Antithrombotic therapy is a cornerstone of acute ischemic stroke (AIS) management and secondary stroke prevention. Since the first version of the Korean Clinical Practice Guideline (CPG) for stroke was issued in 2009, significant progress has been made in antithrombotic therapy for patients with AIS, including dual antiplatelet therapy in acute minor ischemic stroke or high-risk transient ischemic stroke and early oral anticoagulation in AIS with atrial fibrillation. The evidence is widely accepted by stroke experts and has changed clinical practice. Accordingly, the CPG Committee of the Korean Stroke Society (KSS) decided to update the Korean Stroke CPG for antithrombotic therapy for AIS. The writing members of the CPG committee of the KSS reviewed recent evidence, including clinical trials and relevant literature, and revised recommendations. A total of 35 experts were invited from the KSS to reach a consensus on the revised recommendations. The current guideline update aims to assist healthcare providers in making well-informed decisions and improving the quality of acute stroke care. However, the ultimate treatment decision should be made using a holistic approach, considering the specific medical conditions of individual patients.

We used a heterozygous gene deletion library of fission yeasts comprising all essential and non-essential genes for a microarray screening of target genes of the antifungal terbinafine, which inhibits ergosterol synthesis via the erg1 enzyme. We identified 14 heterozygous strains corresponding to 10 non-essential [7 ribosomal-protein (RP) coding genes, spt7, spt20, and elp2] and 4 essential genes (tif302, rpl2501, rpl31, and erg1). Expectedly, their erg1 mRNA and protein levels had decreased compared to the control strain SP286. When we studied the action mechanism of the non-essential target genes using cognate haploid deletion strains, knockout of SAGA-subunit genes caused a down-regulation in erg1 transcription compared to the control strain ED668. However, knockout of RP genes conferred no susceptibility to ergosterol-targeting antifungals. Surprisingly, the RP genes participated in the erg1 transcription as components of repressor complexes as observed in a comparison analysis of the experimental ratio of erg1 mRNA. To understand the action mechanism of the interaction between the drug and the novel essential target genes, we performed isobologram assays with terbinafine and econazole (or cycloheximide). Terbinafine susceptibility of the tif302 heterozygous strain was attributed to both decreased erg1 mRNA levels and inhibition of translation. Moreover, Tif302 was required for efficacy of both terbinafine and cycloheximide. Based on a molecular modeling analysis, terbinafine could directly bind to Tif302 in yeasts, suggesting Tif302 as a potential off-target of terbinafine. In conclusion, this genome-wide screening system can be harnessed for the identification and characterization of target genes under any condition of interest.

Tamoxifen (TAM) is an anticancer drug used to treat estrogen receptor (ER)‒positive breast cancer. However, its ER-independent cytotoxic and antifungal activities have prompted debates on its mechanism of action. To achieve a better understanding of the ER-independent antifungal action mechanisms of TAM, we systematically identified TAM-sensitive genes through microarray screening of the heterozygous gene deletion library in fission yeast (Schizosaccharomyces pombe). Secondary confirmation was followed by a spotting assay, finally yielding 13 TAM-sensitive genes under the drug-induced haploinsufficient condition. For these 13 TAM-sensitive genes, we conducted a comparative analysis of their Gene Ontology (GO) ‘biological process’ terms identified from other genome-wide screenings of the budding yeast deletion library and the MCF7breast cancer cell line. Several TAM-sensitive genes overlapped between the yeast strains and MCF7 in GO terms including ‘cell cycle’ (cdc2, rik1, pas1, and leo1), ‘signaling’ (sck2, oga1, and cki3), and ‘vesicle-mediated transport’ (SPCC126.08c, vps54, sec72, and tvp15), suggesting their roles in the ER-independent cytotoxic effects of TAM. We recently reported that the cki3 gene with the ‘signaling’ GO term was related to the ER-independent antifungal action mechanisms of TAM in yeast. In this study, we report that haploinsufficiency of the essential vps54 gene, which encodes the GARP complex subunit, significantly aggravated TAM sensitivity and led to an enlarged vesicle structure in comparison with the SP286 control strain. These results strongly suggest that the vesicle-mediated transport process might be another action mechanism of the ER-independent antifungal or cytotoxic effects of TAM.

Purpose: Loss of heterozygosity (LOH) at chromosomes 1p and 16q is a poor prognostic factor infavorable histology Wilms tumor (FHWT). This study investigated the prevalence of LOH at1p and 16q and evaluated its prognostic value in Korean children with FHWT. Materials and Methods: We analyzed 101 FHWT patients who were diagnosed between 1996 and 2016 in KoreanSociety of Pediatric Hematology Oncology Group hospitals. Using paraffin-embedded kidneytissue samples sent from each center, we reviewed LOH at 1p and 16q in each patient andassessed the prognostic value of LOH status for clinical parameters affecting event-freesurvival (EFS). Results: Of the 101 patients, 12 (11.9%) experienced recurrence; the 3-year EFS was 87.6%. LOHat 1p or 16q was detected in 19 patients (18.8%), with five having LOH at both 1q and 16q.The frequency of LOH at 1p was higher among younger patients (p=0.049), but there wasno difference in LOH prevalence according to tumor stage. In the multivariate analysis, LOHat 16q was a significant negative prognostic factor affecting EFS (3-year EFS, 73.7% vs.91.1%; hazard ratio, 3.95; p=0.037), whereas LOH at 1p was not (p=0.786). Conclusion LOH at 16q was a significant negative prognostic factor affecting outcome in Korean pediatricFHWT patients. Due to the small sample size of this study, large-scale multicenter trialsare warranted to investigate the prognostic value of LOH at 1p and 16q in Korean childrenwith FHWT.

PURPOSE: The purpose of this study was to evaluate chemotherapy patterns and changes in quality of life (QOL) during first-line palliative chemotherapy for Korean patients with unresectable or metastatic/recurrent gastric cancer (GC). MATERIALS AND METHODS: Thiswas a non-interventional, multi-center, prospective, observational study of 527 patients in Korea. QOL assessments were conducted using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaires (QLQ)-C30 and QLQ-STO22 every 3 months over a 12-month period during first-line palliative chemotherapy. The specific chemotherapy regimens were selected by individual clinicians. RESULTS: Most patients (93.2%) received combination chemotherapy (mainly fluoropyrimidine plus platinum) as their first-line palliative chemotherapy. The median progression-free survival and overall survival were 8.2 and 14.8 months, respectively. Overall, “a little” changes (differences of 5-10 points from baseline)were observed in some of the functioning or symptom scales; none of the QOL scales showed either “moderate” or “very much” change (i.e., ≥ 11 point difference from baseline). When examining the best change in each QOL domain from baseline, scales related to some aspects of functioning, global health status/QOL, and most symptoms revealed significant improvements (p < 0.05). Throughout the course of first-line palliative chemotherapy, most patients' QOL was maintained to a similar degree, regardless of their actual response to chemotherapy. CONCLUSION: This observational study provides important information on the chemotherapy patterns and QOL changes in Korean patientswith advanced GC. Overall, first-line palliative chemotherapy was found to maintain QOL, and most parameters showed an improvement compared with the baseline at some point during the course.
Disease-Free Survival ; Drug Therapy* ; Drug Therapy, Combination ; Global Health ; Humans ; Korea ; Observational Study ; Prospective Studies ; Quality of Life* ; Stomach Neoplasms* ; Weights and Measures

Caroli's disease is a rare autosomal-recessive disorder caused by malformation of the ductal plate during embryonic development. Although it is present at birth, Caroli's disease is typically not diagnosed until between the second and fourth decades of life, as it was in the present patient. Here we report a rare case of Caroli's disease limited to one liver segment, which was initially misdiagnosed as an intraductal papillary neoplasm of the bile duct. The asymptomatic patient was treated with liver segmentectomy.
Adult ; Bile Duct Neoplasms/diagnosis/pathology ; Bile Ducts, Intrahepatic ; Caroli Disease/*diagnosis/pathology ; Diagnostic Errors ; Humans ; Magnetic Resonance Imaging ; Male ; Tomography, X-Ray Computed

Acute duodenal ischemia and periampullary intramural hematoma are rare complications after endoscopic retrograde cholangiopancreatography (ERCP). A 77-year-old man with splenomegaly complained of abdominal pain caused by common bile duct (CBD) stone. After successful removal of the CBD stone without immediate complications, the patient developed intramural hematoma around the ampulla of Vater along with diffuse duodenal edema. The findings were compatible with acute intestinal ischemia, and further evaluation revealed that he had underlying primary myelofibrosis. Myeloproliferative diseases are known to be significantly associated with an increased risk of thrombohemorrhagic complications. Therefore, particular attention should be given to this group of patients when a high-risk procedure such as ERCP is performed.
Abdominal Pain ; Aged ; Ampulla of Vater ; Cholangiopancreatography, Endoscopic Retrograde* ; Common Bile Duct ; Edema ; Hematoma* ; Humans ; Ischemia* ; Primary Myelofibrosis* ; Splenomegaly

BACKGROUND: Even though the five year survival rate and prognosis of childhood solid tumors have been improved through the introduction of dose-escalation using tandem high-dose chemotherapy and autologous stem cell transplantation (HDCT/auto-SCT), changes in cardiac function have not yet been studied. We therefore evaluated cardiac function after tandem HDCT/auto-SCT.METHODS: This study retrospectively analyzed 56 pediatric patients who were diagnosed with solid tumors and who underwent tandem HDCT/auto-SCT at Samsung Medical Center. We investigated the cardiac function of these patients using echocardiography to evaluate the parameters of the left ventricular ejection fraction, e/e', and left ventricular Tei index.RESULTS: The mean left ventricular ejection fraction, e/e', and left ventricular Tei index at one year after the second HDCT/auto-SCT were 65.7%, 0.32, and 8.6, respectively. When compared those with before the first tandem HDCT/auto-SCT, there were no significant negative changes. We evaluated the changes in cardiac function in different subgroups, based on doxorubicin, radiotherapy involving heart, and the age of the patient at diagnosis. There were no significant changes of cardiac function after the treatment in any of the subgroups. Clinical heart failure did not develop in any of the patients.CONCLUSION: This study showed no significant negative changes in cardiac function at one year after tandem HDCT/auto-SCT. However, long-term follow-up studies of cardiac function in survivors and further studies of cardiac function are needed.
Child ; Diagnosis ; Doxorubicin ; Drug Therapy ; Echocardiography ; Follow-Up Studies ; Heart ; Heart Failure ; Humans ; Prognosis ; Radiotherapy ; Retrospective Studies ; Stem Cell Transplantation ; Stroke Volume ; Survival Rate ; Survivors

Since the publication of the first edition of Korean clinical practice guidelines of secondary stroke prevention, encouraging data from recent large clinical trials and meta-analysis have led us to consider many therapeutic options in the treatment of symptomatic extracranial carotid stenosis. Accordingly, the writing group of Clinical Research Center for Stroke decided to provide recent views on the therapeutic revascularization of extracranial carotid stenosis, and timely evidence-based recommendations. In this updated version, new evidences about carotid angioplasty/stenting, treatment timing, and perioperative preparation are given, and qualifying conditions for operator are elucidated. This refinement was based on current consensus between Korean Society of Intravascular Neurosurgery, Korean Society of Interventional Neuroradiology, and Korean Society of Cerebrovascular Surgery and approved by Korean Stroke Society, Korean Neurological Association, and Korean Society of Geriatric Neurology. These recommendations are subject to future correction based on new evidences from ongoing and future studies.
Carotid Arteries ; Carotid Stenosis ; Consensus ; Endarterectomy, Carotid ; Neurology ; Neurosurgery ; Publications ; Secondary Prevention ; Stroke ; Writing

PURPOSE: This study was performed to determine the optimal tile size for the fractal dimension of the mandibular trabecular bone using a tile counting method. MATERIALS AND METHODS: Digital intraoral radiographic images were obtained at the mandibular angle, molar, premolar, and incisor regions of 29 human dry mandibles. After preprocessing, the parameters representing morphometric characteristics of the trabecular bone were calculated. The fractal dimensions of the processed images were analyzed in various tile sizes by the tile counting method. RESULTS: The optimal range of tile size was 0.132 mm to 0.396 mm for the fractal dimension using the tile counting method. The sizes were closely related to the morphometric parameters. CONCLUSION: The fractal dimension of mandibular trabecular bone, as calculated with the tile counting method, can be best characterized with a range of tile sizes from 0.132 to 0.396 mm.
Bicuspid ; Fractals ; Humans ; Incisor ; Mandible ; Molar ; Trabecular Meshwork