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1.  Modifiers of TGF-β1 effector function as novel therapeutic targets of pulmonary fibrosis 
Pulmonary fibrosis is a fatal progressive disease with no effective therapy. Transforming growth factor (TGF)-β1 has long been regarded as a central mediator of tissue fibrosis that involves multiple organs including skin, liver, kidney, and lung. Thus, TGF-β1 and its signaling pathways have been attractive therapeutic targets for the development of antifibrotic drugs. However, the essential biological functions of TGF-β1 in maintaining normal immune and cellular homeostasis significantly limit the effectiveness of TGF-β1-directed therapeutic approaches. Thus, targeting downstream mediators or signaling molecules of TGF-β1 could be an alternative approach that selectively inhibits TGF-β1-stimulated fibrotic tissue response while preserving major physiological function of TGF-β1. Recent studies from our laboratory revealed that TGF-β1 crosstalk with epidermal growth factor receptor (EGFR) signaling by induction of amphiregulin, a ligand of EGFR, plays a critical role in the development or progression of pulmonary fibrosis. In addition, chitotriosidase, a true chitinase in humans, has been identified to have modulating capacity of TGF-β1 signaling as a new biomarker and therapeutic target of scleroderma-associated pulmonary fibrosis. These newly identified modifiers of TGF-β1 effector function significantly enhance the effectiveness and flexibility in targeting pulmonary fibrosis in which TGF-β1 plays a significant role.
PMCID: PMC4028515  PMID: 24851060
Transforming growth factor beta1; Pulmonary fibrosis; Response modifiers; Amphiregulin; Chitotriosidase
2.  The renin-angiotensin system and aging in the kidney 
Aging is associated with progressive functional deterioration and structural changes in the kidney. Changes in the activity or responsiveness of the renin-angiotensin system (RAS) occur with aging. RAS changes predispose the elderly to various fluid and electrolyte imbalances as well as acute kidney injury and chronic kidney disease. Among the multiple pathways involved in renal aging, the RAS plays a central role. This review summarizes the association of the RAS with structural and functional changes in the aging kidney and age-related renal injury, and describes the underlying mechanisms of RAS-related renal aging. An improved understanding of the renal aging process may lead to better individualized care of the elderly and improved renal survival in age-related diseases.
PMCID: PMC4028516  PMID: 24851061
Aging; Kidney; Renin-angiotensin system
4.  Is amlodipine more cardioprotective than other antihypertensive drug classes? 
PMCID: PMC4028518  PMID: 24851063
6.  Survey of perinatal hepatitis B virus transmission after Korean National Prevention Program in a tertiary hospital 
The Ministry of Health and Welfare and the Korea Centers for Disease Control and Prevention in South Korea have been organizing hepatitis B virus (HBV) vertical infection prevention projects since July 2002. In this single-institute study, the results of surveys conducted in target mothers who delivered babies in a tertiary hospital were investigated and analyzed.
Of the 9,281 mothers and their 9,824 neonates born between July 2002 and December 2012, 308 hepatitis B surface antigen (HBsAg)-positive mothers and their 319 neonates were selected for this study, and their records were analyzed retrospectively.
A total of 308 mothers were HBsAg-positive, with an HBV prevalence of 3.32% (308/9,281). There were 319 neonates born to these HBsAg-positive mothers, and 252 were confirmed to as either HBsAg-positive or -negative. Four were confirmed as HBsAg-positive, with a 1.59% (4/252) HBV vertical infection rate. All the mothers of neonates who had an HBV vertical infection were hepatitis B e antigen (HBeAg)-positive. Among the HBsAg-positive neonates, three were HBeAg-positive and had an HBV DNA titer of 1.0 × 108 copies/mL.
The HBV prevalence of mothers was 3.32% (308/9,281), and their vertical infection rate was 1.59% (4/252). Thus, the South Korean HBV vertical infection prevention projects are effective, and, accordingly, HBV prevalence in South Korea is expected to decrease continuously.
PMCID: PMC4028520  PMID: 24851065
Hepatitis B; Vaccination; Vertical infection transmission; Korea
7.  Amlodipine and cardiovascular outcomes in hypertensive patients: meta-analysis comparing amlodipine-based versus other antihypertensive therapy 
This meta-analysis compared the effects of amlodipine besylate, a charged dihydropyridine-type calcium channel blocker (CCB), with other non-CCB antihypertensive therapies regarding the cardiovascular outcome.
Data from seven long-term outcome trials comparing the cardiovascular outcomes of an amlodipine-based regimen with other active regimens were pooled and analyzed.
The risk of myocardial infarction was significantly decreased with an amlodipine-based regimen compared with a non-CCB-based regimen (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.84 to 0.99; p = 0.03). The risk of stroke was also significantly decreased (OR, 0.84; 95% CI, 0.79 to 0.90; p < 0.00001). The risk of heart failure increased slightly with marginal significance for an amlodipine-based regimen compared with a non-CCB-based regimen (OR, 1.14; 95% CI, 0.98 to 1.31; p = 0.08). However, when compared overall with β-blockers and diuretics, amlodipine showed a comparable risk. Amlodipine-based regimens demonstrated a 10% risk reduction in overall cardiovascular events (OR, 0.90; 95% CI, 0.82 to 0.99; p = 0.02) and total mortality (OR, 0.95; 95% CI, 0.91 to 0.99; p = 0.01).
Amlodipine reduced the risk of total cardiovascular events as well as all-cause mortality compared with non-CCB-based regimens, indicating its benefit for high-risk cardiac patients.
PMCID: PMC4028521  PMID: 24851066
Amlodipine; Calcium channel blockers; Hypertension; Meta-analysis
8.  Follicular and Hurthle cell carcinoma of the thyroid in iodine-sufficient area: retrospective analysis of Korean multicenter data 
Follicular thyroid carcinoma (FTC) and Hurthle cell carcinoma (HCC) of the thyroid are relatively uncommon thyroid malignancies in iodine-sufficient areas. In this study we evaluated the clinical behavior, prognostic factors and treatment outcomes of FTC and HCC in Korea.
This multicenter study included 483 patients with FTC and 80 patients with HCC who underwent an initial surgery between 1995 and 2006 in one of the four tertiary referral hospitals in Korea. We evaluated clinicopathological factors associated with distant metastases and recurrence during a median of 6 years of follow-up.
HCC patients were significantly older (49 years vs. 43 years; p < 0.001) and had more lymphovascular invasions (22% vs. 14%; p = 0.03) compared with FTC patients. Distant metastases were confirmed in 40 patients (8%) in the FTC group and in two patients (3%) in the HCC group (p = 0.07). Distant metastases were significantly associated with older age, widely invasive cancer and extrathyroidal invasion. Only 14 patients (3%) had recurrent disease and there was no significant difference between FTC and HCC groups (p = 0.38). Recurrence was associated with larger tumor size and cervical lymph node metastasis.
HCC patients were older and had more lymphovascular invasions than FTC patients. However, FTC and HCC patients had similar initial clinicopathological features. Older age, wide invasiveness and extrathyroidal invasion were independent risk factors for predicting distant metastases in FTC and HCC patients.
PMCID: PMC4028522  PMID: 24851067
Follicular adenocarcinoma; Hurthle cell thyroid cancer; Distant metastases; Prognosis; Iodine
9.  Urinary excretion of β2-microglobulin as a prognostic marker in immunoglobulin A nephropathy 
β2-microglobulin (β2-MG) is freely filtered at the glomerulus and subsequently reabsorbed and catabolized by proximal renal tubular cells. Urinary β2-MG is an early and sensitive biomarker of acute kidney injury; however, its utility as a biomarker of immunoglobulin A nephropathy (IgAN) is unclear.
We included urinary β2-MG levels in the routine laboratory examination of all inpatients with biopsy-proven IgAN at our hospital from 2006 to 2010. We retrospectively analyzed the correlation between β2-MG levels and clinical parameters as a prognostic biomarker of IgAN.
A total of 51 patients (30 males, 21 females; mean age, 33.01 ± 12.73 years) with IgAN were included in this study. Initial demographic, clinical, and laboratory data for all patients are listed. The mean initial estimated glomerular filtration rate and 24-hour urine protein levels were 94.69 ± 34.78 mL/min/1.73 m2 and 1.28 ± 1.75 g/day, respectively. The mean level of urinary β2-MG was 1.92 ± 7.38 µg/mg creatinine. There was a significant correlation between initial serum creatinine (iSCr), urine protein creatinine ratio (UPCR), and the level of β2-MG (r = 0.744, r = 0.667, p < 0.01). There was also a significant correlation between renal function tests and the level of urinary β2-MG (p < 0.01). Cox regression analysis showed that albumin, β2-MG, iSCr, and UPCR were significant predictors of disease progression in IgAN.
Urinary β2-MG levels showed a significant correlation with renal function and proteinuria in IgAN. Thus, we propose that urinary β2-MG may be an additional prognostic factor in patients with IgAN.
PMCID: PMC4028523  PMID: 24851068
Urinary β2-microglobulin; Glomerulonephritis, IGA; Prognostic factor
10.  A mild decrease of renal function is related to increased hemoglobin level during 5-year follow-up period 
We analyzed chronological changes in hemoglobin according to renal function changes over a 5-year follow-up period.
We enrolled 5,266 adults with a glomerular filtration rate (GFR) ≥ 60 mL/min/1.73 m2 at an initial examination at a routine health check-up; a follow-up examination was conducted 5 years later. We categorized the subjects according to GFR ratio (groups 1, 2, and 3, defined as GFRratio ≥ 1.00, 0.75 to 0.99, and < 0.75, respectively).
The mean hemoglobin level in subjects with a GFR of 60 to 74 was higher than in those with a GFR of 75 to 89 or ≥ 90 mL/min/1.73 m2 at the initial examination (all p < 0.001). Among females and males, the frequencies of increased hemoglobin were 46.8% and 40.6% in the GFRratio group 1, 52.4% and 46.1% in group 2, and 59.6% and 52.5% in group 3 over the 5-year period, respectively (all p < 0.001). With multiple logistic regression, group 3 showed 1.594-fold (95% confidence interval [CI], 1.127 to 2.225) and 1.353-fold (95% CI, 1.000 to 1.830) higher likelihoods of increased hemoglobin over the 5-year follow-up period in females and males, respectively. The estimated difference in hemoglobin level was highest in group 3 in both genders. These findings were more evident in subgroups without metabolic syndrome, diabetes mellitus, hypertension, or GFR less than 90 mL/min/1.73 m2.
Among a population with GFR ≥ 60 mL/min/1.73 m2, a mild decrease in GFR over a 5-year follow-up period was associated with an increase in hemoglobin levels.
PMCID: PMC4028524  PMID: 24851069
Chronic kidney failure; Hemoglobins; Erythropoiesis
11.  Clinical characteristics, pathological distribution, and prognostic factors in non-Hodgkin lymphoma of Waldeyer's ring: nationwide Korean study 
In Asia, the incidence of non-Hodgkin lymphoma (NHL) has increased in recent decades. Waldeyer's ring (WR) is the most common site of NHL involving the head and neck. In this study, the pathological distribution of WR-NHL and its clinical features were analyzed retrospectively.
From January 2000 through December 2010, we analyzed the medical records of 328 patients from nine Korean institutions who were diagnosed with WR-NHL.
The study group comprised 197 male and 131 female patients with a median age of 58 years (range, 14 to 89). The rate of localized disease (stage I/II) was 64.9%, and that of low-risk disease (low/low-intermediate, as defined by the International Prognostic Index) was 76.8%. Diffuse large B-cell lymphoma (DLBCL; 240 patients, 73.2%) was the most common pathologic subtype, followed by peripheral T-cell lymphoma (14 patients, 4.3%) and nasal NK/T-cell lymphoma (14 patients, 4.3%). WR-NHL occurred most frequently in the tonsils (199 patients, 60.6%). Extranodal involvement was greater with the T-cell subtype (20 patients, 42.5%) compared with the B-cell subtype (69 patients, 24.5%). Multivariate analyses showed that age ≥ 62 years, T-cell subtype, and failure to achieve complete remission were significant risk factors for overall survival.
DLBCL was found to have a higher incidence in Korea than those incidences reported by other WR-NHL studies. T-cell lymphoma occurred more frequently than did follicular lymphoma. T-cell subtype, age ≥ 62 years, and complete remission failure after first-line treatment were significant poor prognostic factors for overall survival according to the multivariate analysis.
PMCID: PMC4028525  PMID: 24851070
Head and neck; Non-Hodgkin lymphoma; Diffuse large B-cell lymphoma; T-cell lymphoma
12.  Clinical factors and treatment outcomes associated with failure in the detection of urate crystal in patients with acute gouty arthritis 
To investigate the rate of detection of monosodium urate (MSU) crystals in the synovial fluid (SF) of patients with acute gouty arthritis and factors associated with false-negative results.
A total of 179 patients with acute gouty arthritis who had undergone SF crystal examination were identified from the data warehouse of two university hospitals. Clinical and laboratory data were obtained from the medical records.
The overall rate of detection of MSU crystals was 78.8%. In univariate analyses, the only significant differences between the variables of crystal-negative and crystal-positive patients were a lower C-reactive protein level (p = 0.040) and fewer patients undergoing emergent surgery in the crystal-positive group (p = 4.5 × 10-6). In logistic regression analyses, MSU crystal-negative results were significantly associated with the interval from arthritis onset to crystal examination (p = 0.042), and this was the most significant risk factor for arthroscopic surgery (p = 2.1 × 10-4). Seventeen patients who underwent arthroscopic surgery had a significantly longer hospital stay (p = 0.007) and a significant delay in gout treatment (p = 8.74 × 10-5). The distribution of crystal-negative patients differed significantly between the SF samples that were evaluated by both the laboratory medicine and the rheumatology departments (p = 1.2 × 10-14), and the κ value was 0.108.
Although several clinical features were associated with detection failure, SF MSU crystal identification was critically dependent on the observer. Considering the impact on the treatment outcomes, implementation of a quality control program is essential.
PMCID: PMC4028526  PMID: 24851071
Gout; Uric acid; Synovial fluid; Microscopy, polarization
13.  Cryptococcal meningitis in a patient with chronic hepatitis C treated with pegylated-interferon and ribavirin 
Various adverse events have been reported during combination therapy with pegylated (PEG)-interferon-α and ribavirin, although opportunistic infections, especially cryptococcal meningitis, are very rare. A 61-year-old woman complained of headaches and a fever during treatment of a chronic hepatitis C virus (HCV) infection. She had been treated for 7 months. Her headaches were refractory to analgesics, and she developed subtle nuchal rigidity. The cerebral spinal fluid (CSF) revealed a white blood cell count of 205/mm3, 51 mg/dL protein, 35 mg/dL glucose, and negative Cryptococcus antigen. The CSF culture resulted in no growth. Five days later, the CSF was positive for Cryptococcus antigen. We administered amphotericin B and flucytosine, followed by fluconazole. Approximately 2 months later, she was discharged. For the first time, we report a case of cryptococcal meningitis during the treatment of chronic HCV with PEG-interferon-α and ribavirin.
PMCID: PMC4028527  PMID: 24851072
Cryptococcus; Meningitis; PEG-interferon-α; Ribavirin; Hepatitis C
14.  A case of ampullary gangliocytic paraganglioma 
Gangliocytic paragangliomas (GPs) are rare tumors of the duodenum, presenting as single sessile or pedunculated polypoid masses. Clinical manifestations of duodenal GPs can vary from an incidental finding at endoscopy to frequent upper gastrointestinal bleeding caused by mucosal ulceration and abdominal pain. GPs are considered benign, but the disease can recur and spread to regional lymph nodes. A 41-year-old female presented with abdominal pain. Upper gastrointestinal endoscopy revealed a subepithelial tumor of the ampulla of Vater in the second portion of the duodenum. The tumor was resected using the endoscopic mucosal resection technique. The tumor was diagnosed as benign GP of the duodenum using histological and immunohistochemical staining procedures.
PMCID: PMC4028528  PMID: 24851073
Paragangliomas; Duodenum
15.  Acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention 
Acute esophageal necrosis is uncommon in the literature. Its etiology is unknown, although cardiovascular disease, hemodynamic compromise, gastric outlet obstruction, alcohol ingestion, hypoxemia, hypercoagulable state, infection, and trauma have all been suggested as possible causes. A 67-year-old female underwent a coronary angiography (CAG) for evaluation of chest pain. CAG findings showed coronary three-vessel disease. We planned percutaneous coronary intervention (PCI). Coronary arterial dissection during the PCI led to sudden hypotension. Six hours after the index procedure, the patient experienced a large amount of hematemesis. Emergency gastrofibroscopy was performed and showed mucosal necrosis with a huge adherent blood clot in the esophagus. After conservative treatment for 3 months, the esophageal lesion was completely improved. She was diagnosed with acute esophageal necrosis. We report herein a case of acute esophageal necrosis occurring in a patient undergoing percutaneous coronary intervention.
PMCID: PMC4028529  PMID: 24851074
Esophagus; Cardiovascular diseases; Necrosis; Shock; Coronary artery diseases
16.  Distant subcutaneous recurrence of a parathyroid carcinoma: abnormal uptakes in the 99mTc-sestamibi scan and 18F-FDG PET/CT imaging 
We report a rare case of distant subcutaneous parathyroid carcinoma recurrence. A 50-year-old woman was referred to our hospital because of sustained hypercalcemia despite surgical removal of a parathyroid carcinoma. A focal uptake in the upper mediastinal area was detected in a 99mTc-sestamibi scan, and 18F-fluorodeoxyglucose (FDG) positron-emission tomography (PET)/computed tomography (CT) imaging demonstrated a subcutaneous mass. She underwent tumor resection, and the pathological findings were consistent with a parathyroid carcinoma. The postoperative serum parathyroid hormone (PTH) level remained within normal limits. However, a new palpable solitary mass was identified in the upper portion of the left breast 1 year postoperatively. Both a 99mTc-sestamibi scan and 18F-FDG PET/CT imaging revealed an abnormal lesion in the upper breast, and subsequent pathology reports confirmed parathyroid carcinoma metastasis. Serum PTH and calcium levels fell within normal ranges after tumor resection. Two subcutaneous recurrent lesions appeared likely due to tumor seeding during the previous endoscopic operation at a local hospital.
PMCID: PMC4028530  PMID: 24851075
Positron-emission tomography; Hyperparathyroidism; Parathyroid neoplasms; Neoplasm recurrence
17.  Unsupported conclusions in the article "Synephrine-containing dietary supplement precipitating apical ballooning syndrome in a young female" 
PMCID: PMC4028531  PMID: 24851076
p-Synephrine; Bitter orange; Citrus aurantium
18.  A case of Wegener's granulomatosis mimicking recurrent hemophagocytic lymphohistiocytosis 
PMCID: PMC4028532  PMID: 24851077
Wegener's granulomatosis; Lymphohistiocytosis, hemophagocytic; Fever of unknown origin
19.  Native valve endocarditis due to extended spectrum β-lactamase producing Klebsiella pneumoniae 
PMCID: PMC4028533  PMID: 24851078
Extended-spectrum beta-lactamase; Klebsiella pneumoniae; Endocarditis
20.  Unusual metatarsophalangeal joint deformity in an advanced rheumatoid foot 
PMCID: PMC4028534  PMID: 24851079
Rheumatoid arthritis; Forefoot; Metatarsophalangeal joint; Metatarsal deformity
22.  Unusual cause of back pain in a 13-year-old boy: a thoracic osteoblastoma 
PMCID: PMC4028536  PMID: 24851081
23.  Newer treatments for advanced hepatocellular carcinoma 
Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide. The only curative treatment modalities for HCC are surgery, percutaneous ablation, and liver transplantation. Unfortunately, the majority of patients have unresectable disease at diagnosis. Therefore, effective treatment options are needed for patients with advanced HCC. The current standard treatment for patients with advanced HCC, according to the Barcelona Clinic Liver Cancer staging system, is the multikinase inhibitor sorafenib. Other alternative therapies are required, due to the limited treatment response to, and tolerance of, this molecular target agent. Clinical trials of hepatic artery infusion chemotherapy, radioembolization, and multimodal treatments have shown favorable results in advanced HCC patients. This article introduces new treatment modalities for advanced HCC and discusses future therapeutic possibilities.
PMCID: PMC3956982  PMID: 24648795
Hepatocellular carcinoma; Sorafenib; Chemotherapy; Radiotherapy; Combined modality therapy
24.  Current status of functional dyspepsia in Korea 
Dyspepsia refers to group of commonly occurring upper gastrointestinal symptoms. The majority of patients with dyspepsia suffer from functional (nonulcer) dyspepsia. Although there is a lack of epidemiological data from population-based or patient cohort studies in Korea, the current understanding of this condition has been updated using data from various recent research studies, which have facilitated the development of clinical guidelines for functional dyspepsia. According to a survey using the Rome III criteria, more than 40% of respondents who visited primary clinics and tertiary hospitals were defined as having functional dyspepsia, most of who were within a subgroup of patients with postprandial distress syndrome. In addition, a population-based cross-sectional survey revealed considerable overlap between functional dyspepsia and other functional gastrointestinal disorders, including gastroesophageal reflux disease (especially nonerosive reflux disease) and irritable bowel syndrome. In contrast to the results of Western trials, there is insufficient evidence to recommend a Helicobacter pylori test-and-treat strategy as an initial management approach to functional dyspepsia in Korea, suggesting the need for early endoscopic evaluation. Additional studies are necessary to adjust the cutoff age for implementation of immediate endoscopic evaluation of patients without alarm symptoms. Considering the prevalence of H. pylori infection and the limited efficacy of symptomatic relief after its eradication, further well-qualified studies in Korea are warranted.
PMCID: PMC3956983  PMID: 24648796
Functional dyspepsia; Epidemiology; Helicobacter pylori
25.  Urokinase-type plasminogen activator receptor in IgA nephropathy 
PMCID: PMC3956984  PMID: 24648797

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