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.

Methods: Rats were allocated randomly into one of three groups: control, STZ, and STZ-insulin. Diabetes was induced by a single intraperitoneal injection of STZ (65 mg/kg) in the STZ and STZ-insulin groups. The blood glucose level was consistently above 400 mg/ dL in the STZ and STZ-insulin groups 2 weeks after STZ injection. After 2 weeks of STZ injection, the STZ-insulin group was administered insulin treatment (1.5 unit/100 g) daily for up to 4 weeks. Blood glucose of the STZ-insulin rats significantly decreased to normal levels 4 weeks after insulin treatment. The rats were sacrificed 6 weeks after STZ injection, and disc cells and tissues were harvested to investigate the expression of apoptosis markers and matrix metalloproteinases (MMPs). Results: Fas and caspase-8, -9, and -3 expressions were significantly increased in the STZ group, along with increased expressions of MMP-2 and -3. On the contrary, insulin treatment significantly decreased the expressions of Fas, caspase-8, -9, and -3 as well as MMP-2 and -3 in the STZ-insulin group. Conclusions The results of the current study demonstrated that insulin treatment attenuates excessive apoptosis of disc cells and matrix degradation in the diabetic rat model. Accordingly, strict blood glucose control should be recommended to prevent disc degeneration in diabetic patients.

Background and objectives: This study aimed to identify the characteristics and clinical outcomes of cancer patients who developed constrictive physiology (CP) after percutaneous pericardiocentesis. Methods: One-hundred thirty-three cancer patients who underwent pericardiocentesis were divided into 2 groups according to follow-up echocardiography (CP vs. non-CP). The clinical history, imaging findings, and laboratory results, and overall survival were compared. Results: CP developed in 49 (36.8%) patients after pericardiocentesis. The CP group had a more frequent history of radiation therapy. Pericardial enhancement and malignant masses abutting the pericardium were more frequently observed in the CP group. Fever and ST segment elevation were more frequent in the CP group, with higher C-reactive protein levels (6.6±4.3mg/dL vs. 3.3±2.5mg/dL, p<0.001). Pericardial fluid leukocytes counts were significantly higher, and positive cytology was more frequent in the CP group. In baseline echocardiography before pericardiocentesis, medial e′ velocity was significantly higher in the CP group (8.6±2.1cm/s vs. 6.5±2.3cm/s, p<0.001), and respirophasic ventricular septal shift, prominent expiratory hepatic venous flow reversal, pericardial adhesion, and loculated pericardial fluid were also more frequent. The risk of all-cause death was significantly high in the CP group (hazard ratio, 1.53; 95% confidence interval,1.10–2.13; p=0.005). Conclusions CP frequently develops after pericardiocentesis, and it is associated with poor survival in cancer patients. Several clinical signs, imaging, and laboratory findings suggestive of pericardial inflammation and/or direct malignant pericardial invasion are frequently observed and could be used as predictors of CP development.

Background/Aims: High-sensitivity cardiac troponin (hs-TnT) assays detect very low levels of cardiac troponin. This study examined the interval change between initial and subsequent hs-TnT levels and evaluated its ability to predict significant coronary stenosis. Methods: The study analyzed 163 patients who presented with acute coronary syndrome (ACS) and underwent coronary angiography (CAG) between April 2014 and May 2018. The 0 and 3-hour hs-TnT were checked. The patients were subdivided into positive (n = 32) and negative (n = 131) interval change groups. The presence of significant coronary artery stenosis on CAG in the two groups was compared. Results: The positive interval change group was older and had higher 0 and 3-hour hs-TnT and blood glucose levels than the negative interval change group. Significant coronary stenosis was more common in the positive interval change group than in the negative interval change group (68.8% vs. 23.7%, p = 0.001). However, vasospasm was more common in the negative interval change group (6.3% vs. 31.3%, p = 0.003). The positive interval change group had higher rates of bifurcation lesions and received more percutaneous coronary intervention. In multivariate analysis, age, interval change of serial hs-TnT and diabetes mellitus were independent predictors of significant coronary artery stenosis. Conclusions This study identified a relationship between the serial change in cardiac biomarkers and the presence of significant coronary stenosis in patients with ACS. Serial hs-TnT change was associated with real angiographic stenosis in patients with ACS.

Background/Aims: High-sensitivity cardiac troponin (hs-TnT) assays detect very low levels of cardiac troponin. This study examined the interval change between initial and subsequent hs-TnT levels and evaluated its ability to predict significant coronary stenosis. Methods: The study analyzed 163 patients who presented with acute coronary syndrome (ACS) and underwent coronary angiography (CAG) between April 2014 and May 2018. The 0 and 3-hour hs-TnT were checked. The patients were subdivided into positive (n = 32) and negative (n = 131) interval change groups. The presence of significant coronary artery stenosis on CAG in the two groups was compared. Results: The positive interval change group was older and had higher 0 and 3-hour hs-TnT and blood glucose levels than the negative interval change group. Significant coronary stenosis was more common in the positive interval change group than in the negative interval change group (68.8% vs. 23.7%, p = 0.001). However, vasospasm was more common in the negative interval change group (6.3% vs. 31.3%, p = 0.003). The positive interval change group had higher rates of bifurcation lesions and received more percutaneous coronary intervention. In multivariate analysis, age, interval change of serial hs-TnT and diabetes mellitus were independent predictors of significant coronary artery stenosis. Conclusions This study identified a relationship between the serial change in cardiac biomarkers and the presence of significant coronary stenosis in patients with ACS. Serial hs-TnT change was associated with real angiographic stenosis in patients with ACS.

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients. METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death. RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes. CONCLUSIONS Mean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.

We describe the occurrence of acute type A aortic dissection in a patient with situs inversus totalis. A 37-year-old man presented to the emergency department with acute chest pain. Initial chest X-ray findings showed a right-sided heart and a left-sided liver. Contrast-enhanced computed tomography revealed a Stanford type A acute aortic dissection, aortic root dilatation, and situs inversus totalis. All of the thoracic structures were mirror-image reversed and an abnormal coronary artery was observed. The Bentall operation was performed. This report demonstrates that computed tomography and echocardiography were useful for understanding the anatomy and the presence or absence of concurrent anomalies in a patient with situs inversus totalis. The patient’s postoperative course was uneventful.

Kommerell diverticulum is a rare congenital anomaly of the aortic arch characterized by dilation at the proximal descending aorta, which gives rise to an aberrant subclavian artery. Kommerell diverticulum is usually asymptomatic, but can also be associated with symptoms due to compression of the esophagus or trachea, and can rarely be fatal due to dissection or rupture of the diverticulum. Here, we report a rare case of dysphagia caused by compression of the esophagus by Kommerell diverticulum originating from the right-sided aortic arch.

BACKGROUND AND OBJECTIVES: Although anticoagulation with warfarin is recommended as an international normalized ratio (INR) of prothrombin time between 2.0 and 3.0 and mean time in the therapeutic range (TTR) ≥70%, little has been proven that universal criteria might be suitable in Korean atrial fibrillation (AF) patients.METHODS: We analyzed 710 patients with non-valvular AF who took warfarin. INR value and clinical outcomes were assessed during 2-year follow-up. Intensity of anticoagulation was assessed as mean INR value and TTR according to target INR range. Primary net-clinical outcome was defined as the composite of new-onset stroke and major bleeding. Secondary net-clinical outcome was defined as the composite of new-onset stroke, major bleeding and death.RESULTS: Thromboembolism was significantly decreased when mean INR was over 1.6. Major bleeding was significantly decreased when TTR was over 70% and mean INR was less than 2.6. Mean INR 1.6–2.6 significantly reduced thromboembolism (adjusted hazard ratio [HR], 0.40; 95% confidence interval [CI], 0.19–0.85), major bleeding (HR, 0.43; 95% CI, 0.23–0.81), primary (HR, 0.50; 95% CI, 0.29–0.84) and secondary (HR, 0.45; 95% CI, 0.28–0.74) net-clinical outcomes, whereas mean INR 2.0–3.0 did not. Simultaneous satisfaction of mean INR 1.6–2.6 and TTR ≥70% was associated with significant risk reduction of major bleeding, primary and secondary net-clinical outcomes.CONCLUSIONS: Mean INR 1.6–2.6 was better than mean INR 2.0–3.0 for the prevention of thromboembolism and major bleeding. However, INR 1.6–2.6 and TTR ≥70% had similar clinical outcomes to INR 2.0–3.0 and TTR ≥70% in Korean patients with non-valvular AF.
Atrial Fibrillation ; Follow-Up Studies ; Hemorrhage ; Humans ; International Normalized Ratio ; Prothrombin Time ; Risk Reduction Behavior ; Stroke ; Thromboembolism ; Warfarin

BACKGROUND AND OBJECTIVES: Although current guidelines recommend early initiation of statin in patients with acute myocardial infarction (AMI), there is no consensus for optimal timing of statin initiation. METHODS: A total of 3,921 statin-naïve patients undergoing percutaneous coronary intervention were analyzed, and divided into 3 groups according to statin initiation time: group 1 (statin initiation <24 hours after admission), group 2 (24–48 hours) and group 3 (≥48 hours). We also made 3 stratified models to reduce bias: model 1 (<24 hours vs. ≥24 hours), model 2 (<48 hours vs. ≥48 hours) and model 3 (<24 hours vs. 24–48 hours). The endpoint was major adverse cardiac events (MACE; composite of cardiac death, myocardial infarction and target-vessel revascularization) during median 3.8 years. RESULTS: During follow-up, incidence of MACE was lower in early statin group in both model 1 (14.3% vs. 18.4%, hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.66–0.91; p=0.002) and model 2 (14.6% vs. 19.7%, HR, 0.81; 95% CI, 0.67–0.97; p=0.022). After propensity-score matching, results remained unaltered. Statin initiation <24 hours reduced MACE compared to statin initiation ≥24 hours in model 1. Statin initiation <48 hours also reduced MACE compared to statin initiation later in model 2. However, there was no difference in incidence of MACE between statin initiation <24 hours and 24–48 hours) in model 3. CONCLUSIONS: Early statin therapy within 48 hours after admission in statin-naïve patients with AMI reduced long-term clinical outcomes compared with statin initiation later. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02385682
Bias (Epidemiology) ; Consensus ; Death ; Follow-Up Studies ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention