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: Spinopelvic fixation (SPF) has been a challenge for surgeons despite the advancements in instruments and surgical techniques. C-arm fluoroscopy-guided SPF is a widely used safe technique that utilizes the tear drop view. The tear drop view is an image of the corridor from the posterior superior iliac spine to the anterior inferior iliac spine (AIIS) of the pelvis. This study aimed to define the safe optimal tear drop view using three-dimensional reconstruction of computed tomography images. Methods: Three-dimensional reconstructions of the pelvises of 20 individuals were carried out. By rotating the reconstructed model, we simulated SPF with a cylinder representing imaginary screw. The safe optimal tear drop view was defined as the one embracing a corridor with the largest diameter with the inferior tear drop line not below the acetabular line and the lateral tear drop line medial to the AIIS. The distance between the lateral border of the tear drop and AIIS was defined as tear drop index (TDI) to estimate the degree of rotation on the plane image. Tear drop ratio (TDR), the ratio of the distance between the tear drop center and the AIIS to TDI, was also devised for more intuitive application of our simulation in a real operation. Results: All the maximum diameters and lengths were greater than 9 mm and 80 mm, respectively, which are the values of generally used screws for SPF at a TDI of 5 mm and 10 mm in both sexes. The TDRs were 3.40 ± 0.41 and 3.35 ± 0.26 in men and women, respectively, at a TDI of 5 mm. The TDRs were 2.26 ± 0.17 and 2.14 ± 0.12 in men and women, respectively, at a TDI of 10 mm. Conclusions The safe optimal tear drop view can be obtained with a TDR of 2.5 to 3 by rounding off the measured values for intuitive application in the actual surgical field.

Background: Various implants are used to treat intertrochanteric fractures. However, the optimal implant to stabilize intertrochanteric femoral fractures is still a matter of debate. The purpose of the present study was to evaluate the midterm outcomes of patients treated using compression hip nails (CHNs). Methods: Between March 2013 and April 2018, 164 patients with intertrochanteric femoral fractures who were treated with internal fixation using CHNs were enrolled in this study. The mean age of the patients was 79.6 years. We retrospectively collected and estimated information such as reduction state, implant position, operation time, blood loss, hospital stay, time to achieve union, clinical scores (Harris hip score [HHS] and EuroQol five-dimensional [EQ-5D]), intraoperative complications (such as lag jamming and drill bit breakage), failure of fixation, avascular necrosis, and surgical site infection. Results: The mean follow-up period was 39.69 months. Eight percent of the patients required an open reduction. The mean operation time was 131 minutes, the mean blood loss was 221.19 mL, the mean hospital stay was 20.66 days, and the average time to union was 18 weeks. Intraoperative complications included 8 cases of breakage of the drill bit while making distal holes. The failure rate was 3.7% and revision surgery was performed in 6 cases (for cut-out in 5 and pull-out of the lag screw in 1). Asymptomatic venous thromboembolism occurred in 2 cases and hematoma requiring intervention occurred in 1 case. There were no other complications such as avascular necrosis, infection, and lateral irritation. At the 2-year follow-up, the averages of HHS and EQ-5D were 71.54 and 0.68, respectively. Conclusions Among the implants used to treat intertrochanteric femoral fractures, CHNs had a surgical failure of 3.7% and showed good radiologic and clinical results.

Background: Current international guidelines recommend against deep sedation as it is associated with worse outcomes in the intensive care unit (ICU). However, in Korea the prevalence of deep sedation and its impact on patients in the ICU are not well known. Methods: From April 2020 to July 2021, a multicenter, prospective, longitudinal, noninterventional cohort study was performed in 20 Korean ICUs. Sedation depth extent was divided into light and deep using a mean Richmond Agitation–Sedation Scale value within the first 48 hours. Propensity score matching was used to balance covariables; the outcomes were compared between the two groups. Results: Overall, 631 patients (418 [66.2%] and 213 [33.8%] in the deep and light sedation groups, respectively) were included. Mortality rates were 14.1% and 8.4% in the deep and light sedation groups (P = 0.039), respectively. Kaplan-Meier estimates showed that time to extubation (P < 0.001), ICU length of stay (P = 0.005), and death P = 0.041) differed between the groups. After adjusting for confounders, early deep sedation was only associated with delayed time to extubation (hazard ratio [HR], 0.66; 95% confidence inter val [CI], 0.55– 0.80; P < 0.001). In the matched cohort, deep sedation remained significantly associated with delayed time to extubation (HR, 0.68; 95% 0.56–0.83; P < 0.001) but was not associated with ICU length of stay (HR, 0.94; 95% CI, 0.79–1.13; P = 0.500) and in-hospital mortality (HR, 1.19; 95% CI, 0.65–2.17; P = 0.582). Conclusion In many Korean ICUs, early deep sedation was highly prevalent in mechanically ventilated patients and was associated with delayed extubation, but not prolonged ICU stay or in-hospital death.

Purpose: Agonists of the stimulator of interferon genes (STING) play a key role in activating the STING pathway by promoting the production of cytokines. In this study, we investigated the antitumor effects and activation of the systemic immune response of treatment with DMXAA (5,6-dimethylxanthenone-4-acetic acid), a STING agonist, in EML4-ALK lung cancer and CT26 colon cancer. Materials and Methods: The abscopal effects of DMXAA in the treatment of metastatic skin nodules were assessed. EML4-ALK lung cancer and CT26 colon cancer models were used to evaluate these effects after DMXAA treatment. To evaluate the expression of macrophages and T cells, we sacrificed the tumor-bearing mice after DMXAA treatment and obtained the formalin-fixed paraffin-embedded (FFPE) tissue and tumor cells. Immunohistochemistry and flow cytometry were performed to analyze the expression of each FFPE and tumor cell. Results: We observed that highly infiltrating immune cells downstream of the STING pathway had increased levels of chemokines after DMXAA treatment. In addition, the levels of CD80 and CD86 in antigen-presenting cells were significantly increased after STING activation. Furthermore, innate immune activation altered the systemic T cell-mediated immune responses, induced proliferation of macrophages, inhibited tumor growth, and increased numbers of cytotoxic memory T cells. Tumor-specific lymphocytes also increased in number after treatment with DMXAA. Conclusion The abscopal effect of DMXAA treatment on the skin strongly reduced the spread of EML4-ALK lung cancer and CT26 colon cancer through the STING pathway and induced the presentation of antigens.

Purpose: To investigate the limited response to aflibercept after switching to aflibercept in neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 70 eyes with neovascular AMD that were initially treated with ranibizumab and then switched to aflibercept. The incidence and timing of the limited response to aflibercept were identified and visual outcome was compared between eyes with and without limited response. In addition, factors predictive of limited response were analyzed. Results: A limited response to aflibercept was noted in approximately 1/5 of the patients who underwent switching to aflibercept in neovascular AMD. Switching to aflibercept was performed at a mean of 16.2 ± 12.7 months after diagnosis. During the mean 34.7 months of follow-up after switching, limited response was noted in 15 eyes (21.4%) at a mean of 22.0 ± 13.9 months after switching. The degree of reduction in visual acuity was mean logMAR 0.34 ± 0.41 in eyes with limited response and mean 0.06 ± 0.20 in eyes without (p = 0.002). In addition, the duration between the diagnosis and the switching was shorter (p = 0.012), and the number of ranibizumab injections before switching was lower (p = 0.016) in eyes with limited response than in eyes without. Conclusions Patients who showed limited response to aflibercept after switching to aflibercept showed a worse visual outcome. The probability of having a limited response is higher when the switching is performed earlier.

Objectives: ：In this study, socio-demographic, drinking and emotional characteristics, and their correlations were compared among patients with alcohol use disorder (AUD) according to the presence or absence of any type of criminal record. Methods: ：Among patients admitted to the hospital with AUD, 27 with and 31 without criminal records were included. Socio-demographic data and drinking characteristics such as first drinking age, average daily alcohol consumption were collected. In addition, the severity of alcohol problems, the degree of change readiness for drinking alcohol, depressive symptoms, anxiety symptoms, and impulsivity were evaluated using scales and statistically analyzed. Pearson’s correlation test was applied to reveal the differences in correlation of the characteristics according to the presence or absence of criminal records. Results: ：The first drinking age was significantly earlier in the AUD group with criminal records. Interestingly, the degree of change readiness regarding alcohol problem as shown in SOCRATES-K was significantly higher in the AUD group with criminal records. Anxiety symptoms were statistically significantly higher in the AUD group with criminal records. In AUD with criminal records, first drinking age negatively correlated with the degree of change readiness. In AUD without criminal records, first drinking age correlated negatively with the severity of alcohol problem, and the degree of change readiness, and the degree of change readiness negatively with age, and the degree of change readiness positively with the severity of alcohol problem. In Both groups, anxiety symptoms positively correlated with depressive symptoms. Conclusions ：This study showed that AUD patients with criminal record had a faster first drinking age and the higher degree of change readiness regarding alcohol problem. Significantly higher symptoms of anxiety were also presented in AUD patients with criminal record than AUD patients who have no criminal records. Some differences were identified in correlations among characteristics between the two groups.

Purpose: To investigate the limited response to aflibercept after switching to aflibercept in neovascular age-related macular degeneration (AMD). Methods: This retrospective study included 70 eyes with neovascular AMD that were initially treated with ranibizumab and then switched to aflibercept. The incidence and timing of the limited response to aflibercept were identified and visual outcome was compared between eyes with and without limited response. In addition, factors predictive of limited response were analyzed. Results: A limited response to aflibercept was noted in approximately 1/5 of the patients who underwent switching to aflibercept in neovascular AMD. Switching to aflibercept was performed at a mean of 16.2 ± 12.7 months after diagnosis. During the mean 34.7 months of follow-up after switching, limited response was noted in 15 eyes (21.4%) at a mean of 22.0 ± 13.9 months after switching. The degree of reduction in visual acuity was mean logMAR 0.34 ± 0.41 in eyes with limited response and mean 0.06 ± 0.20 in eyes without (p = 0.002). In addition, the duration between the diagnosis and the switching was shorter (p = 0.012), and the number of ranibizumab injections before switching was lower (p = 0.016) in eyes with limited response than in eyes without. Conclusions Patients who showed limited response to aflibercept after switching to aflibercept showed a worse visual outcome. The probability of having a limited response is higher when the switching is performed earlier.

There are limited data on the impact of diabetes control on the risk of subclinical coronary atherosclerosis.

Cell labeling technologies are required to monitor the fate of transplanted cells in vivo and to select target cells for the observation of certain changes in vitro. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) have been transplanted for the treatment of heart injuries or used in vitro for preclinical cardiac safety assessments. Cardiomyocyte (CM) labeling has been used in these processes to facilitate target cell monitoring. However, the functional effect of the labeling agent on hiPSC-CMs has not been studied. Therefore, we investigated the effects of labeling agents on CM cellular functions. 3’-Dioctadecyloxacarbocyanine perchlorate (DiO), quantum dots (QDs), and a DNA plasmid expressing EGFP using Lipo2K were used to label hiPSC-CMs. We conclude that the hiPSC-CM labeling with DiO and QDs does not induce arrhythmogenic effects but rather improves the mRNA expression of cardiac ion channels and Ca2＋ influx by L-type Ca2＋ channels. Thus, DiO and QD labeling agents may be useful tools to monitor transplanted CMs, and further in vivo influences of the labeling agents should be investigated in the future.