33%-65.67%) to 70.13% (95% CI 68.98%-71.27%) and specificity remained unchanged at 98.49% (95% CI 98.45%-98.52%), respectively. The main causes of false negative results in older adults were patients' lung markings, diaphragm or bowel airs (37%, n=14) followed by type I fracture (29%, n=11). The main causes of false negatives in younger adults were limbus-like VFs (45%, n=19), followed by type I fracture (26%, n=11). The overall kappa between AI discrimination and subspecialists' consensus in the older and younger adult populations were 0.77 (95% CI, 0.733-0.805) and 0.72 (95% CI, 0.6524-0.80), respectively. CONCLUSIONS: The developed VF-identifying AI ensemble model based on ground truth of older adults achieved better performance in identifying VFs in older adults and non-fractured thoracic and lumbar vertebrae in the younger adults. Different age distribution may have potential disease diversity and implicate the effect of ground truth generalizability on the AI model performance.

Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial.

OBJECTIVE: To evaluate the safety and efficacy of intra-articular (IA) injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE® for knee osteoarthritis. METHODS: This was a patient-blind, randomized, active-control trial consisted of 4 arms including hyaluronic acid (HA) control and 3 ELIXCYTE® doses. A total of 64 subjects were screened, and 57 subjects were randomized. The primary endpoints included the changes from baseline to post-treatment visit of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at Week 24 and the incidence of adverse events (AEs) and serious adverse events (SAEs). RESULTS: No ELIXCYTE®-related serious adverse events were reported during 96 weeks of follow-up and no suspected unexpected serious adverse reaction (SUSAR) or death was reported. The changes of the primary endpoint, WOMAC pain score at Week 24, showed significant differences in all ELIXCYTE® groups, as well as in HA groups between post-treatment visit and baseline. The ELIXCYTE® groups revealed significant decreases at Week 4 compared to HA group in WOMAC total scores, stiffness scores, functional limitation scores suggested the potential of ELIXCYTE® in earlier onset compared to those from HA. The significant differences of visual analog scale (VAS) pain score and Knee Society Clinical Rating System (KSCRS) functional activities score at Week 48 after ELIXCYTE® administration suggested the potential of ELIXCYTE® in the longer duration of the effectiveness compared to HA group. CONCLUSIONS: ELIXCYTE® for knee osteoarthritis treatment was effective, safe, and well-tolerated. The efficacy results were showed that ELIXCYTE® conferred the earlier onset of reductions in pain scores and improvements in functional scores than HA group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02784964. Registered 16 May, 2016-Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT02784964.

Adsorption Behaviors of a Twin-Tower Hydrogen Purification System Mounted onto Staggered Stainless Steel Sheets Coated with Composite Membrane.

Many studies have been conducted on hydrogen production, storage, purification, and transportation. The use of fixed-bed adsorption towers for hydrogen purification is common. The operating variables involved that could affect the adsorption behavior, such as the amount of adsorbents used, the flow rate, and the concentration of the adsorbate, should be discussed further. In addition, the pressure drop caused by the operation of the adsorption tower still needs to be considered. Therefore, the staggered stainless steel sheet coatings with SiO2/MCM41/activated carbon composite membrane were mounted in a twin-tower adsorption system to purify the hydrogen. Similar to the pressure swing adsorption (PSA) system, the amounts of SiO2, activated carbon, and molecular sieves used in the adsorption tower were changed into the amounts of tetraethoxysilane (TEOS), activated carbon powder, and MCM41 powder added to the casting solution. The experimental results showed that the performance of this twin-tower hydrogen purification system would not be increased when one of the target adsorbents was excessive. In addition, the outflow of non-hydrogen components was found to be early when a certain adsorbent was not sufficient. Finally, the recommended switching time for this system was set at an adsorption capacity reaching about 75% saturated capacity.

Effects of Molecular Properties on Adsorption of Six-Carbon VOCs by Activated Carbon in a Fixed Adsorber.

Gravimetric adsorption equipment with a microbalance was used to measure the adsorption of volatile organic compounds (VOCs) by activated carbon from 288 to 313 K. VOCs [n-hexane, cyclohexane, 1-hexene, 2-methylpentane, 3-methylpentane, 2,2-dimethylbutane, acetone, butanone, and 2-pentanone (Pentan-2-one)] were used as adsorbates in the adsorption system. Considering the geometric barrier, the critical diameter, and the boiling point, the adsorption capacities for six-carbon (C6) alkane isomers decrease in the order of n-hexane, 3-methylpentane, and 2-methylpentane. The adsorbates, including nonpolar or weakly polar substances, and substances with smaller geometric obstacles and smaller molecular weights, were more easily adsorbed by the activated carbon. However, the dipole-dipole interactive force at higher pressures resulted in a higher adsorption capacity for 1-hexene than for n-hexane. Both polarity and molecular size should be considered in the analysis of the adsorption of ketones by activated carbon. The adsorption equilibrium constants decreased with increases in temperature because a higher temperature was unfavorable for adsorption. The results for the Toth adsorption isotherm model fitted by the adsorption data showed that the experimental data and the Toth adsorption isotherm model were consistent with each other, as evidenced by the low deviation between the experimental data and those from the fitted model.

Can a Deep-learning Model for the Automated Detection of Vertebral Fractures Approach the Performance Level of Human Subspecialists?

BACKGROUND: Vertebral fractures are the most common osteoporotic fractures in older individuals. Recent studies suggest that the performance of artificial intelligence is equal to humans in detecting osteoporotic fractures, such as fractures of the hip, distal radius, and proximal humerus. However, whether artificial intelligence performs as well in the detection of vertebral fractures on plain lateral spine radiographs has not yet been reported. QUESTIONS/PURPOSES: (1) What is the accuracy, sensitivity, specificity, and interobserver reliability (kappa value) of an artificial intelligence model in detecting vertebral fractures, based on Genant fracture grades, using plain lateral spine radiographs compared with values obtained by human observers? (2) Do patients' clinical data, including the anatomic location of the fracture (thoracic or lumbar spine), T-score on dual-energy x-ray absorptiometry, or fracture grade severity, affect the performance of an artificial intelligence model? (3) How does the artificial intelligence model perform on external validation? METHODS: Between 2016 and 2018, 1019 patients older than 60 years were treated for vertebral fractures in our institution. Seventy-eight patients were excluded because of missing CT or MRI scans (24% [19]), poor image quality in plain lateral radiographs of spines (54% [42]), multiple myeloma (5% [4]), and prior spine instrumentation (17% [13]). The plain lateral radiographs of 941 patients (one radiograph per person), with a mean age of 76 ± 12 years, and 1101 vertebral fractures between T7 and L5 were retrospectively evaluated for training (n = 565), validating (n = 188), and testing (n = 188) of an artificial intelligence deep-learning model. The gold standard for diagnosis (ground truth) of a vertebral fracture is the interpretation of the CT or MRI reports by a spine surgeon and a radiologist independently. If there were any disagreements between human observers, the corresponding CT or MRI images would be rechecked by them together to reach a consensus. For the Genant classification, the injured vertebral body height was measured in the anterior, middle, and posterior third. Fractures were classified as Grade 1 (< 25%), Grade 2 (26% to 40%), or Grade 3 (> 40%). The framework of the artificial intelligence deep-learning model included object detection, data preprocessing of radiographs, and classification to detect vertebral fractures. Approximately 90 seconds was needed to complete the procedure and obtain the artificial intelligence model results when applied clinically. The accuracy, sensitivity, specificity, interobserver reliability (kappa value), receiver operating characteristic curve, and area under the curve (AUC) were analyzed. The bootstrapping method was applied to our testing dataset and external validation dataset. The accuracy, sensitivity, and specificity were used to investigate whether fracture anatomic location or T-score in dual-energy x-ray absorptiometry report affected the performance of the artificial intelligence model. The receiver operating characteristic curve and AUC were used to investigate the relationship between the performance of the artificial intelligence model and fracture grade. External validation with a similar age population and plain lateral radiographs from another medical institute was also performed to investigate the performance of the artificial intelligence model. RESULTS: The artificial intelligence model with ensemble method demonstrated excellent accuracy (93% [773 of 830] of vertebrae), sensitivity (91% [129 of 141]), and specificity (93% [644 of 689]) for detecting vertebral fractures of the lumbar spine. The interobserver reliability (kappa value) of the artificial intelligence performance and human observers for thoracic and lumbar vertebrae were 0.72 (95% CI 0.65 to 0.80; p < 0.001) and 0.77 (95% CI 0.72 to 0.83; p < 0.001), respectively. The AUCs for Grades 1, 2, and 3 vertebral fractures were 0.919, 0.989, and 0.990, respectively. The artificial intelligence model with ensemble method demonstrated poorer performance for discriminating normal osteoporotic lumbar vertebrae, with a specificity of 91% (260 of 285) compared with nonosteoporotic lumbar vertebrae, with a specificity of 95% (222 of 234). There was a higher sensitivity 97% (60 of 62) for detecting osteoporotic (dual-energy x-ray absorptiometry T-score ≤ -2.5) lumbar vertebral fractures, implying easier detection, than for nonosteoporotic vertebral fractures (83% [39 of 47]). The artificial intelligence model also demonstrated better detection of lumbar vertebral fractures compared with detection of thoracic vertebral fractures based on the external dataset using various radiographic techniques. Based on the dataset for external validation, the overall accuracy, sensitivity, and specificity on bootstrapping method were 89%, 83%, and 95%, respectively. CONCLUSION: The artificial intelligence model detected vertebral fractures on plain lateral radiographs with high accuracy, sensitivity, and specificity, especially for osteoporotic lumbar vertebral fractures (Genant Grades 2 and 3). The rapid reporting of results using this artificial intelligence model may improve the efficiency of diagnosing vertebral fractures. The testing model is available at http://140.113.114.104/vght_demo/corr/. One or multiple plain lateral radiographs of the spine in the Digital Imaging and Communications in Medicine format can be uploaded to see the performance of the artificial intelligence model. LEVEL OF EVIDENCE: Level II, diagnostic study.

Clinical practice recommendations for the use of imaging in the diagnosis and management of axial spondyloarthritis in Taiwan.

OBJECTIVE: Axial spondyloarthritis (axSpA) is a chronic inflammatory disease bearing challenges in early diagnosis. To improve clinical diagnosis and management of axSpA, recommendations were developed with current axSpA classification criteria and recent advances in medical imaging applications. METHODS: A systematic literature review was conducted by 10 rheumatologists and radiologists in Taiwan to retrieve research evidence on the utilization of imaging modalities, including conventional radiography (CR), magnetic resonance imaging (MRI), computed tomography (CT), ultrasound (US), quantitative sacroiliac scintigraphy (QSS), and dual-energy X-ray absorptiometry (DXA). The panel of experts proposed six key issues on the role of imaging in early diagnosis of axSpA, monitoring of disease activity and structural changes, predicting treatment effects, and assessing complications such as osteoporosis and spinal fracture. The consensus was established on the basis of research evidence, clinical experiences and expert opinions. For each recommendation statement, the level of evidence was evaluated, the strength of recommendation was graded and the final level of agreement was determined through voting. RESULTS: In total, four overarching principles and 13 recommendations were formulated. These recommendations outlined different imaging approaches in the diagnosis and management of axSpA disease progression. Considering CT is easy to perform when MRI is less available in Taiwan, the expert panel proposed a concise and practical diagnostic scheme to strengthen the valuable role of MRI and CT in the diagnostic evaluation of axSpA without evident radiographic features. CONCLUSION: These modified recommendations provide guidance for rheumatologists, radiologists and healthcare professionals on timely diagnosis of axSpA and disease management with appropriate imaging modalities.

Correlation of magnetic resonance imaging grades with cytokine levels of synovial fluid of patients with temporomandibular joint disorders: a cross-sectional study.

OBJECTIVES: Magnetic resonance imaging (MRI) is a standardized method for assisting joint diagnosis. To validate the reliability of different imaging-based grading systems, this study examined (1) the associations between grading systems for osseous change, joint effusion, and the Wilkes classification of temporomandibular joint (TMJ) disorders and (2) the correlation between cytokines in synovial fluid and imaging-based joint scores. MATERIALS AND METHODS: Twenty-seven patients, who routinely received numeric rating scale (NRS) and MRI assessment before TMJ arthrocentesis, were enrolled. Each joint was evaluated through the grading criteria for severity of osseous change and joint effusion by blinded observers using MRI. ImageJ was employed for classifying joint effusion. Joint synovial fluid, collected through arthrocentesis, was examined for cytokine expression by using a Luminex multiplex assay. All data were analyzed using the Pearson correlation analysis. RESULTS: The Wilkes classification was strongly correlated with osseous change scores, but not with joint effusion scores. Joint effusion scores significantly correlated with NRS scores, but not with the Wilkes classification and osseous change scores. Compared with osseous change scores, joint effusion scores had a higher correlation with the levels of inflammatory cytokines (interleukin (IL)-8 and soluble IL-6 receptor (sIL-6R)) and with anti-inflammatory cytokines (soluble tumor necrosis factor receptors I and II (sTNF-RI/II)). CONCLUSIONS: In patients with TMJ disorders, MRI grades are strongly correlated with NRS scores and levels of cytokines (IL-8, sIL-6R, and sTNF-RI/II) in the synovial fluid. CLINICAL RELEVANCE: Joint effusion scoring can be a reliable and valid indicator for pathological assessment of TMJ disorders.

Comparison of Tunnel Enlargement and Clinical Outcome Between Bioabsorbable Interference Screws and Cortical Button-Post Fixation in Arthroscopic Double-Bundle Anterior Cruciate Ligament Reconstruction: A Prospective, Randomized Study With a Minimum Follow-Up of 2 Years.

PURPOSE: To investigate the tunnel enlargement rate and clinical function by comparing double-bundle anterior cruciate ligament reconstruction (ACLR) using different fixation devices. METHODS: Patients receiving primary arthroscopic double-bundle ACLR were screened and divided into 2 groups on the basis of the method of graft fixation: bioabsorbable interference screw (BS) group and cortical button (CB) group. Bone tunnel size was assessed digitally using magnetic resonance imaging, which was performed a minimum of 2 years postoperatively. Clinical evaluations were performed using the Knee Injury and Osteoarthritis Outcome Score, International Knee Documentation Committee score, and KT-1000 arthrometer 2 years postoperatively. RESULTS: Sixty patients receiving primary arthroscopic double-bundle ACLR were included. Overall, the BS group showed greater tunnel enlargement than the CB group, as well as a significantly increased rate of tunnel communication (P = .029). The average anteromedial tunnel enlargement rates for the BS and CB groups were 50% and 28%, respectively. The enlargement rate of the posterolateral (PL) femoral tunnel was similar in both groups. In the PL tibial tunnel, the CB group showed a significant increase in enlargement compared with the BS group (64% vs 45%, P = .0001). Both groups showed functional improvement in the Knee Injury and Osteoarthritis Outcome Score and International Knee Documentation Committee score. No significant difference in postoperative functional outcomes was found between the 2 groups. CONCLUSIONS: The BS group showed significantly greater tunnel enlargement in anteromedial tunnels and an increased tunnel communication rate compared with the CB group. On the other hand, the CB group showed greater tunnel enlargement in tibial PL tunnels. Tunnel communication was observed mostly on the tibial side in the BS patients. Equivalent clinical function outcomes were noted at 2 years after surgery in both groups of patients. LEVEL OF EVIDENCE: Level II, randomized controlled clinical trial.

Can imaging distinguish between low-grade and dedifferentiated parosteal osteosarcoma?

BACKGROUND: Most instances of the parosteal osteosarcoma (OGS) are low-grade tumors. However, some parosteal OGSs undergo dedifferentiated transformation. Dedifferentiated parosteal OGS can cause distant metastasis and poor survival, and preoperative chemotherapy may be warranted. This study provides imaging clues for dedifferentiated parosteal OGS before treatment. METHODS: The study retrospectively enrolled 23 patients with histologically proven parosteal OGS, including 69.6% (n = 16) low-grade and 30.4% (n = 7) dedifferentiated types. Preoperative images including radiography and magnetic resonance imaging were reviewed. The following imaging parameters and clinical outcomes were evaluated: 1) average age; 2) sex; 3) tumor size; 4) presence of string sign; 5) necrosis; 6) hemorrhage; 7) solid soft tissue component; 8) perforating vessels; 9) ossification grade; 10) marginal ossification; 11) periosteal reaction; 12) sunburst reaction; 13) bone marrow edema; 14) bone marrow invasion; 15) perifocal soft tissue edema; 16) adjacent joint involvement; 17) adjacent neurovascular bundle compression; 18) regional lymph node; 19) bone metastasis; 20) preoperative lung metastasis; 21) follow-up lung metastasis; and 22) recurrence. RESULTS: The average maximal tumor sizes were 7.1 cm and 10.9 cm in low-grade and dedifferentiated types, respectively (p = 0.033). Sunburst periosteal reaction was visualized in two cases of low-grade type (12.5%) and four cases of the dedifferentiated type (57.1%) (p = 0.025) of parosteal OGS. None of our studied cases revealed preoperative lung metastasis. In the follow-up chest computed tomography, lung metastasis was noted in two cases of conventional type (14.2%), and four cases of dedifferentiated type (57.1%) (p = 0.040) of parosteal OGS. In receiver operating characteristic (ROC) curve analysis, the average tumor size and sunburst periosteal reaction showed good specificity (AUC = 0.070 and 0.072, respectively). CONCLUSION: Compared with low-grade types, dedifferentiated parosteal OGS exhibits a considerably larger tumor size, more sunburst periosteal reaction, and a more frequent development of lung metastasis in the disease course. Tumor size and sunburst periosteal reaction are the most crucial imaging diagnostic factors.

A recurrent WARS mutation is a novel cause of autosomal dominant distal hereditary motor neuropathy.

Distal hereditary motor neuropathy is a heterogeneous group of inherited neuropathies characterized by distal limb muscle weakness and atrophy. Although at least 15 genes have been implicated in distal hereditary motor neuropathy, the genetic causes remain elusive in many families. To identify an additional causal gene for distal hereditary motor neuropathy, we performed exome sequencing for two affected individuals and two unaffected members in a Taiwanese family with an autosomal dominant distal hereditary motor neuropathy in which mutations in common distal hereditary motor neuropathy-implicated genes had been excluded. The exome sequencing revealed a heterozygous mutation, c.770A > G (p.His257Arg), in the cytoplasmic tryptophanyl-tRNA synthetase (TrpRS) gene (WARS) that co-segregates with the neuropathy in the family. Further analyses of WARS in an additional 79 Taiwanese pedigrees with inherited neuropathies and 163 index cases from Australian, European, and Korean distal hereditary motor neuropathy families identified the same mutation in another Taiwanese distal hereditary motor neuropathy pedigree with different ancestries and one additional Belgian distal hereditary motor neuropathy family of Caucasian origin. Cell transfection studies demonstrated a dominant-negative effect of the p.His257Arg mutation on aminoacylation activity of TrpRS, which subsequently compromised protein synthesis and reduced cell viability. His257Arg TrpRS also inhibited neurite outgrowth and led to neurite degeneration in the neuronal cell lines and rat motor neurons. Further in vitro analyses showed that the WARS mutation could potentiate the angiostatic activities of TrpRS by enhancing its interaction with vascular endothelial-cadherin. Taken together, these findings establish WARS as a gene whose mutations may cause distal hereditary motor neuropathy and alter canonical and non-canonical functions of TrpRS.

Sonographic diagnosis of a glomus tumor of the thigh.

Extradigital glomus tumors are a very rare entity. Here, we report a rare case of a glomus tumor in an atypical anatomic site: the thigh. The clinical features together with the results of MRI, and sonography and Doppler sonographic imaging helped to distinguish glomus tumor of the thigh from other soft tissue neoplasms. The tumor arising from the thigh was excised, and following surgery, the patient was symptom free without evidence of complications or recurrence. There have only been a few previously reported cases describing the use of Doppler sonography in the evaluation of extradigital glomus tumors. © 2016 Wiley Periodicals, Inc. J Clin Ultrasound 45:50-52, 2017.

Outcomes of 50 Patients With Ewing Sarcoma Family of Tumors Treated at a Single Institution in Taiwan.

To identify the prognostic factors and long-term outcome of the Ewing sarcoma family of tumors (ESFT), data on 50 patients with ESFT treated at Taipei Veterans General Hospital between February 1991 and March 2014 were retrospectively considered. The influence of patient demographics, tumor features, and clinical and therapeutic parameters on overall survival (OS) and progression-free survival (PFS) rates were assessed. The results revealed that 21 of the 50 patients (42%) were metastatic at diagnosis. The median follow-up time was 1.8 years. The 5-year OS and PFS for patients who were nonmetastatic were 61.6% and 55.5%, respectively, and 18.8% and 15.4% for patients who were metastatic, respectively. The key adverse prognostic factor was metastasis at diagnosis. Radiotherapy for local control was associated with improved PFS. The high rate of primary metastasis and poorer outcomes of nonmetastatic ESFT compared with results from Western studies, along with previously reported low rates of ESFT in Taiwanese people, suggest that genetic factors play a role in the pathogenesis of ESFT and chemotherapy pharmacokinetics and pharmacodynamics. Radiotherapy in local treatment should be considered more aggressively in Taiwanese patients with ESFT.

Improvement in High-Grade Osteosarcoma Survival: Results from 202 Patients Treated at a Single Institution in Taiwan.

The aim of this study was to compare survival before and after 2004 and define the prognostic factors for high-grade osteosarcomas beyond those of typical young patients with localized extremity disease. Few studies have reported the long-term treatment outcomes of high-grade osteosarcoma in Taiwan. A total of 202 patients with primary high-grade osteosarcoma who received primary chemotherapy at Taipei Veterans General Hospital between January 1995 and December 2011 were retrospectively evaluated and compared by period (1995-2003 vs 2004-2011). Patients of all ages and tumor sites and those following or not following controlled protocols were included in analysis of demographic, tumor-related, and treatment-related variables and survival. Overall survival and progression-free survival at 5 years were, respectively, 67.7% and 48% for all patients (n = 202), 77.3% and 57.1% for patients without metastasis (n = 157), and 33.9% and 14.8% for patients with metastasis (n = 45). The survival rates of patients treated after 2004 were significantly higher (by 13%-16%) compared with those of patients treated before 2004, with an accompanying 30% increase in histological good response rate (P = .002). Factors significantly contributing to inferior survival in univariate and multivariate analyses were diagnosis before 2004, metastasis at diagnosis, and being a noncandidate for a controlled treatment protocol. By comparison with the regimens used at our institution before 2004, the current results support the effectiveness of the post-2004 regimens, which consisted of substantially reduced cycles of high-dose methotrexate and a higher dosage of ifosfamide per cycle, cisplatin, and doxorubicin, for treating high-grade osteosarcoma in Asian patients.

Experience of pediatric osteosarcoma of the extremity at a single institution in Taiwan: prognostic factors and impact on survival.

PURPOSE: To identify the prognostic factors and evaluate the impact of chemotherapy regimens on the outcomes of pediatric osteosarcoma of the extremities. METHODS: Patients younger than 18 years and diagnosed with high-grade osteosarcoma of the extremities during the period between January 2004 and December 2011 were included for retrospective analysis. Demographic characteristics and tumor features were compared between nonmetastatic and metastatic patients. Univariate analyses of overall survival (OS) and progression-free survival (PFS) were performed to evaluate the efficacy of various chemotherapy regimens. RESULTS: A total of 74 patients (58 with nonmetastatic and 16 with metastatic disease) were enrolled and treated with three protocols consisting of various cycles of high-dose methotrexate, adriamycin (doxorubicin), cisplatin, and high-dose ifosfamide (MACI regimens) during the 8-year study period. Presence of metastasis was inversely correlated with OS and PFS. Alkaline phosphatase levels at diagnosis and histologic response to preoperative chemotherapy were correlated with OS. Tumor size was correlated with PFS. The 5-year OS and PFS were 77 and 70 % for all patients, and 90.4 and 83.3 % for those with nonmetastatic osteosarcoma; and the rates were both 25 % in those with metastatic osteosarcoma. The chemotherapy regimens increased good response rates by 30 % and survival rates by 20 % compared to the outcomes in patients treated before 2004. CONCLUSIONS: Poor prognostic factors for osteosarcoma in pediatric patients were identified under homogeneous surgical and chemotherapy schemes. The four-drug regimens consisting of MACI contributed to the remarkably increased good response rates and consequent improvement in the survival rates.