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Purpose: Numerous robot-assisted pancreatic surgery are being performed worldwide. This study aimed to evaluate the feasibility and safety of the Revo-i robot system (Meerecompany, Seoul, Republic of Korea) for advanced pancreatic surgery, and also compare this new system with the existing da Vinci™ robot system (Intuitive Surgical, Sunnyvale, CA, USA) in the context of robot-assisted pancreaticoduodenectomy (RPD)., Materials and Methods: This study was a one-armed prospective clinical trial that assessed the Revo-i robot system for advanced pancreatic surgery. Ten patients aged 30 to 73 years were enrolled between December 2019 and August 2020. Postoperative outcomes were retrospectively compared with those of the da Vinci™ surgical system. From March 2017 to August 2020, a total of 47 patients who underwent RPD were analyzed retrospectively., Results: In the prospective clinical trial, pancreaticoduodenectomy was performed in nine patients and one patient underwent central pancreatectomy. Among the 10 study participants, the incidence of major complications was 0% in hospital stay. There were eight postoperative pancreatic fistula (POPF) biochemical leaks (80%). In the retrospective analysis that compared the Revo-i and da Vinci™ robotic systems, 10 patients underwent Revo-i RPD and 37 patients underwent da Vinci™ RPD, with no significant differences in complication or POPF incidence rates between the two groups ( p =0.695, p =0.317)., Conclusion: In this single-arm prospective study with short-term follow-up at a single institution, the Revo-i robotic surgical system was safe and effective for advanced pancreatic surgery. Revo-i RPD is comparable to the da Vinci™ RPD and is expected to have wide clinical application., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2024.)

Purpose: The favorable clinical efficacies of intramuscular injection of autologous blood in patients with atopic dermatitis (AD) and intramuscular injection of autologous serum in patients with chronic urticaria have been demonstrated by randomized clinical trials. In this study, we assessed the clinical effectiveness and safety of the intramuscular injection of autologous serum in patients with AD., Materials and Methods: In this randomized, placebo-controlled, and double-blind trial, 23 adolescent and adult patients with moderate-to-severe AD were enrolled. The patients were randomized to receive eight intramuscular injections of 5 mL of autologous serum (n=11) or saline (n=12) over 4 weeks, and were followed up until week 8. Changes in the clinical severity scores of AD assessed by SCORing Atopic Dermatitis (SCORAD), patient-reported Dermatology Life Quality Index (DLQI) score, and incidence of adverse events were assessed from baseline to week 8., Results: One patient in the treatment group and two patients in the placebo group were lost to follow-up before week 8. The intramuscular administration of autologous serum, compared with saline, decreased the SCORAD clinical severity score (-14.8% vs. 10.7%, p =0.006) and improved the DLQI score (-32.6% vs. 19.5%, p =0.01) from baseline to week 8. Serious adverse events were not observed., Conclusion: Intramuscular injection of autologous serum may be effective in treating AD. Further studies are needed to evaluate the clinical usefulness of this intervention for AD (KCT0001969)., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2023.)

Purpose: Atrial fibrillation (AF) patients with low to intermediate risk, defined as non-gender CHA 2 DS 2 -VASc score of 0-1, are still at risk of stroke. This study verified the usefulness of ABCD score [age (≥60 years), B-type natriuretic peptide (BNP) or N-terminal pro-BNP (≥300 pg/mL), creatinine clearance (<50 mL/min/1.73 m²), and dimension of the left atrium (≥45 mm)] for stroke risk stratification in non-gender CHA 2 DS 2 -VASc score 0-1., Materials and Methods: This multi-center cohort study retrospectively analyzed AF patients with non-gender CHA 2 DS 2 -VASc score 0-1. The primary endpoint was the incidence of stroke with or without antithrombotic therapy (ATT). An ABCD score was validated., Results: Overall, 2694 patients [56.3±9.5 years; female, 726 (26.9%)] were followed-up for 4.0±2.8 years. The overall stroke rate was 0.84/100 person-years (P-Y), stratified as follows: 0.46/100 P-Y for an ABCD score of 0; 1.02/100 P-Y for an ABCD score ≥1. The ABCD score was superior to non-gender CHA 2 DS 2 -VASc score in the stroke risk stratification (C-index=0.618, p =0.015; net reclassification improvement=0.576, p =0.040; integrated differential improvement=0.033, p =0.066). ATT was prescribed in 2353 patients (86.5%), and the stroke rate was significantly lower in patients receiving non-vitamin K antagonist oral anticoagulant (NOAC) therapy and an ABCD score ≥1 than in those without ATT (0.44/100 P-Y vs. 1.55/100 P-Y; hazard ratio=0.26, 95% confidence interval 0.11-0.63, p =0.003)., Conclusion: The biomarker-based ABCD score demonstrated improved stroke risk stratification in AF patients with non-gender CHA 2 DS 2 -VASc score 0-1. Furthermore, NOAC with an ABCD score ≥1 was associated with significantly lower stroke rate in AF patients with non-gender CHA 2 DS 2 -VASc score 0-1., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

This present systematic review examines spine surgery literature supporting augmented reality (AR) technology and summarizes its current status in spinal surgery technology. Database search strategies were retrieved from PubMed, Web of Science, Cochrane Library, Embase, from the earliest records to April 1, 2021. Our review briefly examines the history of AR, and enumerates different device application workflows in a variety of spinal surgeries. We also sort out the pros and cons of current mainstream AR devices and the latest updates. A total of 45 articles are included in our review. The most prevalent surgical applications included are the augmented reality surgical navigation system and head-mounted display. The most popular application of AR is pedicle screw instrumentation in spine surgery, and the primary responsible surgical levels are thoracic and lumbar. AR guidance systems show high potential value in practical clinical applications for the spine. The overall number of cases in AR-related studies is still rare compared to traditional surgical-assisted techniques. These lack long-term clinical efficacy and robust surgical-related statistical data. Changing healthcare laws as well as the increasing prevalence of spinal surgery are generating critical data that determines the value of AR technology., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Purpose: Neuroinflammation is considered an important pathway associated with several diseases that result in cognitive decline. 18 F-THK5351 positron emission tomography (PET) signals might indicate the presence of neuroinflammation, as well as Alzheimer's disease-type tau aggregates. β-amyloid (Aβ)-negative (Aβ-) amnestic mild cognitive impairment (aMCI) may be associated with non-Alzheimer's disease pathophysiology. Accordingly, we investigated associations between 18 F-THK5351 PET positivity and cognitive decline among Aβ- aMCI patients., Materials and Methods: The present study included 25 amyloid PET negative aMCI patients who underwent a minimum of two follow-up neuropsychological evaluations, including clinical dementia rating-sum of boxes (CDR-SOB). The patients were classified into two groups: 18 F-THK5351-positive and -negative groups. The present study used a linear mixed effects model to estimate the effects of 18 F-THK5351 PET positivity on cognitive prognosis among Aβ- aMCI patients., Results: Among the 25 Aβ- aMCI patients, 10 (40.0%) were 18 F-THK5351 positive. The patients in the 18 F-THK5351-positive group were older than those in the 18 F-THK5351-negative group (77.4±2.2 years vs. 70.0±5.5 years; p <0.001). There was no difference between the two groups with regard to the proportion of apolipoprotein E ε4 carriers. Interestingly, however, the CDR-SOB scores of the 18 F-THK5351-positive group deteriorated at a faster rate than those of the 18 F-THK5351-negative group (B=0.003, p =0.033)., Conclusion: The results of the present study suggest that increased 18 F-THK5351 uptake might be a useful predictor of poor prognosis among Aβ- aMCI patients, which might be associated with increased neuroinflammation (ClinicalTrials.gov NCT02656498)., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Purpose: Concerns have been consistently raised in regards to the considerable amount of contrast dye used during transcatheter aortic valve replacement (TAVR) in patients with renal insufficiency. In the present study, we introduced minimal contrast TAVR and compared its 30-day clinical outcomes with conventional TAVR., Materials and Methods: We retrospectively investigated 369 patients who underwent TAVR between July 2011 and April 2020 in our institute. Among them, 93 patients with severe aortic stenosis and renal insufficiency (estimated glomerular filtration rate ≤50 mL/min/1.73 m²) were included and divided into a conventional TAVR group (n=56) and a minimal contrast TAVR group (n=37). In the minimal contrast TAVR group, the total amount of contrast was <10 mL during the entire TAVR procedure. Thirty-day major adverse clinical events (MACE), including death, stroke, implantation of permanent pacemaker, and initiation of hemodialysis, were investigated., Results: The incidence of MACE was significantly lower in the minimal contrast TAVR group than the conventional TAVR group (16.2% vs. 42.9%, p =0.010). Death occurred in 9 patients (16.1%) in the conventional TAVR group and in 0 patients in the minimal contrast group ( p =0.011). Hemodialysis was initiated in 2 patients (5.4%) in the minimal contrast TAVR group and in 7 patients (12.5%) in the conventional TAVR group ( p =0.256). Multivariate regression analysis showed that the minimal contrast TAVR procedure was an independent predictor for reducing MACE (hazard ratio 0.208, 95% confidence interval: 0.080-0.541, p =0.001)., Conclusion: Minimal contrast TAVR is feasible and shows more favorable short-term clinical outcomes than conventional TAVR in patients with renal insufficiency., Competing Interests: Myeong-Ki Hong and Young-Guk Ko are proctors of Medtronic. The other authors have nothing to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Purpose: Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume., Materials and Methods: We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed., Results: Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p =0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2-3 patients than in pN0-1 patients (15.2% vs. 4.4%, p =0.04)., Conclusion: Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Purpose: Acute coronary occlusion is a rare but fatal complication that may occur during trans-catheter aortic valve implantation (TAVI) and appears more frequently in patients with low coronary heights. We evaluated the feasibility of self-expanding valves in patients with low coronary heights undergoing TAVI., Materials and Methods: TAVI for native aortic valve stenosis was conducted in 276 consecutive patients between 2015 and 2019 at our institute. Using multi-detector computed tomography (MDCT), information on the aortic valve, coronary arteries, and vascular anatomy in 269 patients was analyzed. Patients with low coronary heights were defined as those with coronary heights of 10 mm or less during MDCT analysis., Results: Among the 269 patients, 29 (10.8%) patients had coronary arteries with low heights. The mean coronary height was 8.9±1.2 mm in the left coronary artery. These patients with low coronary heights were treated with self-expandable (n=28) or balloon-expandable (n=1) valves. Prophylactic coronary protection with a guidewire, balloon, or stent prepositioned down at-risk coronary arteries was not pursued in all patients. No acute coronary occlusion occurred in any of these patients during TAVI. Five patients (17.9%) died during follow-up (average of 553.8 days), including four from non-cardiogenic causes and one from a cardiogenic (aggravation of heart failure) cause., Conclusion: A considerable number of patients with low coronary heights were observed among TAVI candidates in this study. Use of a self-expandable valve may be feasible for successful TAVI without acute coronary occlusion in patients with low coronary heights., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2021.)

Purpose: Thrombocytopenia (platelet count <150×10³/μL) is associated with poor outcomes in various critical illness settings. However, the prognostic value of platelet count in patients with cardiogenic shock (CS) remains unclear., Materials and Methods: We enrolled 1202 patients between January 2014 and December 2018 from a multicenter retrospective-prospective cohort registry of CS. Clinical characteristics and treatment outcomes were compared between the patients with and without thrombocytopenia., Results: At presentation with CS, 244 (20.3%) patients had thrombocytopenia. The patients with thrombocytopenia had lower blood pressure, hemoglobin level, and worse liver and renal functions compared to the patients without. During hospitalization, the patients with thrombocytopenia had more frequent gastrointestinal bleeding (10.5% vs. 3.8%, p =0.009), sepsis (8.3% vs. 2.6%, p =0.013), requirement of renal replacement therapy (36.5% vs. 18.9%, p <0.001), requirement of mechanical ventilation (65.2% vs. 54.4%, p =0.003), longer intensive care unit stay (8 days vs. 4 days, p <0.001), and thirty-day mortality (40.2% vs. 28.5%, p <0.001) compared to those without. In addition, the platelet count was an independent predictor of 30-day mortality (per 10 3 /μL decrease; adjusted hazard ratio: 1.002, 95% confidence interval: 1.000-1.003, p =0.021)., Conclusion: Thrombocytopenia at CS presentation was associated with worse clinical findings, higher frequencies of complications, and longer stay at the intensive care unit. Also, thrombocytopenia was independently associated with increased 30-day mortality. (Clinical trial registration No. NCT02985008)., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Purpose: Although current guidelines recommend the administration of dual antiplatelet therapy (DAPT) for up to 12 months after the implantation of a drug-eluting stent (DES), extended DAPT is frequently used in real-world practice., Materials and Methods: From the Korean Multicenter Angioplasty Team registry, we identified a total of 1414 patients who used DAPT for >3 years after DES implantation (extended-DAPT group) and conducted a landmark analysis at 36 months after the index procedure. We evaluated the determinants for and long-term outcomes of extended DAPT and compared the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE), defined as the composite of all-cause death, myocardial infarction, stent thrombosis, and stroke, between the extended-DAPT group and the guideline-DAPT group [DAPT <1 year after DES implantation (n=1273)]., Results: Multivariate analysis indicated the occurrence of acute coronary syndrome as the most significant clinical determinant of the use of extended DAPT. Bifurcation, stent diameter ≤3.0 mm, total stented length ≥28 mm, and use of first-generation DESs were also significant angiographic and procedural determinants. MACCE rates were similar between the extended-DAPT group and the guideline-DAPT group in crude analysis [hazard ratio (HR), 1.08; 95% confidence interval (CI), 0.69-1.68; p =0.739] and after propensity matching (HR, 1.22; 95% CI, 0.72-2.07; p =0.453). Major bleeding rates were comparable between the two groups., Conclusion: In patients undergoing percutaneous coronary intervention, indefinite use of DAPT does not show superior outcomes to those of guideline-DAPT. Major bleeding rates are also similar., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Purpose: Osteoarthritis (OA) of the temporomandibular joint (TMJ) elicits cartilage and subchondral bone defects. Growth hormone (GH) promotes chondrocyte growth. The aim of this study was to evaluate the efficacy of intra-articular injections of GH to treat TMJ-OA., Materials and Methods: Monosodium iodoacetate (MIA) was used to induce OA in the TMJs of rats. After confirming the induction of OA, recombinant human GH was injected into the articular cavities of rats. Concentrations of GH and IGF-1 were measured in the blood and synovial fluid, and OA grades of cartilage and subchondral bone degradation were recorded by histological examination and micro-computed tomography., Results: MIA-induced OA in the rat TMJ upregulated insulin-like growth factor-1 (IGF-1) rather than GH levels. GH and IGF-1 concentrations were increased after local injection of GH, compared with controls. Locally injected GH lowered osteoarthritic scores in the cartilage and subchondral bone of the TMJ., Conclusion: Intra-articular injection of GH improved OA scores in rat TMJs in both cartilage and subchondral bone of the condyles without affecting condylar bone growth. These results suggest that intra-articular injection of human GH could be a suitable treatment option for TMJ-OA patients in the future., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2020.)

Purpose: We evaluated the incidence, predictors, and prognosis of coronary artery aneurysm (CAA) after second-generation drug-eluting stent (DES) implantation., Materials and Methods: A total of 976 consecutive patients (1245 lesions) who underwent follow-up angiography after second-generation DES implantation were analyzed. Incidence and predictors of CAA were assessed, and clinical prognosis was compared with 34 cases of CAA after first-generation DES implantation using previous CAA registry data., Results: All 10 cases of CAA (0.80% per lesion) in 10 patients (1.02% per patient) were detected at follow up. Compared to lesions without CAA, those with CAA had greater involvement of the proximal segment (90% vs. 51%, p =0.014), a higher proportion of pre-intervention, a Thrombolysis in Myocardial Infarction score of 0 or 1 flow (80% vs. 16%, p <0.001), more chronic total occlusions (40% vs. 10%, p <0.001), and longer implanted stents (41.9±23.2 mm vs. 28.8±14.8 mm, p =0.006). As for CAA morphology, instances of CAA after second-generation DES were predominantly the single fusiform type (90%), whereas instances of CAA after first-generation DES were multiple saccular (47%) and single saccular (35%) types ( p <0.001). Myocardial infarction with stent thrombosis occurred in 5 patients with CAA after first-generation DES (15%), and no adverse events were observed in patients with CAA after second-generation DES over a median follow-up duration of 4.3 years ( p =0.047, log-rank)., Conclusion: Although CAAs after second-generation DES implantation were detected at a similar incidence to that for CAAs after first-generation DES implantation, second-generation DES-related CAAs had different morphologies and more benign clinical outcomes versus first-generation DES-related CAAs., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Purpose: Discontinuation of offending drugs can prevent drug-induced parkinsonism (DIP) before it occurs and reverse or cure it afterwards. The aim of this study was to investigate the prevalence of DIP and the utilization of offending drugs through an analysis of representative nationwide claims data., Materials and Methods: We selected DIP patients of ages ranging from 40 to 100 years old with the G21.1 code from the Korean National Service Health Insurance Claims database from 2009 to 2015. The annual standardized prevalence of DIP was explored from 2009 to 2015. Trends were estimated using the compound annual growth rate (CAGR) and the Cochran-Armitage test for DIP over the course of 6 years. Additionally, the utilization of offending drugs was analyzed., Results: The annual prevalence of DIP was 4.09 per 100000 people in 2009 and 7.02 in 2015 (CAGR: 9.42%, p <0.001). Levosulpiride use before and after DIP diagnosis showed a clear trend for decreasing utilization (CAGR: -5.4%, -4.3% respectively), whereas the CAGR for itopride and metoclopramide increased by 12.7% and 6.4%, respectively. In 2015, approximately 46.6% (858/1840 persons) of DIP patients were prescribed offending drugs after DIP diagnosis. The most commonly prescribed causative drug after DIP diagnosis was levosulpiride., Conclusion: The prevalence of DIP has increased. To prevent or decrease DIP, we suggest that physicians reduce prescriptions of benzamide derivatives that have been most commonly used, and that attempts be made to find other alternative drugs. Additionally, the need for continuing education about offending drugs should be emphasized., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2019.)

Purpose: The present study investigated the diagnostic accuracy and clinical implications of moderate stenosis (50-69%, Coronary Artery Disease Reporting and Data System, grade 3) on coronary computed tomography angiography (CCTA), compared with invasive coronary angiography (ICA)., Materials and Methods: Two hundred and seventy-six patients who underwent ICA due to moderate stenosis alone on CCTA were selected from our prospective registry cohort., Results: Diagnostic concordance between CCTA and ICA was found in only 50 (18%) patients. Among the 396 vessels and 508 segments with moderate stenosis, diagnostic concordance was found in 132 vessels (33%) and 127 segments (25%). Segments with calcified plaque had lower diagnostic concordance than those with mixed or non-calcified plaque (22% vs. 28% vs. 27%, respectively, p =0.001). While calcified plaque burden did not have an influence on severe stenosis (≥70%) on ICA, higher burden of non-calcified plaque was correlated with a greater incidence of ICA-based severe stenosis, which was more frequent in patients with ≥3 segments of non-calcified plaque (75%) than those without non-calcified plaque (22%, p <0.001). Typical angina and mixed or non-calcified plaque were correlated with a higher incidence of under-diagnosis, while the use of next-generation computed tomography scanners reduced the incidence of under-diagnosis. Increased body weight, left circumflex artery involvement, and calcified plaque were independent factors that increased the risk of over-diagnosis of CCTA., Conclusion: The diagnosis of moderate stenosis by CCTA may be limited in estimating the exact degree of ICA-based anatomical stenosis. Unlike calcific burden, non-calcific burden was positively correlated with the presence of severe stenosis on ICA., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Purpose: This study aimed to compare the effects of ticagrelor and clopidogrel on early neointimal healing assessed with optical coherence tomography (OCT) after drug-eluting stent (DES) implantation in patients with acute myocardial infarction (AMI)., Materials and Methods: AMI patients were randomly assigned to either the ticagrelor or clopidogrel arm. After DES implantation, OCT was performed to assess the percentages of uncovered struts immediately after procedure and 3 months later., Results: Due to early termination, 83 patients out of 106 initially enrolled patients (24% of planned participants) underwent 3-month OCT. Differences in vascular healing patterns between the two groups, including percentage of uncovered struts on 3-month OCT (9.6% vs. 11.7% in ticagrelor vs. clopidogrel, respectively; p=0.867), neointimal thickness, percentage of malapposed struts, and healing scores did not reach statistical significance. The predictors of uncovered strut on 3-month OCT included greater reference vessel diameter [odds ratio (OR)=1.96, p<0.001] and more malapposed struts (OR=1.12, p=0.003)., Conclusion: The current study did not explore favorable effect of ticagrelor on 3-month vascular healing after DES implantation. Our findings should only be considered for generating hypothesis, due to insufficient power., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Purpose: Kawasaki disease (KD) is a mucocutaneous lymph node syndrome. It is mainly seen in young children under the age of five. KD is a multifactorial disorder that includes genetic variants. The present study investigated the association between KD and single nucleotide polymorphisms (SNPs) in the candidate gene early B cell factor 2 (EBF2), which is associated with inflammation markers., Materials and Methods: An SNP analysis was performed by whole exon sequencing of the EBF2 gene. Our study comprised a total of 495 subjects (295 KD patients and 200 unrelated normal controls) from a Korean population. Tag SNPs were discovered using the Haploview program. Genotyping of the EBF2 gene was performed with the TaqMan® assay with real-time PCR methods., Results: Polymorphism of rs10866845 showed a significant difference in allele frequency between KD patients and controls (p=0.040). The EBF2 gene polymorphisms were significantly associated with KD on logistic regression analysis., Conclusion: EBF2 gene variants can contribute to KD in the Korean population., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Purpose: Coronary artery diseases (CADs) are the leading causes of death in the world. Recent studies have reported that differentially expressed microRNAs (miRNAs) are associated with prognosis or major adverse cardiac events (MACEs) in CAD patients. In a previous meta-analysis, the authors made serious mistakes that we aimed to correct through an updated systematic review and meta-analysis of the prognostic value of altered miRNAs in patients with CADs., Materials and Methods: We performed a systematic search of MEDLINE (from inception to May 2017) and EMBASE (from inception to May 2017) for English-language publications. Studies of CADs with results on miRNAs that reported survival data or MACEs were included. Data were extracted from each publication independently by two reviewers., Results: After reviewing 515 articles, a total eight studies were included in this study. We measured pooled hazard ratios (HRs) and 95% confidence intervals (CIs) of miRNA 133a with a fixed-effect model (pooled HR, 2.35; 95% CI, 1.56-3.55). High expression of miRNA 133a, 208b, 126, 197, 223, and 122-5p were associated with high mortality. Additionally, high levels of miRNA 208b, 499-5p, 134, 328, and 34a were related with MACEs., Conclusion: The present study confirmed that miRNA 133a, which was associated with high mortality in CAD patients, holds prognostic value in CAD. More importantly, this study corrected issues raised against a prior meta-analysis and provides accurate information., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Purpose: The present study aimed to evaluate the efficacy and safety of polymer-free drug-coated BioFreedom stent implantation in comparison to coronary artery bypass graft (CABG) before major noncardiac surgery., Materials and Methods: In a multicenter registry, 55 patients required revascularization before major noncardiac surgery that should not be delayed >6 months. Of them, 27 underwent BioFreedom stent implantation and 28 underwent CABG. Primary outcomes included rate of noncardiac surgery, time from revascularization to noncardiac surgery, and occurrence of composite outcomes (all-cause death, myocardial infarction, stent thrombosis, stroke, repeat revascularization, or major bleeding)., Results: The rate of major noncardiac surgery was significantly higher in the BioFreedom group (92.6%) than in the CABG group (64.3%; p=0.027). Time from revascularization to noncardiac surgery was significantly shorter in the BioFreedom group (38.0 days) than in the CABG group (73.0 days; p=0.042). During the hospitalization for revascularization period, the occurrence of primary outcomes did not differ between the groups. However, the BioFreedom group showed a shorter hospitalization period and lower total treatment cost than the CABG group. During the hospital stay for noncardiac surgery, the occurrence of composite outcome was not significantly different between groups (4% vs. 0%; p>0.999): stroke occurred in only 1 case, and there were no cases of death or stent thrombosis in the BioFreedom group., Conclusion: This study demonstrated that BioFreedom stenting as a revascularization strategy before major noncardiac surgery might be feasible and safe in selected patients with less severe coronary artery diseases., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018.)

Purpose: We determined factors associated with long-term outcomes of patients who underwent successful percutaneous mitral balloon valvuloplasty (PMV)., Materials and Methods: Between August 1980 and May 2013, 1187 patients underwent PMV at Severance Hospital, Seoul, Korea. A total of 742 patients who underwent regular clinic visits for more than 10 years were retrospectively analyzed. The endpoints consisted of repeated PMV, mitral valve (MV) surgery, and cardiovascular-related death., Results: The optimal result, defined as a post-PMV mitral valve area (MVA) >1.5 cm² and mitral regurgitation ≤Grade II, was obtained in 631 (85%) patients. Over a mean follow up duration of 214±50 months, 54 (7.3%) patients underwent repeat PMV, 4 (0.5%) underwent trido-PMV, and 248 (33.4%) underwent MV surgery. A total of 33 patients (4.4%) had stroke, and 35 (4.7%) patients died from cardiovascular-related reasons. In a multivariate analysis, echocardiographic score [p=0.003, hazard ratio=1.56, 95% confidence interval (CI): 1.01-2.41] and post-MVA cut-off (p<0.001, relative risk=0.39, 95% CI: 0.37-0.69) were the only significant predictors of long-term clinical outcomes after adjusting for confounding variables. A post-MVA cut-off value of 1.76 cm² showed satisfactory predictive power for poor long-term clinical outcomes., Conclusion: In this long-term follow up study (up to 20 years), an echocardiographic score >8 and post-MVA ≤1.76 cm² were independent predictors of poor long-term clinical outcomes after PMV, including MV reintervention, stroke, and cardiovascular-related death., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018)

Purpose: Contrast-induced acute kidney injury (CI-AKI) is associated with poor outcomes after percutaneous coronary intervention. However, CI-AKI has rarely been evaluated within the neurovascular field. The aim of this study was to investigate the incidence and clinical implication of CI-AKI after coil embolization in patients with an aneurysmal subarachnoid hemorrhage (aSAH)., Materials and Methods: Between January 2005 and March 2016, 192 patients who underwent coil embolization were enrolled in this study. CI-AKI was defined as an increase from baseline serum creatinine concentration of >25% or >0.5 mg/dL within 72 hours after coil embolization. A poor clinical outcome was defined as a score of ≥3 on the modified Rankin Scale at one-year post-treatment., Results: A total of 16 patients (8.3%) died as a result of medical problems within one year. CI-AKI was identified in 14 patients (7.3%). Prominent risk factors for one-year mortality included CI-AKI [odds ratio (OR): 16.856; 95% confidence interval (CI): 3.437-82.664] and an initial Glasgow Coma Scale (GCS) score ≤8 (OR: 5.565; 95% CI: 1.703-18.184). A poor clinical outcome was associated with old age (≥65 years) (OR: 7.921; 95% CI: 2.977-21.076), CI-AKI (OR: 11.281; 95% CI: 2.138-59.525), an initial GCS score ≤8 (OR 31.02; 95% CI, 10.669-90.187), and a ruptured aneurysm (p=0.016, OR: 4.278) in posterior circulation., Conclusion: CI-AKI seems to be an independent predictor of the overall outcomes of aSAH after endovascular treatment., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2018)

Purpose: This study aimed to determine whether upgrade cardiac resynchronization therapy (CRT) shows better outcomes than de novo CRT. To do so, we compared the efficacy of CRT between de novo and upgrade groups, focusing particularly on the effect of upgrade CRT on patients with pacing-induced cardiomyopathy (PiCM)., Materials and Methods: PiCM was defined as new-onset dilated cardiomyopathy following pacemaker implantation in patients with baseline normal ejection fraction ≥50%. Electro-mechanical reverse remodeling and clinical outcomes were compared among the de novo (n=62), PiCM upgrade (n=7), and non-PiCM upgrade (n=8) CRT groups., Results: The PiCM upgrade group showed significantly greater electro-mechanical reverse remodeling than the de novo CRT or non-PiCM upgrade groups at 6-month follow-up. The rate of super-responders was significantly higher in the PiCM upgrade group than the other CRT groups. The group factor of the PiCM upgrade was identified as an independent predictor of super-responder in multivariate analysis (odds ratio 10.4, 95% confidential interval 1.08-99.4, p=0.043). During the median follow-up of 15.8 months, the PiCM upgrade group showed the lowest rate of composite clinical outcomes, including cardiac death, heart transplantation, and heart failure-related rehospitalization (p=0.059)., Conclusion: The upgrade CRT for PiCM patients showed better performance in terms of electro-mechanical reverse remodeling than de novo implantation or upgrade CRT in non-PiCM patients., Competing Interests: The authors have no financial conflicts of interest., (© Copyright: Yonsei University College of Medicine 2017)

Purpose: To evaluate the effects of sex and anthropometry on clinical outcomes in patients who underwent percutaneous coronary intervention (PCI)., Materials and Methods: From three randomized trials (REal Safety and Efficacy of 3-month dual antiplatelet Therapy following Endeavor zotarolimus-eluting stent implantation, Impact of intraVascular UltraSound guidance on outcomes of Xience Prime stents in Long lesions, Chronic Total Occlusion InterVention with drUg-eluting Stents), we compared 333 pairs of men and women matched by propensity scores, all of whom underwent intravascular ultrasound (IVUS)-guided PCI for complex lesions., Results: For 12 months, the incidence of adverse cardiac events, defined as the composite of cardiac death, target lesion-related myocardial infarction, and target lesion revascularization, was not different between women and men (2.4% vs. 2.4%, p=0.939). Using multivariable Cox's regression analysis, post-intervention minimum lumen area [MLA; hazard ratio (HR)=0.620, 95% confidence interval (CI)=0.423-0.909, p=0.014] by IVUS was a predictor of adverse cardiac events. Height on anthropometry and lesions with chronic total occlusion were significantly related to post-intervention MLA. However, female sex was not independently associated with post-intervention MLA. In an age and sex-adjusted model, patients in the low tertile of height exhibited a greater risk for adverse cardiac events than those in the high tertile of height (HR=6.391, 95% CI=1.160-35.206, p=0.033)., Conclusion: Sex does not affect clinical outcomes after PCI for complex lesions. PCI outcomes, however, may be adversely affected by height., Competing Interests: The authors have no financial conflicts of interest.

Purpose: To compare the 1-year outcomes of a durable polymer Zotarolimus-eluting stent (ZES) versus a biodegradable polymer Biolimus-eluting stent (BES) in patients undergoing percutaneous coronary intervention., Materials and Methods: A total of 2083 patients from 2 different registries, 1125 treated with BES in NOBORI registry and 858 received ZES in CONSTANT registry were included in this study. Clinical outcomes were compared with the use of propensity score matching (PSM). The primary endpoint was a composite of major adverse cardiovascular and cerebrovascular events (MACCEs) including cardiac death, myocardial infarction, clinically driven target lesion revascularization and stroke. Secondary end points were individual components of MACCEs as well as the incidence of stent thrombosis at 1-year follow-up., Results: After PSM, 699 matched pairs of patients (n=1398) showed no significant difference between BES and ZES in the risk of composite MACCEs at 1 year (2.6% vs. 1.7%; p=0.36). Cardiac death was not statistically different between groups (0.7% vs. 0.4%, p=0.73). Target lesion revascularization rate was also similar between BES and ZES (1.1% vs. 0.7%, p=0.579). Non-Q wave myocardial infarction, as well as target-vessel revascularization rate, was similar between the two groups (0.14% for BES and 0.72% for ZES). Both stent types were excellent with no cases of stent thrombosis and rate of Q wave myocardial infarction reported during the follow-up period., Conclusion: In this cohort of patients treated with BES or ZES, the rate of MACCEs at 1 year was low and significantly not different between both groups., Competing Interests: The authors have no financial conflicts of interest.

Purpose: Decitabine, a DNA hypomethylating agent, was recently approved for use in Korea for older adults with acute myeloid leukemia (AML) who are not candidates for standard chemotherapy. This study aimed to evaluate the role of decitabine as a first-line treatment for older adults with AML., Materials and Methods: Twenty-four patients with AML who received at least one course of decitabine (20 mg/m²/d intravenously for 5 days every 4 weeks) as a first-line therapy at Severance Hospital were evaluated retrospectively., Results: The median age of the patients was 73.5 years. The longest follow-up duration was 502 days. A total of 113 cycles of treatment were given to 24 patients, and the median number of cycles was four (range, 1-14). Thirteen patients dropped out because of death, no or loss of response, patient refusal, or transfer to another hospital. Twenty-one (87.5%) and 12 (50%) patients completed the second and fourth cycles, respectively, and responses to treatment were evaluated in 17. A complete response (CR) or CR with incomplete blood-count recovery was achieved in six (35.3%) patients, and the estimated median overall survival was 502 days. Ten patients developed grade >2 hematologic or non-hematologic toxicities. In univariate analysis, bone marrow blasts, lactate dehydrogenase, serum ferritin level, and bone marrow iron were significantly associated with response to decitabine., Conclusion: Five-day decitabine treatment showed acceptable efficacy in older patients with AML who are unfit for conventional chemotherapy, with a CR rate 35.3% and about a median overall survival of 18 months., Competing Interests: The authors have no financial conflicts of interest.

Purpose: Although asymptomatic coronary artery occlusive disease is common in stroke patients, the long-term advantages of undergoing evaluation for coronary arterial disease using multi-detector coronary computed tomography (MDCT) have not been well established in stroke patients. We compared long-term cardio-cerebrovascular outcomes between patients who underwent MDCT and those who did not., Materials and Methods: This was a retrospective study in a prospective cohort of consecutive ischemic stroke patients. Of the 3117 patients who were registered between July 2006 and December 2012, MDCT was performed in 1842 patients [MDCT (+) group] and not in 1275 patients [MDCT (-) group]. Occurrences of death, cardiovascular events, and recurrent stroke were compared between the groups using Cox proportional hazards models and propensity score analyses., Results: During the mean follow-up of 38.0±24.8 months, 486 (15.6%) patients died, recurrent stroke occurred in 297 (9.5%), and cardiovascular events occurred in 60 patients (1.9%). Mean annual risks of death (9.34% vs. 2.47%), cardiovascular events (1.2% vs. 0.29%), and recurrent stroke (4.7% vs. 2.56%) were higher in the MDCT (-) group than in the MDCT (+) group. The Cox proportional hazards model and the five propensity score-adjusted models consistently demonstrated that the MDCT (-) group was at a high risk of cardiovascular events (hazard ratios 3.200, 95% confidence interval 1.172-8.735 in 1:1 propensity matching analysis) as well as death. The MDCT (-) group seemed to also have a higher risk of recurrent stroke., Conclusion: Acute stroke patients who underwent MDCT experienced fewer deaths, cardiovascular events, and recurrent strokes during follow-up., Competing Interests: The authors have no financial conflicts of interest.

Purpose: Infliximab is currently used for the treatment of active Crohn's disease (CD). We aimed to assess the efficacy and safety of infliximab therapy and to determine the predictors of response in Korean patients with CD., Materials and Methods: A total of 317 patients who received at least one infliximab infusion for active luminal CD (n=198) and fistulizing CD (n=86) or both (n=33) were reviewed retrospectively in 29 Korean referral centers. Clinical outcomes of induction and maintenance therapy with infliximab, predictors of response, and adverse events were evaluated., Results: In patients with luminal CD, the rates of clinical response and remission at week 14 were 89.2% and 60.0%, respectively. Male gender and isolated colonic disease were associated with higher remission rates at week 14. In week-14 responders, the probabilities of sustained response and remission were 96.2% and 93.3% at week 30 and 88.0% and 77.0% at week 54, respectively. In patients with fistulizing CD, clinical response and remission were observed in 85.0% and 56.2% of patients, respectively, at week 14. In week-14 responders, the probabilities of sustained response and remission were 94.0% and 97.1%, respectively, at both week 30 and week 54. Thirty-nine patients (12.3%) experienced adverse events related to infliximab. Serious adverse events developed in 19 (6.0%) patients including seven cases of active pulmonary tuberculosis., Conclusion: Infliximab induction and maintenance therapy are effective and well tolerable in Korean patients with luminal and fistulizing CD. However, clinicians must be aware of the risk of rare yet critical adverse events., Competing Interests: The authors have no financial conflicts of interest.

Purpose: Appropriate animal models of atherosclerotic plaque are crucial to investigating the pathophysiology of atherosclerosis, as well as for the evaluation of the efficacy and safety of vascular devices. We aimed to develop a novel animal model that would be suitable for the study of advanced atherosclerotic lesions in vivo., Materials and Methods: Atherosclerotic plaque was induced in 24 iliac arteries from 12 rabbits by combining a high cholesterol diet, endothelial denudation, and injection into the vessel wall with either saline (n=5), olive oil (n=6), or inflammatory proteins [n=13, high-mobility group protein B1 (HMGB1) n=8 and tumor necrosis factor (TNF)-α n=5] using a Cricket™ Micro-infusion catheter. Optical coherence tomography (OCT) was performed to detect plaque characteristics after 4 weeks, and all tissues were harvested for histological evaluation., Results: Advanced plaque was more frequently observed in the group injected with inflammatory proteins. Macrophage infiltration was present to a higher degree in the HMGB1 and TNF-α groups, compared to the oil or saline group (82.1±5.1% and 94.6±2.2% compared to 49.6±14.0% and 46.5±9.6%, p-value<0.001), using RAM11 antibody staining. On OCT, lipid rich plaques were more frequently detected in the inflammatory protein group [saline group: 2/5 (40%), oil group: 3/5 (50%), HMGB1 group: 6/8 (75%), and TNF-α group: 5/5 (100%)]., Conclusion: These data indicate that this rabbit model of atherosclerotic lesion formation via direct injection of pro-inflammatory proteins into the vessel wall is useful for in vivo studies investigating atherosclerosis.

Purpose: To evaluate the ability of coronary computed tomographic angiography (CCTA) to predict the need of coronary revascularization in symptomatic patients with stable angina who were referred to a cardiac catheterization laboratory for coronary revascularization., Materials and Methods: Pre-angiography CCTA findings were analyzed in 1846 consecutive symptomatic patients with stable angina, who were referred to a cardiac catheterization laboratory at six hospitals and were potential candidates for coronary revascularization between July 2011 and December 2013. The number of patients requiring revascularization was determined based on the severity of coronary stenosis as assessed by CCTA. This was compared to the actual number of revascularization procedures performed in the cardiac catheterization laboratory., Results: Based on CCTA findings, coronary revascularization was indicated in 877 (48%) and not indicated in 969 (52%) patients. Of the 877 patients indicated for revascularization by CCTA, only 600 (68%) underwent the procedure, whereas 285 (29%) of the 969 patients not indicated for revascularization, as assessed by CCTA, underwent the procedure. When the coronary arteries were divided into 15 segments using the American Heart Association coronary tree model, the sensitivity, specificity, positive predictive value, and negative predictive value of CCTA for therapeutic decision making on a per-segment analysis were 42%, 96%, 40%, and 96%, respectively., Conclusion: CCTA-based assessment of coronary stenosis severity does not sufficiently differentiate between coronary segments requiring revascularization versus those not requiring revascularization. Conventional coronary angiography should be considered to determine the need of revascularization in symptomatic patients with stable angina.

Purpose: To evaluate radiotherapy (RT) and chemotherapy (CT) treatments of early-stage extranodal natural killer/T-cell lymphoma (ENKTL)., Materials and Methods: Fifty-five patients with stage I or II ENKTL [n=39 (71%) and 16 (29%) patients, respectively] who were treated with RT between 1999 and 2013 were analyzed retrospectively. The median age was 54 years (range, 24-81). Patients were grouped by treatment modality as RT alone [n=19 (35%)], upfront CT plus RT [CT+RT, n=16 (29%)], and concurrent chemoradiotherapy [CCRT, n=20 (36%)]. The median RT dose was 48 Gy. Patient characteristics between each treatment group were well balanced. Patterns of failure and survival were analyzed., Results: The overall response rate after RT was 94.6%. Ten patients experienced distant failure, and seven experienced local failure comprising five in-field and two out-field failures. The local and distant failure rates in the RT-alone group were the same (16%). In the CT+RT group, the most common failure sites were local (19%). In the CCRT group, the most common failures were distant (25%). At a median follow-up of 56 months (range, 1-178 months), the 5-year overall survival (OS) and progression-free survival rates were 66% and 54%, respectively. The 5-year OS rate for the RT-alone and CT+RT groups were 76% and 69%, respectively, and the 2-year OS rate for the CCRT group was 62% (p=0.388)., Conclusion: In the era of multimodal treatment for ENKTL, RT alone using advanced techniques should be considered for local disease control, whereas maintenance CT regimens should be considered for distant disease control.

Purpose: Data comparing the clinical benefits of medical treatment with those of percutaneous coronary intervention (PCI) in an elderly population with angina pectoris are limited. Therefore, we evaluated the efficacy of elective PCI versus optimal medical treatment (OMT) in elderly patients (between 75 and 84 years old) with angina pectoris., Materials and Methods: One hundred seventy-seven patients with significant coronary artery stenosis were randomly assigned to either the PCI group (n=90) or the OMT group (n=87). The primary outcome was a composite of major adverse events in the 1-year follow-up period that included cardiovascular death, non-fatal myocardial infarction, coronary revascularization, and stroke., Results: Major adverse events occurred in 5 patients (5.6%) of the PCI group and in 17 patents (19.5%) of the OMT group (p=0.015). There were no significant differences between the PCI group and the OMT group in cardiac death [hazard ratio (HR) for the PCI group 0.454; 95% confidence interval (CI) 0.041-5.019, p=0.520], myocardial infarction (HR 0.399; 95% CI 0.039-4.050, p=0.437), or stroke (HR 0.919; 95% CI 0.057-14.709, p=0.952). However, the PCI group showed a significant preventive effect of the composite of major adverse events (HR 0.288; 95% CI 0.106-0.785, p=0.015) and against the need for coronary revascularization (HR 0.157; 95% CI 0.035-0.703, p=0.016)., Conclusion: Elective PCI reduced major adverse events and was found to be an effective treatment modality in elderly patients with angina pectoris and significant coronary artery stenosis, compared to OMT.

Purpose: An association between baroreflex sensitivity (BRS) and the response to tilt training has not been reported in patients with neurally mediated syncope (NMS). This study sought to investigate the role of BRS in predicting the response to tilt training in patients with NMS., Materials and Methods: We analyzed 57 patients who underwent tilt training at our hospital. A responder to tilt training was defined as a patient with three consecutive negative responses to the head-up tilt test (HUT) during tilt training., Results: After tilt training, 52 patients (91.2%) achieved three consecutive negative responses to the HUT. In the supine position before upright posture during the first session of tilt training for responders and non-responders, the mean BRS was 18.17 ± 10.09 ms/mm Hg and 7.99 ± 5.84 ms/mm Hg (p=0.008), respectively, and the frequency of BRS ≥ 8.945 ms/mm Hg was 45 (86.5%) and 1 (20.0%; p=0.004), respectively. Age, male gender, frequency of syncopal events before HUT, type of NMS, phase of positive HUT, total number of tilt training sessions, and mean time of tilt training did not differ between the study groups. In the multivariate analysis, BRS <8.945 ms/mm Hg in the supine position (odds ratio 23.10; 95% CI 1.20-443.59; p=0.037) was significantly and independently associated with non-response to tilt training., Conclusion: The BRS value in the supine position could be a predictor for determining the response to tilt training in patients with NMS who are being considered for inpatient tilt training.

Purpose: To evaluate the impact of pre-procedural coronary plaque composition assessed by virtual histology intravascular ultrasound (VH-IVUS) on late stent malapposition assessed by optical coherence tomography (OCT) following drug-eluting stent (DES) implantation., Materials and Methods: The study population consisted of 121 patients (121 lesions) who underwent both pre-procedural VH-IVUS and follow-up OCT after DES implantation. The association between pre-procedural plaque composition [necrotic core (NC), dense calcium (DC), fibrotic (FT), and fibro-fatty (FF) volumes] assessed by VH-IVUS and late stent malapposition (percent malapposed struts) or strut coverage (percent uncovered struts) assessed by follow-up OCT was evaluated., Results: Pre-procedural absolute total NC, DC, FT, and FF plaque volumes were 22.9±19.0, 7.9±9.6, 63.8±33.8, and 16.5±12.4 mm³, respectively. At 6.3±3.1 months post-intervention, percent malapposed and uncovered struts were 0.8±2.5% and 15.3±16.7%, respectively. Pre-procedural absolute total NC and DC plaque volumes were positively correlated with percent malapposed struts (r=0.44, p<0.001 and r=0.45, p<0.001, respectively), while pre-procedural absolute total FT plaque volume was weakly associated with percent malapposed struts (r=0.220, p=0.015). Pre-procedural absolute total DC plaque volume was the only independent predictor of late stent malapposition on multivariate analysis (β=1.12, p=0.002). There were no significant correlations between pre-intervention plaque composition and percent uncovered struts., Conclusion: Pre-procedural plaque composition was associated with late stent malapposition but not strut coverage after DES implantation. Larger pre-procedural absolute total DC plaque volumes were associated with greater late stent malapposition.

Purpose: Copeptin has been considered as a useful marker for diagnosis and prediction of prognosis in heart diseases. However, copeptin has not been investigated sufficiently in hemodialysis patients. This study aimed to investigate the general features of copeptin in hemodialysis and to examine the usefulness of copeptin in hemodialysis patients with left ventricular dysfunction (LV dysfunction)., Materials and Methods: This study included 41 patients on regular hemodialysis. Routine laboratory data and peptides such as the N-terminal of the prohormone brain natriuretic peptide and copeptin were measured on the day of hemodialysis. Body fluid volume was estimated by bioimpedance spectroscopy, and the E/Ea ratio was estimated by echocardiography., Results: Copeptin increased to 171.4 pg/mL before hemodialysis. The copeptin had a positive correlation with pre-dialysis body fluid volume (r=0.314; p=0.04). The copeptin level decreased along with body fluid volume and plasma osmolality during hemodialysis. The copeptin increased in the patients with LV dysfunction more than in those with normal LV function (218.7 pg/mL vs. 77.6 pg/mL; p=0.01). Receiver operating characteristic curve analysis showed that copeptin had a diagnostic value in the hemodialysis patients with LV dysfunction (area under curve 0.737; p=0.02) and that the cut-off value was 125.48 pg/mL (sensitivity 0.7, specificity 0.8, positive predictive value 0.9, negative predictive value 0.6)., Conclusion: Copeptin increases in hemodialysis patients and is higher in patients with LV dysfunction. We believe that copeptin can be a useful marker for the diagnosis of LV dysfunction in hemodialysis patients.

Purpose: Although the proteasome inhibitor known as bortezomib can modulate the inflammatory process through the nuclear factor-kappa B signaling pathway, the immunomodulatory effect of pre-incubated bortezomib has not been fully evaluated for inflammation by infectious agents. Therefore, we evaluated the effect of bortezomib on the expression of inflammatory cytokines and mediators in macrophage cell lines and on survival in a murine peritonitis sepsis model., Materials and Methods: Bortezomib was applied 1 hr before lipopolysaccharide (LPS) stimulation in RAW 264.7 cells. The cecal ligation and puncture (CLP) experiments were performed in C57BL/6J mice., Results: Pre-incubation with bortezomib (25 nM or 50 nM) prior to LPS (50 ng/mL or 100 ng/mL) stimulation significantly recovered the number of viable RAW 264.7 cells compared to those samples without pre-incubation. Bortezomib decreased various inflammatory cytokines as well as nitric oxide production in LPS-stimulated cells. The 7-day survival rate in mice that had received bortezomib at 0.01 mg/kg concentration 1 hr prior to CLP was significantly higher than in the mice that had only received a normal saline solution of 1 mL 1 hr prior to CLP. In addition, the administration of bortezomib at 0.01 mg/kg concentration 1 hr before CLP resulted in a significant decrease in inflammation of the lung parenchyma. Collectively, pretreatment with bortezomib showed an increase in the survival rate and changes in the levels of inflammatory mediators., Conclusion: These results support the possibility of pretreatment with bortezomib as a new therapeutic target for the treatment of overwhelming inflammation, which is a characteristic of severe sepsis.

Purpose: To evaluate the effect of statin treatment on strut coverage after drug-eluting stent (DES) implantation., Materials and Methods: In this study, 60 patients were randomly assigned to undergo sirolimus-eluting stent (SES) or biolimus-eluting stent (BES) implantation, after which patients were randomly treated with pitavastatin 2 mg or pravastatin 20 mg for 6 months. The degree of strut coverage was assessed by 6-month follow-up optical coherence tomography, which was performed in 52 DES-implanted patients., Results: The percentages of uncovered struts were 19.4±14.7% in pitavastatin-treated patients (n=25) and 19.1±15.2% in pravastatin-treated patients (n=27; p=0.927). A lower percentage of uncovered struts was significantly correlated with a lower follow-up low-density lipoprotein (LDL) cholesterol level (r=0.486; p=0.009) and a greater decline of the LDL cholesterol level (r=-0.456; p=0.015) in SES-implanted patients, but not in BES-implanted patients. In SES-implanted patients, the percentage of uncovered struts was significantly lower among those with LDL cholesterol levels of less than 70 mg/dL after 6 months of follow-up (p=0.025), but no significant difference in this variable according to the follow-up LDL cholesterol level was noted among BES-implanted patients (p=0.971)., Conclusion: Lower follow-up LDL cholesterol levels, especially those less than 70 mg/dL, might have a protective effect against delayed strut coverage after DES implantation. This vascular healing effect of lower LDL cholesterol levels could differ according to the DES type.

Purpose: The modified Glasgow Prognostic Score (mGPS) consisting of serum C-reactive protein and albumin levels, shows significant prognostic value in several types of tumors. We evaluated the prognostic significance of mGPS in 285 patients with diffuse large B cell lymphoma (DLBCL), retrospectively., Materials and Methods: According to mGPS classification, 204 patients (71.5%) had an mGPS of 0, 57 (20%) had an mGPS of 1, and 24 (8.5%) had an mGPS of 2., Results: Our study found that high mGPS were associated with poor prognostic factors including older age, extranodal involvement, advanced disease stage, unfavorable International Prognostic Index scores, and the presence of B symptoms. The complete response (CR) rate after 3 cycles of R-CHOP chemotherapy was higher in patients with mGPS of 0 (53.8%) compared to those with mGPS of 1 (33.3%) or 2 (25.0%) (p=0.001). Patients with mGPS of 0 had significantly better overall survival (OS) than those with mGPS=1 and those with mGPS=2 (p=0.036). Multivariate analyses revealed that the GPS score was a prognostic factor for the CR rate of 3 cycle R-CHOP therapy (p=0.044) as well as OS (p=0.037)., Conclusion: mGPS can be considered a potential prognostic factor that may predict early responses to R-CHOP therapy in DLBCL patients.

Purpose: The impacts of different time courses and the degree of neointimal growth on neointimal morphology have not yet been sufficiently investigated. Therefore, we evaluated the morphological features of neointimal tissue after drug-eluting stent (DES) implantation using optical coherence tomography (OCT)., Materials and Methods: The morphological features of neointimal tissue in stented segments with a maximal percentage of cross-sectional area (CSA) stenosis of neointima were evaluated in 507 DES-treated lesions with >100 μm mean neointimal thickness on follow-up OCT. Neointimal tissue was categorized as homogeneous, heterogeneous, layered, or neoatherosclerotic., Results: In lesions with <50% of neointimal CSA stenosis, homogeneous neointima (68.2%) was predominant, followed by heterogeneous neointima (14.1%) and layered neointima (14.1%). In lesions with ≥50% of neointimal CSA stenosis, layered neointima was most frequently observed (68.3%), followed by neoatherosclerotic neointima (25.2%). In subgroup analysis of lesions with ≥50% of neointimal CSA stenosis, 89.5% of the lesions with a stent age<30 months were layered neointima, while 62.3% of the lesions with a stent age≥30 months were neoatherosclerotic neointima., Conclusion: This study suggests that the OCT-detected morphology of DES neointimal tissue was different according to the follow-up time course and degree of neointimal hyperplasia.

Purpose: The aim of this study was to evaluate and compare the long-term clinical outcomes of the spot drug-eluting stent (DES) implantation strategy, which is used to minimize implanted stent length and the number of stents, versus full lesion coverage for treatment of coronary artery stenoses., Materials and Methods: We evaluated 1-year clinical outcomes of 1619 patients with stent implantation for a single coronary lesion. They were divided into two groups: those treated by full lesion coverage (n=1200) and those treated with the spot stenting strategy (n=419). The combined occurrence of 1-year target vessel failure (TVF), including cardiac death, target-vessel related myocardial infarction, or ischemia-driven target-vessel revascularization was evaluated., Results: The spot DES implantation group had a shorter stent length (23.14±9.70 mm vs. 25.44±13.24 mm, respectively; p<0.001) and a fewer number of stents (1.09±0.30 vs. 1.16±0.41, respectively; p<0.001), even though the average lesion length was similar to the full lesion coverage group (21.36±10.30 mm vs. 20.58±10.97 mm, respectively; p=0.206). Spot DES implantation was superior to full DES coverage with respect to 1-year TVF (1.4% vs. 3.3%, p=0.044). Cox proportional hazard model analysis showed that the risk for 1-year TVF was almost 60% lower among patients who received spot DESs compared to those who received full DES coverage after adjustment for other risk factors (HR=0.40, 95% confidence interval=0.17-0.98; p=0.046)., Conclusion: Minimizing stent length and the number of stents with overlapping by spot DES implantation may result in reduced rates of 1-year TVF, compared with full DES coverage.

Purpose: Estimation of body fluid volume in hyponatremia is useful for diagnosis and therapeutic decision-making. Physical examination has been generally used to estimate body fluid volume, but it depends on the physician's abilities. Bioimpedance spectroscopy has been suggested to be a reliable method for the estimation of body fluid volume. Therefore, this study investigated whether bioimpedance spectroscopy could replace physical examination in hyponatremia., Materials and Methods: The study included 30 patients with hyponatremia. At the time of the initial visit, body fluid volume was estimated simultaneously by both physical examination and bioimpedance spectroscopy. Estimation of body fluid status by clinical diagnosis was performed as well, which determined body fluid status corresponds with the most likely cause of hyponatremia (clinical body fluid estimation)., Results: The results of body fluid volume estimated by physical examination, bioimpedance spectroscopy, and clinical body fluid estimation showed that 9, 10, and 9 patients, respectively, were hypervolemic; 13, 15 and 16 patients, respectively, were euvolemic; and 8, 5, and 5 patients, respectively, were hypovolemic. Cohen's kappa analysis showed a significant agreement between physical examination and bioimpedance spectroscopy (kappa coefficient, 0.632, p<0.001). In addition, bioimpedance spectroscopy showed a higher level of agreement with clinical body fluid estimation than physical examination (kappa coefficient, 0.602 vs. 0.524)., Conclusion: This study suggests that bioimpedance spectroscopy could replace physical examination for estimating body fluid status in hyponatremia. In addition, bioimpedance spectroscopy might correspond better with clinical diagnosis than physical examination in the estimation of body fluid status in hyponatremia.

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.

Purpose: To identify prognostic factors for the outcomes of empirical antifungal therapy, we performed a multicenter, prospective, observational study in immunocompromised patients with hematological malignancies., Materials and Methods: Three hundred seventy-six patients (median age of 48) who had neutropenic fever and who received intravenous (IV) itraconazole as an empirical antifungal therapy for 3 or more days were analyzed. The patients with possible or probable categories of invasive fungal disease (IFD) were enrolled., Results: The overall success rate was 51.3% (196/376). Age >50 years, underlying lung disease (co-morbidity), poor performance status [Eastern Cooperative Oncology Group (ECOG) ≥2], radiologic evidence of IFD, longer duration of baseline neutropenic fever (≥4 days), no antifungal prophylaxis or prophylactic use of antifungal agents other than itraconazole, and high tumor burden were associated with decreased success rate in univariate analysis. In multivariate analysis, age >50 years (p=0.009) and poor ECOG performance status (p=0.005) were significantly associated with poor outcomes of empirical antifungal therapy. Twenty-two patients (5.9%) discontinued itraconazole therapy due to toxicity., Conclusion: We concluded that empirical antifungal therapy with IV itraconazole in immunocompromised patients is effective and safe. Additionally, age over 50 years and poor performance status were poor prognostic factors for the outcomes of empirical antifungal therapy with IV itraconazole.

Purpose: Our study aims to analyze prognosis after implantable cardioverter-defibrillator (ICD) implantation in Korean patients with Brugada syndrome (BrS)., Materials and Methods: This was a retrospective study of BrS patients implanted with an ICD at one of four centers in Korea between January 1998 and April 2012. Sixty-nine patients (68 males, 1 female) were implanted with an ICD based on aborted cardiac arrest (n=38, 55%), history of syncope (n=17, 25%), or induced ventricular tachyarrhythmia on electrophysiologic study in asymptomatic patients (n=14, 20%). A family history of sudden cardiac death and a spontaneous type 1 electrocardiography (ECG) were noted in 13 patients (19%) and 44 patients (64%), respectively., Results: During a mean follow-up of 59±46 months, 4.6±5.5 appropriate shocks were delivered in 19 patients (28%). Fourteen patients (20%) experienced 5.2±8.0 inappropriate shocks caused by supraventricular arrhythmia, lead failure, or abnormal sensing. Six patients were admitted for cardiac causes during follow-up, but no cardiac deaths occurred. An episode of aborted cardiac arrest was a significant predictor of appropriate shock, and the composite of cardiac events in the Cox proportional hazard model [hazard ratio (95% confidence interval) was 11.34 (1.31-97.94) and 4.78 (1.41-16.22), respectively]. However, a spontaneous type 1 ECG was not a predictor of cardiac events., Conclusion: Appropriate shock (28%) and inappropriate shock (20%) were noted during a mean follow-up of 59±46 months in Korean BrS patients implanted with an ICD. An episode of aborted cardiac arrest was the most powerful predictor of cardiac events.

Purpose: The evaluation of syncope is often disorganized and ineffective. The objective of this study was to examine whether implementation of a standardized emergency department (ED) protocol improves the quality of syncope evaluation., Materials and Methods: This study was a prospective, non-randomized study conducted at a 1900-bed, tertiary teaching hospital in South Korea. We compared two specific periods, including a 12-month observation period (control group, January- December 2009) and a 10-month intervention period after the implementation of standardized approaches, comprising risk stratification, hospital order sets and establishment of a syncope observational unit (intervention group, March-December 2010). Primary end points were hospital admission rates and medical costs related to syncope evaluation., Results: A total of 244 patients were enrolled in this study (116 patients in the control group and 128 patients in the intervention group). The admission rate decreased by 8.3% in the intervention group (adjusted odds ratio 0.31, 95% confidence interval 0.13-0.70, p=0.005). There was a cost reduction of about 30% during the intervention period [369000 Korean won (KRW), interquartile range (IQR) 240000-602000 KRW], compared with the control period (542000 KRW, IQR 316000-1185000 KRW). The length of stay in the ED was also reduced in the intervention group (median: 4.6 hours vs. 3.4 hours)., Conclusion: Standardized approaches to syncope evaluation reduced hospital admissions, medical costs and length of stay in the overcrowded emergency department of a tertiary teaching hospital in South Korea.

Purpose: Most chemical transfection reagents are ineffective for the transfection of cells in suspension, such as leukemic cell and stem cell lineages. We developed two different types of viroplexes, cationic Sendai F/HN viroplexes (CSVs) and protamine sulfate-condensed cationic Sendai F/HN viroplexes (PCSVs) for the efficient transfection of T-leukemic cells., Materials and Methods: The viroplex systems were prepared by reconstitution of fusogenic Sendai F/HN proteins in DMKE (O,O'-dimyristyl-N-lysyl glutamate) cationic liposomes. The viroplexes were further optimized for plasmid DNA and siRNA delivery to suspension cells. The particle size and surface charge of the viroplexes were analyzed with a ζ-sizer. Transfection of plasmid DNA (pDNA) and small interfering RNA (siRNA) by CSVs or PCSV was evaluated by measurement of transgene expression, confocal microscopy, FACS, and RT-PCR., Results: The optimized CSVs and PCSVs exhibited enhanced gene and siRNA delivery in the tested suspension cell lines (Jurkat cells and CEM cells), compared with conventional cationic liposomes. In the case of pDNA transfection, the CSVs and PCSVs show at least 10-fold and 100-fold higher transgene expression compared with DMKE lipoplexes (or lipofectamine 2000), respectively. The CSVs showed more effective siRNA delivery to the suspension cells than cationic liposomes, as assessed by confocal microscopy, FACS, and RT-PCR. The effective transfection by the CSVs and PCSVs is presumably due to fusogenic activity of F/HN proteins resulting in facilitated internalization of pDNA and siRNA., Conclusion: This study suggests that Sendai F/HN viroplexes can be widely applicable for the transfection of pDNA and siRNA to suspension cell lines.

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.

Purpose: Previous studies have reported that over a third of cancer patients experience significant psychological distress with diagnosis and treatment of cancer. Mental adjustment to cancer as well as other biologic and demographic factors may be associated with their distress. We investigated the relationship between mental adjustment and distress in patients with thyroid cancer prior to thyroidectomy., Materials and Methods: One hundred and fifty-two thyroid cancer patients were included in the final analysis. After global distress levels were screened with a distress thermometer, patients were evaluated concerning mental adjustment to cancer, as well as demographic and cancer-related characteristics. A thyroid function test was also performed. Regression analysis was performed to discern significant factors associated with distress in thyroid cancer patients., Results: Our regression model was significant and explained 38.5% of the total variance in distress of this patient group. Anxious-preoccupation and helpless-hopeless factors on the mental adjustment to cancer scale were significantly associated with distress in thyroid cancer patients., Conclusion: Negative emotional response to cancer diagnosis may be associated with distress in thyroid cancer patients awaiting thyroidectomy. Screening of mental coping strategies at the beginning of cancer treatment may predict psychological distress in cancer patients. Further studies on the efficacy of psychiatric intervention during cancer treatment may be needed for patients showing maladaptive psychological responses to cancer.