Efficacy and Safety of Enavogliflozin versus Dapagliflozin as Add-on to Metformin in Patients with Type 2 Diabetes Mellitus: A 24-Week, Double-Blind, Randomized Trial

Background Enavogliflozin is a novel sodium-glucose cotransporter-2 inhibitor currently under clinical development. This study evaluated the efficacy and safety of enavogliflozin as an add-on to metformin in Korean patients with type 2 diabetes mellitus (T2DM) against dapagliflozin. Methods In this multicenter, double-blind, randomized, phase 3 study, 200 patients were randomized to receive enavogliflozin 0.3 mg/day (n=101) or dapagliflozin 10 mg/day (n=99) in addition to ongoing metformin therapy for 24 weeks. The primary objective of the study was to prove the non-inferiority of enavogliflozin to dapagliflozin in glycosylated hemoglobin (HbA1c) change at week 24 (non-inferiority margin of 0.35%) (Clinical trial registration number: NCT04634500). Results Adjusted mean change of HbA1c at week 24 was –0.80% with enavogliflozin and –0.75% with dapagliflozin (difference, –0.04%; 95% confidence interval, –0.21% to 0.12%). Percentages of patients achieving HbA1c <7.0% were 61% and 62%, respectively. Adjusted mean change of fasting plasma glucose at week 24 was –32.53 and –29.14 mg/dL. An increase in urine glucose-creatinine ratio (60.48 vs. 44.94, P<0.0001) and decrease in homeostasis model assessment of insulin resistance (–1.85 vs. –1.31, P=0.0041) were significantly greater with enavogliflozin than dapagliflozin at week 24. Beneficial effects of enavogliflozin on body weight (–3.77 kg vs. –3.58 kg) and blood pressure (systolic/diastolic, –5.93/–5.41 mm Hg vs. –6.57/–4.26 mm Hg) were comparable with those of dapagliflozin, and both drugs were safe and well-tolerated. Conclusion Enavogliflozin added to metformin significantly improved glycemic control in patients with T2DM and was non-inferior to dapagliflozin 10 mg, suggesting enavogliflozin as a viable treatment option for patients with inadequate glycemic control on metformin alone

Enterovirus 71-associated hand, foot and mouth diseases with neurologic symptoms, a university hospital experience in Korea, 2009

PurposeHand-foot-mouth disease (HFMD) is a common viral illness in children, which is usually mild and self-limiting. However, in recent epidemics of HFMD in Asia, enterovirus 71 (EV71) has been recognized as a causative agent with severe neurological symptoms with or without cardiopulmonary involvement. HFMD was epidemic in Korea in the spring of 2009. Severe cases with complications including death have been reported. The clinical characteristics in children with neurologic manifestations of EV71 were studied in Ewha Womans University Mokdong Hospital.MethodsExaminations for EV71 were performed from the stools, respiratory secretion or CSF of children who presented neurologic symptoms associated with HFMD by realtime PCR. Clinical and radiologic data of the patients were collected and analyzed.ResultsEV71 was isolated from the stool of 16 patients but not from respiratory secretion or CSF. Among the 16 patients, meningitis (n=10) was the most common manifestation, followed by Guillain-Barré syndrome (n=3), meningoencephalitis (n=2), poliomyelitis-like paralytic disease (n=1), and myoclonus (n=1). Gene analysis showed that most of them were caused by EV71 subgenotype C4a, which was prevalent in China in 2008.ConclusionBecause EV71 causes severe complications and death in children, a surveillance system to predict upcoming outbreaks should be established and maintained and adequate public health measures are needed to control disease

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

An algorithm for automatic 2D quadrilateral mesh generation with line constraints

Abstract Finite element method (FEM) is a fundamental numerical analysis technique widely used in engineering applications. Although state-ofthe-art hardware has reduced the solving time, which accounts for a small portion of the overall FEM analysis time, the relative time needed to build mesh models has been increasing. In particular, mesh models that must model stiffeners, those features that are attached to the plate in a ship structure, are imposed with line constraints and other constraints such as holes. To automatically generate a 2D quadrilateral mesh with the line constraints, an extended algorithm to handle line constraints is proposed based on the constrained Delaunay triangulation and QMorph algorithm. The performance of the proposed algorithm is evaluated, and numerical results of our proposed algorithm are presented.

A Study on the Community of Waterbirds and Protective value at Gangjin Bay in Jeollanamdo, Korea

AbstractThis study was conducted in Gangjin Bay of Jeollanam-do over a total of 8 sessions, once each month, between October of 2009 and May of 2010. A total of 9,647 birds of 63 species were observed during the study period. The most dominant species was Aythya ferina (18.5%), followed by, in decreasing order, Anas platyrhynchos (11.5%), Calidris alpine (9.6%) and Cygnus Cygnus (7.7%). Species which appeared in all months (100% occurrence rate) included a total of 5 species of Ardea cinerea, Egretta alba modesta, Egretta garzetta, Anas crecca and Anas poecilorhyncha. Furthermore, the study showed a total of 13 government protected species, 3 class-I endangered species, 8 class-II endangered species and 8 natural monument species. The Gangjin Bay region includes the Nakdong estuary, natural monument number 179, and provides stopping grounds for the Cygnus Cygnus, at the next highest number of birds. Furthermore, the region is characterized by the wintering of Cygnus Cygnus at a bird count higher than that of the Jindo Cygnus Cygnus migration destination, natural monument number 101. Therefore, there is a need for the designation of natural monuments and protected wetlands, as well as continued maintenance, in the Gangjin Bay region

Percutaneous medial hemi-epiphysiodesis using a transphyseal screw for caput valgum associated with developmental dysplasia of the hip

Abstract Background The purpose of this study was to evaluate the radiologic outcome of percutaneous medial hemi-epiphysiodesis using a transphyseal screw for the management of caput valgum associated with developmental dysplasia of the hip (DDH). Methods Eighteen hips (18 patients) having caput valgum treated with screw hemi-epiphysiodesis were followed for more than 2 years, and were included in this study. The mean age at the time of the index operation was 8.3 years (range, 4.3 to 10.7 years) and age at the latest follow-up was 12.2 years (range, 9.4 to 16.4 years). The screw in 5 hips was changed into a longer one at postoperative 21.8 months (range, 14 to 29 months) because the proximal femur outgrew the screw. The screws in 11 hips were removed at the mean age of 10.9 years (range, 8.0 to 14.5 years). We retrospectively analyzed the change in various radiologic parameters over time. Results The mean Hilgenreiner-epiphyseal angle (HEA) of the operated side was 5.1 ± 11.3° preoperatively, and increased to 20.6 ± 11.3° at the latest follow-up (p = 0.001). The mean difference of the HEA between the operated and contralateral sides was 16.9 ± 15.1° preoperatively, which decreased to 2.4 ± 12.4° at the latest follow-up (p = 0.008). The mean articulo-trochanteric distance of the operated side, which was 3.2 ± 5.5 mm longer than that of the contralateral side preoperatively, became 5.6 ± 9.1 mm shorter at the latest follow-up (p = 0.001). The ratio of femoral neck length of the operated side to that of the contralateral side decreased over the follow-up period. Acetabular shape as measured by the Sharp angle and acetabular roof angle and femoral head coverage as measured by lateral center-edge angle did not change significantly by the index operation. The ratio of medial joint space width of the operated side to that of the contralateral side did not change significantly. Conclusions Screw medial hemi-epiphysiodesis can effectively correct caput valgum associated with DDH. However, this technique remains coxa brevis and does not seem to significantly affect acetabular morphology or reduce subluxation

Clinical Characteristics of Respiratory Extracorporeal Life Support in Elderly Patients with Severe Acute Respiratory Distress Syndrome

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) strategy is proposed to reduce the ventilator-induced lung injury in acute respiratory distress syndrome (ARDS). As ECMO use has increased, a number of studies on prognostic factors have been published. Age is estimated to be an important prognostic factor. However, clinical evidences about ECMO use in elderly patients are limited. Therefore, we investigated clinical courses and outcomes of ECMO in elderly patients with ARDS. METHODS: We reviewed medical records of patients with severe ARDS who required ECMO support. Study patients were classified into an elderly group (&amp;gt; or = 65 years) and a non-elderly group (&amp;lt; 65 years). Baseline characteristics, ECMO related outcomes and associated factors were retrospectively analyzed according to group. RESULTS: From February 2011 to June 2013, a total of 31 patients with severe ARDS were treated with ECMO. Overall, 14 (45.2%) were weaned from ECMO, 9 (29.0%) survived to the general ward and 7 (22.6%) survived to discharge. Among the 18 elderly group patients, 7 (38.9%) were weaned from ECMO, 4 (22.2%) were survived to the general ward and 2 (11.1%) were survived to discharge. Overall intensive care unit survival was inversely correlated with concomitant acute kidney injury or septic shock. CONCLUSIONS: In this study, ECMO outcome was poor in severe ARDS patients aged over 65 years. Therefore, the routine use of ECMO in elderly patients with severe ARDS is not warranted except in highly selective cases