Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

Background/Aims: Papillary adenocarcinoma is classified to differentiated-type gastric cancer and is indicated for endoscopic submucosal dissection. However, due to its rare nature, there are limited studies on it. The purpose of this study was to determine the outcome of endoscopic submucosal dissection in patients with papillary-type early gastric cancer and to find the risk factors of lymph node metastasis. Methods: Patients diagnosed with papillary-type early gastric cancer at eight medical centers, who underwent endoscopic submucosal dissection or surgical treatment, were retrospectively reviewed. The clinical results and long-term outcomes of post-endoscopic submucosal dissection were evaluated, and the risk factors of lymph node metastasis in the surgery group were analyzed. Results: One-hundred and seventy-six patients with papillary-type early gastric cancer were enrolled: 44.9% (n=79) in the surgery group and 55.1% (n=97) in the endoscopic submucosal dissection group. As a result of endoscopic submucosal dissection, the en bloc resection and curative resection rates were 91.8% and 86.6%, respectively. The procedure-related complication rate was 4.1%, and local recurrence occurred in 3.1% of patients. Submucosal invasion (odds ratio, 3.735; 95% confidence interval, 1.026 to 12.177; p=0.047) and lymphovascular invasion (odds ratio, 7.636; 95% confidence interval, 1.730 to 22.857; p=0.004) were the risk factors of lymph node metastasis in papillary-type early gastric cancer patients. Conclusions The clinical results of endoscopic submucosal dissection in papillary-type early gastric cancer were relatively favorable, and endoscopic submucosal dissection is considered safe if appropriate indications are confirmed by considering the risk of lymph node metastasis.

Partial trisomy 1q is a rare chromosomal disorder characterized by ventriculomegaly with craniofacial, renal, cardiac, and finger and toe anomalies. Most reported cases of partial trisomy1q have involved stillborn or premature deaths due to cardiac or liver failure. This case report describes an 18-month-old patient with partial duplication of the 1q32-44 segments and consequent developmental delays who exhibited improvement in developmental status with rehabilitation. Prenatal ultrasonography and magnetic resonance imaging of the mother revealed ventriculomegaly and atrophic changes in the left cerebral hemisphere of the fetus. The infant was born with micrognathia, microphthalmia, macrocephaly, low-set ears, polydactyly, and long feet at 37+5 weeks of gestation. A chromosomal study revealed an abnormal male karyotype of 46,XY,rec(1)dup(1)(q32.1q44)inv(1)(p36.3q32.1)pat. In this rare case of a patient with partial trisomy, we observed improvement in developmental delays following treatment using appropriate rehabilitation techniques. Further research is required to help validate the findings of this case study and establish a standardized rehabilitation technique that can be subsequently applied to such cases.

Background/Aims: This study aimed to determine changes in endoscopist-driven sedation practices 5 years after the first nationwide survey in 2014 by the Korean Society of Gastrointestinal Endoscopy (KSGE). Methods: A 59-item survey covering current practices was electronically mailed to all members of the KSGE in 2019. Results: In total, 955 (12.8%) out of 7,486 questionnaires were returned. A total of 738 (77.7%) out of 955 respondents attended dedicated sedation education programs. The American Society of Anesthesiologists class was recorded by 464 (51.2%) out of 907 respondents. The recording rate was higher in respondents who completed sedation education (p=0.014) and worked in general or tertiary hospitals (p<0.001). Compared to that reported in the previous survey, the reported use of propofol was higher in 2019. The respondents had higher satisfaction scores for propofol-based sedation compared with midazolam monotherapy (p<0.001). The rates of oxygen supplementation (p<0.001) and oxygen saturation level monitoring (p<0.001) during sedative endoscopy were higher in 2019 than in the previous survey. A total of 876 (98.4%) out of 890 respondents reported a separate recovery bay, and 615 (70.5%) out of 872 respondents reported that personnel were assigned solely to the recovery bay. Conclusions Endoscopist-driven sedation and monitoring practices in 2019 were significantly different than those in 2014. The respondents favored propofol-based sedation and utilized oxygen supplementation and monitoring of O2 saturation more frequently in 2019 than in 2014.

BACKGROUND: The use of mouse bone marrow mesenchymal stem cells (mBMSCs) represents a promising strategy for performing preclinical studies in the field of cell-based regenerative medicine; however, mBMSCs obtained via conventional isolation methods have two drawbacks, i.e., (i) they are heterogeneous due to frequent macrophage contamination, and (ii) they require long-term culturing for expansion. METHODS: In the present study, we report a novel strategy to generate highly pure mBMSCs using liposomal clodronate.This approach is based on the properties of the two cell populations, i.e., BMSCs (to adhere to the plasticware in culture dishes) and macrophages (to phagocytose liposomes). RESULTS: Liposomal clodronate added during the first passage of whole bone marrow culture was selectively engulfed by macrophages in the heterogeneous cell population, resulting in their effective elimination without affecting the MSCs.This method allowed the generation of numerous high-purity Sca-1 ＋ CD44 ＋ F4/80 - mBMSCs ([ 95%) with just one passaging. Comparative studies with mBMSCs obtained using conventional methods revealed that the mBMSCs obtained in the present study had remarkably improved experimental utilities, as demonstrated by in vitro multilineage differentiation and in vivo ectopic bone formation assays. CONCLUSION Our newly developed method, which enables the isolation of mBMSCs using simple and convenient protocol, will aid preclinical studies based on the use of MSCs.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

In preparation for the surge of coronavirus disease 2019 (COVID-19), it is crucial to allocate medical resources efficiently for distinguishing people who remain asymptomatic until the end of the disease. Between January 27, 2020, and April 21, 2020, 517 COVID-19 cases from 13 healthcare facilities in Gyeonggi province, Korea, were identified out of which the epidemiologic and clinical information of 66 asymptomatic patients at the time of diagnosis were analyzed retrospectively. An exposure-diagnosis interval within 7 days and abnormal aspartate aminotransferase levels were identified as characteristic symptom development in asymptomatic COVID-19 patients. If asymptomatic patients without these characteristics at the time of diagnosis could be differentiated early, more medical resources could be secured for mild or moderate cases in this COVID-19 surge.

BACKGROUND: The delivery of recombinant human bone morphogenetic protein 2 (rhBMP2) by using various carriers has been used to successfully induce bone formation in many animal models. However, the effect of multiple administration of rhBMP2 on bone formation and BMP2 antibody production has not been determined. Our aim was to examine the bone formation activity of rhBMP2 and serum levels of anti-BMP2 antibodies following the repeated administration of rhBMP2 in mice. METHODS: Absorbable collagen sponges or polyphosphazene hydrogels containing rhBMP2 were subcutaneously implanted or injected into one side on the back of six-week-old C57BL/6 mice. Three or 4 weeks later, the same amount of rhBMP2 was administered again with the same carrier into the subcutaneous regions on the other side of the back or into calvarial defects. The effects of a single administration of rhBMP2 on the osteoinductive ability in the ectopic model were compared with those of repeated administrations. In vivo ectopic or orthotopic bone formation was evaluated using microradiography and histological analyses. Serum concentrations of anti-rhBMP2 antibodies were measured by ELISAs. RESULTS: Re-administration of the same amount of rhBMP2 into the subcutaneous area showed a comparable production of ectopic bone as after the first administration. The bone forming ability of repeated rhBMP2 administrations was equal to that of single rhBMP2 administration. The administration of rhBMP2 into calvarial defects, following the first subcutaneous administration of rhBMP2 on the back, completely recovered the defect area with newly regenerated bone within 3 weeks. Repeated administration of rhBMP2 at 4-week intervals did not significantly alter the serum levels of antiBMP2 antibodies and did not induce any inflammatory response. The serum obtained from rhBMP2-exposed mice had no effect on the ability of rhBMP2 to induce osteogenic gene expressions in MC3T3-E1. CONCLUSION We suggest that the osteoinductive ability of rhBMP2 is not compromised by repeated administrations. Thus, rhBMP2 can be repeatedly used for bone regeneration at various sites within a short duration.

PURPOSE: To investigate the association of erectile dysfunction (ED), premature ejaculation (PE), and chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in men with late-onset hypogonadism (LOH).MATERIALS AND METHODS: We reviewed the data of 408 enrolled men between January 2014 and January 2019. All participants completed the Androgen Deficiency in the Aging Male (ADAM), international index of erectile function-5 (IIEF-5), National Institutes of Health chronic prostatitis symptom index (NIH-CPSI), and premature ejaculation diagnostic tool (PEDT) questionnaires. Participants were divided by ADAM positive (ADAM+: Group 1) and ADAM negative (ADAM−: Group 2).RESULTS: Total of 289 subjects were in Group 1 and 119 were in Group 2. The mean age was 53.8±7.8 years. The mean total testosterone was 4.8±1.2 ng/dL and showed no differences between the groups (p=0.839). In Groups 1 and 2, ED (IIEF≤21) was identified in 233 (80.6%) versus 37 (31.1%), respectively (p<0.001). The prevalence of PE (PEDT≥9) was 112 (38.7%) versus 13 (10.9%) in Groups 1 and 2, respectively (p<0.001). However, PE (intravaginal ejaculation latency time<5 minutes) showed no differences between the groups (p=0.863). The incidence of chronic prostatitis (NIH-CPSI pain score≥4) showed significant differences with 49 (17.0%) versus 8 (6.7%) in Groups 1 and 2, respectively (p=0.007). IIEF-5 total score showed the significantly highest negative correlation (r=−0.313, p<0.001).CONCLUSIONS: Those who complained of LOH symptoms and positive results in the ADAM questionnaire need to be assessed concurrently with the above questionnaires. This could aid useful to detect of ED, PE, and chronic prostatitis co-occurrence.

Purpose: The purpose of this study was to evaluate the ability of contrast-enhanced ultrasonography (CEUS) with microbubbles to detect metastatic lymph nodes (LNs) for treatment planning and prognosis. Methods: For the metastatic LN model, ground VX2 tumor tissues were injected subcutaneously in 12 rabbits, just below the right hind limb. The rabbits were classified into three groups based on the LN area: group A (n=4, >1.9 cm2 ), group B (n=4, 1-1.9 cm2 ), and group C (n=4, <1 cm2 ). The LNs were monitored on CEUS for 10 seconds after injecting 2.5 mL of microbubbles. The percent area of metastatic LNs was calculated on pathologic images and compared with CEUS images. Results: In group A, the mean percent area of metastasis was 40.7%±19.4%. In all cases of metastasis, round-shaped perfusion defects were clearly observed in CEUS images. The metastatic areas were strongly correlated with pathologic findings. The mean percent area in group B was 21.5%±14.4%. The CEUS findings showed multiple nodular perfusion defects, clearly revealing the metastatic areas. In group B, the CEUS and pathologic findings were concordant for three of the four cases. The mean percent area in group C was 9.1%±6.4%. However, in this group, CEUS only detected a small perfusion defect in one case. Conclusion CEUS has the potential to depict characteristic imaging features of metastatic LNs but still has limitations in early detection.