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1.  Morphologic Alteration of Metastatic Neuroblastic Tumor in Bone Marrow after Chemotherapy 
Korean Journal of Pathology  2013;47(5):433-442.
Background
The aim of this study is to evaluate the histologic features of metastatic neuroblastic tumors (NTs) in bone marrow (BM) before and after chemotherapy in comparison with those of primary NTs.
Methods
A total of 294 biopsies from 48 children diagnosed with NTs with BM metastasis were examined. There were 48 primary neoplasm biopsies, 48 BM biopsies before chemotherapy, 36 primary neoplasm excisional biopsies after chemotherapy, and 162 BM biopsies after chemotherapy.
Results
Metastatic NTs in BM before chemotherapy were composed of undifferentiated and/or differentiating neuroblasts, but had neither ganglion cells nor Schwannian stroma. Metastatic foci of BM after chemotherapy were found to have differentiated into ganglion cells or Schwannian stroma, which became more prominent after further cycles of chemotherapy. Persistence of NTs or tumor cell types in BM after treatment did not show statistically significant correlation to patients' outcome. However, three out of five patients who newly developed poorly differentiated neuroblasts in BM after treatment expired due to disease progression.
Conclusions
Metastatic NTs in BM initially consist of undifferentiated or differentiating neuroblasts regardless of the primary tumor subtype, and become differentiated after chemotherapy. Newly appearing poorly differentiated neuroblasts after treatment might be an indicator for poor prognosis.
doi:10.4132/KoreanJPathol.2013.47.5.433
PMCID: PMC3830990  PMID: 24255631
Neuroblastoma; Bone marrow; Drug therapy; Neoplasm metastasis; Histology
2.  Prospective and Systematic Analysis of Unexpected Requests for Non-Cardiac Surgery or Other Invasive Procedures during the First Year after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2014;55(2):345-352.
Purpose
Unexpected requests for non-cardiac surgery requiring discontinuation of dual antiplatelet therapy (DAPT) frequently occur in daily clinical practice. The objectives of this study were to evaluate prevalence, timing and clinical outcomes of such unexpected requests for non-cardiac surgery or other invasive procedures during the first year after drug-eluting stents (DESs) implantation.
Materials and Methods
We prospectively investigated the prevalence, timing and clinical outcomes of unexpected requests for non-cardiac surgery or other procedures during the first year after DESs implantation in 2117 patients.
Results
The prevalence of requested non-cardiac surgery or invasive procedures was 14.6% in 310 requests and 12.3% in 261 patients. Among 310 requests, those were proposed in 11.3% <1 month, 30.0% between 1 and 3 months, 36.8% between 4 and 6 months and 21.9% between 7 and 12 months post-DES implantation. The rates of actual discontinuation of DAPT and non-cardiac surgery or procedure finally performed were 35.8% (111 of 310 requests) and 53.2% (165 of 310 requests), respectively. On multivariate regression analysis, the most significant determinants for actual discontinuation of DAPT were Endeavor zotarolimus-eluting stent implantation with 3-month DAPT (OR=5.54, 95% CI 2.95-10.44, p<0.001) and timing of request (OR=2.84, 95% CI 1.97-4.11, p<0.001). There were no patients with any death, myocardial infarction, or stent thrombosis related with actual discontinuation of DAPT.
Conclusion
Those unexpected requests with premature discontinuation of DAPT were relatively common and continuously proposed during the first year following DES implantation. No death, myocardial infarction or stent thrombosis occurred in patients with actual discontinuation of DAPT.
doi:10.3349/ymj.2014.55.2.345
PMCID: PMC3936620  PMID: 24532502
Antiplatelet therapy; drug-eluting stents; coronary artery disease
3.  Percutaneous Cardiopulmonary Support in Refractory No-Reflow with Cardiogenic Shock after Coronary Stenting in Acute Myocardial Infarction 
Yonsei Medical Journal  2010;51(4):599-601.
Coronary no-reflow is defined as inadequate myocardial perfusion of a given coronary segment without angiographic evidence of mechanical vessel obstruction. No-reflow is visualized angiographically as a reduction in thrombolysis in myocardial infarction (TIMI) flow grade and is typically accompanied by chest pain, electrocardiographic changes with ST-segment shift and possible hemodynamic compromise. No-reflow during primary percutaneous coronary intervention (PCI) results in increasing mortality and morbidity. Therefore, treatment of noreflow is associated with improved clinical outcomes. Generally, the treatment of no-reflow is based on pharmacotherapy. In this case, despite maximal pharmacotherapy and intraaortic balloon pump (IABP), refractory no-reflow accompanied with cardiogenic shock was successfully treated with percutaneous cardiopulmonary support (PCPS).
doi:10.3349/ymj.2010.51.4.599
PMCID: PMC2880277  PMID: 20499430
No-reflow; percutaneous cardiopulmonary support; acute myocardial infarction
4.  Immunoglobulin G4 Non-Related Sclerosing Disease with Intracardiac Mass Mimicking Mitral Stenosis: Case Report 
Journal of Korean Medical Science  2013;28(12):1830-1834.
The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.
doi:10.3346/jkms.2013.28.12.1830
PMCID: PMC3857383  PMID: 24339717
Immunoglobulin G4 Non-Related Sclerosing Disease; Periaortitis; Left Atrium Mass; Mitral Valve Stenosis
5.  Adenocarcinoma Arising in Gastric Heterotopic Pancreas: A Case Report 
Journal of Korean Medical Science  2004;19(1):145-148.
A heterotopic pancreas in the gastrointestinal tract is mostly found incidentally and its malignant transformation is extremely rare. We describe the second case of adenocarcinoma arising in a gastric heterotopic pancreas of an asymptomatic 35-yr-old man in Korea. Esophagogastroduodenoscopy revealed a submucosal tumor with an irregular central umbilication in the gastric antrum. A wedge resection specimen demonstrated a submucosal oligolocular cystic mass (1.7×1.4×1.2 cm) with a solid portion. Microscopically, the cystic portion was composed of dilated pancreaticobiliary type ducts with adjacent small foci of periductal glandular structures. The adenocarcinoma components in the solid area infiltrated the proper muscle and the overlying mucosa of the stomach. The transitional area between the benign ductal structures and the adenocarcinoma component was found. The follow-up course was uneventful 5 months postoperatively.
doi:10.3346/jkms.2004.19.1.145
PMCID: PMC2822253  PMID: 14966359
Adenomyoma; Stomach Neoplasms; Adenocarcinoma
6.  Comparison of Three BRAF Mutation Tests in Formalin-Fixed Paraffin Embedded Clinical Samples 
Korean Journal of Pathology  2013;47(4):348-354.
Background
Recently, BRAF inhibitors showed dramatic treatment outcomes in BRAF V600 mutant melanoma. Therefore, the accuracy of BRAF mutation test is critical.
Methods
BRAF mutations were tested by dual-priming oligonucleotide-polymerase chain reaction (DPO-PCR), direct sequencing and subsequently retested with a real-time PCR assay, cobas 4800 V600 mutation test. In total, 64 tumors including 34 malignant melanomas and 16 papillary thyroid carcinomas were analyzed. DNA was extracted from formalin-fixed paraffin embedded tissue samples and the results of cobas test were directly compared with those of DPO-PCR and direct sequencing.
Results
BRAF mutations were found in 23 of 64 (35.9%) tumors. There was 9.4% discordance among 3 methods. Out of 6 discordant cases, 4 cases were melanomas; 3 cases were BRAF V600E detected only by cobas test, but were not detected by DPO-PCR and direct sequencing. One melanoma patient with BRAF mutation detected only by cobas test has been on vemurafenib treatment for 6 months and showed a dramatic response to vemurafenib. DPO-PCR failed to detect V600K mutation in one case identified by both direct sequencing and cobas test.
Conclusions
In direct comparison of the currently available DPO-PCR, direct sequencing and real-time cobas test for BRAF mutation, real-time PCR assay is the most sensitive method.
doi:10.4132/KoreanJPathol.2013.47.4.348
PMCID: PMC3759634  PMID: 24009630
BRAF mutation; Melanoma; Real-time polymerase chain reaction; Sanger sequencing; Dual-priming oligonucleotide-PCR
7.  Methylome of Fetal and Maternal Monocytes and Macrophages at the Feto-Maternal Interface 
Problem
Decidual macrophages (dMϕ) of the mother and placental macrophages (Hofbauer cells, HC) of the fetus are deployed at a critical location: the feto-maternal interface. This study was conducted to compare DNA methylome of maternal and fetal monocytes, dMϕ, and HC, and thereby to determine the immunobiological importance of DNA methylation in pregnancy.
Methods of Study
Paired samples were obtained from normal pregnant women at term not in labor and their own neonates. Maternal monocytes (MM) and fetal monocytes (FM) were isolated from peripheral blood of mothers and from fetal cord blood, respectively. dMϕ and HC were obtained from the decidua of fetal membranes and placenta, respectively. DNA methylation profiling was done using the Illumina Infinium Human Methylation27 BeadChip. Quantitative real-time PCR and western blot were performed for validation experiments.
Results
1) Significant differences in DNA methylation were found in each comparison (MM vs. FM, 65 loci; dMϕ vs. HC, 266 loci; MM vs. dMϕ, 199 loci; FM vs. HC, 1,030 loci). 2) Many of the immune response-related genes were hypermethylated in fetal cells (FM and HC) compared to maternal cells (MM and dMϕ). 3) Genes encoding markers of classical macrophage activation were hypermethylated and genes encoding alternative macrophage activation were hypomethylated in dMϕ and HC compared to MM and FM, respectively. 4) mRNA expressions of DNMT1, DNMT3A, and DNMT3B were significantly lower in dMϕ than in HC. 5) 5-azacytidine treatment increased expression of INCA1 in dMϕ.
Conclusions
The findings herein indicate that DNA methylation patterns change during monocyte-macrophage differentiation at the feto-maternal interface. It is also suggested that DNA methylation is an important component of biological machinery conferring an anti-inflammatory phenotype to macrophages at the feto-maternal interface.
doi:10.1111/j.1600-0897.2012.01108.x
PMCID: PMC3479407  PMID: 22385097
Decidua; DNA methylation; DNA methyltransferase; Epigenetics; Epigenome; Hofbauer cell; Placenta; Pregnancy
8.  Use of Drug-eluting Stents Versus Bare-metal Stents in Korea: A Cost-minimization Analysis Using Population Data 
Objectives
The goal of this study was to perform an economic analysis of a primary stenting with drug-eluting stents (DES) compared with bare-metal stents (BMS) in patients with acute myocardial infarction (AMI) admitted through an emergency room (ER) visit in Korea using population-based data.
Methods
We employed a cost-minimization method using a decision analytic model with a two-year time period. Model probabilities and costs were obtained from a published systematic review and population-based data from which a retrospective database analysis of the national reimbursement database of Health Insurance Review and Assessment covering 2006 through 2010 was performed. Uncertainty was evaluated using one-way sensitivity analyses and probabilistic sensitivity analyses.
Results
Among 513 979 cases with AMI during 2007 and 2008, 24 742 cases underwent stenting procedures and 20 320 patients admitted through an ER visit with primary stenting were identified in the base model. The transition probabilities of DES-to-DES, DES-to-BMS, DES-to-coronary artery bypass graft, and DES-to-balloon were 59.7%, 0.6%, 4.3%, and 35.3%, respectively, among these patients. The average two-year costs of DES and BMS in 2011 Korean won were 11 065 528 won/person and 9 647 647 won/person, respectively. DES resulted in higher costs than BMS by 1 417 882 won/person. The model was highly sensitive to the probability and costs of having no revascularization.
Conclusions
Primary stenting with BMS for AMI with an ER visit was shown to be a cost-saving procedure compared with DES in Korea. Caution is needed when applying this finding to patients with a higher level of severity in health status.
doi:10.3961/jpmph.2013.46.4.201
PMCID: PMC3740225  PMID: 23946878
Myocardial infarction; Drug-eluting stents; Costs and cost analysis; Pharmaceutical economics
9.  Functional Properties of Mouse Connexin30.2 Expressed in the Conduction System of the Heart 
Circulation research  2005;96(11):1169-1177.
Gap junction channels composed of connexin (Cx) 40, Cx43, and Cx45 proteins are known to be necessary for impulse propagation through the heart. Here, we report mouse connexin30.2 (mCx30.2) to be a new cardiac connexin that is expressed mainly in the conduction system of the heart. Antibodies raised to the cytoplasmic loop or the C-terminal regions of mCx30.2 recognized this protein in mouse heart as well as in HeLa cells transfected with wild-type mCx30.2 or mCx30.2 fused with enhanced green fluorescent protein (mCx30.2-EGFP). Immunofluorescence analyses of adult hearts yielded positive signals within the sinoatrial node, atrioventricular node, and A-V bundle of the cardiac conduction system. Dye transfer studies demonstrated that mCx30.2 and mCx30.2-EGFP channels discriminate poorly on the basis of charge, but do not allow permeation of tracers >400 Da. Both mCx30.2 and mCx30.2-EGFP gap junctional channels exhibited weak sensitivity to transjunctional voltage (Vj) and a single channel conductance of ≈9 pS, which is the lowest among all members of the connexin family measured in HeLa cell transfectants. HeLa mCx30.2-EGFP transfectants when paired with cells expressing Cx40, Cx43, or Cx45 formed functional heterotypic gap junction channels that exhibited low unitary conductances (15 to 18 pS), rectifying open channel I-V relations and asymmetric Vj dependence. The electrical properties of homo- and hetero-typic junctions involving mCx30.2 may contribute to slow propagation velocity in nodal tissues and directional asymmetry of excitation spread in the AV nodal region.
doi:10.1161/01.RES.0000169271.33675.05
PMCID: PMC3657762  PMID: 15879306
connexin; gap junctions; mCx30.2; sinoatrial node; atrioventricular node
10.  Comparison of Early Clinical Outcomes Following Transcatheter Aortic Valve Implantation versus Surgical Aortic Valve Replacement versus Optimal Medical Therapy in Patients Older than 80 Years with Symptomatic Severe Aortic Stenosis 
Yonsei Medical Journal  2013;54(3):596-602.
Purpose
Transcatheter aortic valve implantation (TAVI) has become an attractive therapeutic strategy for severe aortic stenosis (AS) in elderly patients due to its minimally-invasive nature. Therefore, early results of its clinical outcomes in elderly Korean patients were evaluated.
Materials and Methods
We compared early clinical outcomes of TAVI, surgical aortic valve replacement (SAVR), and optimal medical therapy (OMT) in patients aged ≥80 years with symptomatic severe AS. Treatment groups were allocated as follows: TAVI (n=10), SAVR (n=14), and OMT (n=42).
Results
Baseline clinical characteristics including predicted operative mortality were similar among the three groups. However, patients with New York Heart Association functional class III or IV symptoms and smaller aortic valve area were treated with TAVI or SAVR rather than OMT. In-hospital combined safety endpoints (all-cause mortality, major stroke, peri-procedural myocardial infarction, life-threatening bleeding, major vascular complication, and acute kidney injury) after TAVI or SAVR were significantly lower in the TAVI group than in the SAVR group (10.0% vs. 71.4%, respectively, p=0.005), along with an acceptable rate of symptom improvement and device success. During the follow-up period, the TAVI group showed the lowest rate of 3-month major adverse cardiovascular and cerebrovascular events, a composite of all-cause mortality, myocardial infarction, major stroke, and re-hospitalization (TAVI 0.0% vs. SAVR 50.0% vs. OMT 42.9%, p=0.017).
Conclusion
Treatment with TAVI was associated with lower event rates compared to SAVR or OMT. Therefore, TAVI may be considered as the first therapeutic strategy in selected patients aged ≥80 years with symptomatic severe AS.
doi:10.3349/ymj.2013.54.3.596
PMCID: PMC3635628  PMID: 23549802
Aortic stenosis; transcatheter aortic valve implantation; treatment outcome
11.  Characterization of the transcriptome of chorioamniotic membranes at the site of rupture in spontaneous labor at term 
OBJECTIVE
The purpose of this study was to compare the transcriptome between the site of membrane rupture and the chorioamniotic membranes away from the site of rupture.
STUDY DESIGN
The transcriptome of amnion and chorion (n =20 each) from and distal to the site of rupture from women with spontaneous labor and vaginal delivery at term after spontaneous rupture of membranes was profiled with Illumina HumanHT-12 microarrays. Selected genes were validated with the use of quantitative reverse transcription–polymerase chain reaction.
RESULTS
Six hundred seventy-seven genes were differentially expressed in the chorion between the rupture and nonrupture sites (false discovery rate <0.1; fold change >1.5). Quantitative reverse transcription–polymerase chain reaction confirmed the differential expression in 10 of 14 genes. Enriched biological processes included anatomic structure development, cell adhesion and signal transduction. Extracellular matrix–receptor interaction was the most impacted signaling pathway.
CONCLUSION
The transcriptome of fetal membranes after spontaneous rupture of membranes in term labor is characterized by region-and tissue-specific differential expression of genes that are involved in signature pathways, which include extracellular matrix–receptor interactions.
doi:10.1016/j.ajog.2010.02.045
PMCID: PMC3604885  PMID: 20452490
chorion; extracellular matrix; inflammation; labor; microarray; parturition; spontaneous rupture of membranes
12.  Dorsal-Plantar Loop Technique Using Chronic Total Occlusion Devices via Anterior Tibial Artery 
Yonsei Medical Journal  2013;54(2):534-537.
The effectiveness of below-the-knee (BTK) percutaneous transluminal angioplasty to obtain successful revascularization in patients with critical limb ischemia has been well established, and many of these patients with chronic lower-extremity disease have been treated by endovascular intervention as the firstline treatment. Dorsal-plantaer loop technique is one of the new BTK interventional techiniques, and includes recanalization of both pedal and plantar arteries and their anatomical anastomoses. This method generally needs two approaches simultaneously, including antegrade and retrograde. In this report, however, we describe a case in which dorsal-plantar loop technique with only one antegrade approach, using chronic total occlusion devices via anterior tibial artery, was used to successfully recanalize BTK arteries. We think that this new technique, which may represent a safe and feasible endovascular option to avoid more invasive, time-consuming, and riskier surgical procedures, especially in end-stage renal disease and diabetes, should be considered whenever the foot is at risk, and results of above-the-ankle percutaneous transluminal angioplasty remain unsatisfactory or insufficient to achieve limb salvage.
doi:10.3349/ymj.2013.54.2.534
PMCID: PMC3575960  PMID: 23364993
Ischemia; peripheral arterial disease; angioplasty
13.  Relationship between Angiographic Late Loss and 5-Year Clinical Outcome after Drug-Eluting Stent Implantation 
Yonsei Medical Journal  2012;54(1):41-47.
Purpose
Currently, insufficient data exist to evaluate the relationship between angiographic late loss (LL) and long-term clinical outcome after drug-eluting stent (DES) implantation. In this study, we hypothesized that angiographic LL between 0.3 and 0.6 mm correlate with favorable long-term clinical outcomes.
Materials and Methods
Patients were enrolled in the present study if they had undergone both DES implantation in single coronary vessel and a subsequent follow-up angiogram (n=634). These individuals were then subdivided into three groups based on their relative angiographic LL: group I (angiographic LL <0.3 mm, n=378), group II (angiographic LL between 0.3 and 0.6 mm, n=124), and group III (angiographic LL >0.6 mm, n=134). During a 5-year follow-up period, all subjects were tracked for critical events, defined as any cause of death or myocardial infarction, which were then compared among the three groups.
Results
Mean follow-up duration was 63.0±10.0 months. Critical events occurred in 25 subjects in group I (6.6%), 5 in group II (4.0%), and 17 in group III (12.7%), (p=0.020; group I vs. group II, p=0.293; group II vs. group III, p=0.013). In a subsequent multivariate logistic regression analysis, chronic renal failure [odds ratio (OR)=3.29, 95% confidence interval (CI): 1.48-7.31, p=0.003] and long lesion length, defined as lesion length >28 mm (OR=1.88, 95% CI: 1.02-3.46, p=0.042) were independent predictors of long-term critical events.
Conclusion
This retrospective analysis fails to demonstrate that post-DES implantation angiographic LL between 0.3 and 0.6 mm is protective against future critical events.
doi:10.3349/ymj.2013.54.1.41
PMCID: PMC3521267  PMID: 23225797
Coronary artery disease; stents; outcome assessment
14.  Maternal HLA Panel Reactive Antibodies in Early Gestation Positively Correlates with Chronic Chorioamnionitis: Evidence in Support of the Chronic Nature of Maternal Anti-fetal Rejection 
Problem
Maternal tolerance of the fetus is essential for viviparity, yet anti-fetal rejection occurs in several pregnancy complications. Chronic chorioamnionitis (CCA) is a feature of anti-fetal cellular rejection. There is a robust association between CCA and maternal seropositivity for anti-HLA panel reactive antibodies (PRA) at the time of delivery. This longitudinal study was performed to assess maternal HLA PRA status in early gestation and the temporal evolution of maternal HLA PRA in the context of CCA and thereby to determine whether HLA PRA during the course of pregnancy is useful for the detection of anti-fetal rejection.
Method of Study
Maternal sera obtained before 16 weeks of gestation and at delivery were analyzed for HLA panel reactive antibodies (PRA) in cases with (N=100) and without (N=150) CCA.
Results
IgG but not IgM HLA class I and II PRA positivity at delivery was higher in cases with CCA than in those without CCA. IgG HLA class I PRA positivity before 16 weeks of gestation was higher in cases with CCA than in those without (30.3% vs. 13.3%; p=0.001). Positive conversion (negative HLA PRA before 16 weeks of gestation but positive at delivery) of IgG HLA class I and II PRA was significantly associated with CCA. Fetal HLA class I antigen-specific antibodies were confirmed in 12 of 16 mothers tested who were sensitized to HLA class I antigens before 16 weeks of gestation.
Conclusion
Positive maternal HLA PRA before 16 weeks of gestation and the temporal evolution of maternal HLA PRA are associated with the presence of CCA at the time of delivery. Maternal IgG HLA PRA has potential to be a monitoring tool of anti-fetal rejection. Furthermore, the findings herein indicate that subsets of fetuses are exposed to alloimmune HLA antibodies for months, especially in cases with CCA.
doi:10.1111/j.1600-0897.2011.01066.x
PMCID: PMC3234997  PMID: 21951517
chronic chorioamnionitis; human leukocyte antigen; panel reactive antibody; pregnancy; preterm birth; rejection
15.  The Transcriptome of the Fetal Inflammatory Response Syndrome 
Problem
The fetal inflammatory response syndrome (FIRS) is considered the counterpart of the systemic inflammatory response syndrome (SIRS), but similarities in their regulatory mechanisms are unclear. This study characterizes the fetal mRNA transcriptome of peripheral leukocytes to identify key biological processes and pathways involved in FIRS.
Method of Study
Umbilical cord blood from preterm neonates with FIRS (funisitis, plasma IL-6>11 pg/ml; n=10) and neonates with no evidence of inflammation (n=10) was collected at birth.
Results
Microarray analysis of leukocyte RNA revealed differential expression of 541 unique genes, changes confirmed by qRT-PCR for 41 or of 44 genes tested. Similar to SIRS and sepsis, ontological and pathway analyses yielded significant enrichment of biological processes including antigen processing and presentation, immune response, and processes critical to cellular metabolism. Results are comparable with microarray studies of endotoxin challenge models and pediatric sepsis, identifying 25 genes across all studies.
Conclusions
This study is the first to profile genome-wide expression in FIRS, which demonstrates a substantial degree of similarity with SIRS despite differences in fetal and adult immune systems.
doi:10.1111/j.1600-0897.2009.00791.x
PMCID: PMC3437779  PMID: 20059468
prematurity; preterm birth; chorioamnionitis; FIRS; microarray; transcriptomics
16.  Clinical Characteristics of Acute Aortic Syndrome in Korean Patients: From the Korean Multi-Center Registry of Acute Aortic Syndrome 
Korean Circulation Journal  2012;42(8):528-537.
Background and Objectives
Acute aortic syndrome (AAS) is a heterogeneous group of disorders that often present with severe chest or back pain. It includes acute aortic dissection (AD), intramural hematoma (IMH), dissecting aneurysm, and penetrating aortic ulcer (PAU). The clinical picture of AAS and its prognosis have not been studied in a large number of Korean patients. Therefore, we organized a multi-center registry to identify the clinical characteristics and treatment patterns, as well as long-term outcomes in Korean patients with AAS.
Subjects and Methods
Five-hundred twenty-eight patients, who had been diagnosed with AAS, were enrolled into this registry from 10 centers. On a retrospective basis, we collected demographic, laboratory, imaging data, as well as follow-up clinical outcomes by reviewing medical records from individual centers. All the data were collected in core lab and analyzed in detail.
Results
The mean patient age was 60.1±14.5 years; the male-to-female ratio was M : F=297 : 231. The prevalent risk factors for AAS included hypertension (361, 68.4%) and diabetes (52, 11.1%). The components of AAS that are included in this study are acute AD (446, 84.5%), IMH (57, 10.7%), and PAU (11, 2.1%). By type of AAS, patients diagnosed with Stanford A were 45.6% of enrolled patients, whereas those with Stanford B were 54.4% of enrolled patients. Among nearly half of the patients were treated with medicine (55.7%) alone, whereas 40.0% underwent surgery and 4.3% underwent endovascular treatment. Overall, the in-hospital event rate was 21.2% and the in-hospital death rate was 8.1%. The mean follow-up duration was 42.8 months and there showed 22.9% of total event and 10.1% of death during this period.
Conclusion
By organizing a multi-center registry of AAS, we could identify the characteristics of AAS in real-world Korean patients. Further, prospective study is warranted with a larger number of patients.
doi:10.4070/kcj.2012.42.8.528
PMCID: PMC3438262  PMID: 22977448
Aortic diseases; Dissection; Hematoma; Population characteristics
17.  Comparison between Measured and Calculated Length of Side Branch Ostium in Coronary Bifurcation Lesions with Intravascular Ultrasound 
Yonsei Medical Journal  2012;53(4):680-684.
Purpose
Accurate evaluation of side branch (SB) ostium could be critical to the treatment of bifurcation lesions. We compared measured and calculated values of side branch ostial length (SBOL) in coronary bifurcation lesions with intravascular ultrasound (IVUS).
Materials and Methods
Pre-intervention and post-intervention IVUS was performed in 113 patients who underwent stent implantation of bifurcation lesions. For the IVUS longitudinal reconstruction of the bifurcation lesions, SBOL, SB diameter, and the angle between the distal portion of the main vessel (MV) and SB were directly measured. In addition, SBOL was calculated as: SB diameter/sin (angle between distal MV and SB). The relationship between measured and calculated SBOL was then evaluated.
Results
The angled between the distal MV and SB were 57.3±12.4° at pre-intervention and 59.4±12.6° at post-intervention. The mean measured and calculated SBOL values were 2.91±0.86 mm and 3.06±0.77 mm at pre-intervention and 2.79±0.82 mm and 2.92±0.69 mm at post-intervention, respectively. Differences between measured and calculated SBOL were 0.15±0.44 mm at pre-intervention and 0.13±0.41 mm at post-intervention. We found that calculated SBOL was correlated with measured SBOL (pre-intervention r=0.863, p<0.001; post-intervention r=0.868, p<0.001).
Conclusion
There was a good correlation between measured and calculated SBOLs of the bifurcation lesions in IVUS longitudinal reconstruction. SBOL in the bifurcation lesions can therefore be estimated using the SB diameter and the angle between distal MV and SB.
doi:10.3349/ymj.2012.53.4.680
PMCID: PMC3381491  PMID: 22665331
Coronary artery disease; ultrasonics; bifurcation
18.  Serial Plasma Levels of Angiogenic Factors in Patients With ST-Segment Elevation Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention 
Korean Circulation Journal  2012;42(7):464-470.
Background and Objectives
Patients with acute myocardial infarction show varying degrees of collateral development. However, the relationships between angiogenic factors and degree of collaterals are not well known.
Subjects and Methods
Fifty-nine patients (mean age, 59±10 years) with ST-segment elevation myocardial infarction (STEMI) underwent primary percutaneous coronary intervention (PCI). Patients were divided into one of 2 groups: group I (Rentrop collateral grade 0/1, n=34) or group II (grade 2/3, n=25). Plasma levels of vascular endothelial growth factor (VEGF), soluble VEGF receptor (sFlt-1), angiopoietin (Ang)-2, and soluble Tie-2 at baseline, 24 and 48 hours after PCI were measured.
Results
There were fewer diabetic patients and higher incidence of previous angina and multi-vessel disease in group II. Group II had a lower left ventricular ejection fraction and a trend toward longer pain-to-balloon time. Plasma levels of Ang-2, sFlt-1 were elevated prior to primary PCI and decreased after PCI, whereas plasma level of VEGF was relatively low initially, however rose after PCI. sTie-2 levels showed no significant interval change in group I, but decreased over time in group II. VEGF, sFlt-1, and Tie-2 levels did not differ between the groups at each time point. However, plasma levels of Ang-2 were higher in group I than in group II at baseline and at 48 hours.
Conclusion
Presence of collaterals in STEMI patients undergoing primary PCI was associated with lesser rise in Ang-2 plasma level. VEGF showed a delayed response to acute ischemia compared to Ang-2. Clinical implications of our findings need to be investigated in further studies.
doi:10.4070/kcj.2012.42.7.464
PMCID: PMC3409395  PMID: 22870080
Myocardial infarction; Angiogenesis modulating agents; Vascular endothelial growth factor; Angiopoietin-2
19.  Correlations between Coronary Plaque Tissue Composition Assessed by Virtual Histology and Blood Levels of Biomarkers for Coronary Artery Disease 
Yonsei Medical Journal  2012;53(3):508-516.
Purpose
We investigated correlations of coronary plaque composition determined by virtual histology (VH) intravascular ultrasound (IVUS) and blood levels of biomarkers that represent the vulnerability of coronary plaques.
Materials and Methods
Pre- and postprocedural blood levels of high sensitivity C-reactive protein, soluble CD40 ligand (sCD40L), matrix metalloproteinase-9, and neopterin were measured in 70 patients with stable angina (SA) or unstable angina (UA) who were undergoing percutaneous coronary intervention (PCI) for single lesions. We evaluated the data for correlations between these biomarkers and necrotic core contents in PCI target lesions analyzed by VH.
Results
Clinical characteristics, IVUS, VH, and biomarker blood levels were not different between the SA and the UA group except for more frequent previous statin use (52.3% vs. 23.1%, p=0.017) and lower remodeling index in the SA group (0.98±0.09 vs. 1.10±0.070, p<0.001). Among the biomarkers evaluated, only pre-PCI neopterin level showed a weakly significant correlation with the absolute volume of the necrotic core (r=0.320, p=0.008). Pre- and post-PCI blood levels of sCD40L (r=0.220, p=0.072; r=0.231, p=0.062) and post-PCI blood level of neopterin (r=0.238, p=0.051) showed trends toward weakly positive correlations with the absolute volume of necrotic core.
Conclusion
We found a weakly positive correlation between the pre-PCI neopterin level and necrotic core volume in the PCI-target lesion. The clinical implications of our findings need to be investigated in further studies.
doi:10.3349/ymj.2012.53.3.508
PMCID: PMC3343421  PMID: 22476993
Atherosclerosis; coronary artery disease; inflammation; intravascular ultrasound
20.  Comparison of Optical Coherence Tomographic Assessment between First- and Second-Generation Drug-Eluting Stents 
Yonsei Medical Journal  2012;53(3):524-529.
Purpose
There is a lack of sufficient data in comparison of optical coherence tomographic (OCT) findings between first- and second-generation drug-eluting stents (DES). Compared to first-generation (i.e., sirolimus- or paclitaxel-eluting stents), second-generation DESs (i.e., everolimus- or biolinx-based zotarolimus-eluting stents) might have more favorable neointimal coverage.
Materials and Methods
Follow-up OCT findings of 103 patients (119 lesions) treated with second-generation DESs were compared with those of 139 patients (149 lesions) treated with first-generation DESs. The percentage of uncovered or malapposed struts, calculated as the ratio of uncovered or malapposed struts to total struts in all OCT cross-sections, respectively, was compared between the two groups.
Results
Both DES groups showed similar suppression of neointimal hyperplasia (NIH) on OCT (mean NIH cross-sectional area; second- vs. first-generation=1.1±0.5 versus 1.2±1.0 mm2, respectively, p=0.547). However, the percentage of uncovered struts of second-generation DESs was significantly smaller than that of first-generation DESs (3.8±4.8% vs.7.5±11.1%, respectively, p<0.001). The percentage of malapposed struts was also significantly smaller in second-generation DESs than in first-generation DESs (0.4±1.6% vs.1.4±3.7%, respectively, p=0.005). In addition, intra-stent thrombi were less frequently detected in second-generations DESs than in first-generation DESs (8% vs. 20%, respectively, p=0.004).
Conclusion
This follow-up OCT study showed that second-generation DESs characteristically had greater neointimal coverage than first-generation DESs.
doi:10.3349/ymj.2012.53.3.524
PMCID: PMC3343428  PMID: 22476995
Optical coherence tomography; stent
21.  Spontaneous aortic rupture in a patient with neurofibromatosis type 1 
Neurofibromatosis type I (NF-1) is a rare autosomal dominant genetic disorder occurring in 1 in 3,000 individuals. Vasculopathy is a rarely reported finding in patients with NF-1. Here, we report a case of recurrent aortic pseudoaneurysm after endovascular aneurysm repair in a 49-year-old male patient with NF-1. On the sixth postoperative day following a successful open surgical repair of an aortic pseudoaneurysm, he developed hemoperitoneum due to a delayed rupture of the mesenteric artery branch. This was treated with endovascular coil embolization. We report the clinical features and histologic findings of this rare vascular disorder with a review of the relevant literature.
doi:10.4174/jkss.2012.82.4.261
PMCID: PMC3319782  PMID: 22493769
Aortic aneurysm; Aortic rupture; Neurofibromatosis 1
22.  Clinical Outcomes of Infrapopliteal Angioplasty in Patients With Critical Limb Ischemia 
Korean Circulation Journal  2012;42(4):259-265.
Background and Objectives
With recent advances in equipment and techniques, infrapopliteal angioplasty has shown results that are comparable to those of surgical bypass in patients with critical limb ischemia (CLI). In this study, we evaluated the efficacy and the feasibility of infrapopliteal angioplasty in patients with CLI.
Subjects and Methods
Between March 2002 and May 2008, infrapopliteal angioplasty was performed on 118 limbs of 101 patients (79 males; mean age 66 years) with CLI (Rutherford category 4, 5 or 6). Freedom from reintervention, limb salvage, and overall survival were analyzed.
Results
The median follow-up duration was 30 months. Initial technical and clinical success rates were 69.5% and 83.1%, respectively. No major complication requiring surgical intervention developed after angioplasty. Among 82 limbs with initial technical success, the rate of freedom from any reintervention at 2 years was 70.7% and that from limb salvage was 97.6%. Young age and Rutherford category 6 at initial presentation were independent predictors associated with poor 2 year primary patency in these patients with CLI. Overall survival at 1 year was 86.4% and that at 2 years 76.3%. A history of cerebrovascular accident was an independent predictor associated with poor 2 year survival in these patients.
Conclusion
Infrapopliteal angioplasty as a primary choice of treatment in CLI patients showed favorable clinical outcomes and feasibility.
doi:10.4070/kcj.2012.42.4.259
PMCID: PMC3341423  PMID: 22563339
Ischemia; Limb salvage; Tibial arteries; Peroneal arteries; Angioplasty
23.  Malignant Melanoma of Unknown Primary Origin Presenting as Cardiac Metastasis 
Korean Circulation Journal  2012;42(4):278-280.
Malignant melanoma has a very high propensity to metastasize to the heart. However, melanoma may sometimes present as a metastatic lesion in the absence of a primary lesion, which are called melanomas of unknown primary origin. We report a case in which a patient presented with a metastatic maligant melanoma in the right atrium with pericardial effusion and without a primary origin.
doi:10.4070/kcj.2012.42.4.278
PMCID: PMC3341426  PMID: 22563342
Melanoma; Neoplasma, unknown primary; Unknown primary; Heart neoplasms
24.  1α,25-Dihydroxyvitamin D3 Inhibits C4-2 Prostate Cancer Cell Growth via a Retinoblastoma Protein (Rb)-Independent G1 Arrest 
The Prostate  2011;71(1):98-110.
BACKGROUND
The active metabolite of vitamin D, 1α,25-dihydroxyvitamin D3 (1,25D) reduces the growth of several prostate cancer cell lines, most commonly by inducing a cell cycle arrest in G1. This is mediated, in part, through down-regulation of c-Myc, a positive regulator of the transcription factor, E2F. There is evidence that prostate cancer cells lacking functional retinoblastoma protein (Rb), a negative regulator of E2F activity, are poorly responsive to 1,25D treatment. Since up to 60% of prostate cancers demonstrate a loss of heterozygosity for Rb, we sought to determine whether Rb is required for the growth inhibitory effects of 1,25D.
METHODS
Using siRNA, Rb was reduced in C4-2 prostate cancer cells, and the response of cells to 1,25D treatment or depletion of c-myc measured by [3H]-thymidine incorporation and flow cytometry. The effects of 1,25D treatment on E2F levels and activity, and E2F target gene expression were also measured.
RESULTS
1,25D treatment and c-Myc depletion both cause a G1 arrest inhibiting C4-2 cell proliferation independently of Rb. 1,25D reduces c-Myc expression and causes a decrease in E2F and E2F target genes. Bcl-2, an E2F target and positive regulator of C4-2 cell growth, also is down-regulated by 1,25D independently of Rb.
CONCLUSIONS
Redundant growth inhibitory pathways compensate for the loss of Rb, and tumors lacking functional Rb may be responsive to 1,25D.
doi:10.1002/pros.21226
PMCID: PMC2966519  PMID: 20632309
Vitamin D; Rb; c-Myc; prostate cancer; E2F
25.  Effects of Combination Therapy with Celecoxib and Doxycycline on Neointimal Hyperplasia and Inflammatory Biomarkers in Coronary Artery Disease Patients Treated with Bare Metal Stents 
Yonsei Medical Journal  2011;53(1):68-75.
Purpose
Cyclooxygenase (COX)-2 and matrix metalloproteinase (MMP)-9 play a key role in the pathogenesis of in-stent restenosis. We investigated the effect of a short-term therapy of celecoxib, a COX-2 inhibitor, with or without doxycycline, an MMP inhibitor, after coronary stenting on inflammatory biomarkers and neointimal hyperplasia.
Materials and Methods
A total of 75 patients (86 lesions) treated with bare metal stents were randomized into three groups: 1) combination therapy (200 mg celecoxib and 20 mg doxycycline, both twice daily), 2) celecoxib (200 mg twice daily) only, and 3) non-therapy control. Celecoxib and doxycycline were administered for 3 weeks after coronary stenting. The primary endpoint was neointimal volume obstruction by intravascular ultrasound (IVUS) at 6 months. The secondary endpoints included clinical outcomes, angiographic data, and changes in blood levels of inflammatory biomarkers.
Results
Follow-up IVUS revealed no significant difference in the neointimal volume obstruction among the three treatment groups. There was no difference in cardiac deaths, myocardial infarctions, target lesion revascularization or stent thrombosis among the groups. Blood levels of high-sensitivity C-reactive protein, soluble CD40 ligand, and MMP-9 varied widely 48 hours and 3 weeks after coronary stenting, however, they did not show any significant difference among the groups.
Conclusion
Our study failed to demonstrate any beneficial effects of the short-term therapy with celecoxib and doxycycline or with celecoxib alone in the suppression of inflammatory biomarkers or in the inhibition of neointimal hyperplasia. Large scale randomized trials are necessary to define the role of anti-inflammatory therapy in the inhibition of neointimal hyperplasia.
doi:10.3349/ymj.2012.53.1.68
PMCID: PMC3250318  PMID: 22187234
Celecoxib; coronary artery disease; coronary stent; neointimal hyperplasia; inflammation

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