Improved anti-fibrotic effects by combined treatments of simvastatin and NS-398 in experimental liver fibrosis models

Background/Aims@#Efficient anti-fibrotic therapies are required for the treatment of liver cirrhosis. Hydroxymethylglutaryl-coenzyme A reductase inhibitors (statins) and cyclooxygenase-2 (COX-2) inhibitors have been reported to have anti-fibrotic effects. Here, we investigated whether combined treatment with a statin and a COX-2 inhibitor has synergistic anti-fibrotic effects. @*Methods@#The effects of treatment strategies incorporating both simvastatin and a COX-2 inhibitor, NS-398, were investigated using an immortalized human hepatic stellate cell line (LX-2) and a hepatic fibrosis mouse model developed using thioacetamide (TAA) in drinking water. Cellular proliferation was investigated via 5-bromo-2-deoxyuridine uptake. Pro- and anti-apoptotic factors were investigated through Western blotting and real-time polymerase chain reaction analysis. @*Results@#The evaluation of the anti-proliferative effects on LX-2 cells showed that the observed effects were more pronounced with combination therapy than with single-drug therapy. Moreover, hepatic fibrosis and collagen deposition decreased significantly in TAA-treated mice in response to the combined treatment strategy. The mechanisms underlying the anti-fibrotic effects of the combination therapy were investigated. The effects of the combination therapy were correlated with increased expression levels of extracellular signal-regulated kinase 1/2 signaling molecules, upregulation of the Bax/Bcl-2 signaling pathway, inhibition of the transforming growth factor-β signaling pathway, and inhibition of tissue inhibitor of matrix metalloproteinases 1 and 2. @*Conclusions@#The combination of simvastatin and NS-398 resulted in a synergistic anti-fibrotic effect through multiple pathways. These findings offer a theoretical insight into the possible clinical application of this strategy for the treatment of advanced liver diseases with hepatic fibrosis.

Determinants of Exercise Capacity in Patients With Hypertrophic Cardiomyopathy

Background@#Reduced exercise capacity reflects symptom severity and clinical outcomes in patients with hypertrophic cardiomyopathy (HCM). The present study aimed to identify factors that may affect exercise capacity in patients with HCM. @*Methods@#In 294 patients with HCM and preserved left ventricular (LV) ejection fraction, we compared peak oxygen consumption (peak VO2 ) evaluated by cardiopulmonary exercise testing as a representative parameter of exercise tolerance with clinical and laboratory data, including N-terminal pro-hormone of brain natriuretic peptide (NT-proBNP), diastolic parameters on echocardiography, and the grade of myocardial fibrosis on cardiac magnetic resonance imaging (CMR). @*Results@#Median peak VO2 , was 29.0 mL/kg/min (interquartile range [IQR], 25.0–34.0). Age (estimated β = −0.140, P < 0.001), female sex (β = −5.362, P < 0.001), NT-proBNP (β = −1.256, P < 0.001), and E/e′ ratio on echocardiography (β = −0.209, P = 0.019) were significantly associated with exercise capacity. Peak VO2 was not associated with the amount of myocardial fibrosis on CMR (mean of late gadolinium enhancement 12.25 ± 9.67%LV). @*Conclusion@#Decreased exercise capacity was associated with age, female sex, increased NTproBNP level, and E/e′ ratio on echocardiography. Hemodynamic changes and increased filling pressure on echocardiography should be monitored in this population for improved outcomes.

Challenges and Limitations of Strategies to Promote Therapeutic Potential of Human Mesenchymal Stem Cells for Cell-Based Cardiac Repair

Mesenchymal stem cells (MSCs) represent a population of adult stem cells residing in many tissues, mainly bone marrow, adipose tissue, and umbilical cord. Due to the safety and availability of standard procedures and protocols for isolation, culturing, and characterization of these cells, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative therapy. Once transplanted into a damaged heart, MSCs release paracrine factors that nurture the injured area, prevent further adverse cardiac remodeling, and mediate tissue repair along with vasculature. Numerous preclinical studies applying MSCs have provided significant benefits following myocardial infarction. Despite promising results from preclinical studies using animal models, MSCs are not up to the mark for human clinical trials. As a result, various approaches have been considered to promote the therapeutic potency of MSCs, such as genetic engineering, physical treatments, growth factor, and pharmacological agents. Each strategy has targeted one or multi-potentials of MSCs. In this review, we will describe diverse approaches that have been developed to promote the therapeutic potential of MSCs for cardiac regenerative therapy. Particularly, we will discuss major characteristics of individual strategy to enhance therapeutic efficacy of MSCs including scientific principles, advantages, limitations, and improving factors. This article also will briefly introduce recent novel approaches that MSCs enhanced therapeutic potentials of other cells for cardiac repair.

Challenges and Limitations of Strategies to Promote Therapeutic Potential of Human Mesenchymal Stem Cells for Cell-Based Cardiac Repair

Mesenchymal stem cells (MSCs) represent a population of adult stem cells residing in many tissues, mainly bone marrow, adipose tissue, and umbilical cord. Due to the safety and availability of standard procedures and protocols for isolation, culturing, and characterization of these cells, MSCs have emerged as one of the most promising sources for cell-based cardiac regenerative therapy. Once transplanted into a damaged heart, MSCs release paracrine factors that nurture the injured area, prevent further adverse cardiac remodeling, and mediate tissue repair along with vasculature. Numerous preclinical studies applying MSCs have provided significant benefits following myocardial infarction. Despite promising results from preclinical studies using animal models, MSCs are not up to the mark for human clinical trials. As a result, various approaches have been considered to promote the therapeutic potency of MSCs, such as genetic engineering, physical treatments, growth factor, and pharmacological agents. Each strategy has targeted one or multi-potentials of MSCs. In this review, we will describe diverse approaches that have been developed to promote the therapeutic potential of MSCs for cardiac regenerative therapy. Particularly, we will discuss major characteristics of individual strategy to enhance therapeutic efficacy of MSCs including scientific principles, advantages, limitations, and improving factors. This article also will briefly introduce recent novel approaches that MSCs enhanced therapeutic potentials of other cells for cardiac repair.

Adaptation of the Evidence-Based Nursing Practice Guideline: Prevention and Management of Moisture Associated Skin Damage / 임상간호연구

PURPOSE: This study was done to develop an evidence-based nursing clinical practice guideline for Moisture associated skin damage (MASD) prevention and management for patients in Korea. METHODS: The guideline adaptation process was used and conducted according to the guideline adaptation manual developed by the Korean Hospital Nurses Association. It consists of three main phases and 9 modules including a total of 24 steps. RESULTS: The adapted MASD clinical practice guideline consisted of 4 sections, 8 domains and 28 recommendations. The number of recommendations in each section was: 7 on MASD assessment, 14 on MASD prevention and management, 4 on education, and 3 on organizational policy. Of the recommendations, 3.6% were marked as A grade, 28.6% as B grade, and 67.8% as C grade. CONCLUSION: This MASD clinical practice guideline is the first to be developed in Korea. The developed guideline will contribute to standardized and consistent MASD prevention and management. The guideline can be recommended for dissemination and utilization by nurses nationwide to improve the quality of MASD prevention and management. Regular revision is recommended.

Risk factors for poor prognosis in nosocomial infective endocarditis

BACKGROUND/AIMS@#The aim of our study was to compare the characteristics of nosocomial infective endocarditis (NIE) with community-acquired infective endocarditis (CIE) and to determine independent risk factors for in-hospital death.@*METHODS@#We retrospectively reviewed the medical records of 560 patients diagnosed with infective endocarditis. NIE was defined by a diagnosis made > 72 hours after hospital admission or within 2 months of hospital discharge.@*RESULTS@#Among the 560 cases reviewed, 121 were classified as NIE. Compared with patients with CIE, patients with NIE were older (mean ± SD, 51.30±18.01 vs. 59.76±14.87, p < 0.001). The in-hospital death rate of the NIE group was much higher than that of the CIE group (27.3% vs. 5.9%, p < 0.001). More patients with NIE had central intravenous catheters, and were undergoing hemodialysis (p < 0.001). Methicillin-resistant Staphylococcus aureus (MRSA) was the most common causal microorganism of NIE, and MRSA (p < 0.001) and fungus (p = 0.002) were more common in NIE compared with CIE. On multiple analysis, age, liver cirrhosis, cancer chemotherapy, central intravenous catheter, hemodialysis, and genitourinary tract manipulation were independent clinical risk factors for NIE. Among the patients with NIE, 33 died during their hospital admission. The independent risk factors for in-hospital death were older age (adjusted odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01 to 1.07; p = 0.037) and chemotherapy for malignancy (adjusted OR, 3.89; 95% CI, 1.18 to 12.87; p = 0.026).@*CONCLUSIONS@#Because of the considerable incidence of NIE and its poor prognosis, we should pay attention to early diagnosis and active management of NIE, especially for older patients and patients receiving chemotherapy.

Diverse Phenotypic Expression of Cardiomyopathies in a Family with TNNI3 p.Arg145Trp Mutation

Genetic diagnosis of cardiomyopathies is challenging, due to the marked genetic and allelic heterogeneity and the lack of knowledge of the mutations that lead to clinical phenotypes. Here, we present the case of a large family, in which a single TNNI3 mutation caused variable phenotypic expression, ranging from restrictive cardiomyopathy (RCMP) to hypertrophic cardiomyopathy (HCMP) to near-normal phenotype. The proband was a 57-year-old female with HCMP. Examining the family history revealed that her elder sister had expired due to severe RCMP. Using a next-generation sequencing-based gene panel to analyze the proband, we identified a known TNNI3 gene mutation, c.433C>T, which is predicted to cause an amino acid substitution (p.Arg145Trp) in the highly conserved inhibitory region of the cardiac troponin I protein. Sanger sequencing confirmed that six relatives with RCMP or near-normal phenotypes also carried this mutation. To our knowledge, this is the first genetically confirmed family with diverse phenotypic expression of cardiomyopathies in Korea. Our findings demonstrate familial implications, where a single mutation in a sarcomere protein can cause diverse phenotypic expression of cardiomyopathies.

Association of Left Atrial Enlargement with Cortical Infarction in Subjects with Patent Foramen Ovale / 대한뇌졸중학회지

BACKGROUND AND PURPOSE: Left atrial dysfunction has been reported in patients with patent foramen ovale (PFO). Here we investigated the role of left atrial dysfunction in the development of embolic stroke in patients with PFO. METHODS: We identified consecutive patients with embolic stroke of undetermined sources except for PFO (PFO+ESUS). Healthy subjects with PFO served as controls (PFO+control). A stratified analysis by 10-year age group and an age- and sex- matching analysis were performed to compare echocardiographic markers between groups. In the PFO+ESUS group, infarct patterns of PFO-related stroke were determined (cortical vs. cortico-subcortical) and analyzed in correlation with left atrial function parameters. RESULTS: A total of 118 patients and 231 controls were included. The left atrial volume indices (LAVIs) of the PFO+ESUS patients were higher than those of the PFO+controls in age groups of 40–49, 50–59, and 60–69 years (P28 mL/m2) LAVI was more associated with the cortical infarct pattern (P=0.043 for an acute infarction and P=0.024 for a chronic infarction, both adjusted for age and shunt amount). The degree of right-to-left shunting was not associated with infarct patterns, but with the posterior location of acute infarcts (P=0.028). CONCLUSIONS: Left atrial enlargement was associated with embolic stroke in subjects with PFO. Left atrial physiology might contribute to the development of PFO-related stroke and need to be taken into consideration for optimal prevention of PFO-related stroke.

Systemic Amyloid Protein a Amyloidosis Involving the Heart in a Patient with Rheumatoid Arthritis / 대한내과학회지

Amyloidosis can be identified by the deposition of amyloid fibrils in biopsy specimens from multiple organs, including the heart, kidney, skin, and bowel. Systemic amyloid protein A amyloidosis (AA amyloidosis) is commonly associated with chronic inflammatory diseases or chronic infectious conditions. Cardiac involvement in AA amyloidosis is found in < 1% of reported cases. Here, we report a case of cardiac AA amyloidosis confirmed by heart biopsy in a 54-year-old-female with a medical history of rheumatoid arthritis and stage 4 chronic kidney disease due to renal amyloidosis. She had suffered from progressive aggravation of dyspnea for 2 years. Infiltrative disease involving the heart was suspected by echocardiography, and the patient was diagnosed with AA amyloidosis involving the heart by cardiac biopsy. This is a rare case of cardiac involvement in a patient with systemic AA amyloidosis associated with rheumatoid arthritis.

Factors Influencing the Acceptance of Transrectal Ultrasound-Guided Prostate Biopsies

PURPOSE: This study aimed to improve prostate biopsy compliance by analyzing the factors that influence the acceptance of prostate biopsy by patients to whom transrectal ultrasound (TRUS)-guided prostate biopsy is recommended for suspected prostate cancer. MATERIALS AND METHODS: The subjects of this study were 268 patients to whom TRUS-guided prostate biopsy was recommended from January to June 2011 and who completed a questionnaire. Patients who showed a prostate-specific antigen (PSA) increase to more than 4.0 ng/mL or abnormal findings on a digital rectal examination and TRUS were recommended to undergo prostate biopsy. The questionnaire consisted of 9 questions about the subjects' demographic characteristics and 15 questions that assessed their knowledge of prostate disease. Fisher exact probability test was conducted to assess the influence of the demographic characteristics and levels of knowledge of prostate disease on acceptance of prostate biopsy. RESULTS: The mean age of the subjects was 66.2 years (range, 43-83 years). Of the cohort, 188 patients (70.7%) agreed to the prostate biopsy and 78 patients (29.3%) refused. In terms of demographic characteristics, the patients' acceptance of prostate biopsy was associated only with education level. Patients with relatively lower education levels had a higher acceptance rate for prostate biopsy (80.0% vs. 65.9%, p=0.018). Other demographic factors, as well as the degree of knowledge of prostate disease, had no significant effect on the acceptance rate. CONCLUSIONS: The patients' acceptance of prostate biopsy can be influenced by demographic characteristics, especially education level. Therefore, when prostate biopsy is recommended to patients, their demographic characteristics should be taken into consideration.

Acute Myocardial Infarction after Radiofrequency Catheter Ablation of Typical Atrial Flutter

A 53-yr-old man underwent radiofrequency ablation to treat persistent atrial flutter. After the procedure, the chest pain was getting worse, and the electrocardiogram showed ST-segment elevation in inferior leads with reciprocal changes. Immediate coronary angiography showed total occlusion with thrombi at the distal portion of the right coronary artery, which was very close to the ablation site. Intervention with thrombus aspiration and balloon dilatation was successful, and the patient recovered without any kind of sequelae. Although the exact mechanism is obscure, the most likely explanation is a thermal injury to the vascular wall that ruptured into the lumen and formed thrombus. Vasospasm and thromboembolism can also be other possibilities. This case raise the alarm to cardiologists who perform radiofrequency ablation to treat various kinds of cardiac arrhythmias, in that myocardial infarction has been rarely considered one of the complications.

Unusual Manifestation of Intravascular Large B-Cell Lymphoma: Severe Hypercalcemia with Parathyroid Hormone-Related Protein / Journal of the Korean Cancer Association, 대한암학회지

Intravascular large B-cell lymphoma (IVLBCL) is a rare subtype of non-Hodgkin lymphoma. It usually presents with nonspecific symptoms, such as fever, rather than with overt lymphadenopathy. Reports of hypercalcemia, as the initial presentation of IVLBCL, are limited in the literature, despite it being a well-known complication of various solid cancers. We present a 68-year-old male with severe hypercalcemia and increased levels of serum parathyroid hormone-related protein. He was diagnosed with IVLBCL, involving the bone marrow and spleen, and was successfully treated with rituximab-containing chemotherapy. A few previous case reports have shown hypercalcemia in patients with IVLBCL. Much like our case, previous cases with hypercalcemia had advanced diseases, including bone marrow invasion. Although it was an extremely rare manifestation of IVLBCL, we suggest that IVLBCL should be a part of the differential diagnosis in patients with unexplained hypercalcemia. Therefore, an active work-up might be recommended, including positron emission tomography/computed tomography scan and bone marrow examination, which may be useful for early diagnosis.

Community-Acquired Necrotizing Pneumonia Caused by ST72-SCCmec Type IV-Methicillin-Resistant Staphylococcus aureus in Korea / 결핵및호흡기질환

Methcillin-resistant Staphylococcus aureus (MRSA) has emerged as an important cause of community-acquired infections, which has been recently designated as community-associated (CA) MRSA. Panton-Valentine leukocidin (PVL)-negative multilocus sequence type 72 (ST72)-staphylococcal cassette chromosome mec (SCCmec) type IV has been reported as the predominat CA-MRSA strain in Korea and is commonly associated with skin and soft tissue infections in addition to healthcare-associated pneumonia. However, community-acquired pneumonia (CAP) for this strain has not yet been reported. We hereby report two cases of CAP caused by PVL-negative ST72-SCCmec type IV strain in patients who had no risk factors for MRSA acquisition. While CA-MRSA infections are not yet prevalent in Korea, our cases suggest that CA-MRSA should be considered in cases of severe CAP, especially for cases associated with necrotizing pneumonia.

Immunoglobulin G4 Non-Related Sclerosing Disease with Intracardiac Mass Mimicking Mitral Stenosis: Case Report

The cardiovascular system may be one of the target organs of both immunoglobulin G4 related and non-related systemic multifocal fibrosclerosis. We present a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis on echocardiography. For a more detailed differential diagnosis, we used multimodal imaging techniques. After surgical biopsy around the abdominal aortic area in the retroperitoneum, histological examination revealed IgG4 non-related systemic multifocal fibrosclerosis. We describe the multimodal imaging used to diagnose IgG4 non-related systemic multifocal fibrosclerosis and a positive response to steroid treatment. There have been no previous case reports of IgG4 non-related systemic multifocal fibrosclerosis with intracardiac involvement. Here, we report a case of IgG4 non-related systemic multifocal fibrosclerosis mimicking mitral stenosis.

Predictive Factors of Response to Medical Therapy in Crohn's Disease Patients with Intestinal Obstruction / 대한소화기학회지

BACKGROUND/AIMS: Crohn's disease is a chronic inflammatory bowel disease. Stricture is a very important indication for surgical intervention as strictures can lead to intestinal obstruction. Strictures can be divided into inflammatory and fibrous strictures. Intestinal obstruction due to inflammatory stricture is expected to be resolved with medical treatment. However, factors that can predict the response to medical treatments are unknown. In the present study, we aimed to identify the factors that can predict the response to medical treatments in Crohn's disease patients with intestinal obstruction. METHODS: Data were collected by retrospectively reviewing the medical records of patients with Crohn's disease who visited the emergency department at Samsung Medical Center in Seoul from January 1, 2000 to December 31, 2010 because of intestinal obstruction. Based on the response to medical treatments, we classified the patients as responders and non-responders and compared the clinical, biochemical, and radiological findings of the two groups. RESULTS: A total of 39 patients were enrolled. Twenty-nine patients responded to medical treatments whereas 10 patients did not. Significant differences were observed between the two groups in terms of vomiting and duration of disease before the development of obstruction. CONCLUSIONS: Patients who responded to the medical treatments exhibited a higher incidence of vomiting and longer duration of disease before the development of obstruction. However, further prospective studies are needed to identify the factors that can predict the response to medical treatments.

Churg-Strauss syndrome presenting as acute acalculous cholecystitis

Churg-Strauss syndrome (CSS) is a rare systemic vasculitis. It is characterized by peripheral eosinophilia, asthma, neuropathy, skin manifestation, and less frequently gastrointestinal tract symptoms. Here we report a case of CSS which is initially manifested as acute acalculous cholecystitis. A 67-year-old asthmatic woman visited Emergency Room because of acute abdominal pain. Computed tomography showed acalculous cholecystitis and laparoscopic cholecystectomy was done. Pathology of gallbladder showed marked eosinophilic infiltration with necrotizing vasculitis and granuloma. On the basis of asthma, sinusitis, lung infiltration, combined peripheral eosinophilia and neuropathy, the patient was diagnosed as CSS. To our knowledge, this is the first case of pathologically proven eosinophilic cholecystitis in Korea.

Enthesitis in a Patient with Systemic Lupus Erythematosus: The First Case Report / 대한내과학회지

We present the first case of enthesitis in the lumbar spine in a woman with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS). Enthesopathy is defined as pathological alterations at the site of insertion of a tendon, ligament, joint capsule, or fascia to bone. In particular, enthesitis is the universal hallmark of seronegative spondyloarthropathies (SpA), including ankylosing spondylitis, reactive arthritis, psoriatic arthritis, and spondyloarthropathies associated with inflammatory bowel diseases. A 36-year-old female SLE patient with a history of lupus nephritis and thrombosis from APS presented with low back pain that had been gradually worsening for several months. She reported no previous episodes of trauma. Plain radiography indicated sclerosis at the anterior superior bodies of L3 and L5. Magnetic resonance imaging (MRI) showed low-intensity lesions on T1-weighted images and high-intensity lesions on T2-weighted images at the anterior superior bodies of L3, L4, and L5, consistent with osteitis or enthesitis. A nonsteroidal antiinflammatory drug (NSAID) was used as the first-line therapy in this patient, which improved her symptoms. This is the first report of enthesitis in the context of SLE. Although the possibility of coincidental occurrence of SpA and SLE cannot be excluded, the observations in this case suggest that enthesitis may be one of the manifestations of SLE.

Four patients with hepatitis A presenting with fulminant hepatitis and acute renal failure and who underwent liver transplantation / 대한간학회지

Hepatitis A is generally known as a mild, self-limiting disease of the liver, but in rare instances it can progress to fulminant hepatitis, which may require liver transplantation for recovery. Such cases are known to be related to old age and underlying liver disease. We report four cases of hepatitis A in which patients presented with fulminant hepatitis and acute renal failure and underwent liver transplantation. The following common features were observed in our cases: (1) occurrence in relatively old age (> or =39 years old), (2) association with acute renal failure, (3) presence of hepatomegaly, and (4) microscopic features of submassive hepatic necrosis.

A Case of Blue Rubber Bleb Nevus Syndrome Treated by Endoscopic Band Ligation and Endoscopic Polypectomy / 대한소화기내시경학회지

Blue rubber bleb nevus syndrome (BRBNS) is a rare disorder that is characterized by multiple cutaneous vascular malformations in the skin and gastrointestinal tract and is associated with intestinal hemorrhage and iron deficiency anemia. This syndrome may induce severe or fatal bleeding; however, the causes of this syndrome are unknown. We report here a case of BRBNS that was diagnosed in a 20-year-old male with chronic anemia and a past history of surgery due to cutaneous hemangioma on the shoulder and thigh. One purplish hemangioma on the stomach and multiple bluish hemangiomas on the colon were noted on the endoscopic examination. We successfully treated the GI hemangioma with endoscopic band ligation and endoscopic polypectomy.

Concept Analysis on the Clinical Critical Thinking Ability in Nursing / 성인간호학회지

PURPOSE: The present study was designed to understand the conceptual definition and attributes of the clinical critical thinking ability(CCTA) in nursing and to grasp the characteristics of clinical critical thinking abilities. METHODS: The data were analyzed using the Hybrid model of Schwartz-Barcott and Kim(2000). RESULTS: Having the skills and dispositions to think critically, CCTA refers to something that implies the cognizant ability to interpret contextual meanings, analyze the relationships between materials or circumstances, draw out the best conclusions, predict things using relevant information and evaluate the reliability of information and the strength of inference on the one hand and the emphatic disposition to be curious, open-minded, intellectually integral, systematic and creative and to reflect on things in contextual terms on the other. CONCLUSION: CCTA is characterized by clinical circumstances, such as guessing the reasons for facts, predicting things, connecting theory to practice and approaching individual situation in total terms as well as by the Korean circumstances, such as taking another person's perspective. Hence, this study proposes developing the tools to measure the clinical critical thinking ability and the strategies to improve the clinical critical thinking ability and seeking to verify their validity, on the basis of the findings.