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.

PURPOSE: This study investigated the incidence of adverse events (AEs) and risk factors associated with sedation using chloral hydrate (CH) for brain magnetic resonance imaging (MRI) in the neonatal intensive care unit (NICU). METHODS: This was a retrospective study of infants who received CH for brain MRI in the NICU. Among the enrolled infants (n=143), 12.6% (n=18) were included in the AE group and 87.4% (n=125) were in the non-adverse event group (NAE). RESULTS: Gestational age (GA) at birth and corrected GA at sedation were 35+0±7+2 and 39+5±3+1 respectively. The rate of AEs was 12.6%, included oxygen desaturation (5.6%), aspiration (4.9%), paradoxical agitation (0.7%), tachycardia or bradycardia (0.7%), and arrest (0.7%). In univariate analysis, the AE group was younger in corrected GA at sedation than the NAE group (37+2 [range, 36+0 to 40+0] vs. 40+1 [range, 38+2 to 41+4], P=0.015). There was no significant difference in CH dosage (50.0 [range, 50.0 to 50.0] vs. 50.0 [range, 50.0 to 50.0], P=0.092), cardiopulmonary (33.3% [n=6] vs. 17.6% [n= 22], P=0.209) and central nervous system (61.1% [n=11] vs. 65.6% [n=82], P=0.054) morbidity. In multivariate analysis, CH dosage was the only significant risk factor for AEs associated with sedation (odds ratio, 1.04; 95% confidence interval, 1.01 to 1.07; P=0.0186). CONCLUSION: AEs associated with sedation using CH are not uncommon and should be considered when using high dose CH for diagnostic testing in the NICU.
Bradycardia ; Brain ; Central Nervous System ; Chloral Hydrate ; Diagnostic Tests, Routine ; Dihydroergotamine ; Gestational Age ; Humans ; Incidence ; Infant ; Infant, Newborn ; Intensive Care, Neonatal ; Magnetic Resonance Imaging ; Multivariate Analysis ; Oxygen ; Parturition ; Retrospective Studies ; Risk Factors ; Tachycardia

The Committee of Clinical Practice Guidelines of the Korean Diabetes Association revised and updated the 6th Clinical Practice Guidelines in 2019. Targets of glycemic, blood pressure, and lipid control in type 2 diabetes mellitus (T2DM) were updated. The obese and overweight population is increasing steadily in Korea, and half of the Koreans with diabetes are obese. Evidence-based recommendations for weight-loss therapy for obesity management as treatment for hyperglycemia in T2DM were provided. In addition, evidence from large clinical studies assessing cardiovascular outcomes following the use of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide 1 receptor agonists in patients with T2DM were incorporated into the recommendations.
Blood Pressure ; Diabetes Mellitus, Type 2 ; Diagnosis ; Glucagon-Like Peptide 1 ; Humans ; Hyperglycemia ; Korea ; Obesity ; Overweight

BACKGROUND AND PURPOSE: The clinical implications of echocardiography findings for long-term outcomes in atrial fibrillation (AF)-related stroke patients are unknown. METHODS: This was a substudy of the Korean ATrial fibrillaTion EvaluatioN regisTry in Ischemic strOke patieNts (K-ATTENTION), which is a multicenter-based cohort comprising prospective stroke registries from 11 tertiary centers. Stroke survivors who underwent two-dimensional transthoracic echocardiography during hospitalization were enrolled. Echocardiography markers included the left-ventricle (LV) ejection fraction (LVEF), the left atrium diameter, and the ratio of the peak transmitral filling velocity to the mean mitral annular velocity during early diastole (E/e′ ratio). LVEF was categorized into normal (≥55%), mildly decreased (>40% and <55%), and severely decreased (≤40%). The E/e′ ratio associated with the LV filling pressure was categorized into normal (<8), borderline (≥8 and <15), and elevated (≥15). Kaplan-Meier and Cox regression analyses were performed for recurrent stroke, major adverse cardiac events, and all-cause death. RESULTS: This study finally included 1,947 patients. Over a median follow-up of 1.65 years (interquartile range, 0.42–2.87 years), the rates of recurrent stroke, major adverse cardiac events, and all-cause death were 35.1, 10.8, and 69.6 cases per 1,000 person-years, respectively. Multivariable analyses demonstrated that severely decreased LVEF was associated with a higher risks of major adverse cardiac events [hazard ratio (HR), 3.91; 95% confidence interval (CI), 1.58–9.69] and all-cause death (HR, 1.95; 95% CI, 1.23–3.10). The multivariable fractional polynomial plot indicated that recurrent stroke might be associated with a lower LVEF. CONCLUSIONS: Severe LV systolic dysfunction could be a determinant of long-term outcomes in AF-related stroke.
Atrial Fibrillation ; Cohort Studies ; Diastole ; Echocardiography ; Follow-Up Studies ; Heart Atria ; Hospitalization ; Humans ; Prospective Studies ; Registries ; Stroke ; Survivors

Background & Objective: Hiccups is a disabling condition of lateral medullary infarction (LMI). Unlike other symptoms of LMI, the anatomical lesions of hiccups are not well known. Few studies have evaluated the relationship between the lesional location of LMI and hiccups. We performed this study to correlate hiccups and magnetic resonance imaging (MRI)-based lesional location in pure LMI. Methods: Between January 1997 and February 2013, we identified 24 patients with pure LMI who presented with hiccups in addition to typical lateral medullary syndrome. Sixty six pure LMI patients without hiccups were included as a control group. Clinical and radiologic findings were compared between the two groups. MRI-identified lesions were classified rostrocaudally as rostral, middle and caudal, and horizontally as typical, ventral, large, lateral and dorsal. Results: The pure LMI patients with hiccups had significantly more frequent aspiration pneumonia (P = 0.001) and longer hospital stay (P = 0.03). The patients with hiccups significantly more often had dorsal rather than ventral lesion at horizontal levels (P = 0.012). But, there were no rostro-caudal differences at vertical levels (P = 0.162). Conclusions: We suggest that pure LMI associated with hiccups often locates in the dorsal medulla at horizontal correlation. This MRI-based comparative study has advanced the understanding of the neural substrate for hiccups in LMI, and indicates that hiccups become predictable when specific lesional locations in the lateral medulla are considered.

BACKGROUND: Thrombolysis becomes an emerging therapeutic option for acute ischemic stroke. However, few reports exist on its use in the very elderly. We investigated whether there is a difference in the effectiveness and safety of intravenous (IV) and/or intra-arterial (IA) thrombolysis between patients aged > or =80 years and those aged <80 years. METHODS: A consecutive series of patients hospitalized within 12 hours from stroke onset were selected. We evaluated the effectiveness of thrombolysis with modified Rankin scale (mRS) at 3 months, and the safety with symptomatic hemorrhagic transformation (sHT). The odds ratio (OR) of thrombolysis on the favorable mRS (0-2) was calculated using multivariable logistic regression analysis with adjustments for potential confounders. Whether the effectiveness of thrombolysis is age-dependent or not was analyzed by introducing an interaction term (thrombolysisxage group) into multivariable models. RESULTS: Among 219 patients > or =80 years, 21% of patients received IV or IA or combined thrombolysis while 23% of 980 patients <80 years received thrombolysis (P=0.51). With respect to the favorable mRS, the adjusted ORs of thrombolysis were 1.70 (95% confidence interval, 1.08-2.68) in all subjects, 1.61 (0.58-4.49) in those > or =80 years, and 1.71 (1.05-2.78) in those <80 years. There was no significant interaction between age group and thrombolysis (P=0.91). With respect to sHT, the adjusted OR was 4.72 (1.94-11.45) in all subjects with no significant interaction (P=0.86). CONCLUSION: This study suggests that thrombolysis may be equally safe and effective in stroke patients aged > or =80 years versus <80 years.
Aged ; Electrolytes ; Humans ; Logistic Models ; Odds Ratio ; Stroke ; Treatment Outcome

In general, a 2-yr disease-free duration is recommended before kidney transplantation (KT) in end-stage renal disease (ESRD) patients who also have acute leukemia. However, the optimal disease-free interval has not been specified for all subtypes of acute leukemia. Among these subtypes, acute promyelocytic leukemia (APL) shows a favorable prognosis and low relapse rate compared to other types of leukemia. We here report KT after complete remission (CR) of APL in an ESRD patient. Irreversible kidney injury developed in a 23-yr-old man with APL. First, we induced CR and subsequently performed KT 7 months after the achievement of CR. The patient's clinical course after KT was favorable, without allograft rejection or relapse of APL up to1 yr after KT. On the basis of our clinical experience, it is suggested that a long wait may not be necessary before KT in patients with ESRD and APL.
Adult ; Antineoplastic Agents/therapeutic use ; Arsenicals/therapeutic use ; Bone Marrow Cells/pathology ; Humans ; Kidney Failure, Chronic/*therapy/ultrasonography ; *Kidney Transplantation ; Leukemia, Promyelocytic, Acute/*diagnosis/drug therapy ; Male ; Oxides/therapeutic use ; Receptors, Retinoic Acid/genetics/metabolism ; Remission Induction

A 50-year-old male, renal transplant recipient, was admitted with fever and chest discomfort. At admission, chest radiologic finding was negative and echocardiography showed minimal pericardial effusion. After 2 days of admission, chest pain worsened and blood pressure fell to 60/40 mmHg. Emergency echocardiography showed a large amount of pericardial effusion compressing the entire heart. Pericardiocentesis was performed immediately. Mycobacterium tuberculosis was isolated from pericardial fluid. Tuberculosis pericarditis should be considered as the cause of cardiac tamponade in renal transplant recipients, even with the absence of pericardial effusion in the initial study or suggestive history.
Blood Pressure ; Cardiac Tamponade ; Chest Pain ; Echocardiography ; Emergencies ; Fever ; Heart ; Humans ; Kidney Transplantation ; Male ; Middle Aged ; Mycobacterium tuberculosis ; Pericardial Effusion ; Pericardiocentesis ; Pericarditis ; Thorax ; Transplants ; Tuberculosis

PURPOSE: The aim of this study was to find the dose of agonistic 4-1BB monoclonal antibody (mAb) that results in optimal T cell activation. METHODS: Cancer was induced in mice by an intrahepatic parenchymal injection of 1x10(5) cells of CT26 cells. Cancer-carrying mice (n=84) were divided into seven groups and treated with either rat IgG or agonistic 4-1BB monoclonal antibody (mAb) (5microgram, 10microgram, 20microgram, 100microgram, 200microgram, or 300microgram). All treatments were administered intraperitoneally on days 7, 9, and 11. Mice from each group were sacrificed on days 14, 28, and 42. Harvested livers were weighed and the numbers of T cells in the splenocytes were analyzed with a FACS Vantage flow cytometer. RESULTS: Liver weights increased when 5microgram of agonistic 4-1BB mAb was administered, but showed no additional weight increase for doses greater than 10microgram. The absolute numbers of CD4+ and CD8+ T cells increased in groups treated with low doses of agonistic 4-1BB mAb (5microgram, 10microgram, or 20microgram), but did not increase in the groups treated with high doses of mAb (100microgram, 200microgram, or 300microgram). The levels of CD4/annexin V and CD8/annexin V increased as the dose increased, and the absolute cell numbers of CD4/annexin V were greater than those of CD8/annexin V. CONCLUSION: Liver weight, including the cancer mass, failed to increase at agonistic 4-1BB mAb doses greater than 10microgram. A high dose (> or =100microgram) of agonistic 4-1BB mAb resulted in lower counts of absolute T cells. This study suggests that a low dose (20microgram) of agonistic 4-1BB mAb can be used for optimal T cell activation in combination with other anti-cancer treatments.
Animals ; Cell Count ; Colon ; Colonic Neoplasms ; Immunoglobulin G ; Liver ; Mice ; Neoplasm Metastasis ; Rats ; T-Lymphocytes ; Weights and Measures

OBJECTIVES: Hearing impairment (HI) is the most common sensory deficit in human. The Gap Junction Protein, Beta-2 (GJB2) gene encodes the protein connexin 26, and this gene accounts for up to half of the cases of autosomal recessive nonsyndromic HI. This study was conducted to obtain a set of sequence variations (SVs) of the GJB2 gene among Koreans from the general population for making molecular genetic diagnoses and performing genetic counseling. METHODS: We resequenced the GJB2 gene in 192 chromosomes from 96 adult individuals of Korean descent and who were without a history of hearing difficulty. The data of the SVs was obtained and the haplotypes were reconstructed from the data. RESULTS: Five SVs were observed, including a novel one (c.558G>A; p.T186T), with the allele frequencies ranging from 0.5% (1/192) to 41% (79/192). The linkage disequilibrium study and haplotype construction showed that some of the SVs are in tight linkage, resulting in a limited number of haplotypes. CONCLUSION: We observed SVs of the GJB2 gene with different allele frequencies, and a limited number of haplotypes were constructed. The data from this study can be used as reference data for GJB2-related hearing genetic studies, including studies on the founder effect and population genetics, and this data is particularly relevant to people of East Asian decent.
Adult ; Asian Continental Ancestry Group ; Connexins ; Founder Effect ; Gene Frequency ; Genetic Counseling ; Genetics, Population ; Haplotypes ; Hearing ; Hearing Loss ; Humans ; Korea ; Linkage Disequilibrium ; Molecular Biology