A Functional Polymorphism Downstream of Vitamin A Regulator Gene CYP26B1 Is Associated with Hand Osteoarthritis.

While genetic analyses have revealed ~100 risk loci associated with osteoarthritis (OA), only eight have been linked to hand OA. Besides, these studies were performed in predominantly European and Caucasian ancestries. Here, we conducted a genome-wide association study in the Han Chinese population to identify genetic variations associated with the disease. We recruited a total of 1136 individuals (n = 420 hand OA-affected; n = 716 unaffected control subjects) of Han Chinese ancestry. We carried out genotyping using Axiom Asia Precisi on Medicine Research Array, and we employed the RegulomeDB database and RoadMap DNase I Hypersensitivity Sites annotations to further narrow down our potential candidate variants. Genetic variants identified were tested in the Geisinger's hand OA cohort selected from the Geisinger MyCode community health initiative (MyCode®). We also performed a luciferase reporter assay to confirm the potential impact of top candidate single-nucleotide polymorphisms (SNPs) on hand OA. We identified six associated SNPs (p-value = 6.76 × 10-7-7.31 × 10-6) clustered at 2p13.2 downstream of the CYP26B1 gene. The strongest association signal identified was rs883313 (p-value = 6.76 × 10-7, odds ratio (OR) = 1.76), followed by rs12713768 (p-value = 1.36 × 10-6, OR = 1.74), near or within the enhancer region closest to the CYP26B1 gene. Our findings showed that the major risk-conferring CC haplotype of SNPs rs12713768 and rs10208040 [strong linkage disequilibrium (LD); D' = 1, r2 = 0.651] drives 18.9% of enhancer expression activity. Our findings highlight that the SNP rs12713768 is associated with susceptibility to and severity of hand OA in the Han Chinese population and that the suggested retinoic acid signaling pathway may play an important role in its pathogenesis.

Shoulder joint synovial chondromatosis presenting as multiple axillary masses: A case report.

Synovial chondromatosis is a rare, benign, proliferative cartilaginous lesion arising from the synovial tissue, tenosynovium, or bursal lining. We describe the case of a patient who initially presented with multiple axillary masses. Breast ultrasound (US) was requested due to the concern of a breast tumor with axillary lymph node metastases. US study was helpful and provided adequate information to suggest the diagnosis.

Complications during CT-Guided Lung Nodule Localization: Impact of Needle Insertion Depth and Patient Characteristics.

Although widely used, CT-guided lung nodule localization is associated with a significant risk of complications, including pneumothorax and pulmonary hemorrhage. This study identified potential risk factors affecting the complications associated with CT-guided lung nodule localization. Data from patients with lung nodules who underwent preoperative CT-guided localization with patent blue vital (PBV) dye at Shin Kong Wu Ho-Su Memorial Hospital, Taiwan, were retrospectively collected. Logistic regression analysis, the chi-square test, and the Mann-Whitney test were used to analyze the potential risk factors for procedure-related complications. We included 101 patients with a single nodule (49 with pneumothorax and 28 with pulmonary hemorrhage). The results revealed that men were more susceptible to pneumothorax during CT-guided localization (odds ratio: 2.48, p = 0.04). Both deeper needle insertion depth (odds ratio: 1.84, p = 0.02) and nodules localized in the left lung lobe (odds ratio: 4.19, p = 0.03) were associated with an increased risk of pulmonary hemorrhage during CT-guided localization. In conclusion, for patients with a single nodule, considering the needle insertion depth and patient characteristics during CT-guided localization procedures is probably important for reducing the risk of complications.

A mutation in cartilage oligomeric matrix protein (COMP) causes early-onset osteoarthritis in a large kindred study.

We performed a genome-wide linkage analysis to identify susceptibility loci in a large six-generation extended family previously reported with early-onset osteoarthritis (OA) DNA sequencing was performed to investigate involvement of the COMP (Cartilage oligomeric matrix protein) gene in this family. The region covering D19S884, D19S226, and D19S414 on chromosome 19p following genome-wide scan from 70 individuals of this kindred showed significant linkage, with a maximum point LOD (logarithm of the odds ratio) score of 2.51 at D19S226. Direct sequencing of the COMP gene, the most plausible candidate gene in the region, identified a c.2152C>T substitution in exon 18 which resulted in a substitution of tryptophan for arginine at position 718 located in the C terminal globular domain of the gene product. A total of 26 individuals were identified with this mutation of which 21 affected individuals had the mutation, and the other five younger individuals (18.6 ± 11.3 years of age) carried the mutation without symptoms. The results indicate that COMP is the disease susceptibility gene and the c.2152C>T mutation in exon 18 could cause early-onset OA phenotypes in this kindred, which is compatible with a previous report that this mutation also causes a mild form of multiple epiphyseal dysplasia (MED).

Single institute experience of intraoperative radiation therapy in early-stage breast cancer.

ABSTRACT: Intraoperative radiation therapy (IORT) is an alternative to whole breast irradiation in selected early-stage breast cancer patients. In this single institute analysis, we report the preliminary results of IORT given by Axxent Electronic Brachytherapy (eBT) system.Patients treated with lumpectomy and eBT within a minimum follow-up period of 12 months were analyzed. Eligible criteria include being over the age of 45, having unifocal invasive ductal carcinoma (IDC) or ductal carcinoma in situ <3 cm in diameter, not exhibiting lymph node involvement on preoperative images, and negative sentinel lymph node biopsy. The eBT was given by preloaded radiation plans to deliver a single fraction of 20 Gray (Gy) right after lumpectomy.From January 2016 to April 2019, a total of 103 patients were collected. There were 78 patients with IDC and 25 with ductal carcinoma in situ. At a mean follow-up time of 31.1 months (range, 14.5-54.0 months), the local control rate was 98.1%. Two IDC patients had tumor recurrences (1 local and 1 regional failure). Post-IORT radiotherapy was given to 4 patients. There were no cancer related deaths, no distant metastases, and treatment side effects greater than grade 3 documented.We report the largest single institute analysis using the eBT system in Taiwan. The low recurrence and complication rates at a 31.1 month follow-up time support the use of the eBT system in selected early-stage breast cancer patients.

A large kindred of early-onset osteoarthritis of the knee and hip: excluding the link to COL2A1 gene.

OBJECTIVES: To characterize a large extended family with early-onset OA of the knee and investigate its associations with the COL2A1 gene. METHODS: Phenotype assessments were conducted in a six-generation family to identify individuals affected with OA. Short tandem repeat polymorphic (STRP) markers and DNA sequencing were performed to investigate the involvement of the COL2A1 gene in this family. RESULTS: The kindred affected with OA showed autosomal dominant inheritance. The mean age of onset was 37.3 +/- 19.2, 29.8 +/- 13.7 and 12.0 +/- 7.2 years for generations IV, V and VI, respectively, and 25 +/- 16.1 years for males and 34.3 +/- 15.5 years for females. The height of the affected males was shorter than the unaffected males (155.9 +/- 11.4 vs 164.5 +/- 16.0 cm, P = 0.010). Arm span in the affected males was also significantly shorter than the unaffected males (158.4 +/- 12.5 vs 165.3 +/- 16.7 cm, P = 0.027). However, both height and arm span were not reduced in the affected female OA patients. STRP markers surrounding COL2A1 locus did not show linkage of the COL2A1 locus with the OA. Sequencing of COL2A1 gene revealed three single nucleotide polymorphisms but no mutation was found in the affected patients. CONCLUSIONS: The COL2A1 was not a susceptibility gene responsible for the OA phenotype in a large extended kindred with familial early-onset OA. The availability of DNA samples will allow genome-wide linkage study to identify the susceptibility locus.

Fingerprint verification on medical image reporting system.

The healthcare industry is recently going through extensive changes, through adoption of robust, interoperable healthcare information technology by means of electronic medical records (EMR). However, a major concern of EMR is adequate confidentiality of the individual records being managed electronically. Multiple access points over an open network like the Internet increases possible patient data interception. The obligation is on healthcare providers to procure information security solutions that do not hamper patient care while still providing the confidentiality of patient information. Medical images are also part of the EMR which need to be protected from unauthorized users. This study integrates the techniques of fingerprint verification, DICOM object, digital signature and digital envelope in order to ensure that access to the hospital Picture Archiving and Communication System (PACS) or radiology information system (RIS) is only by certified parties.

Successful Transarterial Embolization of Uterine Arteriovenous Malformation: Report of Three Cases.

Uterine arteriovenous malformations (AVMs) are relatively rare disorders that can cause life-threatening vaginal bleeding. We describe three childbearing-age females, who had abdominal pain and heavy vaginal bleeding, and were diagnosed as uterine AVM by color Doppler and angiography. The patients received successful superselective transarterial embolization (TAE) with N-butyl cyanoacrylate (NBCA). Three years after treatment, one of them was admitted to our hospital for vaginal delivery at 39 weeks of gestation, and the baby was healthy.

Surgical treatment of fractures of the greater trochanter associated with osteolytic lesions.

BACKGROUND: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component. METHODS: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score. RESULTS: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination. CONCLUSIONS: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting.

Application of PET and PEt/CT imaging for cancer screening.

The aim of this study was to evaluate the potential application of 18-fluorodeoxyglucose positron emission tomography (FDG PET) and PET/CT for cancer screening in asymptomatic individuals. The subjects consisted of 3631 physical check-up examinees (1947 men, 1684 women; mean age +/- SD, 52.1 +/- 8.2 y) with non-specific medical histories. Whole-body FDG PET (or PET/CT), ultrasound and tumor markers were performed on all patients. Focal hypermetabolic areas with intensities equal to or exceeding the level of FDG uptake in the brain were considered abnormal and interpreted as neoplasia. Follow-up periods were longer than one year. Among the 3631 FDG PET (including 1687 PET/CT), ultrasound and tumor markers examinations, malignant tumors were discovered in 47 examinees (1.29%). PET findings were true-positive in 38 of the 47 cancers (80.9%). In addition, 32 of the 47 cancers were screened with the PET/CT scan. PET detected cancer lesions in 28 of the 32 examinees. However, the CT detected cancer lesions in only 15 out of 32 examinees. The sensitivity of FDG PET in the detection of a wide variety of cancers is high. Most cancer can be detected with FDG PET at a resectable stage. CT of the PET/CT for localization and characteristics of the lesion showed an increased specificity of the PET scan. The use of ultrasound and tumor markers may complement the PET scan in cancer screening for hepatic and urologic neoplasms.

Disseminated cryptococcosis with pulmonary and marrow involvement mimicking radiological features of malignancy.

The most commonly involved sites of cryptococcosis are the lungs and the central nervous system. Cryptococcal osteomyelitis is a rare complication of disseminated cryptococcosis, and the vertebraes are the most common site of this infection. The most common underlying disease is sarcoidosis, followed by tuberculosis and previous steroid therapy. Conservative treatment alone or treatment with a combination of the medical and surgical curettage is successful in most cases. We report a case of cryptococcal osteomyelitis in a 63-year-old immunocompetent male who presented with lower back pain over the sacral region for several years. Radiologic studies showed a pulmonary mass and a radiolytic lesion involving the left ischial bone, which mimicked pulmonary malignancy with bone metastasis. Biopsy of the lung mass and the bone lesion revealed abundant cryptococcal organisms, and cryptococcal osteomyelitis was diagnosed.

Onyx embolization of a lingual arteriovenous malformation.

Head and neck arteriovenous malformations (AVMs), including lingual AVMs, are unusual and rare. There are many treatment options including sclerotherapy, endovascular or percutaneous embolization, and surgical excision. A combination of preoperative embolization and surgical resection is commonly used for head and neck AVMs. However, in most cases, surgical resection causes significant morbidity. Single-modality approaches such as transarterial embolization are sometimes performed. Herein, we used the copolymer Onyx (ethylene-vinyl alcohol copolymer) as an embolizing agent and obtained satisfactory therapeutic outcomes. To our knowledge, this is the first report of lingual AVMs treated using Onyx embolization.

Evaluation of the screening power of Cognitive Abilities Screening Instrument for probable Alzheimer's disease using voxel-based morphometry.

OBJECTIVE: The aim of this study was to compare two screening methods, total score of the Cognitive Abilities Screening Instrument (CASI(T)) and the combined score for the short-term memory and orientation domains (CASI(R)) for screening and grading probable Alzheimer's disease (AD), based on their correlations with voxel-based morphometry (VBM). MATERIALS AND METHODS: Forty-five subjects with probable AD and normal controls underwent magnetic resonance imaging and CASI testing. Their corresponding T1-weighted magnetic resonance images were analyzed using VBM. RESULTS: VBM results showed that in moderate-to-severe AD subgroups, significant whole-brain gray matter loss was detected using both CASI(T) and CASI(R). Significantly more voxels were detected using the CASI(T) compared with the CASI(R) system in mild AD subjects (P<.05). CONCLUSIONS: Based on their correlations with VBM results, there is no significant difference for CASI(R) and CASI(T) for grading moderate-to-severe AD subgroups, and CASI(R) scoring system may be more accurate and effective than the CASI(T) for screening mild AD.

Potential dose reduction of optimal ECG-controlled tube current modulation for 256-slice CT coronary angiography.

RATIONALE AND OBJECTIVES: The purpose of this study was to design an optimized heart rate (HR)-dependent electrocardiogram (ECG) pulsing protocol for computed tomography coronary angiography (CTCA) on a 256-slice CT scanner and to assess its potential dose reduction retrospectively, based on the retrospective ECG gating data without dose modulation. MATERIALS AND METHODS: A total of 137 patients were enrolled to perform CTCA with a 256-slice scanner. Two independent radiologists graded image quality of coronary artery segments (1 = excellent, no motion artifacts; 4 = poor, severe motion artifacts) to define optimal reconstruction window in end-systolic phase, mid-diastolic phase, and the combination of both cardiac phases. According to statistical analysis for HR against image quality, four HR-depended ECG-pulsing protocols were proposed. We also demonstrated the potential dose reduction of the proposed technique. RESULTS: For patients with HR <59 beats/min (group 1), 60-72 beats/min (group 2), 73-84 beats/min (group 3), and >85 beats/min (group 4), the optimal reconstruction windows were at 74.1-81.3%, 73.4-82.2%, 38.3-82.3%, and 37.2-61.6% of R-R interval, respectively. The ECG-pulsing protocols with minimal radiation dose (ie, no tube current outside the pulsing window) can reduce the effective dose of CTCA by 79.5%, 75.7%, 38.3%, and 57.4% for HR groups 1 to 4, respectively. The corresponding results for reducing tube current by 80% outside the pulsing window were 63.7%, 56.6%, 32.0%, and 46.0%. CONCLUSION: Through the optimization of ECG-pulsed tube-current modulation, radiation exposure can be greatly reduced, especially in patients with HR <72 beats/min or >85 beats/min.

Retrospective gating vs. prospective triggering for noninvasive coronary angiography: Assessment of image quality and radiation dose using a 256-slice CT scanner with 270 ms gantry rotation.

OBJECTIVE: To report our clinical experience with a 256-slice multidetector computed tomography (MDCT) with a 270-ms gantry rotation system in performing CT coronary angiograms (CTCA) using both prospectively gated step and shoot (PGSS) and retrospectively gated helical (RGH) techniques. MATERIALS AND METHODS: We studied 252 patients who received CTCA; 126 patients having mean heart rate (HR) of 72.1 were imaged with RGH CTCA and 126 patients having mean HR of 58.7 were imaged with PGSS CTCA. For patients with a prescan HR ≤70 beats/min, a PGSS acquisitions trigger was used, whereas patients whose prescan HR was >70 beats/min were imaged using an RGH acquisition. The blood vessel accessibility of both PGSS and RGH techniques was evaluated by grading the image quality score from 1 (no motion artifacts) to 4 (severe motion artifacts preventing diagnosis) for each coronary artery segment. Radiation doses of the techniques were also compared. RESULTS: In both groups, more than 50% of segments received the best imaging score. The overall image quality scores for RGH and PGSS groups were 1.522 ± 0.317 and 1.500 ± 0.374, respectively. There was no significant difference in right coronary artery, left anterior descending artery, and left circumflex artery image quality between the two groups. Only 0.1% of segments were nonevaluative with the PGSS technique and all segments were evaluative with RGH. PGSS was associated with a 62% reduction in effective radiation dose as compared to RGH (PGSS, 5.1 mSv; RGH, 13.2 mSv). CONCLUSIONS: There is no significant difference in image quality between PGSS and RGH in this study. Although providing similar image quality as RGH, PGSS was associated with a 62% reduction in effective radiation dose. Further study to confirm the diagnostic accuracy as compared to coronary artery angiography is warranted.

Optimal systolic and diastolic image reconstruction windows for coronary 256-slice CT angiography.

RATIONALE AND OBJECTIVES: The aims of this study were to determine the optimal image reconstruction intervals for the systolic and diastolic phases of coronary computed tomographic angiography on 256-slice computed tomography and to assess their associated motion artifacts. MATERIALS AND METHODS: One hundred twenty-six patients were recruited (mean heart rate [HR], 72.1 beats/min; heart rate variability, 1.3 beats/min). Twenty data sets were reconstructed in 5% steps through 0% to 95% of the R-R interval. Two reviewers discriminated optimal reconstruction intervals for 15 segments distributed in three coronary arteries on the basis of motion artifacts, which were graded from 1 (no motion artifacts) to 4 (severe motion artifacts preventing diagnosis). Patients were then stratified into four HR groups for motion score comparison according to the results of a correlation analysis of HR and motion scores. RESULTS: The optimal systolic and diastolic reconstruction intervals were 44.4 ± 3.8% and 77.4 ± 3.7%, respectively. The mean motion scores for systolic, diastolic, and combined systolic and diastolic (S+D) reconstructions were 1.8 ± 0.3, 1.8 ± 0.5, and 1.5 ± 0.3, respectively. Combined S+D reconstruction improved diagnostic evaluability to 100% and showed fewer motion artifacts compared to single-phase reconstructions for all HR ranges (S+D vs systolic, P < .05 for HR < 85 beats/min; S+D vs diastolic, P < .05 for HRs of 73-84 beats/min). For HRs of 60 to 72 beats/min, motion artifacts were significantly lower for diastole (1.6 ± 0.3) than systole (1.8 ± 0.4) (P < .001), and vice versa for HRs of 73 to 84 beats/min (1.7 ± 0.3 for systole vs 2.0 ± 0.5 for diastole, P < .01). CONCLUSIONS: Optimal systolic and diastolic reconstruction intervals were determined for this 256-slice coronary computed tomographic angiographic study. Combined reconstruction showed fewer motion artifacts compared to single-phase reconstruction. In conclusion, 256-slice computed tomography has the potential to improve the diagnostic accuracy of coronary computed tomographic angiography.

High-resolution gel dosimetry using flat-panel detector cone-beam computed tomography: preliminary study.

This study compares the dose response of irradiated polymer gel with acrylic and styrofoam housing while applying multi-detector CT (MDCT) and cone-beam CT (CBCT). The dose response for MDCT and CBCT, while using an acrylic phantom is 1.34 and 0.67 DeltaHU Gy(-1), respectively, and becomes 1.54 and 0.84 DeltaHU Gy(-1) while using styrofoam, suggesting styrofoam is the better housing material. While the dose response of MDCT is better than that of CBCT, CBCT is yet a promising 3D dosimetry technique, given its potentially better spatial resolution and sensitive dose interpretation capability.

Surgical treatment of fractures of the greater trochanter associated with osteolytic lesions. Surgical technique.

BACKGROUND: A fracture of the greater trochanter through an osteolytic lesion may occur as a late complication after total hip arthroplasty. The optimal treatment for this difficult complication remains controversial. We have treated this problem with internal fixation and allogeneic bone-grafting at the time of revision of a loose acetabular component. METHODS: We retrospectively reviewed the results of treatment of a fracture through an osteolytic lesion of the greater trochanter in nineteen patients seen from 1996 to 2002. All fractures were treated with morselized allogeneic bone grafts and wire fixation at the time of revision of a failed acetabular component. Postoperative care included the use of an abduction orthosis and protected weight-bearing for at least three months. Follow-up of all patients consisted of radiographic examinations and clinical evaluation with use of the Harris hip score. RESULTS: At an average duration of 3.8 years after the revision, eighteen of the nineteen fractures had healed. The average time to healing was five months. The one treatment failure occurred in a patient who did not comply with the use of an abduction orthosis. The average Harris hip score for all patients improved from 32.5 points preoperatively to 91.2 points at the time of the latest follow-up. Polyethylene wear and recurrent osteolysis of the greater trochanter was noted in one hip at the eight-year follow-up examination. CONCLUSIONS: Fractures of the greater trochanter associated with osteolytic lesions can be effectively treated with open reduction, internal fixation with wire, and allogeneic bone-grafting.