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.

Purpose: This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Materials and Methods: Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2–3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. Results: The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4–5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. Conclusion This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

BackgroundUntil now, various types of combined therapy with nucleotide analogs and pegylated interferon (Peg-INF) in patients with hepatitis B patients have been tried. However, studies regarding the benefits of de novo combination, late-add on, and sequential treatment are very limited. The objective of the current study was to identify the efficacy of sequential treatment of Peg-INF after short-term antiviral treatment.

MethodsBetween June 2010 and June 2015, hepatitis B e antigen (HBeAg)-positive patients (n = 162) received Peg-IFN for 48 weeks (mono-treatment group, n = 81) and entecavir (ETV) for 12 weeks with a 48-week course of Peg-IFN starting at week 5 of ETV therapy (sequential treatment group, n = 81). The primary endpoint was HBeAg seroconversion at the end of follow-up period after the 24-week treatment. The primary endpoint was analyzed using Chi-square test, Fisher's exact test, and regression analysis.

ResultsHBeAg seroconversion rate (18.2% vs. 18.2%, t = 0.03, P = 1.000) and seroclearance rate (19.7% vs. 19.7%, t = 0.03, P = 1.000) were same in both mono-treatment and sequential treatment groups. The rate of alanine aminotransferase (ALT) normalization (45.5% vs. 54.5%, t = 1.12, P = 0.296) and serum hepatitis B virus (HBV)-DNA <2000 U/L (28.8% vs. 28.8%, t = 0.10, P = 1.000) was not different in sequential and mono-treatment groups at 24 weeks of Peg-INF. Viral response rate (HBeAg seroconversion and serum HBV-DNA <2000 U/L) was not different in the two groups (12.1% vs. 16.7%, t = 1.83, P = 0.457). Baseline HBV-DNA level (7 logU/ml vs. 7.5 logU/ml, t = 1.70, P = 0.019) and hepatitis B surface antigen titer (3.6 logU/ml vs. 4.0 logU/ml, t = 2.19, P = 0.020) were lower and predictors of responder in mono-treatment and sequential treatment groups, respectively.

ConclusionsThe current study shows no differences in HBeAg seroconversion rate, ALT normalization, and HBV-DNA levels between mono-therapy and sequential therapy regimens.

Trial RegistrationClinicalTrials.gov, NCT01220596; https://clinicaltrials.gov/ct2/show/NCT01220596?term=NCT01220596&rank=1.

BACKGROUND: Despite expanding demands for non-operating room anesthesia (NORA) worldwide, studies in this field are scarce. We compared the overall characteristics and the nature of deaths occurring within 48 hours after surgery between NORA and operating room anesthesia (ORA) cases at a Korean tertiary hospital. METHODS: We retrospectively analyzed the medical records of patients who underwent surgical procedures under anesthesia services in and outside the operating room from January 2013 to November 2017. All of the mortalities were categorized by principal cause into groups such as patient disease or condition, surgery, anesthesia, and others. RESULTS: Overall, 16,383 NORA cases and 183,381 ORA cases were analyzed. Eighty-six deaths were identified. The mortality rate of NORA cases was similar to that of ORA cases (4.9 per 10,000 cases [95% confidence interval (CI), 2.1–9.6] vs. 4.3 per 10,000 cases [95% CI, 3.4–5.3], respectively). Similar to ORA cases, higher American Society of Anesthesiologists physical status and very young age (< 2 years) were significantly associated with mortality in NORA cases. A patient's disease or condition was the most important cause of mortality (65/86, 75.6%), followed by surgery-related causes (16/86, 18.6%). Two cases of anesthesia-related mortality were only identified in the ORA cases, resulting in an overall anesthesia-related mortality of 0.1 per 10,000 cases (95% CI, 0.0–0.4). CONCLUSION: Although NORA cases showed an equivalent perioperative mortality rate compared to ORA cases, there may be more room for improving patient safety when considering their favorable characteristics (healthier patients, less invasive and shorter procedures). Trial registry at Clinical Research Information Service, KCT0002719.
Anesthesia* ; Humans ; Information Services ; Medical Records ; Mortality ; Operating Rooms* ; Patient Safety ; Perioperative Period ; Retrospective Studies ; Tertiary Care Centers*

BACKGROUND/AIMS: To evaluate the efficacy and safety of a controlled release, once-daily formulation of mosapride (UI05MSP015CT) in patients with functional dyspepsia (FD). METHODS: Patients with FD were randomly assigned (1:1) to receive either UI05MSP015CT (15 mg once a day, study group) or mosapride (5 mg three times a day, control group) and corresponding placebo for 4 weeks. The primary endpoint was a change in the gastrointestinal symptom score (GIS) evaluated at enrollment and after 4 weeks. Secondary endpoints were changes in the Nepean Dyspepsia Index-Korean version (NDI-K), rate of satisfactory symptom relief, and rate of adverse events. RESULTS: A total of 138 patients were enrolled (female, 73.9%; mean age, 44.0±15.4 years). After excluding patients who violated the study protocol, 59 and 58 patients from the study and control groups, respectively, were included in the per-protocol analysis. No difference was observed in drug compliance between the control and study groups (97.07%±4.52% vs 96.85%±6.05%, p=0.870). Changes in GIS scores were 9.69±6.44 and 10.01±5.92 in the study and control groups. The mean difference in GIS change between groups was 0.33 (95% confidence interval, 1.75 to 2.41), demonstrating non-inferiority of UI-05MSP015CT (p=0.755). The rate of satisfactory symptom relief was not different between the study and control groups (39.0% vs 56.9%, p=0.053). No differences in change in NDI-K score (14.3 vs 16.9, p=0.263) or rates of adverse events (12.9% vs. 4.4%, p=0.062) were observed between the study and control groups. CONCLUSIONS: Once-daily mosapride is not inferior to conventional mosapride in efficacy and is safe in patients with FD.
Compliance ; Dyspepsia* ; Humans

BACKGROUND: Many difficulties exist in establishing a treatment plan for slow-flow vascular malformation (SFVM). In particular, little research has been conducted on the surgical treatment of SFVMs. Thus, we investigated what proportion of SFVM patients were candidates for surgical treatment in clinical practice and how useful surgical treatment was in those patients. METHODS: This study included 109 SFVM patients who received care at the authors' clinic from 2007 to 2015. We classified the patients as operable or non-operable, and analyzed whether the operability and the extent of the excision varied according to the subtype and location of the SFVM. Additionally, we investigated complications and self-assessed satisfaction scores. RESULTS: Of the 109 SFVM patients, 59 (54%) were operable, while 50 (46%) were non-operable. Total excision could be performed in 44% of the operable SFVM patients. Lymphatic malformations were frequently non-operable, while capillary malformations were relatively operable (P=0.042). Total excision of venous malformations could generally be performed, while lymphatic malformations and combined vascular malformations generally could only undergo partial excision (P=0.048). Complications occurred in 11% of the SFVM patients who underwent surgery; these were minor complications, except for 1 case. The average overall satisfaction score was 4.19 out of 5. CONCLUSIONS: Based on many years of experience, we found that approximately half (54%) of SFVM patients were able to undergo surgery, and around half (44%) of those patients were able to fully recover after a total excision. Among the patients who underwent surgical treatment, high satisfaction was found overall and relatively few complications were reported.
Capillaries ; Follow-Up Studies ; Humans ; Treatment Outcome ; Vascular Malformations*

Transplant renal artery stenosis (TRAS) is an important cause of hypertension, allograft dysfunction, and graft loss. Patient and allograft survival rates are lower in patients with TRAS. Causes of TRAS include acute rejection, cytomegalovirus infection, calcineurin inhibitor toxicity, atherosclerosis of recipient, and/or donor. Technical problems due to surgery are a common cause of early TRAS. A 62-year-old male in end stage renal disease received kidney transplant surgery. There was 5/6 mismatch of human leukocyte antigen and the panel reactive antibody of patient was class I 0% and class II 0%. End to side anastomosis was done between the graft's renal artery and the patient's common iliac artery. His serum creatinine was measured at 6.4 mg/dL before transplantation but his serum creatinine level did not fall below 2.6 mg/dL at 5 days postoperative. His blood pressures was 160/90~180/100 mmHg. There was a significant TRAS (about 80% luminal narrowing) at the arterial anastomosis site on the renal magnetic resonance angiography. We performed percutaneous transluminal angioplasty (PTA) for the stenotic lesion. The balloon angioplasty was done with a 5 mm balloon and low pressure (8 mmHg, nominal pressure was 10 mmHg) at the stenotic lesion. The arterial pressure gradient was 8 mmHg (recipient's common iliac arterial pressure, 147/73 mmHg; poststenotic segmental renal arterial pressure, 139/70 mmHg) just before the balloon angioplasty. After PTA, the arterial pressure gradient became 3 mmHg (recipient's common iliac arterial pressure, 157/66 mmHg; poststenotic segmental renal arterial pressure, 154/65 mmHg). The arterial size and blood flow recovered to within normal range and serum creatinine level was normal after PTA. PTA using low pressure and a small balloon was safe and effective modality in treating early TRAS.
Allografts ; Angioplasty ; Angioplasty, Balloon* ; Arterial Pressure ; Atherosclerosis ; Calcineurin ; Creatinine ; Cytomegalovirus Infections ; Humans ; Hypertension ; Iliac Artery ; Kidney ; Kidney Failure, Chronic ; Kidney Transplantation ; Leukocytes ; Magnetic Resonance Angiography ; Male ; Middle Aged ; Phenobarbital ; Reference Values ; Renal Artery Obstruction* ; Renal Artery* ; Survival Rate ; Tissue Donors ; Transplants

In addition to classical synaptic transmission, information is transmitted between cells via the activation of extrasynaptic receptors that generate persistent tonic current in the brain. While growing evidence supports the presence of tonic NMDA current (INMDA) generated by extrasynaptic NMDA receptors (eNMDARs), the functional significance of tonic I(NMDA) in various brain regions remains poorly understood. Here, we demonstrate that activation of eNMDARs that generate I(NMDA) facilitates the α-amino-3-hydroxy-5-methylisoxazole-4-proprionate receptor (AMPAR)-mediated steady-state current in supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs). In low-Mg2+ artificial cerebrospinal fluid (aCSF), glutamate induced an inward shift in I(holding) (I(GLU)) at a holding potential (V(holding)) of -70 mV which was partly blocked by an AMPAR antagonist, NBQX. NBQX-sensitive I(GLU) was observed even in normal aCSF at V(holding) of -40 mV or -20 mV. I(GLU) was completely abolished by pretreatment with an NMDAR blocker, AP5, under all tested conditions. AMPA induced a reproducible inward shift in I(holding) (I(AMPA)) in SON MNCs. Pretreatment with AP5 attenuated I(AMPA) amplitudes to ~60% of the control levels in low-Mg2+ aCSF, but not in normal aCSF at V(holding) of -70 mV. I(AMPA) attenuation by AP5 was also prominent in normal aCSF at depolarized holding potentials. Memantine, an eNMDAR blocker, mimicked the AP5-induced I(AMPA) attenuation in SON MNCs. Finally, chronic dehydration did not affect I(AMPA) attenuation by AP5 in the neurons. These results suggest that tonic I(NMDA), mediated by eNMDAR, facilitates AMPAR function, changing the postsynaptic response to its agonists in normal and osmotically challenged SON MNCs.
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid* ; Brain ; Cerebrospinal Fluid ; Dehydration ; Glutamic Acid ; Memantine ; N-Methylaspartate* ; Neurons ; Receptors, AMPA ; Receptors, N-Methyl-D-Aspartate* ; Supraoptic Nucleus ; Synaptic Transmission

OBJECTIVE: The aims of the present study were to investigate the women's perspective on influenza infection and vaccination and to evaluate how they influence vaccine acceptability, in Korean women of childbearing age. METHODS: This was a prospective study by random survey of women of childbearing age (20 to 45 years). They were asked to complete a questionnaire assessing their knowledge, attitudes and acceptability of influenza vaccination before and during pregnancy. This study utilized data from the Korea National Health and Nutrition Examination Survey (KNHANES) between 2008 and 2012, to analyze the recent influenza vaccination trends. RESULTS: According to KNHANES (2008-2012), influenza vaccination rates in women of childbearing age have increased up to 26.4%, after 2009. The questionnaire was completed by 308 women. Vaccination rate during pregnancy or planning a pregnancy was 38.6%. The immunization rate increased significantly with the mean number of correct answers (P<0.001). Women who received influenza vaccination were more likely to be previously informed of the recommendations concerning the influenza vaccination before or during pregnancy, received the influenza vaccination in the past, and of the opinion that influenza vaccination is not dangerous during pregnancy, with odds ratios of 14.6 (95% confidence interval [CI], 6.44 to 33.33; P<0.0001), 3.6 (95% CI, 1.84 to 6.97; P=0.0002) and 2.7 (95% CI, 1.34 to 5.47; P=0.0057). CONCLUSION: Influenza vaccination rate in women of childbearing age has increased in this study and national data. More information and recommendation by healthcare workers, especially obstetricians, including safety of vaccination, might be critical for improving vaccination rate in women of childbearing age.
Delivery of Health Care ; Female ; Humans ; Immunization ; Influenza, Human* ; Korea ; Nutrition Surveys ; Odds Ratio ; Pregnancy ; Prospective Studies ; Surveys and Questionnaires ; Vaccination*

Gastrodia elata (GE) is traditionally used for treatment of various disorders including neurodegenerative diseases such as Alzheimer's disease. To investigate the neuroprotective effect of GE, amyloid-beta peptide (Abeta)-treated PC12 cells were cultured with GE aqueous extract. In vitro assay demonstrated that 50 microM of pre-aggregated Abeta was lethal to about a half portion of PC12 cells and that Abeta aggregate-induced cell death was significantly decreased with GE treatment at < or =10 mg/mL in a dose-dependent manner. To further examine in vivo cognitive-improving effects, an artificial amnesic animal model, scopolamine-injected Sprague-Dawley rats, were orally administered the extract for 6 weeks followed by behavioral tests (the passive avoidance test and Morris water maze test). The results showed that an acute treatment with scopolamine (1 mg/kg of body weight) effectively induced memory impairment in normal rats and that the learning and memory capability of scopolamine-treated rats improved after prolonged administration of GE extract (50, 250 and 500 mg/kg of body weight for 6 weeks). These findings suggest that a GE regimen may potentially ameliorate learning and memory deficits and/or cognitive impairments caused by neuronal cell death.
Administration, Oral* ; Alzheimer Disease ; Animals ; Body Weight ; Cell Death ; Gastrodia* ; Learning* ; Memory Disorders ; Memory* ; Models, Animal ; Neurodegenerative Diseases ; Neurons ; Neuroprotective Agents ; PC12 Cells ; Rats* ; Rats, Sprague-Dawley ; Scopolamine Hydrobromide