Until now, rare disease studies have mainly been carried out by detecting simple variants such as single nucleotide substitutions and short insertions and deletions in protein-coding regions of disease-associated gene panels using diagnostic nextgeneration sequencing in association with patient phenotypes. However, several recent studies reported that the detection rate hardly exceeds 50% even when whole-exome sequencing is applied. Therefore, the necessity of introducing wholegenome sequencing is emerging to discover more diverse genomic variants and examine their association with rare diseases.When no diagnosis is provided by whole-genome sequencing, additional omics techniques such as RNA-seq also can be considered to further interrogate causal variants. This paper will introduce a description of these multi-omics techniques and their applications in rare disease studies.

PURPOSE: We tried to evaluate whether high resolution chest CT with a 1,024 matrix has a significant advantage in image quality compared to a 512 matrix. MATERIALS AND METHODS: Each set of 512 and 1024 matrix high resolution chest CT scans with both 0.625 mm and 1.25 mm slice thickness were obtained from 26 patients. Seventy locations that contained twenty-four low density lesions without sharp boundary such as emphysema, and forty-six sharp linear densities such as linear fibrosis were selected; these were randomly displayed on a five mega pixel LCD monitor. All the images were masked for information concerning the matrix size and slice thickness. Two chest radiologists scored the image quality of each arrowed lesion as follows: (1) undistinguishable, (2) poorly distinguishable, (3) fairly distinguishable, (4) well visible and (5) excellently visible. The scores were compared from the the aspects of matrix size, slice thickness and the different observers by using ANOVA tests. RESULTS: The average and standard deviation of image quality were 3.09 (+/-.92) for the 0.625 mmx512 matrix, 3.16 (+/-.84) for the 0.625 mmx1024 matrix, 2.49 (+/-1.02) for the 1.25 mmx512 matrix, and 2.35 (+/-1.02) for the 1.25 mmx1024 matrix, respectively. The image quality on both matrices of the high resolution chest CT scans with a 0.625 mm slice thickness was significantly better than that on the 1.25 mm slice thickness (p < 0.001). However, the image quality on the 1024 matrix high resolution chest CT scans was not significantly different from that on the 512 matrix high resolution chest CT scans (p = 0.678). The interobserver variation between the two observers was not significant (p = 0.691). CONCLUSION: We think that 1024 matrix image reconstruction for high resolution chest CT may not be clinically useful.
Emphysema ; Fibrosis ; Humans ; Image Processing, Computer-Assisted* ; Masks ; Observer Variation ; Thorax* ; Tomography, X-Ray Computed*

PURPOSE: To evaluate the usefulness and the application of three dimensional digital rotational imaging (3D DRI) by the evaluation of fractures. MATERIALS AND METHODS: Sixteen patients with clinically diagnosed or suspicious fracture were involved in this study. The lesion or suspicious sites of all 16 cases were spines (n=7), pelvis (n=3) and so on (n=6; knee, elbow, ankle, wrist and foot). In all cases, conventional radiography, multiplanar 2D (slice thickness/pitch=3 or 5 mm/1:1)and volume rendering 3D reconstructed single detector helical CT (HiSpeed Advantage, GE Medical Systems, Milwaukee, WIS) scans and 3D DRI (Integris V-5000,Philips Medical Systems, The Netherlands) with multiplanar intersection and gray scaling as postprocessing technique were performed. 3D DRI was evaluated and compared with conventional radiography, multiplanar 2D CT and volume rendering 3D CT. RESULTS: 3D DRI provided more detail and additional information in 14 cases (88%), comparing with 2D and 3D CT scans. Two fractures were revealed only on 3D DRI other than conventional radiography and CT scans and one case was revealed on 2D CT and 3D DRI. In all cases, we could acquired more detail and additional information from 3D DRI than from 3D CT in the acquisition of 3D imaging. 3D DRI didn't change the classification of fracture in 12 of 13 cases (92%),which revealed the fracture on the conventional radiography or CT. CONCLUSION: 3D DRI can diagnose and evaluate the fracture rapidly and easily with anatomical and spatial resolution by acquisition of 3D imaging with postprocessing using DRI.
Ankle ; Classification ; Elbow ; Humans ; Imaging, Three-Dimensional ; Knee ; Pelvis ; Radiography ; Spine ; Tomography, Spiral Computed ; Tomography, X-Ray Computed ; Wrist

Aspergillus is a ubiquitous fungus and can cause many levels of disease severity. Chronic necrotizing aspergillosis is a rare disease and few cases have been reported in Korea. We experienced a case of pleural aspergillosis that was treated successfully with medical and surgical interventions. The 52-year-old man who was diagnosed with chronic necrotizing pulmonary aspergillosis underwent surgical treatment including a lobectomy, decortication, and myoplasty. The patient was also medically treated with amphotericin B followed by voriconazole. Pleural irrigation with amphotericin B was also performed. A multi-dimensional approach should be considered for treating chronic necrotizing pulmonary aspergillosis.
Amphotericin B ; Aspergillosis ; Aspergillus ; Fungi ; Humans ; Invasive Pulmonary Aspergillosis ; Korea ; Middle Aged ; Pleural Diseases ; Pyrimidines ; Rare Diseases ; Triazoles

OBJECTIVE: To describe radiologic findings of adenovirus pneumonia and to understand clinico-radiological features associated with progression to acute respiratory distress syndrome (ARDS) in patients with adenovirus pneumonia. MATERIALS AND METHODS: This study included 19 patients diagnosed with adenovirus pneumonia at a tertiary referral center, in the period between March 2003 and April 2015. Clinical findings were reviewed, and two radiologists assessed imaging findings by consensus. Chi-square, Fisher's exact, and Student's t tests were used for comparing patients with and without subsequent development of ARDS. RESULTS: Of 19 patients, nine were immunocompromised, and 10 were immunocompetent. Twelve patients (63%) progressed to ARDS, six of whom (32%) eventually died from the disease. The average time for progression to ARDS from symptom onset was 9.6 days. Initial chest radiographic findings were normal (n = 2), focal opacity (n = 9), or multifocal or diffuse opacity (n = 8). Computed tomography (CT) findings included bilateral (n = 17) or unilateral (n = 2) ground-glass opacity with consolidation (n = 14) or pleural effusion (n = 11). Patients having subsequent ARDS had a higher probability of pleural effusion and a higher total CT extent compared with the non-ARDS group (p = 0.010 and 0.007, respectively). However, there were no significant differences in clinical variables such as patient age and premorbid condition. CONCLUSION: Adenovirus pneumonia demonstrates high rates of ARDS and mortality, regardless of patient age and premorbid conditions, in the tertiary care setting. Large disease extent and presence of pleural effusion on CT are factors suggestive of progression to ARDS.
Adenoviridae* ; Adult* ; Consensus ; Humans ; Mortality ; Pleural Effusion ; Pneumonia* ; Radiography, Thoracic ; Respiratory Distress Syndrome, Adult* ; Tertiary Care Centers ; Tertiary Healthcare

To determine overall detection rates of lung cancer by low-dose CT (LDCT) screening and to compare histopathologic and imaging differences of detected cancers between high- and low-risk groups, this study included 6,406 asymptomatic Korean adults with >or=45 yr of age who underwent LDCT for lung cancer screening. All were classified into high- (>or=20 pack-year smoking; 3,353) and low-risk (3,053; <20 pack-yr smoking and non-smokers) groups. We compared CT findings of detected cancers and detection rates between high- and low-risk. At initial CT, 35% (2,255 of 6,406) had at least one or more non-calcified nodule. Lung cancer detection rates were 0.36% (23 of 6,406). Twenty-one non-small cell lung cancers appeared as solid (n=14) or ground-glass opacity (GGO) (n=7) nodules. Cancer likelihood was higher in GGO nodules than in solid nodules (p<0.01). Fifteen of 23 cancers occurred in high-risk group and 8 in low-risk group (p=0.215). Therefore, LDCT screening help detect early stage of lung cancer in asymptomatic Korean population with detection rate of 0.36% on a population basis and may be useful for discovering early lung cancer in low-risk group as well as in high-risk group.
Adenocarcinoma/diagnosis ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung/diagnosis ; Carcinoma, Squamous Cell/diagnosis ; Comparative Study ; Female ; Humans ; Korea ; Lung Neoplasms/*diagnosis ; Male ; Mass Screening/*methods ; Middle Aged ; Risk Factors ; Tomography, X-Ray Computed/*methods

The main mechanism of evolution is that biological entities change, are selected, and reproduce. We propose a different concept in terms of the main agent or atom of evolution: in the biological world, not an individual object,but its interactive network is the fundamental unit of evolution. The interaction network is composed of interaction pairs of information objects that have order information. This indicates a paradigm shift from 3D biological objects to an abstract network of information entities as the primary agent of evolution. It forces us to change our views about how organisms evolve and therefore the methods we use to analyze evolution.

Phyllodes tumor of the breast is a relatively rare fibroepithelial tumor. Turner syndrome is a condition that affects approximately 50 per 100,000 females and includes total or partial absence of one X chromosome in all or part of the cells, reduced final height, absence of female sex hormone, and infertility. In this case report, we describe the first case of a benign phyllodes tumor mimicking a malignancy at breast US in a 26-year-old woman with Turner syndrome who had been undergoing hormone replacement therapy.
Adult ; Breast ; Female ; Hormone Replacement Therapy ; Humans ; Infertility ; Phyllodes Tumor ; Turner Syndrome ; X Chromosome

Purpose: Acute kidney injury (AKI) in cancer patients is associated with increased morbidity and mortality. The incidence of AKI in lung cancer seems to be relatively higher compared with other solid organ malignancies, although its impact on patient outcomes remains unclear. Materials and Methods: The patients newly diagnosed with lung cancer from 2004 to 2013 were enrolled in this retrospective cohort study. The patients were categorized according to the presence and severity of AKI. We compared all-cause mortality and long-term renal outcome according to AKI stage. Results: A total of 3,202 patients were included in the final analysis. AKI occurred in 1,783 (55.7%) patients during the follow-up period, with the majority having mild AKI stage 1 (75.8%). During the follow-up of 2.6±2.2 years, total 1,251 patients (53.7%) were died and 5-year survival rate was 46.9%. We found that both AKI development and severity were independent risk factors for all-cause mortality in lung cancer patients, even after adjustment for lung cancer-specific variables including the stage or pathological type. In addition, patients suffered from more severe AKI tend to encounter de novo chronic kidney disease development, worsening kidney function, and end-stage kidney disease progression. Conclusion In this study, more than half of the lung cancer patients experienced AKI during their diagnosis and treatment period. Moreover, AKI occurrence and more advanced AKI were associated with a higher mortality risk and adverse kidney outcomes.

Background: Early identification of patients with coronavirus disease 2019 (COVID-19) who are at high risk of mortality is of vital importance for appropriate clinical decision making and delivering optimal treatment. We aimed to develop and validate a clinical risk score for predicting mortality at the time of admission of patients hospitalized with COVID-19. Methods: Collaborating with the Korea Centers for Disease Control and Prevention (KCDC), we established a prospective consecutive cohort of 5,628 patients with confirmed COVID-19 infection who were admitted to 120 hospitals in Korea between January 20, 2020, and April 30, 2020. The cohort was randomly divided using a 7:3 ratio into a development (n = 3,940) and validation (n = 1,688) set. Clinical information and complete blood count (CBC) detected at admission were investigated using Least Absolute Shrinkage and Selection Operator (LASSO) and logistic regression to construct a predictive risk score (COVID-Mortality Score).The discriminative power of the risk model was assessed by calculating the area under the curve (AUC) of the receiver operating characteristic curves. Results: The incidence of mortality was 4.3% in both the development and validation set.A COVID-Mortality Score consisting of age, sex, body mass index, combined comorbidity, clinical symptoms, and CBC was developed. AUCs of the scoring system were 0.96 (95% confidence interval [CI], 0.85–0.91) and 0.97 (95% CI, 0.84–0.93) in the development and validation set, respectively. If the model was optimized for > 90% sensitivity, accuracies were 81.0% and 80.2% with sensitivities of 91.7% and 86.1% in the development and validation set, respectively. The optimized scoring system has been applied to the public online risk calculator (https://www.diseaseriskscore.com). Conclusion This clinically developed and validated COVID-Mortality Score, using clinical data available at the time of admission, will aid clinicians in predicting in-hospital mortality.