Purpose: Recently, we developed allele-discriminating priming system (ADPS) technology. This method increases the sensitivity of conventional quantitative polymerase chain reaction up to 100 folds, with limit of detection, 0.01%, with reinforced specificity. This prospective study aimed to develop and validate the accuracy of ADPS epidermal growth factor receptor (EGFR) Mutation Test Kit using clinical specimens. Materials and Methods: In total 189 formalin-fixed paraffin-embedded tumor tissues resected from patients with non–small cell lung cancer were used to perform a comparative evaluation of the ADPS EGFR Mutation Test Kit versus the cobas EGFR Mutation Test v2, which is the current gold standard. When the two methods had inconsistent results, next-generation sequencing–based CancerSCAN was utilized as a referee. Results: The overall agreement of the two methods was 97.4% (93.9%-99.1%); the positive percent agreement, 95.0% (88.7%-98.4%); and the negative percent agreement, 100.0% (95.9%-100.0%). EGFR mutations were detected at a frequency of 50.3% using the ADPS EGFR Mutation Test Kit and 52.9% using the cobas EGFR Mutation Test v2. There were 10 discrepant mutation calls between the two methods. CancerSCAN reproduced eight ADPS results. In two cases, mutant allele fraction was ultra-low at 0.02% and 0.06%, which are significantly below the limit of detection of the cobas assay and CancerSCAN. Based on the EGFR genotyping by ADPS, the treatment options could be switched in five patients. Conclusion The highly sensitive and specific ADPS EGFR Mutation Test Kit would be useful in detecting the patients who have lung cancer with EGFR mutation, and can benefit from the EGFR targeted therapy.

Objective: To prospectively investigate the influence of the menstrual cycle on the background parenchymal signal (BPS) and apparent diffusion coefficient (ADC) of the breast on diffusion-weighted MRI (DW-MRI) in healthy premenopausal women. Materials and Methods: Seven healthy premenopausal women (median age, 37 years; range, 33–49 years) with regular menstrual cycles participated in this study. DW-MRI was performed during each of the four phases of the menstrual cycle (four examinations in total). Three radiologists independently assessed the BPS visual grade on images with b-values of 800 sec/mm2 (b800), 1200 sec/mm2 (b1200), and a synthetic 1500 sec/mm2 (sb1500). Additionally, one radiologist conducted a quantitative analysis to measure the BPS volume (%) and ADC values of the BPS (ADCBPS) and fibroglandular tissue (ADCFGT). Changes in the visual grade, BPS volume (%), ADCBPS, and ADCFGT during the menstrual cycle were descriptively analyzed. Results: The visual grade of BPS in seven women varied from mild to marked on b800 and from minimal to moderate on b1200 and sb1500. As the b-value increased, the visual grade of BPS decreased. On b800 and sb1500, two of the seven volunteers showed the highest visual grade in the early follicular phase (EFP). On b1200, three of the seven volunteers showed the highest visual grades in EFP. The BPS volume (%) on b800 and b1200 showed the highest value in three of the six volunteers with dense breasts in EFP. Three of the seven volunteers showed the lowest ADCBPS in the EFP. Four of the seven volunteers showed the highest ADCBPS in the early luteal phase (ELP) and the lowest ADCFGT in the late follicular phase (LFP). Conclusion Most volunteers did not exhibit specific BPS patterns during their menstrual cycles. However, the highest BPS and lowest ADCBPS were more frequently observed in EFP than in the other menstrual cycle phases, whereas the highest ADCBPS was more common in ELP. The lowest ADCFGT was more frequent in LFP.

Purpose: The purpose of this study was to investigate the concordance rate of PIK3CA mutations between primary and matched distant metastatic sites in patients with breast cancer and to verify whether there are differences in the frequency of PIK3CA hotspot mutations depending on the metastatic sites involved. Materials and Methods: Archived formalin-fixed paraffin-embedded (FFPE) specimens of primary breast and matched distant metastatic tumors were retrospectively obtained for 49 patients. Additionally, 40 archived FFPE specimens were independently collected from different breast cancer metastatic sites, which were limited to three common sites: the liver, brain, and lung. PIK3CA mutations were analyzed using droplet digital PCR, including hotspots involving exons 9 and 20. Results: After analysis of 49 breast tumors with matched metastasis sites, 87.8% showed concordance in PIK3CA mutation status. According to PIK3CA hotspot mutation testing in 89 cases of breast cancer metastatic sites, the proportion of PIK3CA mutations at sites of metastasis involving the liver, brain, and lung was 37.5%, 28.6%, and 42.9%, respectively, which did not result in statistical significance. Conclusion The high concordance of PIK3CA mutation status between primary and matched metastasis sites suggests that metastatic sites, regardless of the metastatic organ, could be considered sample sources for PIK3CA mutation testing for improved therapeutic strategies in patients with metastatic breast cancer.

Background: and Purpose Recent studies suggested an increased incidence of cerebral venous thrombosis (CVT) during the coronavirus disease 2019 (COVID-19) pandemic. We evaluated the volume of CVT hospitalization and in-hospital mortality during the 1st year of the COVID-19 pandemic compared to the preceding year. Methods: We conducted a cross-sectional retrospective study of 171 stroke centers from 49 countries. We recorded COVID-19 admission volumes, CVT hospitalization, and CVT in-hospital mortality from January 1, 2019, to May 31, 2021. CVT diagnoses were identified by International Classification of Disease-10 (ICD-10) codes or stroke databases. We additionally sought to compare the same metrics in the first 5 months of 2021 compared to the corresponding months in 2019 and 2020 (ClinicalTrials.gov Identifier: NCT04934020). Results: There were 2,313 CVT admissions across the 1-year pre-pandemic (2019) and pandemic year (2020); no differences in CVT volume or CVT mortality were observed. During the first 5 months of 2021, there was an increase in CVT volumes compared to 2019 (27.5%; 95% confidence interval [CI], 24.2 to 32.0; P<0.0001) and 2020 (41.4%; 95% CI, 37.0 to 46.0; P<0.0001). A COVID-19 diagnosis was present in 7.6% (132/1,738) of CVT hospitalizations. CVT was present in 0.04% (103/292,080) of COVID-19 hospitalizations. During the first pandemic year, CVT mortality was higher in patients who were COVID positive compared to COVID negative patients (8/53 [15.0%] vs. 41/910 [4.5%], P=0.004). There was an increase in CVT mortality during the first 5 months of pandemic years 2020 and 2021 compared to the first 5 months of the pre-pandemic year 2019 (2019 vs. 2020: 2.26% vs. 4.74%, P=0.05; 2019 vs. 2021: 2.26% vs. 4.99%, P=0.03). In the first 5 months of 2021, there were 26 cases of vaccine-induced immune thrombotic thrombocytopenia (VITT), resulting in six deaths. Conclusions During the 1st year of the COVID-19 pandemic, CVT hospitalization volume and CVT in-hospital mortality did not change compared to the prior year. COVID-19 diagnosis was associated with higher CVT in-hospital mortality. During the first 5 months of 2021, there was an increase in CVT hospitalization volume and increase in CVT-related mortality, partially attributable to VITT.

Epilepsy is a brain disorder that affects millions of people worldwide. It is characterized by recurrent and unpredictable seizures that are usually controlled with antiepileptic/anticonvulsive drugs. However, most antiepileptic drugs produce various side effects such as tolerance and sedation. Thus, there is a growing interest for alternative anticonvulsive drugs, preferably from natural or herbal sources. In this study, we evaluated the anticonvulsive effects of Rehmannia glutinosa (RG). The anticonvulsive effect of RG extract was evaluated using electroshock- and chemical-induced seizure tests in mice. To identify its probable mechanism of action, the effects of RG extract on Cl− influx was measured in vitro. We found that RG extract has anticonvulsive effects against electroshock-induced seizures, as indicated by an increased seizure threshold in mice. The RG extract also decreased the percentage of seizure responses induced by the GABAergic antagonist, pentylenetetrazole. These results suggest that the anticonvulsive effects of RG extract are mediated through a GABAergic mechanism. In support of this mechanism, our in vitro test showed that RG extract increases intracellular Cl− influx. Furthermore, RG extract did not show sedative and/or muscle relaxant effects in the open-field and rota-rod tests. Altogether, these results confirm that RG extract could be a herbal anticonvulsant and a potential alternative for clinical use.
Animals ; Anticonvulsants ; Brain Diseases ; Epilepsy ; gamma-Aminobutyric Acid* ; In Vitro Techniques ; Mice ; Pentylenetetrazole ; Rehmannia* ; Seizures* ; Water*

This study aimed to evaluate the reproducibility of apparent diffusion coefficient (ADC) measurements in malignant breast masses, and to determine the influence of mammographic parenchymal density on this reproducibility. Sixty-six patients with magnetic resonance findings of the mass were included. Two breast radiologists measured the ADC of the malignant breast mass and the same area on the contralateral normal breast in each patient twice. The effects of mammographic parenchymal density, histology, and lesion size on reproducibility were also assessed. There was no significant difference in the mean ADC between repeated measurements in malignant breast masses and normal breast tissue. The overall reproducibility of ADC measurements was good in both. The 95% limits of agreement for repeated ADCs were approximately 30.2%-33.4% of the mean. ADC measurements in malignant breast masses were highly reproducible irrespective of mass size, histologic subtype, or coexistence of microcalcifications; however, the measurements tended to be less reproducible in malignant breast masses with extremely dense parenchymal backgrounds. ADC measurements in malignant breast masses are highly reproducible; however, mammographic parenchymal density can potentially influence this reproducibility.
Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Breast Neoplasms/*pathology ; Diffusion Magnetic Resonance Imaging/*methods ; Female ; Humans ; Image Enhancement/*methods ; Image Interpretation, Computer-Assisted/*methods ; Middle Aged ; Reproducibility of Results ; Sensitivity and Specificity

OBJECTIVE: To synthesize mesoporous silica-core-shell magnetic nanoparticles (MNPs) encapsulated by liposomes (Lipo [MNP@m-SiO2]) in order to enhance their stability, allow them to be used in any buffer solution, and to produce trastuzumab-conjugated (Lipo[MNP@m-SiO2]-Her2Ab) nanoparticles to be utilized in vitro for the targeting of breast cancer. MATERIALS AND METHODS: The physiochemical characteristics of Lipo[MNP@m-SiO2] were assessed in terms of size, morphological features, and in vitro safety. The multimodal imaging properties of the organic dye incorporated into Lipo[MNP@m-SiO2] were assessed with both in vitro fluorescence and MR imaging. The specific targeting ability of trastuzumab (Her2/neu antibody, Herceptin(R))-conjugated Lipo[MNP@m-SiO2] for Her2/neu-positive breast cancer cells was also evaluated with fluorescence and MR imaging. RESULTS: We obtained uniformly-sized and evenly distributed Lipo[MNP@m-SiO2] that demonstrated biological stability, while not disrupting cell viability. Her2/neu-positive breast cancer cell targeting by trastuzumab-conjugated Lipo[MNP@m-SiO2] was observed by in vitro fluorescence and MR imaging. CONCLUSION: Trastuzumab-conjugated Lipo[MNP@m-SiO2] is a potential treatment tool for targeted drug delivery in Her2/neu-positive breast cancer.
3T3 Cells ; Animals ; Antibodies, Monoclonal, Humanized/*administration & dosage ; Antineoplastic Agents/*administration & dosage ; Breast Neoplasms/chemistry/*drug therapy ; Cell Line, Tumor ; Drug Delivery Systems/methods ; Female ; Ferric Compounds/chemistry ; Humans ; Liposomes ; Magnetite Nanoparticles/administration & dosage/*chemistry ; Mice ; Molecular Targeted Therapy/methods ; Nanoconjugates/administration & dosage/*chemistry ; Nanoparticles/chemistry ; *Receptor, erbB-2/immunology ; Silicon Dioxide/administration & dosage/*chemical synthesis/chemistry

BACKGROUND/AIMS: To investigate the gastroprotective effects of grape seed proanthocyanidin extracts (GSPEs) against nonsteroid anti-inflammatory drug (NSAID)-induced gastric mucosal injury in rats. METHODS: Sprague-Dawley rats were randomly allocated to the normal control, indomethacin, low-dose GSPE, high-dose GSPE and misoprostol groups. All groups except the normal control group received pretreatment drugs for 6 consecutive days. On the 5th and 6th day, indomethacin was administered orally to all groups except for normal control group. The microscopic features of injury were analyzed. The levels of gastric mucosal glutathione, gastric mucosal prostaglandin E2 (PGE2), and proinflammatory cytokines were investigated. RESULTS: The total areas of ulceration in the GSPE and misoprostol groups were significantly decreased compared with the indomethacin group (p<0.05). However, a difference in ulcer formation among the drug treatment groups was not observed. Meanwhile, the glutathione levels in the high-dose GSPE group were higher than those of both the indomethacin and misoprostol groups (p<0.05) and were similar to those of the normal control group. Additionally, there was no difference among the groups in the levels of gastric mucosal PGE2 and proinflammatory cytokines. CONCLUSIONS: High-dose GSPE has a strong protective effect against NSAID-induced gastric mucosal injury, which may be associated with the antioxidant effects of GSPE.
Animals ; Antioxidants ; Cytokines ; Dinoprostone ; Glutathione ; Grape Seed Extract ; Indomethacin ; Misoprostol ; Proanthocyanidins ; Rats ; Rats, Sprague-Dawley ; Seeds ; Ulcer ; Vitis

BACKGROUND/AIMS: The diagnosis of primary billiary cirrhosis (PBC)-autoimmune hepatitis (AIH) overlap syndrome remains challenging. In 2008, a simplified scoring system was proposed by the International Autoimmune Hepatitis Group, which aimed for wider applicability in routine clinical practice. We evaluated the performance of the new simplified AIH scoring criteria as a diagnostic tool for overlap syndrome. METHODS: We retrospectively reviewed the clinical histories, chemistry, autoimmune studies, and liver biopsy results of 25 patients diagnosed with PBC who visited Soonchunhyang University Hospital, Bucheon and Seoul, between November 2004 and December 2009. Parameters relevant to the revised and simplified scoring criteria were recorded, and outcomes were compared between those with and without features of overlap syndrome. RESULTS: Of 25 patients with a definite diagnosis of PBC, five (20%) were diagnosed with overlap syndrome using the revised criteria, and 18 patients (72%) were diagnosed with the simplified criteria. Those patients diagnosed according to the simplified scoring criteria revealed an increased frequency of anti-nuclear antibody (p = 0.030) and serum IgG levels (p = 0.092). Additionally, advanced fibrosis was significantly more frequent in patients with overlap syndrome (p = 0.017). CONCLUSIONS: The simplified scoring criteria seemed to be useful as a diagnostic tool to recognize overlap syndrome in Korea. However, a relatively small number of patients were included in our study, so further clinical trials based on larger populations should be performed.
Biopsy ; Fibrosis ; Hepatitis ; Hepatitis, Autoimmune ; Humans ; Immunoglobulin G ; Korea ; Liver ; Liver Cirrhosis ; Retrospective Studies

OBJECTIVE: To analyze the clinical experiences of patients who treated with levonorgestrel-releasing intrauterine system (LNG-IUS) for adenomyosis associated with dysmenorrhea and/or menorrhagia. METHODS: The LNG-IUS was inserted into 103 patients who were diagnosed with adenomyosis on ultrasound examination and suffered from dysmenorrhea or menorrhagia at CHA Gangnam Medical Center between January 2009 and December 2009. Symptomatic changes of dysmenorrhea and menorrhagia, side effects, and failure rates were evaluated, retrospectively. RESULTS: During the follow-up periods, dysmenorrhea was improved in 91.4% and menorrhagia was improved in 90.4% of patients. Most common side effects were prolonged vaginal spotting in 41 (39.8%), and expulsion of LNG-IUS in 32 (31.1%) patients. Six (5.7%) patients were premature removal of LNG-IUS and 9 (8.5%) patients were underwent hysterectomy. Overall 77 (74.8%) patients continued to use of LNG-IUS. CONCLUSION: The LNG-IUS is effective treatment option for management of dysmenorrhea and menorrhagia for patients with clinical diagnosis of adenomyosis. It seemed to be an alternative treatment method before hysterectomy.
Adenomyosis ; Dysmenorrhea ; Female ; Follow-Up Studies ; Humans ; Hysterectomy ; Menorrhagia ; Metrorrhagia