Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Background: and Purpose: Blood pressure (BP) control is strongly recommended, but BP control rate has not been well studied in patients with stroke. We evaluated the BP control rate with fimasartan-based antihypertensive therapy initiated in patients with recent cerebral ischemia. Methods: This multicenter, prospective, single-arm trial involved 27 centers in South Korea. Key inclusion criteria were recent cerebral ischemia within 90 days and high BP [systolic blood pressure (SBP) >140 mm Hg or diastolic blood pressure (DBP) >90 mm Hg]. BP lowering was initiated with fimasartan. BP management during the follow-up was at the discretion of the responsible investigators. The primary endpoint was the target BP goal achievement rate (<140/90 mm Hg) at 24 weeks. Key secondary endpoints included achieved BP and BP changes at each visit, and clinical events (ClinicalTrials.gov Identifier: NCT03231293). Results: Of 1,035 patients enrolled, 1,026 were included in the safety analysis, and 951 in the efficacy analysis. Their mean age was 64.1 years, 33% were female, the median time interval from onset to enrollment was 10 days, and the baseline SBP and DBP were 162.3±16.0 and 92.2±12.4 mm Hg (mean±SD). During the study period, 55.5% of patients were maintained on fimasartan monotherapy, and 44.5% received antihypertensive therapies other than fimasartan monotherapy at at least one visit. The target BP goal achievement rate at 24-week was 67.3% (48.6% at 4-week and 61.4% at 12-week). The mean BP was 139.0/81.8±18.3/11.7, 133.8/79.2±16.4/11.0, and 132.8/78.5±15.6/10.9 mm Hg at 4-, 12-, and 24-week. The treatment-emergent adverse event rate was 5.4%, including one serious adverse event. Conclusions Fimasartan-based BP lowering achieved the target BP in two-thirds of patients at 24 weeks, and was generally well tolerated.

Background: Acute myeloid leukemia (AML) with internal tandem duplication in FMS-like tyrosine kinase 3 (FLT3-ITD) is associated with poor outcomes. This study aimed to analyze the outcomes of pediatric AML patients with FLT3-ITD mutations in the pre-FLT3 inhibitor era. Methods: We retrospectively reviewed and identified 18 patients diagnosed with non-M3 AML with FLT3-ITD mutations at Seoul National University Children’s Hospital between May 2008 and August 2019. Results: The median age was 13 years (range, 6‒19 yr). The median follow-up time was 43 months (range, 6‒157 mo). Fourteen patients received BH-AC-based (N4-Behenoy1-1-β-D-arabinofuranosy1cytosine) and 4 received cytarabine-based induction chemotherapy.Complete remission (CR) was achieved in 72.2% of the patients after the first induction chemotherapy and 80% of the patients achieved CR after salvage therapy. The overall CR rate was 94% (17/18 patients). These 17 patients underwent hematopoietic stem cell transplantation (9 matched unrelated donors, 5 matched related donors, and 3 haploidentical donors). Relapse occurred in 22% of the patients. Event free survival and overall survival rates were 53.8±12.1% and 53.6±12.1%, respectively, and they were not significantly different according to the type of induction chemotherapy (P=0.690) or the type of donor (P =0.102). Conclusion This study outlines the outcomes of pediatric AML patients with FLT3-ITD-mutations in one institution over a decade. Outcomes were significantly improved in this study compared to our previous report in 2004, where RFS and EFS were 0%. This study can provide baseline data for pediatric patients in the pre-FLT3 inhibitor era.

Growth hormone (GH) deficiency is caused by congenital or acquired causes and occurs in childhood or adulthood. GH replacement therapy brings benefits to body composition, exercise capacity, skeletal health, cardiovascular outcomes, and quality of life. Before initiating GH replacement, GH deficiency should be confirmed through proper stimulation tests, and in cases with proven genetic causes or structural lesions, repeated GH stimulation testing is not necessary. The dosing regimen of GH replacement therapy should be individualized, with the goal of minimizing side effects and maximizing clinical improvements. The Korean Endocrine Society and the Korean Society of Pediatric Endocrinology have developed a position statement on the diagnosis and treatment of GH deficiency. This position statement is based on a systematic review of evidence and expert opinions.

Angiotensin II (Ang II) induces the pathological process of vascular structures, including renal glomeruli by hemodynamic and nonhemodynamic direct effects. In kidneys, Ang II plays an important role in the development of proteinuria by the modification of podocyte molecules. We have previously found that Ang II suppressed podocyte AMP-activated protein kinase (AMPK) via Ang II type 1 receptor and MAPK signaling pathway. In the present study, we investigated the roles of AMPK on the changes of p130Cas of podocyte by Ang II. We cultured mouse podocytes and treated them with various concentrations of Ang II and AMPK-modulating agents and analyzed the changes of p130Cas by confocal imaging and western blotting. In immunofluorescence study, Ang II decreased the intensity of p130Cas and changed its localization from peripheral cytoplasm into peri-nuclear areas in a concentrated pattern in podocytes. Ang II also reduced the amount of p130Cas in time and dose-sensitive manners. AMPK activators, metformin and AICAR, restored the suppressed and mal-localized p130Cas significantly, whereas, compound C, an AMPK inhibitor, further aggravated the changes of p130Cas. Losartan, an Ang II type 1 receptor antagonist, recovered the abnormal changes of p130Cas suppressed by Ang II. These results suggest that Ang II induces the relocalization and suppression of podocyte p130Cas by the suppression of AMPK via Ang II type 1 receptor, which would contribute to Ang II-induced podocyte injury.
AMP-Activated Protein Kinases/antagonists & inhibitors/chemistry/*metabolism ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Angiotensin II/*pharmacology ; Angiotensin II Type 1 Receptor Blockers/pharmacology ; Animals ; Blotting, Western ; Cell Line ; Cell Nucleus/metabolism ; Crk-Associated Substrate Protein/*metabolism ; Cytoplasm/metabolism ; Focal Adhesion Kinase 1/metabolism ; Losartan/pharmacology ; Metformin/pharmacology ; Mice ; Microscopy, Confocal ; Podocytes/cytology/drug effects/metabolism ; Protein Kinase Inhibitors/*pharmacology ; Ribonucleotides/pharmacology ; Signal Transduction/*drug effects

Percutaneous transhepatic biliary drainage (PTBD) is a modality that is used to decompress obstructive jaundice due to impacted stones, benign stricture or cancer. The PTBD catheter is removed percutaneously after the restoration of internal biliary drainage. We experienced a case of a 62-year-old man with peritonitis due to the migration of the PTBD catheter into the peritoneal cavity; we successfully removed it using peroral endoscopy. Although rare, the PTBD catheter may migrate into the peritoneal cavity during the removal of it. In these cases, clinicians should consider the peroral endoscopic removal of the PTBD catheter.
Catheters* ; Cholestasis ; Constriction, Pathologic ; Drainage* ; Endoscopes ; Endoscopy ; Humans ; Jaundice, Obstructive ; Middle Aged ; Peritoneal Cavity ; Peritonitis*

Vascular cell adhesion molecule 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), P- and E-selectin play a pivotal role for initiation of atherosclerosis. Ginsenoside, a class of steroid glycosides, is abundant in Panax ginseng root, which has been used for prevention of illness in Korea. In this study, we investigated the mechanism(s) by which ginsenoside Rg2 may inhibit VCAM-1 and ICAM-1 expressions stimulated with lipopolysaccharide (LPS) in human umbilical vein endothelial cell (HUVEC). LPS increased VCAM-1 and ICAM-1 expression. Ginsenoside Rg2 prevented LPS-mediated increase of VCAM-1 and ICAM-1 expression. On the other hand, JSH, a nuclear factor kappa B (NF-kappaB) inhibitor, reduced both VCAM-1 and ICAM-1 expression stimulated with LPS. SB202190, inhibitor of p38 mitogen-activated protein kinase (p38 MAPK), and wortmannin, phosphatidylinositol 3-kinase (PI3-kinase) inhibitor, reduced LPS-mediated VCAM-1 but not ICAM-1 expression. PD98059, inhibitor of mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) did not affect VCAM-1 and ICAM-1 expression stimulated with LPS. SP600125, inhibitor of c-Jun N-terminal kinase (JNK), reduced LPS-mediated ICAM-1 but not VCAM-1 expression. LPS reduced IkappaBalpha (IkappaBalpha) expression, in a time-dependent manner within 1 hr. Ginsenoside Rg2 prevented the decrease of IkappaBalpha expression stimulated with LPS. Moreover, ginsenoside Rg2 reduced LPS-mediated THP-1 monocyte adhesion to HUVEC, in a concentration-dependent manner. These data provide a novel mechanism where the ginsenoside Rg2 may provide direct vascular benefits with inhibition of leukocyte adhesion into vascular wall thereby providing protection against vascular inflammatory disease.
Androstadienes ; Anthracenes ; Atherosclerosis ; E-Selectin ; Endothelial Cells ; Flavonoids ; Ginsenosides ; Glycosides ; Hand ; Humans ; I-kappa B Proteins ; Imidazoles ; Intercellular Adhesion Molecule-1 ; JNK Mitogen-Activated Protein Kinases ; Korea ; Leukocytes ; Monocytes ; NF-kappa B ; Panax ; Phosphatidylinositol 3-Kinase ; Phosphotransferases ; Protein Kinases ; Pyridines ; Umbilical Veins ; Vascular Cell Adhesion Molecule-1

Akt/protein kinase B is a well-known cell survival factor and activated by many stimuli including mechanical stretching. Therefore, we evaluated the cardioprotective effect of a brief mechanical stretching of rat hearts and determined whether activation of Akt through phosphatidylinositol 3-kinase (PI3K) is involved in stretch-induced cardioprotection (SIC). Stretch preconditioning reduced infarct size and improved post-ischemic cardiac function compared to the control group. Phosphorylation of Akt and its downstream substrate, GSK-3beta, was increased by mechanical stretching and completely blocked by wortmannin, a PI3K inhibitor. Treatment with lithium or SB216763 (GSK-3beta inhibitors) before ischemia induction mimicked the protective effects of SIC on rat heart. Gadolinium (Gd3+), a blocker of stretch-activated ion channels (SACs), inhibited the stretch-induced phosphorylation of Akt and GSK-3beta. Furthermore, SIC was abrogated by wortmannin and Gd3+. In vivo stretching induced by an aorto-caval shunt increased Akt phosphorylation and reduced myocardial infarction; these effects were diminished by wortmannin and Gd3+ pretreatment. Our results showed that mechanical stretching can provide cardioprotection against ischemia-reperfusion injury. Additionally, the activation of Akt, which might be regulated by SACs and the PI3K pathway, plays an important role in SIC.
Androstadienes/pharmacology ; Animals ; Gadolinium/pharmacology ; Glycogen Synthase Kinase 3/*metabolism ; Indoles/pharmacology ; *Ischemic Preconditioning, Myocardial ; Lithium/pharmacology ; Male ; Maleimides/pharmacology ; Myocardial Reperfusion Injury/enzymology/physiopathology/*prevention & control ; Phosphatidylinositol 3-Kinase/*antagonists & inhibitors/metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/*metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Specific Pathogen-Free Organisms

Since laparoscopic liver resection was first introduced in 2001, Korean surgeons have chosen a laparoscopic procedure as one of the treatment options for benign or malignant liver disease. We distributed and analyzed a nationwide questionnaire to members of the Korean Laparoscopic Liver Surgery Study Group (KLLSG) in order to evaluate the current status of laparoscopic liver resection in Korea. Questionnaires were sent to 24 centers of KLLSG. The questionnaire consisted of operative procedure, histological diagnosis of liver lesions, indications for resection, causes of conversion to open surgery, and postoperative outcomes. A laparoscopic liver resection was performed in 416 patients from 2001 to 2008. Of 416 patients, 59.6% had malignant tumors, and 40.4% had benign diseases. A total laparoscopic approach was performed in 88.7%. Anatomical laparoscopic liver resection was more commonly performed than non-anatomical resection (59.9% vs 40.1%). The anatomical laparoscopic liver resection procedures consisted of a left lateral sectionectomy (29.3%), left hemihepatectomy (19.2%), right hemihepatectomy (6%), right posterior sectionectomy (4.3%), central bisectionectomy (0.5%), and caudate lobectomy (0.5%). Laparoscopy-related serious complications occurred in 12 (2.8%) patients. The present study findings provide data in terms of indication, type and method of liver resection, and current status of laparoscopic liver resection in Korea.
*Hepatectomy/statistics & numerical data ; Humans ; *Laparoscopy/statistics & numerical data ; Liver/*surgery ; Liver Diseases/pathology/surgery ; Liver Neoplasms/pathology/surgery ; Postoperative Complications/epidemiology ; Questionnaires ; Republic of Korea

We evaluated the malignancy and nondiagnostic rates using fine needle aspiration cytology (FNAC) results in thyroid nodules smaller than 1 cm according to the subdivided size. We retrospectively reviewed the medical records of all subjects underwent FNAC from 2003 to 2009 in our hospital, and 2,756 patients of subcentimeter thyroid nodules with one or more suspicious sonographic features and 7,105 with nodule sized 1 cm or more were included. The malignancy rate was higher in those subcentimeter nodules with suspicious sonographic findings than the nodule sized 1cm or more (19.7% vs 7.8%, P < 0.001). We grouped the nodules based on size with mm interval and observed that the malignancy rate did not decrease but the nondiagnostic results increased its size decrement. When we divided the subjects arbitrarily into a 5 mm or smaller and a 6-9 mm sized group, nondiagnostic cytology findings were reported more frequently in the smaller group (24.3% vs 18.1%, P = 0.001), while the rate of "malignant" was similar (18.3% vs 15.5%, P = 0.123) and the rate of "suspicious for malignancy" was higher (6.8% vs 2.9%, P < 0.001). Therefore when we decide to perform FNAC or not in subcentimeter-sized nodules, we should consider sonographic findings and other clinical risk factors but not the nodular size itself.
Adult ; Biopsy, Fine-Needle ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Thyroid Gland/pathology/ultrasonography ; Thyroid Neoplasms/diagnosis/*pathology/*ultrasonography ; Thyroid Nodule/diagnosis/*pathology/*ultrasonography