Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Objective: To gather the opinions of hands-on workers for successful introduction of the Development Safety Update Report (DSUR) according to a five-year comprehensive plan for clinical trial development [Ministry of Food and Drug Safety, 2019]. Methods: We conducted a survey on considerations that industry stakeholders may have related to the enforcement of the DSUR. A questionnaire was distributed among pharmacovigilance specialists from 13 pharmaceutical companies in South Korea on June 4, 2020. The questionnaire comprised two sections: 1) current status of the Drug Safety Data Management System and 2) considerations on the implementation and management of the DSUR. Results: All respondents have agreed the introduction of DSUR is inevitable for regulatory harmonization and safety of trial subject. However, most respondents (85%) felt concern about additional workload with DSUR implementation. They answered that format and operation system of DSUR should be harmonized with those of international standards and authorities need to minimize double burden due to related report. Conclusion All respondents asserted that domestic DSUR should be harmonized with International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) E2F guidelines. Respondents from global companies also suggested regulatory authorities allow DSUR written in English to replace Korean version considering their deadline for submission.Moreover, every respondent agreed regulatory authorities need delicate effort when implementing mandatory submission of DSUR to ensure that even small pharmaceutical companies with no experience in DSUR can comply with the system.

Reproductive toxicology is relatively new to the field of gene therapy, and is a very important issue for the safety. An important safety concern of gene therapy products is the distribution of vector beyond target organs. This is particularly important if vector distributes to gonads, raising the possibility of inadvertent germ-line transmission. In addition, for indications such as prostate cancer and ovarian cancer, the proximity of the point of viral administration to organs of the reproductive system raises concerns regarding inadvertent germ-line transmission of genes carried by the virus. To evaluate the reproductive toxicity of in vivo E1-deleted replication-incompetent adenoviral vector encoding p53 or lacZ, we studied the biodistribution and potential germ-line transmission of the vector. Both male and female Balb/c mice were injected with 1x10(8) pfu of Ad-CMV-LacZ or Ad-CMV-p53. DNA and RNA extracted from major organs including gonadal tissues were analyzed for vector sequences and expression. The PCR analysis showed that there were detectable vector sequences in liver, kidney, spleen, seminal vesicle, epididymis, prostate, ovary, and uterus. The RT-PCR analysis showed that Ad-CMV-LacZ or Ad-CMV-p53 viral RNA were present in spleen, prostate and ovary. Vectoradministered female and male mice were mated and their offspring were evaluated for germ-line transmission of the adenoviral vector. The PCR analysis showed no evidence of germ-line transmission, although vector sequences were detected in DNA extracted from gonadal tissues. Together, we conclude that the risk of the inadvertent germ-line transmission of vector sequences following intraperitoneal injection of adenovirus is extremely low, although vector distributed to gonadal tissues.
Adenoviridae* ; Animals ; DNA ; Epididymis ; Female ; Genetic Therapy ; Gonads ; Humans ; Injections, Intraperitoneal ; Kidney ; Liver ; Male ; Mice* ; Ovarian Neoplasms ; Ovary ; Polymerase Chain Reaction ; Prostate ; Prostatic Neoplasms ; RNA ; RNA, Viral ; Seminal Vesicles ; Spleen ; Toxicology ; Uterus

PURPOSE: Mycobacterium tuberculosis is endemic in Korea. Because tuberculous peritonitis is characterized by ascites, abdominal pain, abdominal mass and elevation of serum CA-125, it can be confused with ovarian malignancies. The aim of this study was to evaluate the significance of serum CA-125 level in the differential diagnosis of tuberculous peritonitis and ovarian malignancy in a Mycobacterium tuberculosis-endemic area. MATERIALS AND METHODS: The medical records of patients diagnosed with tuberculous peritonitis (n=48) or epithelial ovarian malignancy (n=370) at Samsung Medical Center from January 2000 to October 2009 were retrospectively reviewed. RESULTS: Median serum CA-125 level in the epithelial ovarian cancer group was significantly higher than that in the tuberculous peritonitis group (p< or =0.01). Only one patient (2.1%) in the tuberculous peritonitis group had a serum CA-125 level over 2000 U/mL. However, 109 patients (29.5%) in the epithelial ovarian cancer group had a serum CA-125 level over 2000 U/mL. At the CA-125 ranges of 400 to 599 and 600 to 799, the proportions of those with tuberculous peritonitis were 24% and 21.9%, respectively. At a serum CA-125 level over 1000 U/mL, however, the proportion of tuberculous peritonitis was much lower (2.1%). CONCLUSION: Tuberculous peritonitis should be considered in the evaluation of female patients with ascites and high serum CA-125.
Ascites/*blood ; CA-125 Antigen/*blood ; Diagnosis, Differential ; Female ; Humans ; Multivariate Analysis ; Ovarian Neoplasms/blood/*diagnosis ; Peritonitis, Tuberculous/blood/*diagnosis ; Republic of Korea ; Retrospective Studies

BACKGROUND/AIMS: The aromatase inhibitors (AIs) are well known anti-hormonal therapy in endocrine-responsive breast cancer patients. It can lead to dyslipidemia and be the risk factor of cardiovascular disease due to low estrogen level. However, some recent studies comparing AIs with placebo have shown controversial results. The aim of this study was to investigate lipid profiles, measurement of carotid intima-media thickness (IMT) and the presence of plaque among endocrine-responsive breast cancer treated with AIs compared to ones that were not treated with AIs. METHODS: A total of 85 postmenopausal women, who underwent breast cancer surgery during the age of 50 to 64 without history of statin use were included. There were 42 patients who were treated with AIs over 1 year (group 1) and 43 patients without AIs use (group 2). Serum total cholesterol, high density lipoprotein cholesterol, triglycerides, fasting blood glucose, carotid IMT, and presence of plaque were assessed. RESULTS: The baseline characteristics were similar between two groups and there was no significant difference in carotid IMT irrespective of AIs administration. However, ultrasonographic evaluation of carotid artery revealed that the presence of plaque in AI users was significantly higher than in non-AI users (66.7% vs. 41.9%, p = 0.02; odds ratio, 4.21 in adjusted model; p = 0.01). History of diabetes was also the significant risk factor for the plaque formation. CONCLUSIONS There was no significant difference in lipid profile itself between two groups, but more importantly the presence of the plaque was much higher indicating possible detrimental effect of AI on cardiovascular system.

Though acute kidney injury (AKI) is a prevalent complication in critically ill patients, knowledge on the epidemiological differences and clinical characteristics of patients with AKI admitted to medical and surgical intensive care units (ICUs) remains limited. Methods: Electronic medical records of patients in ICUs in Pusan National University Hospital and Pusan National University Hospital Yangsan, from January 2011 to December 2020, were retrospectively analyzed. Different characteristics of AKI between patients were analyzed. The contribution of AKI to the in-hospital mortality rate was assessed using a Cox proportional hazards model. Results: A total of 7,150 patients were included in this study. AKI was more frequent in medical (48.7%) than in surgical patients (19.7%), with the severity of AKI higher in medical patients. In surgical patients, hospital-acquired AKI was more frequent (51.0% vs. 49.0%), whereas community-acquired AKI was more common in medical patients (58.5% vs. 41.5%). 16.9% and 5.9% of medical and surgical patients died in the hospital, respectively. AKI affected patient groups to different degrees. In surgical patients, AKI patients had 4.778 folds higher risk of mortality (95% confidence interval [CI], 3.577–6.382; p < 0.001) than non-AKI patients; whereas in medical AKI patients, it was 1.239 (95% CI, 1.051–1.461; p = 0.01). Conclusion: While the prevalence of AKI itself is higher in medical patients, the impact of AKI on mortality was stronger in surgical patients compared to medical patients. This suggests that more attention is needed for perioperative patients to prevent and manage AKI.

Continuous kidney replacement therapy (CKRT) is crucial in the management of acute kidney injury in intensive care units (ICUs). Nonetheless, the optimal anticoagulation strategy for patients with bleeding tendencies remains debated. This study aimed to evaluate patient outcomes and safety of nafamostat mesylate (NM) compared with no anticoagulation (NA) in critically ill patients with bleeding tendencies who were undergoing CKRT. Methods: This retrospective study enrolled 2,313 patients who underwent CKRT between March 2013 and December 2022 at the third affiliated hospital in South Korea. After applying the exclusion criteria, 490 patients were included in the final analysis, with 245 patients in the NM and NA groups each, following 1:1 propensity score matching. Subsequently, in-hospital mortality, incidence of bleeding complications, agranulocytosis, hyperkalemia, and length of hospital stay were assessed. Results: No significant differences were observed between the groups regarding the lengths of hospital and ICU stays or the incidence of agranulocytosis and hyperkalemia. The NM group showed a smaller decrease in hemoglobin levels during CKRT (–1.90 g/dL vs. –2.39 g/dL) and less need for blood product transfusions than the NA group. Furthermore, the NM group exhibited a survival benefit in patients who required transfusion of all three blood products. Conclusion: NM is an effective and safe anticoagulant for CKRT in critically ill patients, especially those requiring transfusion of all three blood products. Although these findings are promising, further multicenter studies are needed to validate them and explore the mechanisms underlying the observed benefits.

Ginsenosides from Panax ginseng are well known for their diverse pharmacological effects including antithrombotic activity. Since adventitious roots of mountain ginseng (ARMG) also contain various ginsenosides, blood flow-improving effects of the dried powder and extract of ARMG were investigated. Rats were orally administered with dried powder (PARMG) or ethanol extract (EARMG) of ARMG (125, 250 or 500 mg/kg) or aspirin (30 mg/kg, a reference control) for 3 weeks. Forty min after the final administration, carotid arterial thrombosis was induced by applying a 70% FeCl₃-soaked filter paper outside the arterial wall for 5 min, and the blood flow was monitored with a laser Doppler probe. Both PARMG and EARMG delayed the FeCl₃-induced arterial occlusion in a dose-dependent manner, doubling the occlusion time at high doses. In mechanism studies, a high concentration of EARMG inhibited platelet aggregation induced by collagen in vitro. In addition, EARMG improved the blood lipid profiles, decreasing triglyceride and cholesterol levels. Although additional action mechanisms remain to be clarified, it is suggested that ARMG containing high amount of ginsenosides such as Rg₃ improves blood flow not only by inhibiting oxidative thrombosis, but also by modifying blood lipid profiles.
Animals ; Aspirin ; Cholesterol ; Collagen ; Ethanol ; Ginsenosides ; In Vitro Techniques ; Panax* ; Platelet Aggregation ; Rats ; Thrombosis ; Triglycerides

In this article, So-Young Park is inadvertently omitted from the listed author names. In the Acknowledgement section, funding source is incorrectly cited and has been changed upon request of authors.

BACKGROUND: We aimed to assess the risk for coronary artery calcification (CAC) according to groups subdivided by body mass index (BMI) and waist circumference (WC) in apparently healthy Korean adults. METHODS: Thirty-three thousand four hundred and thirty-two participants (mean age, 42 years) in a health screening program were divided into three groups according to BMI: <23 kg/m² (normal), 23 to 25 kg/m² (overweight), and >25 kg/m² (obese). In addition, the participants were divided into two groups according to WC. Coronary artery calcium score (CACS) was measured with multi-detector computed tomography in all participants. Presence of CAC was defined as CACS >0. RESULTS: When logistic regression analysis was performed with the presence of CAC as the dependent variable, the risk for CAC increased as BMI increased after adjusting for confounding variables (1.102 [95% confidence interval (CI), 1.000 to 1.216]; 1.284 [95% CI, 1.169 to 1.410]; in the overweight and obese groups vs. the normal weight group). When the participants were divided into six groups according to BMI and WC, the subjects with BMI and WC in the obese range showed the highest risk for CAC (1.321 [95% CI, 1.194 to 1.461]) and those with BMI in the overweight range and WC in the obese range showed the second highest risk for CAC (1.235 [95% CI, 1.194 to 1.461]). CONCLUSION: Participants with obesity defined by both BMI and WC showed the highest risk for CAC. Those with BMIs in the overweight range but with WC in the obese range showed the second highest risk for CAC, suggesting that WC as a marker of obesity is more predictive of CAC than BMI.
Adult* ; Body Mass Index* ; Calcium ; Confounding Factors (Epidemiology) ; Coronary Vessels* ; Humans ; Logistic Models ; Mass Screening ; Obesity* ; Overweight ; Waist Circumference*