Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is closely related to gut-microbiome. There is a paucity of research on which strains of gut microbiota affect the progression of NAFLD. This study explored the NAFLD-associated microbiome in humans and the role of Lactobacillus in the progression of NAFLD in mice. Methods: The gut microbiome was analyzed via next-generation sequencing in healthy people (n=37) and NAFLD patients with elevated liver enzymes (n=57). Six-week-old male C57BL/6J mice were separated into six groups (n=10 per group; normal, Western, and four Western diet + strains [109 colony-forming units/g for 8 weeks; L. acidophilus, L. fermentum, L. paracasei, and L. plantarum]). Liver/body weight ratio, liver pathology, serum analysis, and metagenomics in the mice were examined. Results: Compared to healthy subjects (1.6±4.3), NAFLD patients showed an elevated Firmicutes/Bacteroidetes ratio (25.0±29.0) and a reduced composition of Akkermansia and L. murinus (P<0.05). In the animal experiment, L. acidophilus group was associated with a significant reduction in liver/body weight ratio (5.5±0.4) compared to the Western group (6.2±0.6) (P<0.05). L. acidophilus (41.0±8.6), L. fermentum (44.3±12.6), and L. plantarum (39.0±7.6) groups showed decreased cholesterol levels compared to the Western group (85.7±8.6) (P<0.05). In comparison of steatosis, L. acidophilus (1.9±0.6), L. plantarum (2.4±0.7), and L. paracasei (2.0±0.9) groups showed significant improvement of steatosis compared to the Western group (2.6±0.5) (P<0.05). Conclusions Ingestion of Lactobacillus, such as L. acidophilus, L. fermentum, and L. plantarum, ameliorates the progression of nonalcoholic steatosis by lowering cholesterol. The use of Lactobacillus can be considered as a useful strategy for the treatment of NAFLD.

Mice deficient in the toll-like receptor (TLR) or the myeloid differentiation factor 88 (MyD88) are resistant to acute liver failure (ALF) with sudden death of hepatocytes. Chalcone derivatives from medicinal plants protect from hepatic damages including ALF, but their mechanisms remain to be clarified. Here, we focused on molecular basis of piperidylmethyloxychalcone (PMOC) in the treatment of TLR/MyD88-associated ALF. C57BL/6J mice were sensitized with D-galactosamine (GalN) and challenged with Escherichia coli lipopolysaccharide (LPS, TLR4 agonist) or oligodeoxynucleotide containing unmethylated CpG motif (CpG ODN, TLR9 agonist) for induction of ALF. Post treatment with PMOC sequentially ameliorated hepatic inflammation, apoptosis of hepatocytes, severe liver injury and shock-mediated death in ALF-induced mice. As a mechanism, PMOC inhibited the catalytic activity of TGF-β-activated kinase 1 (TAK1) in a competitive manner with respect to ATP, displaced fluorescent ATP probe from the complex with TAK1, and docked at the ATP-binding active site on the crystal structure of TAK1. Moreover, PMOC inhibited TAK1 auto-phosphorylation, which is an axis in the activating pathways of nuclear factor-κB (NF-κB) or activating protein 1 (AP1), in the liver with ALF in vivo or in primary liver cells stimulated with TLR agonists in vitro. PMOC consequently suppressed TAK1-inducible NF-κB or AP1 activity in the inflammatory injury, an early pathogenesis leading to ALF. The results suggested that PMOC could contribute to the treatment of TLR/MyD88-associated ALF with the ATP-binding site of TAK1 as a potential therapeutic target.
Adenosine Triphosphate ; Animals ; Apoptosis ; Catalytic Domain ; Chalcone ; Death, Sudden ; Escherichia coli ; Hepatocytes ; In Vitro Techniques ; Inflammation ; Liver ; Liver Failure, Acute* ; Mice ; Myeloid Differentiation Factor 88 ; Phosphotransferases ; Plants, Medicinal ; Toll-Like Receptors

Amniotic fluid embolism is rare but is one of the most catastrophic complications in the peripartum period. This syndrome is caused by a maternal anaphylactic reaction to the introduction of fetal material into the pulmonary circulation. When amniotic fluid embolism is suspected, the immediate application of extracorporeal mechanical circulatory support such as veno-arterial extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass should be considered. Without the application of extracorporeal mechanical circulatory support, medical supportive care might not be sufficient to maintain cardiopulmonary stabilization in severe cases of amniotic fluid embolism. In this report, we present the case of a 36-year-old pregnant woman who developed an amniotic fluid embolism immediately after a cesarean section. Her catastrophic event started with the sudden onset of severe hypoxia, followed by circulatory collapse within 8 minutes. The veno-arterial mode of extracorporeal membrane oxygenation was initiated immediately. She was successfully resuscitated but with impaired cognitive function. Thus, urgent ECMO should be considered when amniotic fluid embolism syndrome is suspected in patients presenting acute cardiopulmonary collapse.
Adult ; Amniotic Fluid* ; Anaphylaxis ; Anoxia ; Cardiopulmonary Bypass ; Cesarean Section ; Cognition ; Embolism, Amniotic Fluid* ; Extracorporeal Membrane Oxygenation* ; Female ; Humans ; Peripartum Period ; Pregnancy ; Pregnant Women ; Pulmonary Circulation ; Shock

Amniotic fluid embolism is rare but is one of the most catastrophic complications in the peripartum period. This syndrome is caused by a maternal anaphylactic reaction to the introduction of fetal material into the pulmonary circulation. When amniotic fluid embolism is suspected, the immediate application of extracorporeal mechanical circulatory support such as veno-arterial extracorporeal membrane oxygenation (ECMO) or cardiopulmonary bypass should be considered. Without the application of extracorporeal mechanical circulatory support, medical supportive care might not be sufficient to maintain cardiopulmonary stabilization in severe cases of amniotic fluid embolism. In this report, we present the case of a 36-year-old pregnant woman who developed an amniotic fluid embolism immediately after a cesarean section. Her catastrophic event started with the sudden onset of severe hypoxia, followed by circulatory collapse within 8 minutes. The veno-arterial mode of extracorporeal membrane oxygenation was initiated immediately. She was successfully resuscitated but with impaired cognitive function. Thus, urgent ECMO should be considered when amniotic fluid embolism syndrome is suspected in patients presenting acute cardiopulmonary collapse.
Adult ; Amniotic Fluid ; Anaphylaxis ; Anoxia ; Cardiopulmonary Bypass ; Cesarean Section ; Cognition ; Embolism, Amniotic Fluid ; Extracorporeal Membrane Oxygenation ; Female ; Humans ; Peripartum Period ; Pregnancy ; Pregnant Women ; Pulmonary Circulation ; Shock

PURPOSE: To investigate the differences in the cancer detection rate and pathological findings on a second prostate biopsy according to benign diagnosis, high-grade prostatic intraepithelial neoplasia (HGPIN), and atypical small acinar proliferation (ASAP) on first biopsy. MATERIALS AND METHODS: We retrospectively reviewed the records of 1,323 patients who underwent a second prostate biopsy between March 1995 and November 2012. We divided the patients into three groups according to the pathologic findings on the first biopsy (benign diagnosis, HGPIN, and ASAP). We compared the cancer detection rate and Gleason scores on second biopsy and the unfavorable disease rate after radical prostatectomy among the three groups. RESULTS: A total of 214 patients (16.2%) were diagnosed with prostate cancer on a second biopsy. The rate of cancer detection was 14.6% in the benign diagnosis group, 22.1% in the HGPIN group, and 32.1% in the ASAP group, respectively (p<0.001). When patients were divided into subgroups according to the number of positive cores, the rate of cancer detection was 16.7%, 30.5%, 31.0%, and 36.4% in patients with a single core of HGPIN, more than one core of HGPIN, a single core of ASAP, and more than one core of ASAP, respectively. There were no significant differences in Gleason scores on second biopsy (p=0.324) or in the unfavorable disease rate after radical prostatectomy among the three groups (benign diagnosis vs. HGPIN, p=0.857, and benign diagnosis vs. ASAP, p=0.957, respectively). CONCLUSIONS: Patients with multiple cores of HGPIN or any core number of ASAP on a first biopsy had a significantly higher cancer detection rate on a second biopsy. Repeat biopsy should be considered and not be delayed in those patients.
Aged ; Biopsy, Needle/methods ; Humans ; Kallikreins/blood ; Male ; Middle Aged ; Neoplasm Grading ; Precancerous Conditions/*pathology/surgery ; Predictive Value of Tests ; Prostate-Specific Antigen/blood ; Prostatectomy ; Prostatic Intraepithelial Neoplasia/*pathology/surgery ; Prostatic Neoplasms/*pathology/surgery ; Retrospective Studies

PURPOSE: Partial nephrectomy has a similar oncologic outcome to radical nephrectomy while reducing cardiac and metabolic morbidity. However, previous studies reported that partial nephrectomy had been underutilized. The purpose of this study is to analyze trends in the use of partial nephrectomy in Korea and evaluate which individual factors and hospital factor influenced the operative approach. MATERIALS AND METHODS: Using URO-PDS database, 11560 patients underwent nephrectomy for renal cell carcinoma between 2006 and 2010 were identified. International Classification of Disease (ICD-9) diagnosis codes were applied to target subject of interest. Logistic regression was applied to identify determinants of partial nephrectomy. RESULTS: Over the study period, the proportion of partial nephrectomies has steadily increased from 9.4% in 2006 to 30.4% in 2010 (p<0.001). Deviation of utilization in partial nephrectomy has been observed based on the area (p<0.001) and type of surgery (p<0.001). Individual of younger age, as well as male, were more likely to be treated with partial nephrectomy (p<0.001 for each). Furthermore, Patient treated at hospitals with higher nephrectomy volume were more prone to be treated with partial nephrectomy (p<0.001 for each). CONCLUSIONS: Partial nephrectomies have been increasingly performed over the study period but are still underutilized.
Carcinoma, Renal Cell* ; Classification ; Diagnosis ; Humans ; Korea* ; Logistic Models ; Male ; Nephrectomy*

PURPOSE: Current management for patients with differentiated thyroid cancer includes near total thyroidectomy and radioactive iodine therapy followed by administration of supraphysiological doses of levothyroxine (L-T4). Although hyperthyroidism is a well known risk factor for osteoporosis, the effects of L-T4 treatment on bone mineral density (BMD) in patients with thyroid cancer do not appear to be as significant as with endogenous hyperthyroidism. In this study, we evaluated the impact of long-term suppressive therapy with L-T4 on BMD and bone turn over markers in Korean female patients receiving L-T4 suppressive therapy. METHODS: We enrolled 94 female subjects (mean age, 50.84 +/- 11.43 years) receiving L-T4 after total or near total thyroidectomy and radioactive iodine therapy for thyroid cancer (mean follow-up period, 12.17 +/- 4.27 years). The subjects were divided into three groups by thyroid stimulating hormone (TSH) level (group 1 with TSH level < or =0.001 microIU/mL, group 2 with TSH level between 0.001 and 0.17 microIU/mL, group 3 with TSH level >0.17 microIU/mL) and four groups by quartile of free T4 level. L-T4 dosage, BMD (examined by dual-energy x-ray absorptiometry), and bone turnover markers were evaluated according to TSH and free T4 levels. RESULTS: No significant decrease was detected in BMD or bone turnover markers according to TSH level or free T4 level. Also, the prevalence of osteoporosis and osteopenia was not different among groups. CONCLUSION: Long-term L-T4 suppressive therapy after thyroid cancer management did not affect bone density or increase the prevalence of osteoporosis even though TSH levels were supraphysiologically suppressed.
Bone Density* ; Bone Diseases, Metabolic ; Female ; Follow-Up Studies ; Humans ; Hyperthyroidism ; Iodine ; Osteoporosis ; Prevalence ; Risk Factors ; Thyroid Gland* ; Thyroid Neoplasms* ; Thyroidectomy ; Thyrotropin ; Thyroxine*

Trans-radial (TR) approach is increasingly recognized as an alternative to the routine use of trans-femoral (TF) approach. However, there are limited data comparing the outcomes of these two approaches for the treatment of coronary bifurcation lesions. We evaluated outcomes of TR and TF percutaneous coronary interventions (PCI) in this complex lesion. Procedural outcomes and clinical events were compared in 1,668 patients who underwent PCI for non-left main bifurcation lesions, according to the vascular approach, either TR (n = 503) or TF (n = 1,165). The primary outcome was major adverse cardiac events (MACE), including cardiac death, myocardial infarction (MI), and target lesion revascularization (TLR) in all patients and in 424 propensity-score matched pairs of patients. There were no significant differences between TR and TF approaches for procedural success in the main vessel (99.6% vs 98.6%, P = 0.08) and side branches (62.6% vs 66.7%, P = 0.11). Over a mean follow-up of 22 months, cardiac death or MI (1.8% vs 2.2%, P = 0.45), TLR (4.0% vs 5.2%, P = 0.22), and MACE (5.2% vs 7.0%, P = 0.11) did not significantly differ between TR and TF groups, respectively. These results were consistent after propensity score-matched analysis. In conclusion, TR PCI is a feasible alternative approach to conventional TF approaches for bifurcation PCI (clinicaltrials.gov number: NCT00851526).
Aged ; Angioplasty, Balloon, Coronary/adverse effects/*methods ; Coronary Angiography ; Coronary Stenosis/mortality/radiography/*therapy ; Coronary Vessels/radiography/surgery ; *Drug-Eluting Stents ; Female ; Follow-Up Studies ; Hemorrhage/etiology ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Myocardial Infarction/etiology ; Myocardial Revascularization ; Proportional Hazards Models ; Registries

BACKGROUND AND OBJECTIVES: Recent studies indicate that in response to vasoconstrictor stimuli, the small GTPase RhoA and its down-stream effector, Rho-associated kinase 2 (ROCK)/Rho-kinase, are associated with hypercontraction of the vascular smooth muscle of coronary arteries through augmentation of myosin light chain phosphorylation and Ca2+ sensitization. Expression of ROCK/Rho-kinase mRNA was significantly increased and up-regulated in the spastic coronary artery in a porcine model, and a specific inhibitor of ROCK/Rho-kinase inhibited coronary artery spasm in humans. We therefore explored the role of ROCK2 polymorphisms in the pathogenesis of vasospastic angina (VA). SUBJECTS AND METHODS: We studied 106 patients with VA who exhibited spontaneous or provoked coronary spasm during coronary angiography and compared the prevalence of ROCK2 polymorphisms between this group of patients with VA and controls whose angiograms were normal, and in whom the ergonovine test did not cause spasm (n=107). Five single nucleotide polymorphisms (SNPs) of the ROCK2 gene were selected. SNPs were genotyped by high-resolution melting. Linkage disequilibrium and haplotype analyses were performed using the SHEsis program. RESULTS: The prevalence of genotypes of the 5 interesting SNPs in patients with VA was not different from that in the control group. In haplotype analysis, the haplotype G-T-C-T-G (in order of rs978906, rs2271621, rs2230774, rs1515210, and rs3771106) was significantly associated with a decreased risk of VA (p=0.007). CONCLUSION: The haplotype G-T-C-T-G in the ROCK2 gene had a protective effect against VA, suggesting the involvement of ROCK2 in VA pathogenesis.
Coronary Angiography ; Coronary Vasospasm ; Coronary Vessels ; Ergonovine ; Freezing ; Genotype ; GTP Phosphohydrolases ; Haplotypes ; Humans ; Linkage Disequilibrium ; Muscle Spasticity ; Muscle, Smooth, Vascular ; Myosin Light Chains ; Phosphorylation ; Polymorphism, Single Nucleotide ; Prevalence ; rho-Associated Kinases ; RNA, Messenger ; Spasm

BACKGROUND: Three-dimensional (3D) echocardiography has been reported to be valuable for evaluating the geometry of cardiac chambers. We validated the accuracy of 3D transthoracic echocardiography for quantifying aortic root geometry in comparison with cardiac multi-detector computed tomography (MDCT). METHODS: Twenty-three patients who underwent cardiac MDCT and showed normal left ventricular ejection fraction (> 55%), as assessed by 2-dimensional transthoracic echocardiography, were enrolled (12 male, mean 53 +/- 9 years). We defined the aortic root volume as the volume from the aortic annulus to the sinotubular junction. The aortic root volume at end-diastole measured by both cardiac MDCT and 3D echocardiography was assessed. RESULTS: The cross-sectional area of the aortic root was asymmetric. At the annulus level, the cross-sectional area showed asymmetric triangle. From the aortic annulus to the most dilated point of the sinus of Valsalva, the asymmetric triangular shape was maintained. From the most dilated point of the sinus of Valsalva to the sinotubular junction, the cross-sectional shape of the aortic root changed to oval. The average aortic root volumes measured by 3D echocardiography (ARV-3DE) were 13.6 +/- 4.8 mL at end-diastole and 14.1 +/- 5.3 mL at end-systole, respectively. The average aortic root volume measured by MDCT at end-diastole (ARV-CT) was 14.1 +/- 5.7 mL. At end-diastole, the ARV-3DE correlated well with the ARV-CT (R2 = 0.926, difference = 0.5 +/- 1.7 mL), and the two methods were in excellent agreement (the percent difference was 0%). CONCLUSION: Our results demonstrate both the feasibility and accuracy of 3D echocardiography for the clinical assessment of the geometry of the aortic root.
Echocardiography ; Echocardiography, Three-Dimensional ; Humans ; Male ; Sinus of Valsalva ; Stroke Volume