Background: It is well known that a large number of patients with diabetes also have dyslipidemia, which significantly increases the risk of cardiovascular disease (CVD). This study aimed to evaluate the efficacy and safety of combination drugs consisting of metformin and atorvastatin, widely used as therapeutic agents for diabetes and dyslipidemia. Methods: This randomized, double-blind, placebo-controlled, parallel-group and phase III multicenter study included adults with glycosylated hemoglobin (HbA1c) levels >7.0% and <10.0%, low-density lipoprotein cholesterol (LDL-C) >100 and <250 mg/dL. One hundred eighty-five eligible subjects were randomized to the combination group (metformin+atorvastatin), metformin group (metformin+atorvastatin placebo), and atorvastatin group (atorvastatin+metformin placebo). The primary efficacy endpoints were the percent changes in HbA1c and LDL-C levels from baseline at the end of the treatment. Results: After 16 weeks of treatment compared to baseline, HbA1c showed a significant difference of 0.94% compared to the atorvastatin group in the combination group (0.35% vs. −0.58%, respectively; P<0.0001), whereas the proportion of patients with increased HbA1c was also 62% and 15%, respectively, showing a significant difference (P<0.001). The combination group also showed a significant decrease in LDL-C levels compared to the metformin group (−55.20% vs. −7.69%, P<0.001) without previously unknown adverse drug events. Conclusion The addition of atorvastatin to metformin improved HbA1c and LDL-C levels to a significant extent compared to metformin or atorvastatin alone in diabetes and dyslipidemia patients. This study also suggested metformin’s preventive effect on the glucose-elevating potential of atorvastatin in patients with type 2 diabetes mellitus and dyslipidemia, insufficiently controlled with exercise and diet. Metformin and atorvastatin combination might be an effective treatment in reducing the CVD risk in patients with both diabetes and dyslipidemia because of its lowering effect on LDL-C and glucose.

We assessed the risk factors for major amputation of diabetic foot ulcers (DFUs) in patients with diabetic kidney disease (DKD) stages 3b–5. For DFU assessment, in addition to DFU location and presence of infection, ischemia, and neuropathy, vascular calcification was assessed using the medial arterial calcification (MAC) score. Of 210 patients, 26 (12.4%) underwent major amputations. Only the location and extension of DFU, represented by Texas grade differed between the minor and major amputation groups. However, after adjusting for covariates, ulcer location of mid- or hindfoot (vs. forefoot, odds ratio [OR] = 3.27), Texas grades 2 or 3 (vs. grade 0, OR = 5.78), and severe MAC (vs. no MAC, OR = 4.46) was an independent risk factor for major amputation (all P < 0.05). The current use of antiplatelets was a possible protective factor for major amputations (OR = 0.37, P = 0.055). In conclusion, DFU with severe MAC is associated with major amputation in patients with DKD.

Background: To investigate the efficacy and safety of moderate-intensity rosuvastatin/ezetimibe combination compared to highintensity rosuvastatin in high atherosclerotic cardiovascular disease (ASCVD) risk patients with type 2 diabetes mellitus (T2DM). Methods: This study was a randomized, multicenter, open, parallel phase 4 study, and enrolled T2DM subjects with an estimated 10-year ASCVD risk ≥7.5%. The primary endpoint was the low-density lipoprotein cholesterol (LDL-C) change rate after 24-week rosuvastatin 10 mg/ezetimibe 10 mg treatment was non-inferior to that of rosuvastatin 20 mg. The achievement proportion of 10-year ASCVD risk <7.5% or comprehensive lipid target (LDL-C <70 mg/dL, non-high-density lipoprotein cholesterol <100 mg/dL, and apolipoprotein B <80 mg/dL) without discontinuation, and several metabolic parameters were explored as secondary endpoints. Results: A hundred and six participants were assigned to each group. Both groups showed significant reduction in % change of LDL-C from baseline at week 24 (–63.90±6.89 vs. –55.44±6.85, combination vs. monotherapy, p=0.0378; respectively), but the combination treatment was superior to high-intensity monotherapy in LDL-C change (%) from baseline (least square [LS] mean difference, –8.47; 95% confidence interval, –16.44 to –0.49; p=0.0378). The combination treatment showed a higher proportion of achieved comprehensive lipid targets rather than monotherapy (85.36% vs. 62.22% in monotherapy, p=0.015). The ezetimibe combination significantly improved homeostasis model assessment of β-cell function even without A1c changes (LS mean difference, 17.13; p=0.0185). Conclusion In high ASCVD risk patients with T2DM, the combination of moderate-intensity rosuvastatin and ezetimibe was not only non-inferior but also superior to improving dyslipidemia with additional benefits compared to high-intensity rosuvastatin monotherapy.

Background: This study investigates the long-term efficacy and safety of evogliptin add-on therapy in patients with inadequately controlled type 2 diabetes mellitus (T2DM) previously received dapagliflozin and metformin (DAPA/MET) combination. Methods: In this multicenter randomized placebo-controlled phase 3 trial, patients with glycosylated hemoglobin (HbA1c) levels 7.0% to 10.5% (n=283) previously used DAPA 10 mg plus MET (≥1,000 mg) were randomly assigned to the evogliptin 5 mg once daily or placebo group (1:1). The primary endpoint was the difference in the HbA1c level from baseline at week 24, and exploratory endpoints included the efficacy and safety of evogliptin over 52 weeks (trial registration: ClinicalTrials.gov NCT04170998). Results: Evogliptin add-on to DAPA/MET therapy was superior in HbA1c reduction compared to placebo at weeks 24 and 52 (least square [LS] mean difference, –0.65% and –0.55%; 95% confidence interval [CI], –0.79 to –0.51 and –0.71 to –0.39; P<0.0001). The proportion of patients achieving HbA1c <7% was higher in the triple combination group at week 52 (32.14% vs. 8.51% in placebo; odds ratio, 5.62; P<0.0001). Evogliptin significantly reduced the fasting glucose levels and mean daily glucose levels with improvement in homeostatic model assessment of β-cell function (LS mean difference, 9.04; 95% CI, 1.86 to 16.21; P=0.0138). Adverse events were similar between the groups, and no serious adverse drug reactions were reported in the evogliptin group. Conclusion Long-term triple combination with evogliptin added to DAPA/MET showed superior HbA1c reduction and glycemic control compared to placebo at 52 weeks and was well tolerated.

Background: Unlike gestational diabetic mellitus (GDM), which is strictly managed by most patients and physicians, obesity does not have proper management guidelines, and the importance of its management during pregnancy is often ignored. The aim of this study was to compare maternal and neonatal outcomes according to obesity and GDM, alone or in combination. Methods: This was a retrospective cohort study of 3,078 consecutive pregnant women who experienced prenatal care and delivery of a live singleton neonate between January 2016 and December 2020 at our institution. Study participants were categorized into 4 mutually exclusive groups, as follows: group 1, no GDM without obesity; group 2, GDM without obesity; group 3, no GDM with obesity; and group 4, GDM with obesity. Results: Compared to group 2, group 3 had higher rates of pre-eclampsia, cesarean section including emergent cesarean section rate. Also, neonates in group 3 were heavier and had lower glucose levels compared to those in group 2. Of note, there was no significant difference in maternal or neonatal outcomes except the rate of large-for-gestational-age (LGA) between group 1 and group 2. Among the GDM groups, group 4 had higher risks for pre-eclampsia, cesarean section, and LGA infant status than group 2. Conclusion Our data showed that obese women without GDM face higher risk of adverse pregnancy outcomes than women with supervised GDM and non-obese women. We also confirmed that adverse pregnancy outcomes associated with GDM were mainly attributable to obesity among women receiving GDM education.

This study aimed to determine the influence of pre-pregnancy body mass index on pregnancy outcomes in gestational diabetes mellitus (GDM), comparing underweight patients with GDM with normal weight patients with GDM. Maternal baseline characteristics, ultrasonographic results, and pregnancy and neonatal outcomes were reviewed in 946 women with GDM with singleton pregnancies. Underweight patients with GDM showed a benign course in most aspects during pregnancy, except for developing a higher risk of giving birth to small for gestational age neonates. Underweight women with GDM required less insulin treatment, had a higher rate of vaginal delivery, and had a lower rate of cesarean delivery. In addition, their neonates were more likely to have fetal abdominal circumference and estimated fetal weight below the 10th percentile both at the time of GDM diagnosis and before delivery. Notably, their risk for preeclampsia and macrosomia were lower. Collectively, our data suggest that underweight women with GDM may require a different approach in terms of diagnosis and management throughout their pregnancy.

Objectives: . Sensitization to specific inhalant allergens is a major risk factor for the development of atopic diseases, which impose a major socioeconomic burden and significantly diminish quality of life. However, patterns of inhalant allergic sensitization have yet to be precisely described. Therefore, to enhance the understanding of aeroallergens, we performed a cluster analysis of inhalant allergic sensitization using a computational model. Methods: . Skin prick data were collected from 7,504 individuals. A positive skin prick response was defined as an allergen-to-histamine wheal ratio ≥1. To identify the clustering of inhalant allergic sensitization, we performed computational analysis using the four-parameter unified-Richards model. Results: . Hierarchical cluster analysis grouped inhalant allergens into three clusters based on the Davies-Bouldin index (0.528): cluster 1 (Dermatophagoides pteronyssinus and Dermatophagoides farinae), cluster 2 (mugwort, cockroach, oak, birch, cat, and dog), and cluster 3 (Alternaria tenus, ragweed, Candida albicans, Kentucky grass, and meadow grass). Computational modeling revealed that each allergen cluster had a different trajectory over the lifespan. Cluster 1 showed a high level (>50%) of sensitization at an early age (before 19 years), followed by a sharp decrease in sensitization. Cluster 2 showed a moderate level (10%–20%) of sensitization before 29 years of age, followed by a steady decrease in sensitization. However, cluster 3 revealed a low level (<10%) of sensitization at all ages. Conclusion . Computational modeling suggests that allergic sensitization consists of three clusters with distinct patterns at different ages. The results of this study will be helpful to allergists in managing patients with atopic diseases.

Primary hepatic mixed germ cell tumor (GCT) is very rare, and less than 10 cases have been reported. We report a case of mixed GCT composed of a choriocarcinoma and yolk sac tumor, which occurred in the liver of a 40-year-old woman. A large mass was detected by computed tomography solely in the liver. Serum β-human chorionic gonadotropin (hCG) was highly elevated, otherwise, other serum tumor markers were slightly elevated or within normal limits. For hepatic choriocarcinoma, neoadjuvant chemotherapy was administered, followed by right lobectomy. Histologic features of the resected tumor revealed characteristic choriocarcinoma features with diffuse positivity for hCG in the syncytiotrophoblasts and diffuse positivity for α-fetoprotein and Sal-like protein 4 in the yolk sac tumor components. Primary malignant GCT in the liver is associated with a poor prognosis and requires specific treatment. Therefore, GCT should be considered during a differential diagnosis of a rapidly growing mass in the liver.

Objective: This study aimed to evaluate the reliability and validity of the Korean version of the Pornography Craving Questionnaire (K-PCQ) using classical test theory and item response theory. Methods: The goodness of fit test and differential item functioning (DIF) analysis based on the Rasch model, confirmatory factor analysis (CFA), exploratory factor analysis (EFA), and correlation analysis were used to test its reliability and validity. Results: Response data from 226 students were analyzed. According to the goodness of fit test, the outfit mean square value of only one item, Item 11, was greater than 2. The CFA results revealed that all items of the K-PCQ measured a single construct. The EFA results revealed that the K-PCQ had excellent internal reliability. The DIF analysis results showed that the measurement of pornography craving using the K-PCQ did not differ based on gender. The result of Poly-DIMTEST supported the unidimensionality of the K-PCQ. The cut-off value of pornography craving was suggested as a measure of -0.0908 which corresponds to 46 (54.8%) out of a maximum score of 84. Conclusion The items of the K-PCQ are unidimensional and have good reliability and validity. The K-PCQ will be useful in clinical practice and research as a screening tool for pornography craving.

Purpose: Postoperative pain and delayed wound healing are the main complications following anal surgery associated with poor quality of life. Hyaluronic acid (HA) supports tissue regeneration and rapid wound healing by promoting cell proliferation and migration. We investigated the effects of HA on perianal wound healing in a rat model. Methods: Forty-eight 8-week-old Sprague-Dawley rats with perianal wounds created by biopsy punch were divided into 3 groups: simple dressing with gauze (control), dressing with topical HA film, and dressing with topical HA gel. HA agents were not reapplied postoperatively. Wound healing was evaluated by measuring the healed area, and histological analyses were randomly performed using hematoxylin and eosin and Masson trichrome staining. Results: Fewer mean days were required for complete wound healing in the HA film and HA gel groups than in the control group (11.6 vs. 11.9 vs. 13.8 days, respectively; P = 0.010). The healed area in the HA film group on day 11 was larger than that in the HA gel and control groups (80.2% vs. 61.9% vs. 53.2%, respectively; P < 0.001). Histologically, the HA film group showed accelerated reepithelialization, a rapid transition to lymphocyte-predominant inflammation, and increased fibroblastic proliferation and collagen deposition compared to the other groups. There was no treatment-related toxicity in the HA application groups. Conclusion Topical application of HA film to perianal wounds improves the wound healing rate in a rat model. This finding suggests a potential benefit of HA film application in promoting wound healing after anal surgery in humans.