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.

Patients with heart failure undergoing surgery that requires general anesthesia face substantial perioperative risks; however, clear guidelines are not available for anesthesia management in patients with a reduced left ventricular ejection fraction. Traditional intravenous and volatile anesthetics require careful administration to prevent severe hypotension and bradycardia in patients with heart failure. Remimazolam has emerged as a promising alternative to conventional anesthetics because of its reduced cardiovascular depressive effects. We present three cases illustrating the successful use of remimazolam to induce and maintain general anesthesia in patients with heart failure and reduced cardiac function. Our cases demonstrate the safe use of remimazolam for general anesthesia in patients with heart failure and a reduced ejection fraction.

Purpose: To investigate chorioretinal vascular changes in the non-surgical eyes of patients who underwent vitreoretinal surgery under general anesthesia using optical coherence tomography angiography (OCTA). Methods: Data from 40 patients who underwent retinal surgery were retrospectively analyzed. Ophthalmologic examinations (including OCTA) were performed in the morning before and after surgery. The presence of intraoperative hypotension (IOH; mean arterial pressure <70 mmHg) was determined based on medical records. The vessel density of superficial and deep retinal capillary plexus layers, choriocapillaris void features, and thickness of the choroid and retina were quantified after image processing. Associations between retinal OCTA parameters and anesthesia profiles were also assessed. Results: DCP vessel density was increased after general anesthesia (p < 0.05). Among the patients who experienced IOH, there was no statistical difference in chorioretinal vessel parameters before and after general anesthesia. Also, we did not observe a difference in chorioretinal vessel parameters after general anesthesia between healthy patients and patients with chronic disease, including hypertension and diabetes (p > 0.05). The duration of anesthesia and average size of the choriocapillaris void (p < 0.05, r = -0.32), and the intraoperative mean arterial pressure (MAP) fluctuation and DCP, showed statistically significant negative linear correlations (p < 0.05, r = -0.38). The choriocapillaris void size and intraoperative MAP fluctuation also displayed a significant negative correlation (p < 0.05, r = -0.37), while the average size signal void showed a weak positive linear correlation (p < 0.01, r = 0.41; and p < 0.01, r = 0.44, respectively). Conclusions This is the first study to assess the effects of general anesthesia on chorioretinal vessels using OCTA. The Vessel density of the DCP was significantly increased in the non-surgical eye after total vitrectomy under general anesthesia. Furthermore, we found a correlation between MAP fluctuation and choriocapillaris void features. More studies are needed to confirm and expand on these observations.

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM).

Background: Only few studies have shown the efficacy and safety of glucose-control strategies using the quadruple drug combination. Therefore, the aim of the present study was to investigate the usefulness of the quadruple combination therapy with oral hypoglycemic agents (OHAs) in patients with uncontrolled type 2 diabetes mellitus (T2DM). Methods: From March 2014 to December 2018, data of patients with T2DM, who were treated with quadruple hypoglycemic medications for over 12 months in 11 hospitals in South Korea, were reviewed retrospectively. We compared glycosylated hemoglobin (HbA1c) levels before and 12 months after quadruple treatment with OHAs. The safety, maintenance rate, and therapeutic patterns after failure of the quadruple therapy were also evaluated. Results: In total, 357 patients were enrolled for quadruple OHA therapy, and the baseline HbA1c level was 9.0%±1.3% (74.9± 14.1 mmol/mol). After 12 months, 270 patients (75.6%) adhered to the quadruple therapy and HbA1c was significantly reduced from 8.9%±1.2% to 7.8%±1.3% (mean change, –1.1%±1.2%; P<0.001). The number of patients with HbA1c <7% increased significantly from 5 to 68 (P<0.005). In addition, lipid profiles and liver enzyme levels were also improved whereas no changes in body weight. There was no significant safety issue in patients treated with quadruple OHA therapy. Conclusion This study shows the therapeutic efficacy of the quadruple OHA regimen T2DM and demonstrates that it can be an option for the management of T2DM patients who cannot use insulin or reject injectable therapy.

The flowability of a root canal sealer is clinically important because it improves the penetration of the sealer into the complex root canal system. The purpose of this study was to compare the flowabilities of four root canal sealers, measured using the simple press method (ISO 6876), and their viscosities, measured using a strain-controlled rheometer. A newly developed, calcium phosphate-based root canal sealer (Capseal) and three commercial root canal sealers (AH Plus, Sealapex and Pulp Canal Sealer EWT) were used in this study. The flowabilities of the four root canal sealers were measured using the simple press method (n=5) and their viscosities were measured using a strain-controlled rheometer (n=5). The correlation between these two values was statistically analysed using Spearman's correlation test. The flow diameters and the viscosities of the root canal sealers were strongly negatively correlated (ρ=-0.8618). The viscosity of Pulp Canal Sealer EWT was the lowest and increased in the following order: AH Plus Materials Testing ; Rheology ; Root Canal Filling Materials ; Temperature ; Viscosity

PURPOSE: Stem cell-based therapies represent new promises for the treatment of urinary incontinence. This study was performed to assess optimized cell passage number, cell dose, therapeutic efficacy, feasibility, toxicity, and cell trafficking for the first step of the pre-clinical evaluation of human amniotic fluid stem cell (hAFSC) therapy in a urinary incontinence animal model. MATERIALS AND METHODS: The proper cell passage number was analyzed with hAFSCs at passages 4, 6, and 8 at week 2. The cell dose optimization included 1x10(4), 1x10(5), and 1x10(6) cells at week 2. The in vivo cell toxicity was performed with 0.25x10(6), 0.5x10(6), and 1x10(6) cells at weeks 2 and 4. Cell tracking was performed with 1x10(6) cells at weeks 2 and 4. RESULTS: The selected optimal cell passage number was smaller than 6, and the optimal cell dose was 1x10(6) for the mouse model. In our pre-clinical study, hAFSC-injected animals showed normal values for several parameters. Moreover, the injected cells were found to be non-toxic and non-tumorigenic. Furthermore, the injected hAFSCs were rarely identified by in vivo cell trafficking in the target organs at week 2. CONCLUSION: This study demonstrates for the first time the pre-clinical efficacy and safety of hAFSC injection in the urinary incontinence animal model and provides a basis for future clinical applications.
Amniotic Fluid/*cytology ; Animals ; Cell Movement ; Disease Models, Animal ; Humans ; Injections ; Mice ; Stem Cell Transplantation/*methods ; Stem Cells/*cytology ; Treatment Outcome ; Urinary Incontinence/*therapy

Background The clinical significance of complete revascularization for ST segment elevation myocardial infarction (STEMI) pa-tients during admission is still debatable. Methods A total of 1406 STEMI patients from the Korean Myocardial Infarction Registry with multivessel diseases without cardiogenic shock who underwent primary percutaneous coronary intervention (PPCI) were analyzed. We used propensity score matching (PSM) to control differences of baseline characteristics between culprit only intervention (CP) and multivessel percutaneous coronary interventions (MP), and between double vessel disease (DVD) and triple vessel disease (TVD). The major adverse cardiac event (MACE) was analyzed for one year after discharge. Results TVD patients showed higher incidence of MACE (14.2%vs. 8.6%, P=0.01), any cause of revascularization (10.6%vs. 5.9%, P=0.01), and repeated PCI (9.5%vs. 5.7%, P=0.02), as compared to DVD patients during one year after discharge. MP reduced MACE effectively (7.3%vs. 13.8%, P=0.03), as compared to CP for one year, but all cause of death (1.6%vs. 3.2%, P=0.38), MI (0.4%vs. 0.8%, P=1.00), and any cause of revascularization (5.3%vs. 9.7%, P=0.09) were comparable in the two treatment groups. Conclusions STEMI patients with TVD showed higher rate of MACE, as compared to DVD. MP performed during PPCI or ad hoc during admission for STEMI patients without cardiogenic shock showed lower rate of MACE in this large scaled database. Therefore, MP could be considered as an effective treatment option for STEMI patients without cardiogenic shock.

PURPOSE: The underlying cause of myasthenia gravis (MG) is unknown, although it likely involves a genetic component. However, no common genetic variants have been unequivocally linked to autoimmune MG. We sought to identify the genetic variants associated with an increased or decreased risk of developing MG in samples from a Korean Multicenter MG Cohort. MATERIALS AND METHODS: To determine new genetic targets related to autoimmune MG, a whole genome-based single nucleotide polymorphisms (SNP) analysis was conducted using an Axiom(TM) Genome-Wide ASI 1 Array, comprising 598375 SNPs and samples from 109 MG patients and 150 neurologically normal controls. RESULTS: In total, 641 SNPs from five case-control associations showed p-values of less than 10(-5). From regional analysis, we selected seven candidate genes (RYR3, CACNA1S, SLAMF1, SOX5, FHOD3, GABRB1, and SACS) for further analysis. CONCLUSION: The present study suggests that a few genetic polymorphisms, such as in RYR3, CACNA1S, and SLAMF1, might be related to autoimmune MG. Our findings also encourage further studies, particularly confirmatory studies with larger samples, to validate and analyze the association between these SNPs and autoimmune MG.
Antigens, CD/genetics ; Asian Continental Ancestry Group/genetics ; Calcium Channels/genetics ; Female ; Genetic Predisposition to Disease/genetics ; Genotype ; Humans ; Male ; Myasthenia Gravis/*etiology ; Polymorphism, Single Nucleotide/genetics ; Receptors, Cell Surface/genetics ; Ryanodine Receptor Calcium Release Channel/genetics