Endoscopic retrograde cholangiopancreatography-related adverse events in Korea: A nationwide assessment.

BACKGROUND: Although endoscopic retrograde cholangiopancreatography (ERCP) is a pivotal procedure for the diagnosis and treatment of a variety of pancreatobiliary diseases, it has been known that the risk of procedure-related adverse events (AEs) is significant. OBJECTIVE: We conducted this nationwide cohort study since there have been few reports on the real-world data regarding ERCP-related AEs. METHODS: Patients who underwent ERCP were identified between 2012 and 2015 using Health Insurance Review and Assessment database generated by the Korea government. Incidence, annual trends, demographics, characteristics according to the types of procedures, and the risk factors of AEs were assessed. RESULTS: A total of 114,757 patients with male gender of 54.2% and the mean age of 65.0 ± 15.2 years were included. The most common indication was choledocholithiasis (49.4%) and the second malignant biliary obstruction (22.8%). Biliary drainage (33.9%) was the most commonly performed procedure, followed by endoscopic sphincterotomy (27.4%), and stone removal (22.0%). The overall incidence of ERCP-related AEs was 4.7% consisting of post-ERCP pancreatitis (PEP; 4.6%), perforation (0.06%), and hemorrhage (0.02%), which gradually increased from 2012 to 2015. According to the type of procedures, ERCP-related AEs developed the most commonly after pancreatic stent insertion (11.4%), followed by diagnostic ERCP (5.9%) and endoscopic sphincterotomy (5.7%). Younger age and diagnostic ERCP turned out to be independent risk factors of PEP. CONCLUSIONS: ERCP-related AEs developed the most commonly after pancreatic stent insertion, diagnostic ERCP and endoscopic sphincterotomy. Special caution should be used for young patients receiving diagnostic ERCP due to increased risk of PEP.

Evaluation of Estrogen Receptor Agonistic Activity of Medicinal Herbs Using Organization for Economic Cooperation and Development Transactivation Assay with Rat Liver S9 Fraction.

A number of studies employing different in vitro assays have demonstrated the estrogen-like activity of natural substances. All assays have their advantages and limitations as a screening tool. No single in vitro assay is considered ideal for predicting estrogenic action in a complex in vivo system. To assess agonistic activities of several medicinal herbs on the estrogen receptor (ER) and their metabolic alteration, the Organization for Economic Cooperation and Development (OECD) Performance-Based Test Guideline No. 455 in vitro assay was performed in this study using recombinant VM7Luc4E2 cells in combination with rat liver S9 fractions. Ethanol extracts of medicinal herbs showed binding affinities for ER-α and ER-ß at different levels. However, luciferase reporter assay using VM7Luc4E2 cells revealed that only two test extracts [Pueraria lobata root extract (PLE); Glycyrrhiza glabra root extract (GGE)] exhibited ER transcriptional activity when their activities were compared with the response by 17ß-estradiol. Importantly, incubation of PLE or GGE with rat liver S9 fractions increased their ER transcriptional activities, in particular when phase I metabolic enzymes were activated. Puerarin and glabridin were the most abundant isoflavones found in PLE and GGE, respectively. The present results demonstrate that PLE and GGE possess potential as ER agonists with their metabolic activation. This study also suggests that the application of OECD in vitro assay with rat liver S9 fraction is an efficient screening tool to evaluate estrogenic activities of natural substances.

Palliative endoscopic retrograde biliary drainage for malignant biliary obstruction in Korea: A nationwide assessment.

BACKGROUND: Malignant biliary obstruction (MBO) is usually caused by biliary tract cancer or pancreatic cancer. This study was performed to summarize the current situation regarding palliative endoscopic retrograde biliary drainage (ERBD) for MBO in Korea and to determine its clinical significance by analyzing representative nationwide data. METHODS: Patients that underwent palliative ERBD for MBO between 2012 and 2015 were identified using the Health Insurance Review and Assessment database, which covers the entire Korean population. We assessed clinical characteristics and complications and compared the clinical impacts of initial metal and plastic stenting in these patients. RESULTS: A total of 9,728 subjects (mean age, 65 ± 11.4 years; male, 61.4%) were identified and analyzed. The most common diagnosis was malignant neoplasm of liver and intrahepatic bile ducts (32.1%) and this was followed by extrahepatic or Ampulla of Vater cancer and pancreatic cancer. Initial plastic stent(s) placement was performed in 52.9% of the study subjects, and metal stent(s) placement was performed in 23.3%. The number of sessions of endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic biliary drainage (PTBD) was significantly higher in patients that underwent initial plastic stenting than in patients that underwent metal stenting (2.2 ± 1.7 vs 1.8 ± 1.4, P < 0.0001), but rates of post-ERCP pancreatitis, hospital days, and time to second ERCP or PTBD were not significantly different. CONCLUSION: This nationwide assessment study suggests that initial metal stenting is associated with fewer sessions of total ERCP or PTBD following the initial procedure, despite the preference for initial plastic stenting in Korea.

[Nutritional Assessment and Management for Patients with Chronic Liver Disease].

When liver disease is severe, the prognosis can be worse if the patient is malnourished. Adequate nutritional support for patients with liver diseases can improve the patient's condition and prognosis. In the case of liver cirrhosis, malnutrition can occur due to a variety of causes, including poor oral intake, maldigestion, malabsorption, associated renal disease, and metabolic abnormalities. For a nutritional assessment, it is important to check the dietary intake, change in body composition, including anthropometry, and a functional assessment of muscle. Counselling and oral or enteral nutrition is preferred over parenteral nutrition as in other diseases. If esophageal varices are present, care should be taken when installing a feeding tube, but if there are ascites, percutaneous endoscopic gastrostomy is contraindicated because of the risk of complications. Calories of 30-35 kcal/kg/day and protein from 1.2 to 1.5 g/kg/day are appropriate. Protein restriction is unnecessary unless the hepatic encephalopathy is severe. A late evening snack and branched chain amino acids can be helpful. In the case of cholestasis, the supply of manganese and copper should be restricted. Sarcopenia in patients with liver cirrhosis is also prevalent and associated with the prognosis.

Robust H∞ cost guaranteed integral sliding mode control for the synchronization problem of nonlinear tele-operation system with variable time-delay.

This paper is devoted to the synchronization problem of tele-operation systems with time-varying delay, disturbances, and uncertainty. Delay-dependent sufficient conditions for the existence of integral sliding surfaces are given in the form of Linear Matrix Inequalities (LMIs). This guarantees the global stability of the tele-operation system with known upper bounds of the time-varying delays. Unlike previous work, in this paper, the controller gains are designed but not chosen, which increases the degree of freedom of the design. Moreover, Wirtinger based integral inequality and reciprocally convex combination techniques used in the constructed Lypunove-Krasoviskii Functional (LKF) are deemed to give less conservative stability condition for the system. Furthermore, to relax the analysis from any assumptions regarding the dynamics of the environment and human operator forces, H∞ design method is used to involve the dynamics of these forces and ensure the stability of the system against these admissible forces in the H∞ sense. This design scheme combines the strong robustness of the sliding mode control with the H∞ design method for tele-operation systems which is coupled using state feedback controllers and inherit variable time-delays in their communication channels. Simulation examples are given to show the effectiveness of the proposed method.

Single-Molecule Investigations on Histone H2A-H2B Dynamics in the Nucleosome.

Nucleosomes impose physical barriers to DNA-templated processes, playing important roles in eukaryotic gene regulation. DNA is packaged into nucleosomes by histone proteins mainly through strong electrostatic interactions that can be modulated by various post-translational histone modifications. Investigating the dynamics of histone dissociation from the nucleosome and how it is altered upon histone modifications is important for understanding eukaryotic gene regulation mechanisms. In particular, histone H2A-H2B dimer displacement in the nucleosome is one of the most important and earliest steps of histone dissociation. Two conflicting hypotheses on the requirement for dimer displacement are that nucleosomal DNA needs to be unwrapped before a dimer can displace and that a dimer can displace without DNA unwrapping. In order to test the hypotheses, we employed three-color single-molecule FRET and monitored in a time-resolved manner the early kinetics of H2A-H2B dimer dissociation triggered by high salt concentration and by histone chaperone Nap1. The results reveal that dimer displacement requires DNA unwrapping in the vast majority of the nucleosomes in the salt-induced case, while dimer displacement precedes DNA unwrapping in >60% of the nucleosomes in the Nap1-mediated case. We also found that acetylation at histone H4K16 or H3K56 affects the kinetics of Nap1-mediated dimer dissociation and facilitates the process both kinetically and thermodynamically. On the basis of these results, we suggest a mechanism by which histone chaperone facilitates H2A-H2B dimer displacement from the histone core without requiring another factor to unwrap the nucleosomal DNA.

Photomechanical effect on Type I collagen using pulsed diode laser.

BACKGROUND: As the most abundant protein in human tissues, the use of collagen is essential in the fields of biological science and medicine. OBJECTIVE: The aim of this study is to investigate the mechanical effect of pulsed laser irradiation on collagen tissue. METHODS: With various laser parameters such as peak power, pulse width, and repetition rate, the induced stresses on samples were measured and analyzed. Monte Carlo simulation was performed to investigate the effect of laser parameters on the collagen sample. RESULTS: The results indicated that the magnitude of mechanical stress could be controlled by various laser parameters. CONCLUSIONS: This study can be used in biostimulation for therapy and mechanoreceptor stimulation for tactile application.

South Korean endoscopists' attitudes toward endoscopic ultrasound for the evaluation of gastrointestinal diseases.

BACKGROUND/AIMS: Despite the common use of endoscopic ultrasound (EUS) for various gastrointestinal diseases in Asia, little is known about Asian endoscopists' attitudes toward the practice. The aim of our study was to provide a profile of Korean endoscopists' attitudes toward EUS use. MATERIALS AND METHODS: Self-administered questionnaires were distributed to endoscopists who attended the 4th EndoFest symposium of the Korean Society of Gastrointestinal Endoscopy on March 24, 2012. We evaluated opinions on the need for EUS for assessing gastrointestinal diseases and the perceived barriers to widespread EUS use. RESULTS: Data from 214 (32.4%) responders were analyzed. Positive opinions (agree plus strongly agree) were given on the need for EUS in the evaluation of the following gastrointestinal diseases were: subepithelial tumor (94.9%), early esophageal cancer (88.8%), early gastric cancer (86%), pancreatic cancer (84.1%), early rectal cancer (83.6%), gallbladder polyp (73.4%), advanced esophageal cancer (47.7%), colon cancer (32.2%), advanced gastric cancer (31.8%), and advanced rectal cancer (28.5%). Significant differences were observed when they were asked about the need for EUS with respect to early versus advanced cancers of the esophagus, stomach, and rectum (all p<0.001). The most commonly cited barrier to widespread use of EUS was lack of experienced endosonographers (66.2%). CONCLUSION: This is the first study to assess Korean attitudes toward using EUS for evaluating gastrointestinal diseases. Korean endoscopists highly value the use of EUS in the evaluation of early esophageal, gastric, and rectal cancers, as well as subepithelial lesions.

Impedance Analysis Using High-resolution Impedance Manometry Facilitates Assessment of Pharyngeal Residue in Patients With Oropharyngeal Dysphagia.

BACKGROUND/AIMS: Impedance analysis using high-resolution impedance manometry (HRIM) enables the recognition of pharyngeal residue in patients with oropharyngeal dysphagia. The aims of this study were to evaluate appropriate criteria for impedance analysis in a large patient cohort, as well as the diagnostic accuracy and agreement of analysis performed by HRIM trainees. METHODS: We reviewed 33 controls (13 males; median age, 61.2 years) and 104 oropharyngeal dysphagia patients (61 males; median age, 70.4 years) who underwent a flexible endoscopic evaluation of swallowing study (FEES) and HRIM. Two experts compared the pharyngeal residue on FEES and impedance color pattern at 1,000, 1,500 and 2,000 Ω of the impedance bar. Three trainees were given a 60 minutes tutorial to determine the diagnostic accuracy and agreement of this analysis. RESULTS: The diagnostic sensitivity of experts for predicting liquid residue was 73.1% for 1,000 Ω, 96.2% for 1,500 Ω and 100% for 2,000 Ω. Significantly higher sensitivity was observed at 1,500 Ω compared to 1,000 Ω (P < 0.001). The diagnostic specificity of experts for liquid residue was 98.3% for 1,000 Ω, 96.6% for 1,500 Ω and 83.1% for 2,000 Ω. There was a higher specificity at 1,500 Ω compared to 2,000 Ω (P = 0.008). The κ value among the 3 trainees was 0.89 and the diagnostic accuracy of the trainees for liquid residue was comparable to that of the experts. CONCLUSIONS: The impedance analysis at 1,500 Ω provides more accurate information for the detection of liquid residue, irrespective of the level of expertise.

Comparison of international guidelines of dermal absorption tests used in pesticides exposure assessment for operators.

The number of farmers who have suffered from non-fatal acute pesticide poisoning has been reported to vary from 5.7% to 86.7% in South Korea since 1975. Absorption through the skin is the main route of exposure to pesticides for farmers who operate with them. Several in vitro tests using the skins of humans or animal and in vivo tests using laboratory animals are introduced for the assessment of human dermal absorption level of pesticides. The objective of this study is to evaluate and compare international guidelines and strategies of dermal absorption assessments and to propose unique approaches for applications into pesticide registration process in our situation. Until present in our situation, pesticide exposure level to operator is determined just using default value of 10 as for skin absorption ratio because of data shortage. Dermal absorption tests are requested to get exposure level of pesticides and to ultimately know the safety of pesticides for operators through the comparison with the value of AOEL. When the exposure level is higher than AOEL, the pesticide cannot be approved. We reviewed the skin absorption test guidelines recommended by OECD, EFSA and EPA. The EPA recommends assessment of skin absorption of pesticides for humans through the TPA which includes all the results of in vitro human and animal and animal in vivo skin absorption studies. OECD and EFSA, employ a tiered approach, which the requirement of further study depends on the results of the former stage study. OECD guidelines accept the analysis of pesticide level absorbed through skin without radioisotope when the recovery using the non-labeled method is within 80~120%. Various factors are reviewed in this study, including the origin of skin (gender, animal species and sites of skin), thickness, temperature and, etc., which can influence the integrity of results.

Extracting kinetics information from single-molecule fluorescence resonance energy transfer data using hidden markov models.

Hidden Markov models (HMM) have been proposed as a method of analysis for noisy single-molecule fluorescence resonance energy transfer (SM FRET) data. However, there are practical and fundamental limits in applying HMM to SM FRET data due to the short photobleaching lifetimes of fluorophores and the limited time resolution of detection devices. The fast photobleaching fluorophores yield short SM FRET time traces, and the limited detection time resolution generates abnormal FRET values, which result in systematic underestimation of kinetic rates. In this work, a HMM algorithm is implemented to optimize one set of HMM parameters with multiple short SM FRET traces. The FRET efficiency distribution function for the HMM optimization was modified to accommodate the abnormal FRET values resulting from limited detection time resolution. Computer simulations reveal that one set of HMM parameters is optimized successfully using multiple short SM FRET traces and that the degree of the kinetic rate underestimation is reduced by using the proposed modified FRET efficiency distribution. In conclusion, it is demonstrated that HMM can be used to reproducibly analyze short SM FRET time traces.