Three-dimensional (3D) echocardiography has been conceived as one of the most promising methods for the diagnosis of valvular heart disease, and recently has become an integral clinical tool thanks to the development of high quality real-time transesophageal echocardiography (TEE). In particular, for mitral valve diseases, this new approach has proven to be the most unique, powerful, and convincing method for understanding the complicated anatomy of the mitral valve and its dynamism. The method has been useful for surgical management, including robotic mitral valve repair. Moreover, this method has become indispensable for nonsurgical mitral procedures such as edge to edge mitral repair and transcatheter closure of paravaluvular leaks. In addition, color Doppler 3D echo has been valuable to identify the location of the regurgitant orifice and the severity of the mitral regurgitation. For aortic and tricuspid valve diseases, this method may not be quite as valuable as for the mitral valve. However, the necessity of 3D echo is recognized for certain situations even for these valves, such as for evaluating the aortic annulus for transcatheter aortic valve implantation. It is now clear that this method, especially with the continued development of real-time 3D TEE technology, will enhance the diagnosis and management of patients with these valvular heart diseases.
Echocardigraphy; Mitral valve; Aortic valve; Three-dimensional
The Korea Acute Myocardial Infarction Registry (KAMIR) was the first nationwide registry data collection designed to track outcomes of patients with acute myocardial infarction (AMI). These studies reflect the current therapeutic approaches and management for AMI in Korea. The results of KAMIR could help clinicians to predict the prognosis of their patients and identify better diagnostic and treatment tools to improve the quality of care. The KAMIR score was proposed to be a predictor of the prognosis of AMI patients. Triple antiplatelet therapy, consisting of aspirin, clopidogrel and cilostazol, was effective at preventing major adverse clinical outcomes. Drug-eluting stents were effective and safe in AMI patients with no increased risk of stent thrombosis. Statin therapy was effective in Korean AMI patients, including those with very low levels of low density cholesterol. The present review summarizes the 10-year scientific achievements of KAMIR from admission to outpatient care during long-term clinical follow-up.
Acute myocardial infarction; Prognosis; Therapeutics
Recent advances in the treatment of aplastic anemia (AA) made most of patients to expect to achieve a long-term survival. Allogeneic stem cell transplantation (SCT) from HLA-matched sibling donor (MSD-SCT) is a preferred first-line treatment option for younger patients with severe or very severe AA, whereas immunosuppressive treatment (IST) is an alternative option for others. Horse anti-thymocyte globuline (ATG) with cyclosporin A (CsA) had been a standard IST regimen with acceptable response rate. Recently, horse ATG had been not available and replaced with rabbit ATG in most countries. Subsequently, recent comparative studies showed that the outcomes of patients who received rabbit ATG/CsA were similar or inferior compared to those who received horse ATG/CsA. Therefore, further studies to improve the outcomes of IST, including additional eltrombopag, are necessary. On the other hand, the upper age limit of patients who are able to receive MSD-SCT as first-line treatment is a current issue because of favorable outcomes of MSD-SCT of older patients using fludarabine-based conditioning. In addition, further studies to improve the outcomes of patients who receive allogeneic SCT from alternative donors are needed. In this review, current issues and the newly emerging trends that may improve their outcomes in near futures will be discussed focusing the management of patients with AA.
Anemia, aplastic; Allogeneic stem cell transplantation; Immunosuppressive treatment; Iron chelation therapy
We compared the long-term outcomes of balloon dilation versus botulinum toxin injection in Korean patients with primary achalasia and identified factors predicting remission.
We included 73 patients with achalasia newly diagnosed between January 1988 and January 2011. We ultimately enrolled 37 of 55 patients with primary achalasia through telephone interviews, who were observed for over 1 year. Short-term outcomes were evaluated from the medical records based on symptom relief after 1 month of treatment. Long-term outcomes were evaluated in a telephone interview using a questionnaire.
Twenty-five patients were administered a botulinum toxin injection and 12 underwent balloon dilation. One month after the botulinum toxin injection, improvements were seen in chest pain (14 [56.0%] to 4 patients [16.0%]), regurgitation (16 [64.0%] to 4 [16.0%]), and dysphagia (25 [100.0%] to 5 [20.0%]). In the balloon dilation group, chest pain (8 [66.7%] to 1 [8.3%]), regurgitation (11 [91.7%] to 1 [8.3%]), and dysphagia (12 [100.0%] to 1 [8.3%]) had improved. A significant difference was observed in the mean remission duration between the botulinum toxin injection and balloon dilation groups (13 months [range, 1 to 70] vs. 29 months [range, 6 to 72], respectively; p = 0.036). Independent factors predicting long-term remission included treatment type (odds ratio [OR], 6.982; p = 0.036) and the difference in the lower esophageal sphincter pressure (OR, 7.198; p = 0.012).
Balloon dilation may be more efficacious than botulinum toxin for providing long-term remission in Korean patients with achalasia. Follow-up manometry may predict the long-term outcome.
Achalasia; Balloon dilation; Botulinum toxins
Amiodarone is one of the most widely used antiarrhythmic agents; however, amiodarone-induced pulmonary toxicity (APT) can be irreversible and sometimes fatal. The aim of this study was to evaluate the feasibility of chest computed tomography (CT) as a diagnostic tool for APT and to assess the utility of the CT APT score as an index for predicting the severity of APT.
Patients underwent amiodarone treatment for various reasons, most often atrial fibrillation, for more than 2 years, and those that received a cumulative dose > 100 g were enrolled. A total of 34 patients who underwent chest CT between December 2011 and June 2012 were enrolled, whether or not they had clinical symptoms. The APT CT score was defined as the number of involved regions in the lung, which was divided into 18 regions (right and left, upper, middle, and lower, and central, middle, and peripheral). The CT findings were evaluated according to the total dose and duration of amiodarone treatment and the results of a pulmonary function test. Clinical symptoms and outcomes were also evaluated according to APT CT scores.
Seven patients had positive APT CT scores (interstitial fibrosis in five, organizing pneumonia in one, and mixed interstitial fibrosis and organizing pneumonia in one), and these patients exhibited significantly lower diffusion capacity for carbon monoxide in the lungs compared with patients without an increased APT CT score (70.2% ± 6.9% vs. 89.7% ± 19.4%; p = 0.011). Three of the seven patients experienced overt APT that required hospital admission.
Chest CT is a useful diagnostic tool for APT, and the APT CT score might be a useful index for assessing the severity of APT.
Amiodarone; Pulmonary toxicity; Computed tomography; Cumulative dose
This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear.
The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin.
The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371).
Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.
Hydroxymethylglutaryl-CoA reductase inhibitors; Pitavastatin; Heart failure; Exercise capacity
The effect of high-flux (HF) dialysis on mortality rates could vary with the duration of dialysis. We evaluated the effects of HF dialysis on mortality rates in incident and prevalent hemodialysis (HD) patients.
Incident and prevalent HD patients were selected from the Clinical Research Center registry for end-stage renal disease (ESRD), a Korean prospective observational cohort study. Incident HD patients were defined as newly diagnosed ESRD patients initiating HD. Prevalent HD patients were defined as patients who had been receiving HD for > 3 months. The primary outcome measure was all-cause mortality.
This study included 1,165 incident and 1,641 prevalent HD patients. Following a median 24 months of follow-up, the mortality rates of the HF and low-flux (LF) groups did not significantly differ in the incident patients (hazard ratio [HR], 1.046; 95% confidence interval [CI], 0.592 to 1.847; p = 0.878). In the prevalent patients, HF dialysis was associated with decreased mortality compared with LF dialysis (HR, 0.606; 95% CI, 0.416 to 0.885; p = 0.009).
HF dialysis was associated with a decreased mortality rate in prevalent HD patients, but not in incident HD patients.
Dialysis; Renal dialysis; Mortality
This study investigated the expression of nuclear factor κB (NF-κB) and the chemokine receptor (CXCR4) in patients with diffuse large B-cell lymphoma (DLBCL) who received rituximab-based therapy.
Seventy patients with DLBCL and treated with rituximab-CHOP (R-CHOP) were included, and immunohistochemistry was performed to determine the expression of NF-κB (IκB kinase α, p50, and p100/p52) and CXCR4. To classify DLBCL cases as germinal center B-cell-like (GCB) and non-GCB, additional immunohistochemical expression of CD10, bcl-6, or MUM1 was used in this study. The expression was divided into two groups according to the intensity score (negative, 0 or 1+; positive, 2+ or 3+).
The median age of the patients was 66 years (range, 17 to 87), and 58.6% were male. Twenty-seven patients (38.6%) had stage III or IV disease at diagnosis. Twenty-three patients (32.9%) were categorized as high or high-intermediate risk according to their International Prognostic Indexs (IPIs). The overall incidence of bone marrow involvement was 5.7%. Rates of positive NF-κB and CXCR4 expression were 84.2% and 88.6%, respectively. High NF-κB expression was associated with CXCR4 expression (p = 0.002), and 56 patients (80.0%) showed coexpression. However, the expression of NF-κB or CXCR4 was not associated with overall survival and EFS. On multivariate analysis that included age, gender, performance status, stage, and the IPI, no significant association between the grade of NF-κB or CXCR4 expression and survival was observed.
The current study suggests that the tissue expression of NF-κB and CXCR4 may not be an independent prognostic marker in DLBCL patients treated with R-CHOP.
Lymphoma; NF-kappa B; CXCR4
The goal of this study was to monitor tuberculosis (TB)-specific T-cell responses in cerebrospinal fluid-mononuclear cells (CSF-MCs) and peripheral blood mononuclear cells (PBMCs) in patients with tuberculous meningitis (TBM) over the course of anti-TB therapy.
Adult patients (≥ 16 years) with TBM admitted to Asan Medical Center, Seoul, South Korea, were prospectively enrolled between April 2008 and April 2011. Serial blood or CSF samples were collected over the course of the anti-TB therapy, and analyzed using an enzyme-linked immunosorbent spot (ELISPOT) assay.
Serial ELISPOT assays were performed on PBMCs from 17 patients (seven definite, four probable, and six possible TBM) and CSF-MC from nine patients (all definite TBM). The median number of interferon-gamma (IFN-γ)-producing T-cells steadily increased during the first 6 months after commencement of anti-TB therapy in PBMCs. Serial CSF-MC ELISPOT assays revealed significant variability in immune responses during the first 6 weeks of anti-TB therapy, though early increases in CSF-MC ELISPOT results were associated with treatment failure or paradoxical response.
Serial analysis of PBMCs by ELISPOT during the course of treatment was ineffective for predicting clinical response. However, increases in TB-specific IFN-γ-producing T-cells in CSF-MC during the early phase of anti-TB therapy may be predictive of clinical failure.
Tuberculosis; Meningitis; Enzyme-linked immunosorbent assay; Cerebrospinal fluid
Chronic urticaria (CU) is defined as itchy wheals lasting 6 weeks or more. As the aged population increases worldwide, it is essential to identify the specific features of this disease in the elderly population.
We investigated the prevalence and clinical features of CU in elderly patients. Medical records of 837 CU patients from the outpatient Allergy Clinic of Ajou University Hospital, Korea were analyzed retrospectively. Patients with chronic spontaneous urticaria according to the EAACI/GA2LEN/EDF/WAO guidelines were included. Patients older than 60 years were defined as elderly.
Of the 837 patients, 37 (4.5%) were elderly. In elderly versus nonelderly CU patients, the prevalence of atopic dermatitis (AD) was significantly higher (37.8% vs. 21.7%, respectively; p = 0.022), while that of aspirin intolerance was lower (18.9% vs. 43.6%, respectively; p = 0.003) in terms of comorbid conditions. The prevalences of serum specific immunoglobulin E antibodies to staphylococcal enterotoxin A and staphylococcal enterotoxin B were considerably higher in elderly CU patients with AD than in those without AD (37.5% vs. 0%, respectively).
Elderly patients with CU had a higher prevalence of AD. Therefore, there is a need to recognize the existence of AD in elderly CU patients.
Chronic urticaria; Aged; Dermatitis, atopic; Specific IgE to staphylococcal superantigen
Our aim was to assess whether short-term treatment with soluble tumor necrosis factor (TNF) receptor affects circulating markers of bone metabolism in rheumatoid arthritis (RA) patients.
Thirty-three active RA patients, treated with oral disease-modifying antirheumatic drugs (DMARDs) and glucocorticoids for > 6 months, were administered etanercept for 12 weeks. Serum levels of bone metabolism markers were compared among patients treated with DMARDs at baseline and after etanercept treatment, normal controls and naive RA patients not previously treated with DMARDs (both age- and gender-matched).
Bone-specific alkaline phosphatase (BSALP) and serum c-telopeptide (CTX)-1 levels were lower in RA patients treated with DMARDs than in DMARD-naive RA patients. After 12 weeks of etanercept treatment, serum CTX-1 and sclerostin levels increased. In patients whose DAS28 improved, the sclerostin level increased from 1.67 ± 2.12 pg/mL at baseline to 2.51 ± 3.03 pg/mL, which was statistically significant (p = 0.021). Increases in sclerostin levels after etanercept treatment were positively correlated with those of serum CTX-1 (r = 0.775), as were those of BSALP (r = 0.755).
RA patients treated with DMARDs showed depressed bone metabolism compared to naive RA patients. Increases in serum CTX-1 and sclerostin levels after short-term etanercept treatment suggest reconstitution of bone metabolism homeostasis.
Arthritis, rheumatoid; Bone remodeling; TNFR-Fc fusion protein
We investigated the electromyography (EMG) findings and demographic, clinical, and laboratory features that may predict the development of malignancy in patients with idiopathic inflammatory myopathy (IIM).
In total, 61 patients, 36 with dermatomyositis and 25 with polymyositis, were included. Patients were divided into those with and without malignancies, and comparisons were made between the groups in terms of their demographic, clinical, laboratory, and EMG findings.
The frequencies of malignancies associated with dermatomyositis and polymyositis were 22% and 8%, respectively. Patients with malignancies showed a significantly higher incidence of dysphagia (odds ratio [OR], 21.50; 95% confidence interval [CI], 3.84 to 120.49), absence of interstitial lung disease (ILD; OR, 0.12; 95% CI, 0.01 to 0.98), and complex repetitive discharge (CRD) on the EMG (OR, 26.25; 95% CI, 2.67 to 258.52), versus those without. After adjustment for age, dysphagia and CRD remained significant, while ILD showed a trend for a difference but was not statistically significant. Multivariate analysis revealed that the CRD conferred an OR of 25.99 (95% CI, 1.27 to 531.86) for malignancy. When the frequency of malignancy was analyzed according to the number of risk factors, patients with three risk factors showed a significantly higher incidence of malignancy, versus those with fewer than two (p = 0.014).
We demonstrated for the first time that CRD on the EMG was an additional independent risk factor for malignancy in IIM. Further studies on a larger scale are needed to confirm the importance of CRD as a risk factor for malignancy in IIM.
Dermatomyositis; Polymyositis; Malignancy; Risk factors; Electromyography
Fractional flow reserve; Coronary artery anomaly; Single coronary artery
Graves disease; Renal infarction
Erlotinib; Acquired resistance; Neuroendocrine
Percutaneous lung biopsy; Computed tomography; Chest wall infection
This study was conducted to assess the disease burden of pneumonia according to age and presence of underlying diseases in patients admitted with community-acquired pneumonia (CAP).
We performed a retrospective, observational study and collected data targeting patients with CAP (≥ 50 years) from 11 hospitals. Disease burden was defined as total per-capita medical fee, severity (CURB-65), hospital length of stay (LOS), and mortality.
Of the 693 enrolled subjects, elderly subjects (age, ≥ 65 years) had a higher mean CURB-65 score (1.56 vs. 0.25; p < 0.01) and higher mortality than nonelderly subjects (4.4% [n = 21] vs. 0.5% [n = 1]; p = 0.00). In addition, the total cost of pneumonia treatment was higher in elderly patients compared to in nonelderly patients (KRW 2,088,190 vs. US $1,701,386; p < 0.01). Those with an underlying disease had a higher CURB-65 score (1.26 vs. 0.68; p < 0.01), were much older (mean age, 71.24 years vs. 64.24 years; p < 0.01), and had a higher mortality rate than those without an underlying disease (3.5% [n = 20] vs. 1.7% [n = 2]; p = 0.56). Total per-capita medical fees were higher (KRW 2,074,520 vs. US $1,440,471; p < 0.01) and hospital LOS was longer (mean, 8.38 days vs. 6.42 days; p < 0.01) in patients with underlying diseases compared to those without.
Due to the relatively high disease burden in Korea, particularly in the elderly and in those with an underlying disease, closer and more careful observation is needed to improve the outcomes of patients with CAP.
Pneumonia; Costs and cost analysis; Comorbidity; Age factors
Induced pluripotent stem cells (iPSCs) were first described in 2006 and have since emerged as a promising cell source for clinical applications. The rapid progression in iPSC technology is still ongoing and directed toward increasing the efficacy of iPSC production and reducing the immunogenic and tumorigenic potential of these cells. Enormous efforts have been made to apply iPSC-based technology in the clinic, for drug screening approaches and cell replacement therapy. Moreover, disease modeling using patient-specific iPSCs continues to expand our knowledge regarding the pathophysiology and prospective treatment of rare disorders. Furthermore, autologous stem cell therapy with patient-specific iPSCs shows great propensity for the minimization of immune reactions and the provision of a limitless supply of cells for transplantation. In this review, we discuss the recent updates in iPSC technology and the use of iPSCs in disease modeling and regenerative medicine.
Induced pluripotent stem cells; Reprogramming technique; Gene editing; Disease model; Regenerative medicine
The epidemiology, genetics, and clinical manifestations of Crohn's disease (CD) vary considerably among geographic areas and ethnic groups. Thus, identifying the characteristics of Korean CD is important for establishing management strategies appropriate for Korean patients. Since the mid-2000s, many studies have investigated the characteristic features of Korean CD. The incidence and prevalence rates of CD have been increasing rapidly in Korea, especially among the younger population. Unlike Western data, Korean CD shows a male predominance and a lower proportion of isolated colonic disease. Perianal lesions are more prevalent than in Western countries. Genome-wide association studies have confirmed that genetic variants in TNFSF15, IL-23R, and IRGM, but not ATG16L1, are associated with CD susceptibility in the Korean population. Studies of the associations between genetic mutations and the clinical course of CD are underway. Although it has been generally accepted that the clinical course of Korean CD is milder than that in Western countries, recent studies have shown a comparable rate of intestinal resection in Korean and Western CD patients. An ongoing nationwide, hospital-based cohort study is anticipated to provide valuable information on the natural history and prognosis of Korean CD in the near future.
Crohn disease; Epidemiology; Genetics; Prognosis; Korea