Search

To ensure therapeutic equivalence between the long-acting injectable (LAI) products, additional PK metrics other than C max and AUC were considered necessary. However, regarding the selection of additional PK metrics for bioequivalence (BE) assessment of exenatide LAI, a discrepancy existed between EMA's and USFDA's product-specific guidance. The EMA recommends that both the maximum plasma concentration in the initial-release phase (C max,1 ) and the extended-release phase (C max,2 ) should be determined. Nevertheless, the USFDA recommends the use of the partial area under the curve (i.e., the area under the curve from week 4 to the last sampling point; pAUC 4w-t ). The focus of this study was to compare the sensitivity of different PK metrics, including C max,1 , C max,2 , pAUC 4w-t , early and late pAUC metrics truncated at different time points (three, four, five, six and seven weeks), to formulation-related parameters and pharmacodynamic (PD) markers of glycemic control. A sensitivity analysis was conducted using the published PK/PD model of exenatide LAI. The results indicated that C max,1 and C max,2 exhibited comparable sensitivities. AUC 4w-t was sensitive to changes in detecting the differences in formulation-related parameters and PD markers of glycemic control, but did not provide superior sensitivity performance compared to C max,1 and C max,2 . Among all tested PK metrics, AUC 7w-t was found to be the most sensitive. The optimal cut-off time point for the pAUC should be set at the time of maximum plasma concentration in the extended-release phase (approximately 6-7 weeks). These results may provide useful insights into the selection of appropriate PK metrics for BE determination of exenatide LAI., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024. Published by Elsevier B.V.)

Purpose: Although many staging systems have been proposed for hepatocellular carcinoma (HCC), there is no globally accepted system due to the extreme heterogeneity of the disease. We aimed to compare the results of the 7th/8th American Joint Committee on Cancer (AJCC) and the modified Union for International Cancer Control (mUICC) staging systems in patients with HCC., Materials and Methods: We collected data from 792 patients who underwent hepatic resection at our center. The Kaplan-Meier method was used to determine disease-free survival and overall survival. To evaluate homogeneity, '-2 log likelihood' was calculated using Cox proportional hazards regression. To measure discriminatory ability, the linear trend chi method and the Cochran-Armitage test for trend were used. The ability to accurately predict survival was verified by cross-validation analysis., Results: Kaplan-Meier curves for disease-free survival and overall survival showed mUICC to be superior to the 7th/8th AJCC. The homogeneity test indicated that mUICC was the best for both disease-free survival and overall survival. In the discriminatory ability test, the chi-square value of mUICC was the best for disease-free survival, while the 7th AJCC had the best value for overall survival. In the cross-validation analysis, all three staging systems had significant predictive power., Conclusion: mUICC seemed to be superior to the 7th/8th AJCC after analyzing the data of our surgical patients, although the geographic heterogeneity of HCC might result in differences between the staging systems. We believe that, while the three staging systems allow for the clear stratification of patients into prognostic groups, mUICC may be more appropriate in HCC., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Introduction: Histological subtypes of lung adenocarcinomas (ADCs) classified by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) system have been investigated using radiomic approaches. However, the results have had limitations since <80% of invasive lung ADCs were heterogeneous, with two or more subtypes. To reduce the influence of heterogeneity during radiomic analysis, computed tomography (CT) images of lung ADCs with near-pure ADC subtypes were analyzed to extract representative radiomic features of different subtypes., Methods: We enrolled 95 patients who underwent complete resection for lung ADC and a pathological diagnosis of a "near-pure" (≥70%) IASLC/ATS/ERS histological subtype. Conventional histogram/morphological features and complex radiomic features (grey-level-based statistical features and component variance-based features) of thin-cut CT data of tumor regions were analyzed. A prediction model based on leave-one-out cross-validation (LOOCV) and logistic regression (LR) was used to classify all five subtypes and three pathologic grades (lepidic, acinar/papillary, micropapillary/solid) of ADCs. The validation was performed using 36 near-pure ADCs in a later cohort., Results: A total of 31 lepidic, 14 papillary, 32 acinar, 10 micropapillary, and 8 solid ADCs were analyzed. With 21 conventional and complex radiomic features, for 5 subtypes and 3 pathological grades, the prediction models achieved accuracy rates of 84.2% (80/95) and 91.6% (87/95), respectively, while accuracy was 71.6% and 85.3%, respectively, if only conventional features were used. The accuracy rate for the validation set (n = 36) was 83.3% (30/36) and 94.4% (34/36) in 5 subtypes and 3 pathological grades, respectively, using conventional and complex features, while it was 66.7% and 77.8% only using conventional features, respectively., Conclusion: Lung ADC with high purity pathological subtypes demonstrates strong stratification of radiomic values, which provide basic information for accurate pathological subtyping and image parcellation of tumor sub-regions., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: To determine the association in amount of daily coffee consumption with incidence of stroke in a broad cohort, considering other vascular risk factors., Methods: We utilized the Third National Health and Nutrition Examination Survey (1988-1994; NHANES III) data on participants aged ≥17 years old to examine coffee consumption and stroke. Multivariate logistic regression models related the amount of coffee use reported in a food frequency questionnaire with stroke, controlling for other vascular risk factors., Results: Of 33 994 NHANES III subjects, coffee consumption and stroke data in adults ≥17 years old were available in 19 994. Daily coffee consumption ranged from 0 to 20 (median 1) cups and 644 (3.2%) participants had a stroke diagnosed by a physician. Coffee intake varied with age, gender, and ethnicity (P < 0.001). Interestingly, heart failure, diabetes, and hypertension were less frequent, and high cholesterol more frequent in those consuming ≥3 cups per day (P < 0.001). Smoking was more frequent in all coffee drinkers (P < 0.0001). Multivariate analyses revealed an independent effect of heavier coffee consumption (≥3 cups/day) on reduced stroke (OR 0.44, 95% CI 0.22-0.87, P < 0.02) in healthy subjects that was attenuated by vascular risk factors (OR 0.78, 95% CI 0.58-1.07, P ≈ 0.12)., Conclusion: Heavier daily coffee consumption is associated with decreased stroke prevalence, despite smoking tendency in heavy coffee drinkers.

At present, multiple myeloma (MM) remains an incurable disease and cologenic cells may be responsible for disease relapse. It has been proposed that CD20+/CD138- NCI-H929 cells could be hallmarks of MM clonogenic cells. Here, the immunology phenotype of NCI-H929 cells is described. Only a small population of CD20+/CD138- cells (<1%) was found in the NCI-H929 cell line, but CD20+/CD138- cells were not detected. We found that CD20+/CD138+ cells were able to exhibit cologenic capacity by colony formation assay and continuous passage culture. Proteins were analyzed by 1D-SDS-PAGE and TMT based quantitative differential liquid chromatography tandem mass spectrometry (LC-MS/MS). 1,082 non-redundant proteins were identified, 658 of which were differentially expressed with at least a 1.5-fold difference. 205 proteins in CD20+ cells were expressed at higher levels and 453 proteins were at lower levels compared with CD20- cells. Most proteins had catalytic and binding activity and mainly participated in metabolic processes, cell communication and molecular transport. These results proved that there are different biological features and protein expression profile between CD20+ and CD20- cells in the NCI-H929 cell line.

This article explores the location, size of the site, and medical activities of the Gurhigae Jejoongwon. Relevant documents such as reminiscences, diplomatic notes, newspaper accounts, maps, and photographs were referred for this study. The Gurhigae Jejoongwon located on a hill that, at present, covers the area from Ulchi-ro to MyungDong Cathedral. Its main entrance was towards Ulchi-ro. Real estate including the buildings of the Gurhigae Jejoongwon was returned to the Chosun government in 1905, and the estimated size of its site varied from 1,810 pyung to 5,036 pyung. The site of the Gurhigae Jejoongwon was 2 - 5 times larger than the 862.16-pyung-site of the Jejoongwon in its Jaedong days. With such larger size, the Jejoongwon could take care of more patients. Dr. Avison started medical education again. The Gurhigae Jejoongwon took the central part in medical treatment activities for public in Seoul, as it carried out the prevention activities against Cholera in 1895. The Chosun government highly recognized its medical treatment activities for the common people.