Background/Aims: To compare the effects of abatacept and conventional synthetic disease modifying anti-rheumatic drugs (csDMARDs) on the progression and development of rheumatoid arthritis-associated interstitial lung disease (RA-ILD). Methods: This multi-center retrospective study included RA patients receiving abatacept or csDMARDs who underwent at least two pulmonary function tests and/or chest high-resolution computed tomography (HRCT). We compared the following outcomes between the groups: progression of RA-ILD, development of new ILD in RA patients without ILD at baseline, 28-joint Disease Activity Score with the erythrocyte sedimentation rate (DAS28-ESR), and safety. Longitudinal changes were compared between the groups by using a generalized estimating equation. Results: The study included 123 patients who were treated with abatacept (n = 59) or csDMARDs (n = 64). Nineteen (32.2%) and 38 (59.4%) patients treated with abatacept and csDMARDs, respectively, presented with RA-ILD at baseline. Newly developed ILD occurred in one patient receiving triple csDMARDs for 32 months. Among patients with RA-ILD at baseline, ILD progressed in 21.1% of cases treated with abatacept and 34.2% of cases treated with csDMARDs during a median 21-month follow-up. Longitudinal changes in forced vital capacity and diffusing capacity for carbon monoxide were comparable between the two groups. However, the abatacept group showed a more significant decrease in DAS28-ESR and glucocorticoid doses than csDMARDs group during the follow-up. The safety of both regimens was comparable. Conclusions Abatacept and csDMARDs showed comparable effects on the development and stabilization of RA-ILD. Nevertheless, compared to csDMARDs, abatacept demonstrated a significant improvement in disease activity and led to reduced glucocorticoid use.

Objective: To compare the outcomes of digital breast tomosynthesis (DBT) screening combined with ultrasound (US) with those of digital mammography (DM) combined with US in women with dense breasts. Materials and Methods: A retrospective database search identified consecutive asymptomatic women with dense breasts who underwent breast cancer screening with DBT or DM and whole-breast US simultaneously between June 2016 and July 2019. Women who underwent DBT + US (DBT cohort) and DM + US (DM cohort) were matched using 1:2 ratio according to mammographic density, age, menopausal status, hormone replacement therapy, and a family history of breast cancer. The cancer detection rate (CDR) per 1000 screening examinations, abnormal interpretation rate (AIR), sensitivity, and specificity were compared. Results: A total of 863 women in the DBT cohort were matched with 1726 women in the DM cohort (median age, 53 years; interquartile range, 40–78 years) and 26 breast cancers (9 in the DBT cohort and 17 in the DM cohort) were identified. The DBT and DM cohorts showed comparable CDR (10.4 [9 of 863; 95% confidence interval {CI}: 4.8–19.7] vs. 9.8 [17 of 1726;95% CI: 5.7–15.7] per 1000 examinations, respectively; P = 0.889). DBT cohort showed a higher AIR than the DM cohort (31.6% [273 of 863; 95% CI: 28.5%–34.9%] vs. 22.4% [387 of 1726; 95% CI: 20.5%–24.5%]; P < 0.001). The sensitivity for both cohorts was 100%. In women with negative findings on DBT or DM, supplemental US yielded similar CDRs in both DBT and DM cohorts (4.0 vs. 3.3 per 1000 examinations, respectively; P = 0.803) and higher AIR in the DBT cohort (24.8% [188 of 758; 95% CI: 21.8%–28.0%] vs. 16.9% [257 of 1516; 95% CI: 15.1%–18.9%; P < 0.001). Conclusion DBT screening combined with US showed comparable CDR but lower specificity than DM screening combined with US in women with dense breasts.

Objective: To compare the performance of simulated abbreviated breast MRI (AB-MRI) and full diagnostic (FD)-MRI in distinguishing between benign and malignant lesions detected by MRI and investigate the features of discrepant lesions of the two protocols. Materials and Methods: An AB-MRI set with single first postcontrast images was retrospectively obtained from an FD-MRI cohort of 111 lesions (34 malignant, 77 benign) detected by contralateral breast MRI in 111 women (mean age, 49.8. ± 9.8;range, 28–75 years) with recently diagnosed breast cancer. Five blinded readers independently classified the likelihood of malignancy using Breast Imaging Reporting and Data System assessments. McNemar tests and area under the receiver operating characteristic curve (AUC) analyses were performed. The imaging and pathologic features of the discrepant lesions of the two protocols were analyzed. Results: The sensitivity of AB-MRI for lesion characterization tended to be lower than that of FD-MRI for all readers (58.8– 82.4% vs. 79.4–100%), although the findings of only two readers were significantly different (p < 0.05). The specificity of AB-MRI for lesion characterization was higher than that of FD-MRI for 80% of readers (39.0–74.0% vs. 19.5–45.5%, p ≤ 0.001). The AUC of AB-MRI was comparable to that of FD-MRI for all readers (p > 0.05). Fifteen percent (5/34) of the cancers were false-negatives on AB-MRI. More suspicious margins or internal enhancement on the delayed phase images were related to the discrepancies. Conclusion The overall performance of AB-MRI was similar to that of FD-MRI in distinguishing between benign and malignant lesions. AB-MRI showed lower sensitivity and higher specificity than FD-MRI, as 15% of the cancers were misclassified compared to FD-MRI.

Objective: To compare the utility and diagnostic performance of automated breast ultrasound system (ABUS) with that of handheld ultrasound (HHUS) in evaluating pure non-mass enhancement (NME) lesions on breast magnetic resonance imaging (MRI). Materials and Methods: One hundred twenty-six consecutive MRI-visible pure NME lesions of 122 patients with breast cancer were assessed from April 2016 to March 2017. Two radiologists reviewed the preoperative breast MRI, ABUS, and HHUS images along with mammography (MG) findings. The NME correlation rate and diagnostic performance of ABUS were compared with that of HHUS, and the imaging features associated with ABUS visibility were analyzed. Results: Among 126 pure NME lesions, 100 (79.4%) were malignant and 26 (20.6%) were benign. The overall correlation rate was 87.3% (110/126) in ABUS and 92.9% (117/126) in HHUS. The sensitivity and specificity were 87% and 50% for ABUS and 92% and 42.3% for HHUS, respectively, with no significant differences (p = 0.180 and 0.727, respectively). Malignant NME was more frequently visualized than benign NME lesions on ABUS (93% vs. 65.4%, p = 0.001). Significant factors associated with the visibility of ABUS were the size of NME lesions on MRI (p < 0.001), their distribution pattern (p < 0.001), and microcalcifications on MG (p = 0.027). Conclusion ABUS evaluation of pure NME lesions on MRI in patients with breast cancer is a useful technique with high visibility, especially in malignant lesions. The diagnostic performance of ABUS was comparable with that of conventional HHUS in evaluating NME lesions.

Genetically engineered mouse models are used in high-throughput phenotyping screens to understand genotype-phenotype associations and their relevance to human diseases. However, not all mutant mouse lines with detectable phenotypes are associated with human diseases. Here, we propose the “Target gene selection system for Genetically engineered mouse models” (TarGo). Using a combination of human disease descriptions, network topology, and genotype-phenotype correlations, novel genes that are potentially related to human diseases are suggested. We constructed a gene interaction network using protein-protein interactions, molecular pathways, and co-expression data. Several repositories for human disease signatures were used to obtain information on human disease-related genes. We calculated disease- or phenotype-specific gene ranks using network topology and disease signatures. In conclusion, TarGo provides many novel features for gene function prediction.
Animals ; Computational Biology ; Genes, vif ; Genetic Association Studies ; Humans ; Mice ; Phenotype ; Systems Biology

BACKGROUND AND OBJECTIVES: Some patients with Kawasaki disease (KD) present with fever and cervical lymphadenopathy alone. The purpose of this study was to characterize the clinical features of these unusual KD patients and determine whether this is a severe form of KD associated with increased risks of intravenous immunoglobulin (IVIG) resistance and coronary artery lesions (CALs). SUBJECTS AND METHODS: A total of 146 children with KD were reviewed retrospectively, and classified into two groups according to initial clinical features. Those presenting with only fever and cervical lymphadenopathy (LKD) were classified as LKD patients. Other-KD patients included all except the LKD patients. RESULTS: Among 146 KD patients, 13 (8.9%) were classified as LKD patients. The LKD patients were significantly older and admitted earlier. The duration between fever onset and KD diagnosis was significantly longer in the LKD patients (5.9 days vs. 4.9 days, p=0.023). The frequency of IVIG resistance was not different between the two groups., In the LKD patients, the incidence of CALs was significantly higher in the acute phase, and without significant difference in the convalescent phase. The percentage of neutrophils and C-reactive protein, albumin, and total bilirubin levels were significantly higher in LKD patients. CONCLUSION: Even though LKD patients were older, admitted earlier, and had higher inflammatory marker levels, they did not have a greater risk of CALs or IVIG resistance. However, echocardiography may be helpful in the acute stage if patients have only fever and cervical lymphadenopathy and are unresponsive to empirical antibiotics.
Anti-Bacterial Agents ; Bilirubin ; C-Reactive Protein ; Child ; Coronary Vessels ; Diagnosis ; Echocardiography ; Fever* ; Humans ; Immunoglobulins ; Immunoglobulins, Intravenous ; Incidence ; Lymphatic Diseases* ; Mucocutaneous Lymph Node Syndrome* ; Neck ; Neutrophils ; Retrospective Studies

BACKGROUND: Abacavir is a widely-used nucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus (HIV) infection. Mandatory postmarketing surveillance was conducted in Korea to monitor the safety and evaluate the effectiveness of Ziagen® (abacavir sulfate 300 mg; ViiV Healthcare, Middlesex, UK). MATERIALS AND METHODS: An open-label, multi-center, non-interventional postmarketing surveillance study was conducted from June 2010 to June 2016 to monitor the safety and effectiveness of Ziagen across 12 hospitals in Korea. Subjects older than 18 years taking Ziagen according to prescribing information were enrolled. The primary outcome was defined as the occurrence of any adverse events after Ziagen administration. Secondary outcomes included the occurrence of adverse drug reactions, occurrence of serious adverse events, and effectiveness of Ziagen administration. RESULTS: A total of 669 patients were enrolled in this study, with a total observation period of 1047.8 person-years. Of these, 90.7% of patients were male. The mean age of patients was 45.8±11.9 years. One-hundred ninety-six (29.3%) patients reported 315 adverse events, and four patients reported seven serious adverse events, without any fatal events. There was one potential case of an abacavir hypersensitivity reaction. Among the 97 adverse drug reactions that were reported from 75 patients, the most frequent adverse drug reactions included diarrhea (12 events), dyspepsia (10 events), and rash (9 events). No ischemic heart disease was observed. In the effectiveness analysis, 91% of patients achieved HIV-1 RNA under 50 copies/mL after 24 months of observation with abacavir administration. CONCLUSION: Our data showed the safety and effectiveness of Ziagen in a real-world setting. During the study period, Ziagen was well-tolerated, with one incident of a clinically suspected abacavir hypersensitivity reaction. The postmarketing surveillance of Ziagen did not highlight any new safety information. These data may be helpful in understanding abacavir and the HIV treatment practices in Korea.
Delivery of Health Care ; Diarrhea ; Drug-Related Side Effects and Adverse Reactions ; Dyspepsia ; Exanthema ; HIV ; HIV-1 ; Humans ; Hypersensitivity ; Korea ; Male ; Myocardial Ischemia ; Pharmacoepidemiology ; RNA ; RNA-Directed DNA Polymerase

Overtube provides a conduit for the passage of endoscope into the digestive tract. Esophageal perforation with mediastinitis is a rare overtube-related complication. Until now, no reports have been published regarding the esophageal perforation which developed many months after the original procedure using the overtube. A 56-year-old female visited our hospital complaining of chest pain and back pain that began 14 days ago. The patient underwent esophageal variceal ligation using the overtube 12 months earlier. She was diagnosed with esophageal perforation with mediastinitis which extended to intervertebral and epidural space. The cause of this condition was considered to have been related to the use of overtube. Management of delayed perforation remains controversial. Although surgical management might be the preferred mode of treatment, she underwent local N-butyl 2-cyanoacrylate injection therapy and temporary stent therapy with antibiotics due to high operative risk. Herein, we report a case of overtube-related delayed esophageal perforation with mediastinitis that was successfully treated by nonoperative management.
Anti-Bacterial Agents ; Back Pain ; Chest Pain ; Endoscopes ; Epidural Space ; Esophageal Perforation* ; Female ; Gastrointestinal Tract ; Humans ; Ligation ; Mediastinitis* ; Middle Aged ; Stents

PURPOSE: The higher prevalence of respiratory allergic disease may be due to increased exposure to inhalation allergens. We conducted a survey of allergic diseases in autumn and winter with detection of major indoor allergens in major cities in Korea. METHODS: We enrolled 110 subjects from the fourth Korea National Health and Nutrition Examination Survey with stratified, cluster, and systematic sampling procedures. All participants answered a health questionnaire as well as underwent a skin prick test (SPT) and ImmunoCAP for 11 indoor major allergens. We also measured the levels of 5 major allergens (Der f 1, Der p 1, Can f 1, Bla g 1, and Asp f 1) in fine indoor dust from the houses of 60 subjects with a 2-site ELISA. RESULTS: The prevalence of allergic rhinitis and asthma were 25.5% and 7.3%, respectively. The most common sensitized allergens identified by SPT and ImmunoCAP were Dermatophagoides farinae (40.9%, 36.8%), followed by cockroach (23.6%, 19.5%), mugwort (13.6%, 22.9%), oak (9.1%, 22.9%), Japanese hop (9.1%, 8.6%), and dog dander (8.2%, 6.9%). There was a modest discrepancy between SPT and ImmunoCAP. Der f 1 and Der p 1 were detected in 91.7% and 45.0% of the enrolled houses, respectively. Der f 1 indicated high concentrations in all specific provinces in Korea; however, Der p 1 measured high only in the south. Dog dander allergens were present in 71.7% of houses; however, Bla g 1 was present in only 11.7% of houses and Asp f 1 was not detected in any houses. CONCLUSIONS: The most important inhalant allergens in Korea are house dust mites followed by cockroach, mugwort, oak, Japanese hop, and dog dander in indoor environment, in which The dominant species of house dust mites were different according to region.
Allergens* ; Animals ; Artemisia ; Asian Continental Ancestry Group ; Asthma ; Cockroaches ; Dander ; Dermatophagoides farinae ; Dogs ; Dust ; Enzyme-Linked Immunosorbent Assay ; Humans ; Humulus ; Inhalation ; Korea ; Nutrition Surveys ; Prevalence ; Pyroglyphidae ; Rhinitis ; Skin ; Skin Tests ; Viperidae ; Surveys and Questionnaires

Bisphenol A (BPA) has been reported to possess hepatic toxicity. We investigated the hypothesis that BPA, below the no observed adverse effect level (NOAEL), can induce hepatic damage and mitochondrial dysfunction by increasing oxidative stress in the liver. Two doses of BPA, 0.05 and 1.2 mg/kg body weight/day, were administered intraperitoneally for 5 days to mice. Both treatments impaired the structure of the hepatic mitochondria, although oxygen consumption rate and expression of the respiratory complex decreased only at the higher dose. The hepatic levels of malondialdehyde (MDA), a naturally occurring product of lipid peroxidation, increased, while the expression of glutathione peroxidase 3 (GPx3) decreased, after BPA treatment. The expression levels of proinflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) also increased. In HepG2 cells, 10 or 100 nM of BPA also decreased the oxygen consumption rate, ATP production, and the mitochondrial membrane potential. In conclusion, doses of BPA below the NOAEL induce mitochondrial dysfunction in the liver, and this is associated with an increase in oxidative stress and inflammation.
Adenosine Triphosphate/metabolism ; Animals ; Glutathione Peroxidase/metabolism ; Hep G2 Cells ; Humans ; Inflammation/chemically induced/metabolism/pathology ; Injections, Intraperitoneal ; Interleukin-6/metabolism ; Lipid Peroxidation/drug effects ; Liver/*drug effects/metabolism/pathology ; Male ; Malondialdehyde/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Mice ; Mice, Inbred C57BL ; Mitochondria/drug effects/*metabolism ; Oxidative Stress/drug effects ; Oxygen Consumption/drug effects ; Phenols/*toxicity ; Tumor Necrosis Factor-alpha/metabolism