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.

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.

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.

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.

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.

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.

Incidence patterns of primary bone cancer in taiwan (2003-2010): a population-based study.

BACKGROUND: Primary bone cancer (BC) incidence by age has not been surveyed in Asia. METHODS: The incidence patterns of nine subtypes of primary BCs registered between 2003 and 2010 were analyzed from Taiwan cancer registry data. More specific analyses were conducted within age groups (Group I: 0-24 years; Group II: 25-59 years; and Group III: 60-85+ years). RESULTS: A total of 1,238 newly diagnosed subjects were registered with an age-standardized incidence rate (ASR) of 6.70 per million person-years. Overall, osteosarcoma (OS: 45 %) was the most common, followed by chondrosarcoma (CS: 18 %), and Ewing sarcoma (ES: 8 %). The percentages of cases and ASRs for age groups I, II, and III were 36.3, 43.0, and 20.7 %, and 7.00, 5.48, and 10.28 per million, respectively. Significant male predilections were observed for all BCs combined, and the CS, chordoma, and malignant ameloblastoma subtypes. Our findings demonstrated an upward trend of 4.8 % per year over the study period, and was more significant for females (6.7 %). A significant increase in trend existed in the incidence of BC among females in Group II, and the incidence of OS and ES among females in Group I. CONCLUSIONS: This population-based study has allowed us to confidently define the incidence rates among three age groups of Taiwanese. Despite overall low rates, the upward trend in BC incidence among females may invoke a concern. The results suggest areas for further study into the underlying causes for these cancer trends.

Follow-up after primary treatment of soft tissue sarcoma of extremities: impact of frequency of follow-up imaging on disease-specific survival.

BACKGROUND AND OBJECTIVES: We explored the impact of frequency of surveillance imaging on disease-specific survival (DSS) in patients with extremity soft tissue sarcoma (STS). METHODS: Locoregional imaging (LRI) and chest imaging (CI) were used to detect local recurrence (LR) and distant metastasis (DM), respectively. Relapsing patients were retrospectively assigned to more frequent surveillance (MFS) or less frequent surveillance (LFS) groups, according to the median interval for each follow-up modality. Outcome measures included overall DSS (O-DSS), post-LR DSS, and post-DM DSS. RESULTS: We assigned 165 patients to three distinct risk groups according to tumor size (≤5 vs. >5 cm), depth (superficial- vs. deep-seated), grade (I vs. II or III), and surgical margin (≥10 vs. <10 mm). Data for 80 patients who relapsed were analyzed. Among 50 high-risk (with all four risk factors) relapsing patients, those in the MFS group for either LRI or CI had better O-DSS (LRI, median 44.07 vs. 27.43 months, P = 0.008; CI, median 43.60 vs. 36.93 months, P = 0.036), post-LR DSS (median 27.20 vs. 10.63 months, P = 0.028) and post-DM DSS (median 13.20 vs. 6.24 months, P = 0.031). CONCLUSION: More frequent follow-up were associated with improved survival in high-risk relapsing patients with extremity STS by providing greater opportunities for adequate reoperation.

Brain, the last fortress of sarcoma: similar dismal outcome but discrepancy of timing of brain metastasis in bone and soft tissue sarcoma.

BACKGROUND AND OBJECTIVE: Brain metastasis is a rare but dismal event in sarcomas. However, the pattern of occurrence and the prognostic factors associated with post-brain metastasis survival (PBMS) are not yet well-characterized. METHODS: Sarcoma patients treated at one institute within 10-year period were retrospectively reviewed and those with brain metastasis were identified. The incidence of brain metastasis was demonstrated by case per person-years and cumulative incidence curves. Univariate factors associated with PBMS were analyzed. RESULTS: Among 611 sarcoma patients, 20 (3.3%) developed brain metastasis. Alveolar soft part sarcoma (ASPS) and osteosarcoma were the most common subtypes. Overall, the cumulative incidence was 3.9% at 5 years and 8.4% at 10 years. However, the incidence in STS patients continued to rise up to 10 years after primary diagnosis, whereas it reached a plateau in bone sarcoma patients at 3 years. Median PBMS was 1.67 months. Univariate factors associated with better PBMS included ASPS histology, initial surgical treatment, and brain irradiation for non-surgically treated patients. CONCLUSION: Our study revealed a discrepancy in the timing of occurrence of brain metastasis between STS and bone sarcoma. However, patients with brain metastasis had a poor prognosis, implicating the brain as the last fortress of sarcoma.

Soft tissue sarcoma of extremities: the prognostic significance of adequate surgical margins in primary operation and reoperation after recurrence.

BACKGROUND: Adult soft tissue sarcomas (STS) of extremities are prone to recurrence despite apparently complete resection. This study aimed to explore the impact of clinicopathological factors on outcome and to define an "oncological safe margin" in these patients. METHODS: A total of 181 patients with extremity STS were enrolled in a retrospective study. The prognostic influence of margin status and other clinicopathological characteristics on local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), and disease-specific survival (DSS), were examined by univariate and multivariate analyses. The influence of surgical margins on postrecurrence survival (PRS) of patients undergoing reoperation for relapsed lesions during follow-up was analyzed by the Kaplan-Meier method. RESULTS: Surgical margin width <10 mm and deep tumor depth at primary operation were consistently statistically significant independent adverse factors for LRFS, DMFS, and DSS. Patients with liposarcoma or low grade tumors had significantly higher chances of achieving adequate margins. Of 83 patients who experienced recurrence or metastasis, 53 (63.9%) received reoperation for their relapsed lesions. Patients who achieved microscopically negative margins (R0) at reoperation had significantly better PRS than those who did not (P < 0.007). Overall, patients with no recurrences had the best DSS, while relapsed patients receiving R0 reoperation had better DSS than those receiving either non-R0 reoperation or no reoperation at all. CONCLUSION: Surgical margins prognostically influence survival in both patients undergoing primary surgery and those undergoing reoperation for relapse of extremity STS. In primary surgery, the chance of achieving adequate margin may reflect the underlying aggressiveness of tumors.

Identification of chromosomal aberrations associated with disease progression and a novel 3q13.31 deletion involving LSAMP gene in osteosarcoma.

Five osteosarcoma (OS) cell lines, 37 OS tumors and 9 corresponding non-neoplastic samples were genotyped by Affymetrix 10 K 2.0 SNP array. Regions of high level amplification and homozygous deletion were identified and validated by quantitative PCR and FISH. Certain recurrent cytogenetic alterations were more frequent in recurrent/metastatic than in primary OS. These included deletion of 6q14.1, 6q16.2-q22.31, and 8p23.2-p12, amplification of 8q21.12, 8q22.3-q24.3 and 17p12, and loss of heterozygosity (LOH) at 2q24.3-q31.2, 5q11.2, 6p21.31-p21.1, 6q14.1-q16.2, 8p22-p12, 9q22.1, 10q21.1-q22.1, 10q23.31-q24.1, 12q15-q21.1 and 21q21.2-q21.3. Most of the LOH calls were associated with deletion, but a subset of them was associated with normal or increased copy number (CN). A consensus 3q13.31 deletion localized to a region within the limbic system-associated membrane protein (LSAMP) gene was also identified. The FISH evaluations demonstrated highly-localized homozygous or heterozygous LSAMP deletions in 6 of 11 primary OS. qRT-PCR evaluations of the two major alternative LSAMP transcripts demonstrated reduced expression of 1b isoform transcript in each of three OS with LSAMP exon 1b deletion. Further, the 1a isoform transcripts in these same OS had either reduced expression or a premature termination codon in LSAMP exon 2. This SNP genotyping study identified chromosomal aberrations associated with disease progression in OS and disclosed LSAMP as a novel tumor suppressor gene in OS. The study also demonstrated that CN and LOH analyses were able to detect distinct subsets of genetic abnormalities in OS.

Ultrasonographic and MR findings of alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare soft-tissue sarcoma, commonly occurring in children and adolescents. The tumor mostly involves the lower extremities. The prognosis of the patient depends on whether there is metastasis. We present a 19-year-old female with ASPS in her right lower leg. Grayscale and color Doppler ultrasound showed a well-defined hypoechoic lesion with hypervascularity and very low resistive index (RI). Magnetic resonance imaging revealed iso signal intensity to muscle on T1-weighted images, high signal intensity to muscle on T2-weighted images with signal voids, and good enhancement after gadolinium administration. In a mass with hypervascularity and very low RI on sonography and hypervascularity with flow voids on magnetic resonance imaging, ASPS should be considered.

Imaging evaluation of meniscal injury of the knee joint: a comparative MR imaging and arthroscopic study.

To evaluate the efficacy of MR imaging in the diagnosis and classification of meniscal tear of the knee joint, we retrospectively characterized the MR features of 78 meniscal tears in 148 patients according to the Mesgarzadeh's criteria. The results showed that the sensitivity and specificity for meniscal tears were 92% and 87%, respectively. Type VI meniscal tear was the most common type, especially in displaced meniscal tear. MR is a reliable diagnostic tool for meniscal tears and associated cruciate ligament injury.

Do we get a "real" alignment of knee in the preoperative planning of high tibia osteotomy: a prospective study of reproducibility.

BACKGROUND: Precise preoperative measurement of knee alignment is needed to calculate the accurate angle of correction at proximal tibia osteotomy for medial gonarthrosis. METHODS: We performed a prospective study to compare the reproducibility of measuring the mechanical and anatomical axes. Thirty-two patients (32 knees) with medial compartment osteoarthritis to be treated with proximal tibia osteotomy were included in this study. Preoperatively, whole lower limb roentgenographs were obtained twice, and 2 independent radiologists measured the mechanical and anatomical axes from each roentgenograph. RESULTS: Measurement of mechanical and anatomical axes had a mean variability of 2.22 and 1.88 degrees, respectively, which was not statistically significant (p = 0.267) in the assessment of reproducibility. With the anatomic axis, however, we found 0.61 degree of variability to the roentgenographic procedures and 1.30 degree to the radiologists (p = 0.007). With the mechanical axis, the corresponding findings were 1.30 degree and 1.02 degree (p = 0.167). Despite the relative small number of patients in this series, errors in measurement of the anatomical axis seem mostly to originate from different radiologists, whereas errors in measurement of the mechanical axis seem to originate from both the radiologists and the procedures. The maximum variability in measuring both axes was 3 degrees, which is highly significant for a reliable calculation of the wedge when performing proximal tibia osteotomy. CONCLUSIONS: We suggest that, for accuracy and economy, measurement of the anatomical axis might be better. Furthermore, by measuring either mechanical or anatomical axis, the errors originating from roentgenographic measurement of knee alignment should be considered in preoperative planning.