Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Background: The purpose of this study was to detect signals of adverse events (AEs) of DPP-IV inhibitors using the KIDs-Korea Adverse Event Reporting System (KAERS) database. Methods: This study was conducted using AEs reported from January 2009to December 2018 in the KIDs-KAERS database. For signal detection, disproportionality analysis was performed. Signals of DPPIV inhibitor that satisfied the data-mining indices of reporting odds ratio (ROR) were detected. Results: Among the total number of 10,364 AEs to all oral hypoglycemic agents, the number of reported AEs related to DPP-IV inhibitors was 1,674. Analysis of re-ported AEs of DPP-IV inhibitors at the SOC levels showed that Respiratory system disorders were the highest at 4.31 (95% CI 3.01-6.17), followed by Skin and appendages disorders at 2.04 (95% CI 1.74-2.38). When analyzing AEs reported at the PT level, phar-yngitis was the highest at 73.90 (95% CI 17.59-310.49), followed by arthralgia at 6.08 (95% CI 2.04-18.11), and coughing at 5.21 (95% CI 2.07-13.15). Conclusions Based on the result of the study, deeper consideration is required according to the characteristics of the patients in prescribing DPP-IV inhibitors among oral hypoglycemic agents, and continuous monitoring of the occurrence of related Adverse Drug Reactions during administration is also required.

Background/Aims: Heme oxygenase-1 (HO-1) plays a central role in cellular defense against inflammatory insults, and its induction in macrophages potentiates their efferocytic activity. In this study, we explored the potential role of macrophage HO-1 in the resolution of experimentally induced colitis. Methods: To induce colitis, male C57BL/6 mice were treated with 2% dextran sulfate sodium (DSS) in the drinking water for 7 days. To investigate efferocytosis, apoptotic colon epithelial CCD 841 CoN cells were coincubated with bone marrow-derived macrophages (BMDMs). Results: Administration of the HO-1 inhibitor zinc protoporphyrin IX (ZnPP) blunted the resolution of DSS-induced intestinal inflammation and expression of the proresolving M2 macrophage marker CD206. BMDMs treated with apoptotic colonic epithelial cells showed significantly elevated expression of HO-1 and its regulator Nrf2. Under the same experimental conditions, the proportion of CD206-expressing macrophages was also enhanced. ZnPP treatment abrogated the upregulation of CD206 expression in BMDMs engulfing apoptotic colonic epithelial cells. This result was verified with BMDMs isolated from HO-1-knockout mice. BMDMs, when stimulated with lipopolysaccharide, exhibited increased expression of CD86, a marker of M1 macrophages.Coculture of lipopolysaccharide-stimulated BMDMs with apoptotic colonic epithelial cell debris dampened the expression of CD86 as well as the pro-inflammatory cytokines in an HO-1-dependent manner. Genetic ablation as well as pharmacologic inhibition of HO-1 significantly reduced the proportion of efferocytic BMDMs expressing the scavenger receptor CD36. Conclusions HO-1 plays a key role in the resolution of experimentally induced colitis by modulating the polarization of macrophages.

Purpose: Treatment with 4 cycles of docetaxel and cyclophosphamide (TC) in the adjuvant setting is associated with better outcomes than treatment with doxorubicin and cyclophosphamide (AC). However, Western guidelines have indicated that TC confers a high risk (>20%) of febrile neutropenia (FN), while AC confers an intermediate risk (10%–20%) of FN. Threrefore, we evaluated the incidence of FN and the clinical utilization of pegfilgrastim prophylaxis after adjuvant TC chemotherapy. Methods: We categorized 201 patients who received adjuvant TC chemotherapy into 3 groups according to the method of prophylaxis and compared neutropenic events, other adverse events, and hospital care costs in the 3 groups. Results: The incidence of grade 4 neutropenia decreased from 93.0% in patients without prophylaxis to 82.4% in those who received secondary prophylaxis and 16.7% in those who received primary prophylaxis. Although the incidence of FN was not different between patients without prophylaxis and patients who received secondary prophylaxis (15.7% and 14.9%), none of the patients who received primary prophylaxis developed FN. Moreover, a decrease in neutropenic events resulted in a significant decrease in the mean duration of neutropenia (2.50 days to 0.08 days, P < 0.001), the risk of hospitalization (29.8% to 2.2%, P < 0.001), and the mean total hospital care cost for all chemotherapy cycles (790.80 to 486.00 US dollars, P < 0.001). Conclusion The use of pegfilgrastim prophylaxis during adjuvant TC chemotherapy is associated with significant decreases in the incidence of neutropenic events, hospitalization, and hospital care cost compared to those seen in patients without prophylaxis.

Background: Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear. Methods: The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death. Results: In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18). Conclusion Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.

Background: Patients with chronic kidney disease (CKD) are at a high risk of stroke-related morbidity, mortality, and bleeding. However, the overall risk/benefit of anticoagulant therapy among patients with CKD remains unclear. Methods: The MEDLINE, EMBASE, and CENTRAL databases were comprehensively searched until July 31, 2020, to investigate the safety and efficacy of apixaban in patients with stage 4 or 5 CKD, as compared with warfarin. The primary outcome was an incidence of major bleeding. Secondary outcomes included composite bleeding (major, clinically relevant, and minor bleeding), venous thromboembolism (VTE), stroke, and death. Results: In total, seven studies consisting of 10,816 patients were included. Compared with warfarin, apixaban was associated with a reduced risk of major bleeding (OR 0.49, 95% CI 0.41-0.58). In terms of composite bleeding, apixaban tended to pose a significantly lower risk than warfarin (OR 0.51, 95% CI 0.37-0.71). There was no difference between apixaban and warfarin with respect to the risk of stroke or death (stroke: OR 1.23, 95% CI 0.49-3.12; death: OR 0.73, 95% CI 0.45-1.18). Conclusion Among patients with stage 4 or 5 CKD, the use of apixaban was associated with a lower risk of bleeding compared to warfarin and was also found to pose no excess risk of thromboembolic events.

Purpose: Intraoperative frozen section biopsy is used to reduce the margin positive rate and re-excision rate and has been reported to have high diagnostic accuracy. A majority of breast surgeons in the Republic of Korea routinely perform frozen section biopsy to assess margins intraoperatively, despite its long turnaround time and high resource requirements. This study aims to determine whether omitting frozen section biopsy for intraoperative margin evaluation in selected patients is non-inferior to performing frozen section biopsy in terms of resection margin positivity rate. Methods This study is a phase III, randomized controlled, parallel-group, multicenter non-inferiority clinical trial. Patients meeting the inclusion criteria and providing written informed consent will be randomized to the “frozen section biopsy” or “frozen section biopsy omission” group after lumpectomy. Patients with clinical stage T1–T3 disease who are diagnosed with invasive breast cancer by core-needle biopsy and plan to undergo breast-conserving surgery will be included in this study. If a daughter nodule, non-mass enhancement, or microcalcification is identified on preoperative imaging, these features must be within 1 cm of the main mass for inclusion in the trial. The target sample size is 646 patients per arm. The primary endpoint will be the resection margin positive rate, and the secondary endpoints include the reoperation rate, operating time, residual cancer after reoperation, residual cancer after re-excision according to the frozen section biopsy result, resection volume, patient quality of life, and cost-effectiveness.Discussion: This is the first randomized clinical trial utilizing frozen section biopsy for intraoperative margin evaluation and aims to determine the non-inferiority of omitting frozen section biopsy in selected patients compared to performing frozen section biopsy.We expect that this trial will help surgeons perform the procedure more efficiently while ensuring patient safety.