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Background and aims: This study aimed to evaluate whether the use of antiplatelet agents increases the risk of bleeding after gastric endoscopic submucosal dissection (ESD) and to determine the appropriate time to discontinue antiplatelet agents to minimize complications. Methods: This retrospective observational study utilized a collected dataset of patients who underwent ESD for gastric adenoma and cancer between January 2010 and December 2020. Patients were classified into three groups according to antiplatelet agent use and discontinuation status. We investigated the risk of post-ESD bleeding with different interruption times and antiplatelet agent types. Results: Of 1879 patients, 1389 were non-users, 190 were in the continuous group, and 203 were in the interrupted group. The rates of overall and delayed bleeding were significantly higher in patients who continued or were interrupted within three days before ESD than in the non-users and interrupted group (6.3% vs. 1.2%, p < 0.001, 6.3% vs. 2.5%, p = 0.01, respectively). Significant differences in delayed bleeding between the continuous and interrupted groups decreased with longer cessation periods. In multivariate analysis, continuous antiplatelet agents were still the strongest risk factor for bleeding (OR 2.81, 95% CI 1.14–6.90). Lower third location and longer procedure times were also independent risk factors for post-ESD bleeding (OR 2.75; 95% CI 1.08–6.97; OR 1.02; 95% CI 1.01–1.02). Conclusion: Continuous antiplatelet agent use increases the risk of delayed bleeding after gastric ESD. Therefore, the optimal timing of interruption, rather than the type of antiplatelet agent, should be considered to avoid an additional risk of bleeding and thromboembolism. [ABSTRACT FROM AUTHOR]

Background/Aims: A high-fat diet (HFD) can cause intestinal inflammation and alter the gut microbiota; probiotics, however, are known to have anti-inflammatory effects. This study aimed to investigate the response of rat colon to HFD and the effect of Clostridium butyricum on HFD-induced intestinal inflammation and production of short-chain fatty acids (SCFAs) according to sex. Methods: Male and female 6-week-old Fischer-344 rats were fed a chow diet or HFD for 8 weeks, and Biovita or three different concentrations of C. butyricum were orally gavaged. The levels of tight junction proteins (TJPs), inflammatory markers in the ascending colonic mucosa, and bile acids (BAs) and SCFAs in stool were measured. Results: HFD significantly increased the histological inflammation scores and fat proportions. Fecal BA levels were higher in the HFD group than in the control group, with a more prominent increase in deoxycholic acid/cholic acid after probiotics administration in females; however, no statistically significant differences were observed. TJPs showed an opposite response to HFD depending on sex, and tended to increase and decrease after HFD in males and females, respectively. The HFD-reduced TJPs were recovered by probiotics, with some statistical significance in females. HFD-decreased butyric acid in stools appeared to be recovered by probiotics in males, but not in females. The expression of inflammatory markers (TNF-α) was increased by HFD in males and decreased with medium-concentration probiotic supplementation. The opposite was observed in females. MPO was increased by HFD in both sexes and decreased by probiotic supplementation. Conclusions: The probiotic C. butyricum improved indicators of HFD-induced colonic inflammation such as levels of inflammatory markers and increased the production of SCFAs and the expression of TJPs. These effects tended to be more pronounced in male rats, showing sex difference. [ABSTRACT FROM AUTHOR]

Background: Failure of Helicobacter pylori (H. pylori) eradication is principally caused by antimicrobial resistance. Nowadays, multidrug resistance could be a major determinant of eradication failure. To assess minimal inhibitory concentration (MIC), antimicrobial resistance rates and trends in H. pylori isolated from patients with upper gastrointestinal disease with long‐term period. Materials and Methods: Patients who had H. pylori colonies isolated from culture were consecutively enrolled during the period of 2003–2022. From each patient, one to ten isolates were collected from culture of mucosal biopsy. MIC test was performed for amoxicillin, clarithromycin, metronidazole, tetracycline, levofloxacin, and moxifloxacin using agar dilution method. Trends in MIC distribution, prevalence of resistances with single and multiple were investigated which were suspected to be related to the failure of empirical H. pylori eradication treatment. Results: From 2003 to 2022, a total of 873 patients were enrolled and 2735 H. pylori isolates were successfully collected. Increase in the primary resistance rate was found in clarithromycin (16.1%–31.0%, p =.022), metronidazole (30.6%–38.1%, p < 0.001), and both of levofloxacin and moxifloxacin (7.3%–35.7%, p < 0.001). The prevalence of multidrug resistance to both clarithromycin and metronidazole (9.2%–37.9%, p < 0.001), clarithromycin and fluoroquinolone (2.8%–41.7%, p < 0.001), and clarithromycin, metronidazole, and fluoroquinolone (1.4%–28.2%, p < 0.001) was found to significantly increase. Conclusions: The prevalence of multiple resistance against H. pylori in Korea is ongoing. Its trend should be considered when establishing an empirical treatment strategy (ClinicalTrials. gov: NCT05247112). [ABSTRACT FROM AUTHOR]

Although lactose-free dairy products for the clinical management of lactose intolerance (LI) are widely available, scientific evidence on their efficacy is still lacking. This study comparatively analyzed the efficacy of flavored lactose-free milk (LFM) and whole milk (WM) in reducing symptoms in South Korean adults with LI. This prospective study was conducted in adults suspected of LI. All screened participants underwent the hydrogen breath test (HBT) using 570 mL of chocolate-flavored WM (20 g of lactose) and responded to a symptom questionnaire. LI was confirmed when the ΔH2 peak exceeded 16 ppm above baseline values and with the occurrence of symptoms after WM consumption. The participants who were diagnosed with LI underwent the HBT again with 570 mL of chocolate-flavored LFM (0 g of lactose), followed by the symptom questionnaire survey after 1 week. After excluding 40 participants who did not meet the diagnostic criteria for LI and 2 who were lost to follow-up, a total of 28 lactose-intolerant individuals were enrolled in the study. The ΔH2 values in the first HBT were significantly higher than those in the second HBT (33.3 ± 21.6 ppm vs. 8.6 ± 6.3 ppm, P < .001). Similarly, there was a significant reduction in the total symptom score in the second HBT (4.18 ± 1.51 vs. 0.61 ± 0.98, P < .001). Flavored LFM is well tolerated in South Korean adults diagnosed with LI based on the HBT and symptom questionnaire results. Therefore, LFM may be a viable alternative to WM. [ABSTRACT FROM AUTHOR]

Background: During treatment for peptic ulcer bleeding (PUB), it is imperative to determine the effect of antiplatelet agents on recurrent bleeding in order to balance risks and benefits.Aims: We compared the rate of recurrent bleeding in antiplatelet users and non-users.Methods: This retrospective study analyzed prospectively collected data from PUB patients treated by endoscopic modalities between August 2007 and December 2014. We evaluated and compared the rate of recurrent bleeding within 30 days in antiplatelet users and non-users; we also categorized antiplatelet users into continuation (≤3 days) and withdrawal (>3 days) groups.Results: A total of 490 patients were enrolled in the study, 302 (61.6 %) and 188 (38.4 %) in the non-user and antiplatelet user groups, respectively. The recurrent bleeding rate among antiplatelet users (10.1 %) was significantly higher than that among non-users (5.0 %; p = 0.029). Among 188 antiplatelet users, 51 (27.1 %) and 137 (72.9 %) were assigned to the continuation and withdrawal groups, respectively. The rate of recurrent bleeding did not differ significantly between groups (11.7 vs. 5.9 %, p = 0.241). Multivariate analysis revealed chronic kidney disease as a risk factor [odds ratio (OR) 2.890, 95 % confidence interval (CI) 1.079-7.742, p = 0.035]. However, antiplatelet use (OR 1.691, 95 % CI 0.813-3.517, p = 0.160) was not.Conclusions: This study highlights the need for clinicians to consider underlying diseases in antiplatelet users under the appropriate antiplatelet therapy during the post-hemostasis period. Furthermore, the optimal time to resume antiplatelet agents may be 3 days after successful endoscopic hemostasis in patients with PUB. [ABSTRACT FROM AUTHOR]

Background: The platelet-to-white blood cell ratio (PWR) is a hematologic marker of the systemic inflammatory response. Recently, the PWR was revealed to have a role as an independent prognostic factor for mortality in patients with hepatitis B virus (HBV)-related acute-on-chronic failure (ACLF) and HBV-related liver cirrhosis (LC) with acute decompensation (AD). However, the prognostic role of the PWR still needs to be investigated in LC patients with AD. In this study, we analyzed whether the PWR could stratify the risk of adverse outcomes (death or liver transplantation (LT)) in these patients. Methods: A prospective cohort of 1670 patients with AD of liver cirrhosis ((age: 55.2 ± 7.8, male = 1226 (73.4%)) was enrolled and evaluated for 28-day and overall adverse outcomes. Results: During a median follow-up of 8.0 months (range, 1.9–15.5 months), 424 (25.4%) patients had adverse outcomes (death = 377, LT = 47). The most common etiology of LC was alcohol use (69.7%). The adverse outcome rate was higher for patients with a PWR ≤ 12.1 than for those with a PWR > 12.1. A lower PWR level was a prognostic factor for 28-day adverse outcomes (PWR: hazard ratio 1.707, p = 0.034) when adjusted for the etiology of cirrhosis, infection, ACLF, and the MELD score. In the subgroup analysis, the PWR level stratified the risk of 28-day adverse outcomes regardless of the presence of ACLF or the main form of AD but not for those with bacterial infection. Conclusions: A lower PWR level was associated with 28-day adverse outcomes, indicating that the PWR level can be a useful and simple tool for stratifying the risk of 28-day adverse outcomes in LC patients with AD. [ABSTRACT FROM AUTHOR]

Background: The eradication rate of clarithromycin-based standard triple therapy (STT) for Helicobacter pylori infection has decreased due to clarithromycin resistance (CR). We evaluated the cost-effectiveness of tailored therapy according to CR test results, and compared the results of STT with those of empirical bismuth quadruple therapy (BQT). Methods: The prospectively collected data of 490 H. pylori-positive patients with chronic gastritis or peptic ulcer disease were retrospectively analyzed. Among them, 292 patients underwent CR testing using dual-priming oligonucleotide-based polymerase chain reaction. The tailored group (n = 292) consisted of patients treated with STT for 7 days and BQT for 10 days as per their CR test results. The remaining patients were assigned to the empirical group (n = 198) and received BQT for 10 days without a CR test. The eradication rate, adverse events and medical costs associated with H. pylori eradication therapy were investigated. Results: In the tested patients (tailored group), the CR-positive rate was 32.2% (n = 94/292). The eradication rate according to an intention-to-treat analysis was 87.7% in the tailored group and 91.8% in the empirical group (P = 0.124); the respective rates were 94.4% and 97.9% by per-protocol analysis (P = 0.010). The frequency of adverse events was lower in the empirical group than the tailored group (35.1% vs. 52.7%, P < 0.001). Total per capita medical costs were $406.50 and $503.50, respectively. Conclusions: Ten-day empirical BQT was more effective, safer, and less expensive than tailored therapy based on a CR test for H. pylori eradication. [ABSTRACT FROM AUTHOR]

Background: Undifferentiated-type early gastric cancer (UD EGC) shows lower curative resection rates after endoscopic submucosal dissection (ESD). Additional surgery is recommended after non-curative resection. We evaluated the long-term outcomes of ESD followed by additional surgery after non-curative resection in UD EGC compared to those for surgery as initial treatment. Methods: We reviewed 1139 UD EGC patients who underwent ESD at 18 hospitals and 1956 patients who underwent surgery at two hospitals between February 2005 and May 2015. We enrolled 636 patients with non-curative ESD and 1429 surgery subjects beyond the curative ESD criteria. Among them, 133 patients with additional surgery after ESD (ESD + OP group) and 252 patients without additional surgery (ESD-only group) were matched 1:1 using propensity scores to patients with surgery as initial treatment (surgery group). Overall survival (OS) and recurrence-free survival (RFS) were compared. Results: Signet ring cell carcinoma and poorly differentiated adenocarcinoma (PDA) were observed in 939 and 1126 cases, respectively. OS was significantly longer in the surgery group than in the ESD + OP group, especially for PDA. However, RFS was shorter in the ESD-only group than those in the ESD + OP and surgery groups. RFS did not differ significantly between the ESD + OP and surgery groups. Compared to the surgery group, the ESD-only and ESD + OP groups had an overall hazard ratio for RFS of 3.58 (95% confidence interval 1.44–8.88) and 0.46 (0.10–2.20), respectively. Conclusions: ESD followed by additional surgery after non-curative resection showed comparable cancer-specific outcomes to initial surgery in UD EGC. [ABSTRACT FROM AUTHOR]

Background and Aim: Besifovir dipivoxil maleate (BSV) was reported to have comparable antiviral efficacy and superior renal and bone safety to tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients. The present study aims to evaluate changes of liver histology and intrahepatic covalently closed circular DNA (cccDNA) levels by BSV treatment in comparison with TDF therapy. Methods: This is a subset study of the phase 3 trial comparing BSV with TDF. Among them, only CHB patients willing to participate in a histologic evaluation study were enrolled. Liver histologic examination and intrahepatic cccDNA quantification were performed. Results: A total of 46 CHB patients received liver biopsies (BSV, n = 29; TDF, n = 17). After 48 weeks of treatment, virological response rate was comparable between the groups (P = 0.707). Follow‐up liver biopsies showed that necroinflammation was significantly improved in the both groups. However, the histological response rate defined as the proportion of subjects whose modified histologic activity index score decreased by ≥ 2 without deterioration in fibrosis was higher in the BSV group than in the TDF group (77.8% vs 36.4%, P = 0.048). The proportion of subjects with Ishak fibrosis score 3 or more decreased from 77.7% to 55.5% in the BSV and that decreased from 72.7% to 45.4% in the TDF group. The intrahepatic cccDNA significantly decreased from baseline after 48 weeks of BSV or TDF treatment (P < 0.001) without intergroup differences (P = 0.349). Conclusions: The BSV therapy improves hepatic histology and decreases intrahepatic cccDNA in CHB patients. [ABSTRACT FROM AUTHOR]

Background: Endoscopic submucosal dissection (ESD) is an effective treatment for early gastric cancer (EGC); however, its curative resection rate is low for undifferentiated-type EGC. We developed and externally validated a prediction model for curative ESD of undifferentiated-type EGC. Methods: In this cross-sectional study, we included 448 patients who underwent ESD for undifferentiated-type EGC at 18 hospitals in Korea between 2005 and 2015 in the development cohort and 1342 patients who underwent surgery at two hospitals in the validation cohort. A prediction model was developed using the logistic regression model. Results: Endoscopic tumor size 1–2 cm (odds ratio [OR], 2.40; 95% confidence interval [CI] 1.54–3.73), tumor size > 2 cm (OR, 14.00; 95% CI 6.81–28.77), and proximal tumor location from the lower to upper third of the stomach (OR, 1.45; 95% CI 1.03–2.04) were independent predictors of non-curative ESD. A six-score prediction model was developed by assigning points to endoscopic tumor size > 2 cm (five points), tumor size 1–2 cm (two points), upper third location (two points), and middle third location (one point). The rate of curative ESD ranged from 70.6% (score 0) to 11.6% (score 5) with an area under the receiver operating characteristic curve (AUC) of 0.720 (95% CI 0.673–0.766). The model also showed good performance in the validation cohort (AUC, 0.775; 95% CI 0.748–0.803). Conclusions: This six-score prediction model may help in predicting curative ESD and making informed decisions about the treatment selection between ESD and surgery for undifferentiated-type EGC. [ABSTRACT FROM AUTHOR]

OBJECTIVES:There are few data on cold snare polypectomy (CSP) in direct comparison with cold forceps polypectomy (CFP) for colonoscopic resection of diminutive colorectal polyps (DCPs; ≤5 mm). The primary aim of this study was to compare the histologic polyp eradication rate of CSP with that of CFP using double-biopsy technique.METHODS:This was a randomized controlled trial at a single academic hospital. Of the 165 patients invited, 54 consecutive patients having 117 eligible polyps were enrolled in this study. To evaluate histologic eradication of polyps, two or more additional biopsies were taken from the base and edges of the polypectomy site.RESULTS:The mean size of polyps was 3.66 mm (±1.13). Most polyps evaluated were tubular adenomas (69.9%). The rate of histologic eradication was significantly higher in the CSP group than in the CFP group (93.2% vs. 75.9%, P=0.009). The time taken for polypectomy was significantly shorter in the CSP group (14.29 vs. 22.03 s, P<0.001). Failure of tissue retrieval was noted in 6.8% of polyps resected by CSP. Multivariate analysis revealed that the method of polypectomy (CFP) and the polyp size (≥4 mm) were independent predictors associated with incomplete histologic eradication (odds ratio (OR) 4.750 (95% confidence interval (CI): 1.459-15.466), OR 4.375 (95% CI: 1.345-14.235); all P<0.05, respectively).CONCLUSIONS:CSP is superior to CFP for the endoscopic removal of DCPs with regard to completeness of polypectomy. CSP technique should be considered the primary method for endoscopic treatment of polyps in the 4-5-mm size range (ClinicalTrials.gov number: NCT01646242). [ABSTRACT FROM AUTHOR]

We prospectively investigated the changes of liver stiffness (LS) and the occurrence of hepatocellular carcinoma (HCC) after hepatitis C virus (HCV) eradication using direct antiviral agents (DAA) over three years. LS measurement using transient elastography and serum fibrosis surrogate markers before treatment and at 48, 96, 144 weeks after starting direct-acting antivirals (DAA) according to the protocol were evaluated. Patients were also compared with historical cohort treated with pegylated interferon (peg-IFN). Sustained viral response (SVR) was observed in 95.8%. LS value in the patients achieving SVR significantly decreased over time (19.4 ± 12.9 kPa [baseline], 13.9 ± 9.1 kPa [48 weeks], 11.7 ± 8.2 kPa [96 weeks], 10.09 ± 6.23 [144 weeks], all p < 0.001). With matched analysis, the decrease in LS value was significantly larger in DAA group than peg-IFN group at both 48 weeks (29% vs. 9%) and 96 weeks (39% vs. 17%). The incidence of HCC was not significantly different between DAA and peg-IFN groups (5.5% vs. 5.4%) at 144 weeks. HCV eradication with DAA can lead to improvement of liver stiffness over time. The regression of fibrosis was greater in the group with DAA than peg-IFN. Clinical trials registration: ClinicalTrials.gov (NCT02865369). [ABSTRACT FROM AUTHOR]

Background and Aim Common endoscopic findings in stomachs with Helicobacter pylori infections include antral nodularity, thickened gastric folds, and visible submucosal vessels. These findings are suggestive but not diagnostic of H. pylori infection. Magnifying endoscopy can reveal more precisely the abnormal mucosal patterns in an H. pylori-infected stomach; however, it requires more training, expertise, and time. We aimed to establish a new classification for predicting H. pylori-infected stomachs by non-magnifying standard endoscopy alone. Methods A total of 617 participants who underwent gastroscopy were prospectively enrolled from August 2011 to January 2012. We performed a careful close-up examination of the corpus at the greater curvature maintaining a distance ≤ 10 mm between the endoscope tip and the mucosal surface. We classified gastric mucosal patterns into four categories: normal regular arrangement of collecting venules (numerous minute red dots), mosaic-like appearance (type A; swollen areae gastricae or snakeskin appearance), diffuse homogenous redness (type B), and untypical pattern (type C; irregular redness with groove) to predict H. pylori infection status. Results The frequencies of H. pylori infection in patients with a normal regular arrangement of collecting venules pattern and types A, B, and C patterns were 9.4%, 87.7%, 98.1%, and 90.9%, respectively. The sensitivity, specificity, and positive and negative predictive values of all abnormal patterns for prediction of H. pylori infection were 93.3%, 89.1%, 92.3%, and 90.6%, respectively. The overall accuracy was 91.6%. Conclusions Careful close-up observation of the gastric mucosal pattern with standard endoscopy can predict H. pylori infection status. [ABSTRACT FROM AUTHOR]

This paper deals with design and operating tests of prototype hybrid superconducting fault current limiter (SFCL) which is series connected non-inductive solenoid resistive coil and asymmetric non-inductively wound coils. The role of resistive SFCL is for reducing the fault current in the first swing. Moreover, resistive SFCL can reduce a load of dielectric strength in hybrid SFCL. Two kinds of high temperature superconductor (HTS) wires were used to fabricate asymmetric HTS coil. These HTS wires had different quench characteristics such as different critical current and n-value. Unbalanced current distribution between two HTS wires in the asymmetric HTS coil during the fault should occur. Thus, the asymmetric HTS coil generates impedance and repulsive force from magnetic flux. The finite element method was performed to calculate maximum repulsive force. From experimental tests and FEM simulation results, proper combination of HTS wires and configuration of asymmetric HTS coil with fast switch were determined to increase maximum repulsive force. Also, the prototype hybrid SFCL with fast switch was fabricated and performed. [ABSTRACT FROM PUBLISHER]

Uncertainty and complexity due to expanded adoption of renewable energy resources, distributed energy resources as well as expanded electric transportation and dynamic demand response technologies in the power industry present significant challenges in grid operations. It is thus required to develop smart protection and control actions for ensuring highly reliable and healthy electric power infrastructure by increasing resiliency against component failures or natural disasters, i.e. self-healing ability. This paper, in particular focuses on the self-healing in the context of grid protection using smart superconducting fault current controller (Smart FCC). A systematic framework and technological requirements are presented for realizing the envisioned self-healing protection capability using Smart FCC while minimizing the electric loss near zero through superconducting coil. Illustrative examples, modeling and simulation studies demonstrate the validity and efficacy of the proposed framework and envisioned technology. [ABSTRACT FROM PUBLISHER]

Abstract: For the design of superconducting fault current limiter, the research about recovery time and AC loss is essential issue because this characteristic is closely related to stability and efficiency. In general, superconducting fault current limiter (SFCL) modules can be made into pancake or solenoid type coil. While the pancake type coil has smaller AC loss, it has longer recovery time compared with the solenoid type coil. In this paper, a new pancake type coil was proposed to decrease recovery time by improving their cryogenic condition. A new pancake type coil is made with spacers between adjacent superconducting tapes. However, as the thickness of the spacer was increased, the AC loss was increased unlike the recovery characteristic. From the experimental results, our group confirmed that the pancake type coil with the spacer has trade-off relationship between AC loss and recovery characteristics with the spacer thickness. The proposed results in this paper would be utilized to design superconducting fault current limiters. [Copyright &y& Elsevier]

The initial neutral beam heating experiment in Versatile Experiment Spherical Torus (VEST) has been conducted via neutral beam characterizations such as neutralization efficiency, beam fraction, and shine-through loss. For the neutralization efficiency and shine-through loss estimation, a secondary electron emission (SEE) detector, which can be used in rapidly changing plasma, has been developed. The measurement results of the monatomic fraction by Doppler shift spectroscopy and the neutralization efficiency by SEE detector are 65%, and 70%, respectively. The shine-through loss measurement shows that the injection of a 12 keV neutral beam into a typical ohmic discharge of VEST results in a large amount of shine-through loss. To reduce the shine-through loss, a new target plasma discharge (0.17 T, 120 kA, 13 ms) with increased plasma density of ~ 2 × 10 19 m − 3 is developed by providing additional gas injection. The electron-heating effect has been successfully observed for this target plasma with a 200 kW neutral beam injection at the beam energy of 12 keV. The electron temperature increases from 20 to 68 eV without significant density change when the neutral beam is injected. [ABSTRACT FROM AUTHOR]

Background: Failure of second or third‐line eradication treatment against Helicobacter pylori (H. pylori) is principally caused by antimicrobial resistance and reduced treatment adherence. Aims: To evaluate the efficacy and safety of culture‐based rescue eradication treatments in patients who have previously experienced failed eradication treatment. Methods: Patients who had persistent H. pylori infection following at least one eradication treatment were recommended to undergo culture analysis to determine the minimal inhibitory concentrations of various antimicrobials via endoscopic resection. Consenting patients were assigned one of four therapeutic treatments based on an algorithm determined by antimicrobial resistance. These treatments consisted of 7 or 14‐day administration of clarithromycin‐containing proton pump inhibitor (PPI) triple therapy; esomeprazole, moxifloxacin, and amoxicillin (MEA) therapy; esomeprazole, bismuth, metronidazole, and tetracycline (quadruple) therapy; or lansoprazole, rifabutin, and amoxicillin (RLA) therapy. Eradication efficacy, adherence, and adverse events were assessed aside clinical outcomes. Results: A total of 132 patients were enrolled, with 84 patients completing the study. The overall resistance rates to amoxicillin, clarithromycin, metronidazole, and moxifloxacin were 13.1%, 83.3%, 47.6%, and 71.4%, respectively. The patients were allocated to the PPI triple (n = 11), MEA (n = 15), quadruple (n = 53), or RLA triple (n = 5) therapy group. The eradication rates in the intention‐to‐treat and per‐protocol analyses were 90.5% (76 of 84 patients) and 93.8% (76 of 81 patients), respectively. Nausea was the most frequent adverse event (25.0%). Conclusions: As a rescue therapy, culture‐based susceptibility‐guided eradication treatment was both effective and safe, even for patients exhibiting high antimicrobial resistance. [ABSTRACT FROM AUTHOR]

Background/aim: We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at an academic hospital in Korea. Exosomes were extracted from serum samples, followed by next-generation sequencing (NGS) of miRNAs and targeted real-time quantitative polymerase chain reaction. A model was derived to discriminate advanced fibrosis based on miRNA levels and the performance of this model was evaluated. Validation of the effect of miRNA on liver fibrosis in vitro was followed. Results: NGS data revealed that exosomal miR-660-5p, miR-125a-5p, and miR-122 expression were changed significantly with the progression of liver fibrosis, of which miR-122 exhibited high read counts enough to be used as a biomarker. The level of exosomal miR-122 decreased as the pathologic fibrosis grade progressed and patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P < 0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis especially in combination with fibrosis-4 score and transient elastography. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker was greatly improved. Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of various fibrosis related proteins. Conclusion: Exosomal miR-122 may serve as a useful non-invasive biomarker for liver fibrosis, especially in patients with non-viral etiologies of chronic liver disease. [ABSTRACT FROM AUTHOR]

Antiviral therapy improves survival in patients with hepatitis B virus (HBV)‐induced hepatocellular carcinoma (HCC). However, the effect of antiviral therapy in patients with low‐level viremia HBV‐HCC receiving non‐curative therapy remains unclear. We aimed to evaluate the role of antiviral therapy in patients with low‐level viremia and treated with transarterial chemoembolization (TACE). This retrospective study evaluated 206 patients with HBV‐HCC who underwent TACE as an initial treatment. Of those, 135 patients received antiviral therapy (antiviral group), and 71 did not (non‐antiviral group). The definition of low‐level viremia was an HBV DNA level <2000 IU/ml. Kaplan‐Meier curves, log‐rank tests and Cox regression analysis were used for statistical analyses. The median follow‐up duration was 39 months (1–174 months). Overall survival (OS) did not differ between groups (P =.227). Barcelona Clinic Liver Cancer stage (BCLC), Child‐Pugh (CP) class and α‐fetoprotein level were independent prognostic factors for OS. Antiviral therapy (hazard ratio [HR], 0.503, P =.022) was a prognostic factor for 2‐year survival. On subgroup analysis, antiviral therapy improved short‐term survival in patients with BCLC stage 0 and A (P =.037) and CP class A (P =.04). In patients with low‐level viremia, antiviral therapy yielded short‐term survival benefits, particularly in patients with early‐stage HCC. [ABSTRACT FROM AUTHOR]

Background: Patients with liver cirrhosis have an increased risk of in-hospital mortality or postoperative complication after surgery. However, large-scale studies on the prognosis of these patients after surgery are lacking. The aim of the study was to investigate the adverse outcomes of patients with liver cirrhosis after surgery over five years. Methods and findings: We used the Health Insurance Review and Assessment Service-National Inpatient Samples (HIRA-NIS) between 2012 and 2016. In-hospital mortality and hospital stay were analyzed using the data. Mortality rates according to the surgical department were also analyzed. Of the 1,662,887 patients who underwent surgery, 16,174 (1.0%) patients had cirrhosis. The in-hospital mortality (8.0% vs. 1.0%) and postoperative complications such as respiratory (6.0% vs. 5.3%) or infections (2.8% vs. 2.4%) was significantly higher in patients with cirrhosis than in those without cirrhosis. In addition, the total hospitalization period and use of the intensive care unit were significantly higher in patients with liver cirrhosis. In propensity score matching analysis, liver cirrhosis increased the risk of adverse outcome significantly [adjusted OR (aOR) 1.67, 95% CI 1.56–1.79, P<0.001], especially in-hospital mortality. In liver cirrhosis group, presence of decompensation or varices showed significantly increased postoperative complication or mortality. Adverse outcomes in patients with cirrhosis was the highest in patients who underwent otorhinolaryngology surgery (aOR 1.86), followed by neurosurgery (aOR 1.72), thoracic and cardiovascular surgery (aOR 1.56), and plastic surgery (aOR 1.36). Conclusion: The adverse outcomes of patients with cirrhosis is significantly high after surgery, despite advances in cirrhosis treatment. [ABSTRACT FROM AUTHOR]

Aging is associated with widespread physiological changes, including skeletal muscle weakening, neuron system degeneration, hair loss, and skin wrinkling. Previous studies have identified numerous molecular biomarkers involved in these changes, but their regulatory mechanisms and functional repercussions remain elusive. In this study, we conducted next-generation sequencing of DNA methylation and RNA sequencing of blood samples from 51 healthy adults between 20 and 74 years of age and identified aging-related epigenetic and transcriptomic biomarkers. We also identified candidate molecular targets that can reversely regulate the transcriptomic biomarkers of aging by reconstructing a gene regulatory network model and performing signal flow analysis. For validation, we screened public experimental data including gene expression profiles in response to thousands of chemical perturbagens. Despite insufficient data on the binding targets of perturbagens and their modes of action, curcumin, which reversely regulated the biomarkers in the experimental dataset, was found to bind and inhibit JUN, which was identified as a candidate target via signal flow analysis. Collectively, our results demonstrate the utility of a network model for integrative analysis of omics data, which can help elucidate inter-omics regulatory mechanisms and develop therapeutic strategies against aging. [ABSTRACT FROM AUTHOR]

Background and aims: Endoscopic submucosal dissection (ESD) for undifferentiated early gastric cancer (UD EGC) has debate due to the risk of lymph node metastasis. We investigated the outcomes of ESD compared to those of surgery for the UD EGC within expanded indication. Methods: We reviewed 971 UD EGC patients performed ESD across 18 hospitals in Korea and 1812 patients who underwent surgical resection in two hospitals between February 2005 and May 2015. Of these cases, we enrolled a curative resected ESD group of 328 patients and surgery group of 383 cases within an expanded indication. Overall outcomes and one-to-one propensity score-matched (218 ESD group vs 218 surgery group cases) outcomes for these two groups were analyzed. Results: Over the 75.6 month median follow-up period for the 711 enrolled cases, recurrences occurred in 22 patients (6.7%) in the ESD group but not in the surgery group. Overall survival (OS) was higher in the surgery group (p = 0.0316) in all cases, but there was no significant difference after propensity score matching (p = 0.069). According to the histologic type in propensity score matching, the OS of signet ring cell carcinoma and poorly differentiated carcinoma patients did not differ between the ESD and surgery groups (p = 0.1189 and p = 0.3087, respectively). In the surgery group involving expanded criteria, lymph node metastasis was found in six cases (1.56%). Conclusions: Although ESD shows comparable outcomes to surgery for the UD EGC within expanded indications, appropriate patient selection is needed for the ESD due to the possibility of lymph node metastasis. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2 cm as the only non-curative factor. Methods: From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2 cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59 months for recurrence and 90 months for overall survival. Results: Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5- and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. Conclusion: The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2 cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status. [ABSTRACT FROM AUTHOR]

Background and Aims: Sorafenib is a proven first-line treatment recommended for hepatocellular carcinoma (HCC) patients with portal vein invasion (PVI). However, multiple treatment modalities are used in clinical practice as a first-line option. This study is a prospective, observational, multicenter, cohort study evaluating patterns of treatment modalities and outcomes for HCC patients with PVI. Methods: The baseline characteristics, treatment modalities, and outcomes were prospectively collected for 287 newly diagnosed HCC patients with PVI between August 2015 and July 2016 from 16 sites in Korea. Results: During a median 7.8 months of follow-up (range 0.3–24.6 months), mortality was observed in 123 (42.9%) patients. Decision tree analysis classified patients into five subgroups with different outcomes. The patterns of treatment were very heterogeneous, and there was no dominant treatment modality. The most commonly used treatment modality was transarterial chemoembolization (TACE) (20.2%) followed by TACE plus external beam radiation therapy (17.8%) and sorafenib (12.5%). When stratified according to the extent of PVI, sorafenib treatment showed comparable outcomes when the PVI extent was lobal or main/bilateral, yet showed worse outcomes when the PVI extent was limited to the segmental level compared to those who received treatment other than sorafenib. Conclusions: HCC patients with PVI comprise a heterogeneous population and are treated with various treatment modalities with diverse clinical outcomes in clinical practice. Subclassification of HCC patients with PVI is required to minimize heterogeneity and should be considered for the selection of treatment modalities and future clinical trials. [ABSTRACT FROM AUTHOR]

The treatment of multidrug‐resistant (MDR) chronic hepatitis B (CHB) is challenging. Herein, we report a multicenter prospective cohort study for the evaluation of tenofovir disoproxil fumarate (TDF)‐based therapy for MDR CHB in a real‐life setting. The inclusion criteria comprised patients with resistance to more than two nucleos(t)ide analogue (NA) classes and hepatitis B virus (HBV) DNA level of ≥200 IU/mL. The primary end‐point was virologic response (VR), defined as undetectable HBV DNA (<20 IU/mL) after 60 months. A total of 236 patients met the inclusion criteria. The mean HBV DNA level was 4.16 ± 1.44 log IU/mL; 26.7% of patients had liver cirrhosis. Before the initiation of TDF, 33.5%, 44.9% and 21.6% of patients had mutations resistant to L‐NA + adefovir, L‐NA + entecavir (ETV) and L‐NA + adefovir + ETV, respectively. A total of 184 patients received TDF‐based combination therapy [TDF + ETV (n = 178) or TDF + L‐NA (n = 6)], and 52 patients received TDF monotherapy. In the entire cohort, the VR rates were 77.2%, 89.9% and 92.2% at 12, 36 and 60 months, respectively. The VR rates were not significantly different between the combination therapy and the monotherapy group after 12 (76.2% vs 80.4%, P =.533), 36 (89.8% vs 90.3%, P = 1.000) or 60 (92.9% vs 87.5%, P =.499) months. Also, there was no significant difference in the cumulative VR rates for 5 years between the treatment groups (P =.910). Newly developed antiviral resistance was not observed. TDF‐based therapy was effective for the treatment of MDR CHB. The efficacy of TDF monotherapy was not different from that of the TDF‐based combination therapy. [ABSTRACT FROM AUTHOR]

Background and Aims: This prospective observational study aimed to evaluate the best serum and urine markers to assess predictability for the prognosis of patients with decompensated cirrhosis. Methods: Serum creatinine and cystatin C (CysC), and urinary N‐acetyl‐beta‐D glucosaminidase (uNAG) and neutrophil gelatinase‐associated lipocalin (uNGAL) levels were measured from hospitalized patients with decompensated cirrhosis. Results: In total, 328 patients (mean age, 57.2 ± 12.0 years; 237 men) with decompensated cirrhosis were included. Alcoholic liver disease was the most frequent underlying liver disease (68.0%). Acute kidney injury (AKI) was concomitantly present in 41 patients (12.5%) at baseline. INR, serum creatinine and CysC levels, and uNAG and uNGAL levels were significantly higher in patients with AKI. During hospitalization, AKI had progressed in 37 patients (11.3%). In 287 patients without AKI, the incidence of AKI at 3, 6, 9 and 12 months was 15.4%, 22.2%, 28.6% and 32.5% respectively. On multivariate analysis, serum CysC and uNAG levels were independent predictors of AKI, and their optimal cut‐off values were 1.055 mg/L and 23.1 U/g urinary Cr respectively. When patients were classified into three groups with these cut‐off values of serum CysC and uNAG levels (group 1, both low; group 2, one of two high; and group 3, both high), progression of AKI during hospitalization (P =.001), incidence of AKI in patients without AKI at baseline (P =.001) and mortality rate (P <.001) differed significantly according to serum CysC and uNAG levels. Conclusion: Serum CysC and uNAG levels are useful prognostic markers for renal outcomes and mortality in patients with decompensated cirrhosis. [ABSTRACT FROM AUTHOR]

The relation between the imaging characteristics of parallax images (PIs) and the system parameters of the double diffraction grating (DDG) imaging system is analyzed. DDG imaging method may produce parallax images (PIs) efficiently. However, a geometrical analysis is required to improve the applicability of the imaging system. The system parameters considered include the wavelength of light source, the spatial resolution of the diffraction grating, and positions of diffraction gratings and an imaging lens. The imaging characteristics of the DDG imaging defined and described in terms of positions and parallax angles of PIs. The ray-optical analysis is performed for the explanation of the imaging characteristics. [ABSTRACT FROM AUTHOR]

Background & Aims: Tamoxifen is associated with an increased risk of developing fatty liver. The aim of this systematic review and meta‐analysis was to evaluate the prevalence and incidence of fatty liver developed after tamoxifen treatment in breast cancer patients. Methods: A systematic search of PubMed (Medline), EMBASE, OVID Medline, the Cochrane Library and other databases was performed for this review. The abstracts obtained from the search were reviewed by two investigators who chose manuscripts for full‐text review. The event rates were calculated with a random‐effects model and quality‐effects model. Results: The search yielded 165 references. Of these, 24 were included in the quantitative summary. We analysed the data of a total of 6,962 patients treated with tamoxifen and 975 patients not treated with tamoxifen. The prevalence of fatty liver among patients with breast cancer taking tamoxifen was 40.25 per 100 patients and the incidence rate was 12.37 per 100 person‐years. The incidence of fatty liver was much higher in the tamoxifen group than in the control group [incidence rate ratio: 3.12, 95% CI (confidence interval): 2.05‐4.75, I2 = 61%], regardless of region. The main risk factors were body mass index (BMI) [hazard ratio (HR): 1.15, 95% CI: 1.09‐1.22] and hypercholesterolaemia (HR: 1.01, 95% CI: 1.00‐1.02). Conclusion: The use of tamoxifen was associated with increased risks in the incidence and prevalence of fatty liver, especially in patients with high BMI and hypercholesterolaemia. [ABSTRACT FROM AUTHOR]

Backgrounds & Aims: The Baveno VI guidelines proposed criteria including liver stiffness (LS) and platelet count to avoid screening endoscopy in patients with compensated advanced chronic liver disease (cACLD). This study was performed to validate the Baveno IV criteria and to compare its diagnostic accuracy with other non‐invasive models. Methods: Patients with cACLD who underwent laboratory tests, upper gastrointestinal endoscopy and abdominal ultrasound within 6 months of transient elastography were included. Results: A total of 1218 patients with cACLD were included. VNT occurred in 249 patients (20.4%). With the Baveno VI criteria, the VNT miss rate was 1.9% with a 25.7% saved endoscopy rate. Using two criteria of LS <20 kPa and platelet count >110 × 109 cells/L or LS <25 kPa and platelet count >120 × 109 cells/L, the saved endoscopy rate was 39.1% while maintaining the VNT miss rate <5%. The optimal LS and platelet count‐based criteria for predicting VNT differed according to the underlying liver disease. The area under the receiver operating characteristic curve of LS‐spleen diameter to platelet score (LSPS) was 0.780 (95% confidence interval: 0.774‐0.820), which was significantly higher than other models. The optimal cut‐off value of the LSPS for predicting VNT was 1.47. Conclusion: Liver stiffness and platelet count‐based criteria are useful for discriminating patients with very low risk of having VNT among patients with cACLD and are partly affected by the type of underlying liver disease. Conversely, the LSPS is a predictor of VNT in patients with cACLD regardless of the type of underlying liver disease. [ABSTRACT FROM AUTHOR]

Graphical abstract Highlights • Renal function overestimation occurs frequently in patients with liver cirrhosis when using serum creatinine. • Decreased muscle mass impacts on overestimation of kidney function especially in male patients with cirrhosis. • Compared to creatinine, cystatin C correlated better with mGFR and had a higher predictive ability for clinical outcomes. • Cystatin C might be a promising marker to accurately assess renal function in cirrhotic patients. Background & Aims Accurate evaluation of renal function in patients with liver cirrhosis is critical for clinical management. However, there are still discrepancies between the measured glomerular filtration rate (mGFR) and creatinine-based estimated GFR (eGFR). In this study, we compared the performance of 2 common eGFR measurements with mGFR and evaluated the impact of low muscle mass on overestimation of renal function in patients with cirrhosis. Methods This study included 779 consecutive cirrhotic patients who underwent 51Cr-ethylenediamine tetra acetic acid (EDTA) (as a mGFR) and abdominal computed tomography (CT). The eGFR was calculated using creatinine or cystatin C. Muscle mass was assessed in terms of the total skeletal muscle at L3 level using CT. Results Modification of diet in renal disease (MDRD)-eGFR was overestimated in 47% of patients. A multivariate analysis showed that female sex (adjusted odds ratio [aOR] 4.91), Child B and C vs. A (aOR 1.69 and 1.84) and skeletal muscle mass (aOR 0.89) were independent risk factors associated with overestimation. Interestingly, the effect of skeletal muscle mass on overestimation varied based on sex. Decreased muscle mass significantly enhanced the risk of overestimation of MDRD-eGFR in male patients, but not in female patients. Cystatin C-based eGFR showed a better correlation with mGFR than MDRD-eGFR; it was also better at predicting overall survival and the incidence of acute kidney injury than MDRD-eGFR. Conclusions The risk factors associated with overestimation included female sex, impaired liver function, and decreased muscle mass in males. In particular, eGFR in male patients with sarcopenia should be carefully interpreted. Creatinine-based eGFR was overestimated more often than cystatin C-based eGFR, with overestimation of eGFR closely related to poor prognostic performance. Lay summary Overestimation of renal function frequently occurs in patients with liver cirrhosis when using serum creatinine. Decreased muscle mass has a great impact on overestimation of kidney function especially in male patients with cirrhosis. Compared with creatinine, cystatin C was more closely correlated with measured glomerular filtration rate and had a higher predictive ability for renal complications and survival than creatinine. [ABSTRACT FROM AUTHOR]

Patients with liver cirrhosis and hepatocellular carcinoma (HCC) are often ineligible for resection or local ablation therapy due to poor liver function and/or difficult location. The aim of this study is to evaluate therapeutic outcomes of stereotactic body radiotherapy (SBRT) combined with transarterial chemoembolization (TACE) compared with TACE alone for HCC measuring less than 5 cm. From March 2011 to December 2016, 85 patients underwent SBRT with TACE (SBRT-TACE group) and 114 underwent TACE (TACE group) at 4 tertiary hospitals. Local control rate (LCR), progression-free survival (PFS) and overall survival (OS) were compared after propensity-score matching (1:1 ratio). The SBRT-TACE group showed significantly higher 1- and 3-year LCR than the TACE group (91.1% and 89.9%, respectively vs 69.9% and 44.8%, respectively; P < 0.001). The SBRT-TACE group showed better 1- and 3-year PFS than the TACE group (56.5% and 32.3%, respectively vs 42.2% and 21.6%, respectively; P = 0.022). However, 1-, 3- and 5-year OS was not different between the SBRT-TACE and TACE groups (98.8%, 89.1% and 80.7%, respectively vs 99.7%, 83.3% and 71.0%, respectively; P = 0.206). In multivariate analysis, the overall SBRT added to TACE did not contribute to extend PFS. However, in patients with less than 2 tumors, the combined therapy was effective (HR 0.590, 95% CI 0.392–0.889, P = 0.012). SBRT-TACE is superior to TACE in terms of LCR. Particularly, SBRT-TACE may be an effective alternative in patients with HCC number (≤2), which is not indicated for resection or local ablation. [ABSTRACT FROM AUTHOR]

Objectives: For the prevention of spontaneous bacterial peritonitis (SBP) in cirrhotic patients with ascites, norfloxacin 400 mg per day is recommended as a standard regimen. This study aims to investigate whether ciprofloxacin once weekly administration is not inferior to norfloxacin once daily administration for the prevention of SBP.Methods: This is an investigator-initiated open-label randomized controlled trial conducted at seven tertiary hospitals in South Korea. Liver cirrhosis patients with ascites were screened, and enrolled in this randomized controlled trial if ascitic protein ≤1.5 g/dL or the presence of history of SBP. Ascitic polymorphonucleated cell count needed to be <250/mm3. Patients were randomly assigned into norfloxacin daily or ciprofloxacin weekly group, and followed-up for 12 months. Primary endpoint was the prevention of SBP.Results: One hundred twenty-four patients met enrollment criteria and were assigned into each group by 1:1 ratio (62:62). Seven patients in the norfloxacin group and five patients in the ciprofloxacin group were lost to follow-up. SBP developed in four patients (4/55) and in three patients (3/57) in each group, respectively (7.3% vs. 5.3%, P = 0.712). The transplant-free survival rates at 1 year were comparable between the groups (72.7% vs. 73.7%, P = 0.970). Incidence of infectious complication, hepatorenal syndrome, hepatic encephalopathy, and variceal bleeding rates were not significantly different (all P = ns). The factors related to survival were models representing underlying liver function.Conclusion: Once weekly ciprofloxacin was as effective as daily norfloxacin for the prevention of SBP in cirrhotic patients with ascites. [ABSTRACT FROM AUTHOR]

Convincing data that support routine use of preventive therapy against hepatitis B virus (HBV) reactivation in radiotherapy (RT) for hepatocellular carcinoma (HCC) are lacking. The aim of this study was to investigate the incidence, clinical significance, and risk factors of HBV reactivation after RT. Medical records of 133 HBsAg (+) HCC patients who received radiotherapy from March 2009 to February 2016 were reviewed. Patients were divided into two groups: 1) non-antiviral group, those who did not receive antiviral therapy before RT (n = 27); and antiviral group (those who underwent antiviral therapy before RT) (n = 106). Factors related to HBV reactivation in HCC patients were evaluated. 17 (12.7%) of 133 patients developed HBV reactivation after RT. Patients in the antiviral group had significantly lower rates of HBV reactivation than those in the non-antiviral group (7.5% vs. 33.3%, p<0.001). HBV related hepatitis was also lower in the antiviral group (3.8% vs. 14.8%, p = 0.031). In multivariate analysis, absence of antiviral treatment (OR: 8.339, 95% CI: 2.532–27.470, p<0.001) and combined treatment of RT with transarterial chemoembolizatoin (TACE) (OR: 5.313, 95% CI: 1.548–18.232, p = 0.008) were risk factors for HBV reactivation. HBV reactivation can occur after radiotherapy. Combination treatment of RT with TACE and non-antiviral treatment are major risk factors for HBV reactivation during or after RT. Therefore, preventive antiviral therapy should be recommended for patients with HCC who are scheduled to receive RT. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: Although serum cystatin C level is considered a more accurate marker of renal function in patients with liver cirrhosis, its prognostic efficacy remains uncertain. This study aimed to evaluate the prognostic efficacy of serum cystatin C level in patients with cirrhotic ascites. Methods: Patients with cirrhotic ascites from 15 hospitals were prospectively enrolled between September 2009 and March 2013. Cox regression analyses were performed to identify independent predictive factors of mortality and development of type 1 hepatorenal syndrome (HRS‐1). Results: In total, 350 patients were enrolled in this study. The mean age was 55.4 ± 10.8 years, and 267 patients (76.3%) were men. The leading cause of liver cirrhosis was alcoholic liver disease (64.3%), followed by chronic viral hepatitis (29.7%). Serum creatinine and cystatin C levels were 0.9 ± 0.4 mg/dL and 1.1 ± 0.5 mg/L, respectively. Multivariate analyses revealed that international normalized ratio and serum bilirubin, sodium, and cystatin C levels were independent predictors of mortality and international normalized ratio and serum sodium and cystatin C levels were independent predictors of the development of HRS‐1. Serum creatinine level was not significantly associated with mortality and development of HRS‐1 on multivariate analysis. Conclusion: Serum cystatin C level was an independent predictor of mortality and development of HRS‐1 in patients with cirrhotic ascites, while serum creatinine level was not. Predictive models based on serum cystatin C level instead of serum creatinine level would be more helpful in the assessment of the condition and prognosis of patients with cirrhotic ascites. [ABSTRACT FROM AUTHOR]

Abstract: Background and Aim: The aim of this study was to validate the chronic liver failure‐sequential organ failure assessment score (CLIF‐SOFAs), CLIF consortium organ failure score (CLIF‐C OFs), CLIF‐C acute‐on‐chronic liver failure score (CLIF‐C ACLFs), and CLIF‐C acute decompensation score in Korean chronic liver disease patients with acute deterioration. Methods: Acute‐on‐chronic liver failure was defined by either the Asian Pacific Association for the study of the Liver ACLF Research Consortium (AARC) or CLIF‐C criteria. The diagnostic performances for short‐term mortality were compared by the area under the receiver operating characteristic curve. Results: Among a total of 1470 patients, 252 patients were diagnosed with ACLF according to the CLIF‐C (197 patients) or AARC definition (95 patients). As the ACLF grades increased, the survival rates became significantly lower. The areas under the receiver operating characteristic of the CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs were significantly higher than those of the Child–Pugh, model for end‐stage liver disease, and model for end‐stage liver disease‐Na scores in ACLF patients according to the CLIF‐C definition (all P < 0.05), but there were no significant differences in patients without ACLF or in patients with ACLF according to the AARC definition. The CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs had higher specificities with a fixed sensitivity than liver specific scores in ACLF patients according to the CLIF‐C definition, but not in ACLF patients according to the AARC definition. Conclusions: The CLIF‐SOFAs, CLIF‐C OFs, and CLIF‐C ACLFs are useful scoring systems that provide accurate information on prognosis in patients with ACLF according to the CLIF‐C definition, but not the AARC definition. [ABSTRACT FROM AUTHOR]

In the screening of natural products for the development as cosmetic ingredients, the EtOAc-soluble fraction of Humulus japonicus showed tyrosinase inhibitory activity. HPLC-MS/MS coupled online tyrosinase assay of EtOAc-soluble fraction of H. japonicus characterized the twenty-eight constituents including two unknown ones and their tyrosinase inhibitory activity. Fractionation of H. japonicus using various chromatographic techniques yielded thirty-eight compounds. The chemical structures of isolated compounds were identified by spectroscopic analysis. As characterized by HPLC-MS/MS analysis, we isolated twenty-four predicted compounds and further identified two unknown ones, named humulusides A ( 1 ) and B ( 2 ). Additional ten compounds were also identified by purification. Tyrosinase inhibitory activity of isolated compounds were evaluated, which was closely correlated with the results from HPLC-MS/MS coupled online tyrosinase assay. Consistent with predicted data, two major compounds, trans - N -coumaroyltyramine ( 14 ) and cis - N -coumaroyltyramine ( 15 ) showed tyrosinase inhibition with IC 50 values of 40.6 and 36.4 μM. Taken together, H. japonicus is suggested as whitening ingredient in cosmetic products. In addition, HPLC-MS/MS coupled tyrosinase assay is powerful tool for predicting active compounds with short time and limited amounts, although identification of new compounds and verification of predicted data are also needs to be demonstrated by further experiment. [ABSTRACT FROM AUTHOR]

Background/Aims: Hepatopulmonary syndrome (HPS) is characterized by a defect in oxygenation induced by pulmonary vascular dilatation in cirrhosis. While severe HPS is responsible for a high rate of mortality, the prevalence and pathophysiology of HPS are not fully elucidated. We evaluated the prevalence and pathophysiology of HPS in patients with cirrhosis. Methods: A total of 142 patients with cirrhosis who underwent saline-agitated contrast echocardiography were enrolled in this prospective observational study. HPS was defined by positive findings on contrast echocardiography, cirrhosis, and the presence of an oxygenation defect (alveolar-arterial oxygen gradient > 15 mmHg). HPS grades from 0 to 3 were assigned based on the density and spatial distribution of microbubbles in the left ventricle. The primary endpoint was the prevalence of HPS. The secondary endpoints included clinical characteristics and levels of lipopolysaccharide (LPS), LPS-binding protein (LBP), nitric oxide, and endothelin-1 in HPS. Results: Fifty-nine patients (41.5%) were diagnosed with HPS (grade 1: 24, grade 2: 23, and grade 3: 12 patients). The mean levels of LPS (0.36 ± 0.02, 1.02 ± 0.18, 2.86 ± 0.77, and 6.56 ± 1.46 EU/mL, p < 0.001) and LBP (7026 ± 3336, 11,445 ± 1247, 11,947 ± 1164, and 13,791 ± 2032 ng/mL, p = 0.045) were found to be increased according to HPS grade (negative, grade 1-3). Endothelin-1 levels were significantly elevated according to HPS grade (1.83 ± 0.17, 2.62 ± 0.22, 3.69 ± 0.28, and 4.29 ± 0.34 pg/mL, p < 0.001), demonstrating a significant difference between each grade ( p < 0.05). Conclusions: HPS is a common complication with a prevalence of 41.5% in patients with cirrhosis. Bacterial translocation and portal pulmonary vascular dilatation are key mechanism involved in the progression of HPS. [ABSTRACT FROM AUTHOR]

Background/aims: Recent studies have demonstrated the utility of the FibroScan® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. Methods: A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. Results: There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κCAP = 0.77, P<0.001; κultrasonography = 0.60, P<0.001; κHSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826–0.972)], 0.859 (95% CI = 0.779–0.939), and 0.766 (95% CI = 0.655–0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. Conclusion: The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages. [ABSTRACT FROM AUTHOR]

A nuclear magnetic resonance (NMR) magnet composed of a high-temperature superconductor (HTS) is expected to contribute to a smaller size and a higher magnetic field (>1 GHz) of the NMR magnet due to its high critical current density under high magnetic field and better mechanical properties. The high operating temperature of HTS NMR magnets also makes conduction cooling by a cryocooler available. The conduction cooling system combined with a cryocooler is compact and user-friendly but has critical issues about the design of conduction cooling passages and the mechanical vibration. The small-scale HTS magnet with the conduction cooling system is fabricated and tested to check the issues and establish the design basis as a preliminary step for the development of a 400-MHz HTS NMR magnet. Thermal analysis for heat loads and thermal resistances at main joints is performed from the temperature distribution of the cooling system. The vibration levels at the crycooler and the vacuum chamber are discussed in comparison to the vibration criterion of NMR magnets. In addition, the design approach to the conduction cooling system for the HTS NMR magnet is discussed. [ABSTRACT FROM PUBLISHER]

A 3-T 100-mm winding bore conduction-cooled REBCO magnet has been designed, constructed, and tested. It consists of a stack of double pancake coils wound with metallic cladding (MC) REBCO tapes, for which 1–2 \mu \textm stainless steel was clad in a hermetic way around the tapes. This approach, first proposed by the SuNAM Company Ltd. in 2015, is expected to substantially reduce the charging time delay of a no-insulation magnet, which in turn will be effective in the manipulation of screening currents in such a way as to improve the field homogeneity of magnets, particularly for nuclear magnetic resonance or MRI. This paper presents test results for our approach on the current sweep cycling, which is used to reduce the screening current-induced fields in a newly constructed 3-T 100-mm MC all-REBCO magnet [ABSTRACT FROM PUBLISHER]

Background: Mannose-binding lectin (MBL) acts in the innate immune response to Helicobacter pylori. Interleukin 8 (IL-8) is a potent cytokine produced by gastric epithelial cells in response to H. pylori. We aimed to investigate whether polymorphisms in MBL2 and IL-8 influence susceptibility to H. pylori infection, and the associations of these polymorphisms with the risk of gastroduodenal diseases in a Korean population.Methods: We consecutively enrolled 176 H. pylori-negative control subjects, 221 subjects with H. pylori-positive non-atrophic gastritis, 52 mild atrophic gastritis (AG), 61 severe AG, 175 duodenal ulcer, and 283 gastric cancer (GC). Allele-specific PCR-RFLP was conducted for polymorphisms in MBL2 exon 1 (codon 52, 54, and 57) and IL-8 -251 T > A. IL-8 levels in gastric mucosal tissues and serum MBL levels were measured by enzyme-linked immunosorbent assay.Results: MBL2 exon 1 polymorphic variants were found only in codon 54, and the allele frequencies did not differ significantly between the control and disease groups. Although serum MBL levels in codon 54 A/A mutants were markedly low, it did not influence susceptibility to H. pylori infection or the risk of gastroduodenal diseases. IL-8 levels were significantly different between T/T wild type, T/A heterozygote, and A/A mutant genotypes. IL-8 -251 A allele carriers (A/A + T/A) showed increased IL-8 levels, and were significantly associated with the risk of severe AG and GC.Conclusions: We suggest that a combination of H. pylori infection and the IL-8 -251 T > A polymorphism might increase the risk of severe AG and GC in a Korean population. [ABSTRACT FROM AUTHOR]

We propose a depth resolution improved target depth image extraction method in integral imaging by using the convolution property between periodic functions (CPPF) with image interpolation algorithm. We derive the depth resolution equation of a direct pickup system and analyze the factors related to the change of the depth resolution which are the focal length of an elemental lens and the resolution of an elemental image. We investigate the effect according to the change of these factors. The simulation results show that the key factor to change the depth resolution is the resolution of an elemental image. To show the feasibility of the proposed method, we carry out the preliminary experiments and present the results. [ABSTRACT FROM AUTHOR]

17β-estradiol (E2) is known to have a protective effect in colorectal cancer (CRC); thus, E2 may be effective for cancer immunotherapy in CRC. The aim of this study is to evaluate the effect of combination therapy with E2 and anti-programmed cell death receptor-1 ligand (PD-L1) antibodies, and the effects of sex and estrogen on colon tumor growth, PD-L1 expression, and tumor-associated cell populations in an MC38 colon tumor model. Male mice showed increased MC38 colon tumor growth and PD-L1 expression in tumor sections as well as higher proportion of cancer-associated fibroblasts (CD45-CD31-CD140a+), PD-L1-expressing tumor cells (CD45-CD274+) and tumor-associated macrophages (TAMs) (CD11b+F4/80+CD274+) compared to female mice. E2 treatment prior to MC38 injection significantly reduced these phenomena in male mice. Furthermore, co-treatment with E2 and anti-PD-L1 antibodies significantly inhibited MC38 tumor growth and reduced PD-L1-expressing cells in male mice compared to treatment with either E2 or anti-PD-L1 antibodies alone. Combination treatment with E2 and anti-PD-L1 decreased TAM population (CD11b+F4/80+) in the tumor mass while increasing M1 TMAs (CD11b+F4/80+CD86+). These results suggest that estrogen inhibits MC38 tumor growth by downregulating PD-L1 expression and regulating tumor-associated cell populations. Furthermore, estrogen boosted the effect of anti-PD-L1 antibody in the MC38 tumor model. [ABSTRACT FROM AUTHOR]

Background/aims: The accuracy of noninvasive markers to discriminate nonalcoholic steatohepatitis (NASH) is unsatisfactory. We investigated whether transient elastography (TE) could discriminate patients with NASH from those with nonalcoholic fatty liver disease (NAFLD). Methods: The patients suspected of NAFLD who underwent liver biopsy and concomitant TE were recruited from five tertiary centers between November 2011 and December 2013. Results: The study population (n = 183) exhibited a mean age of 40.6 years and male predominance (n = 111, 60.7%). Of the study participants, 89 (48.6%) had non-NASH and 94 (51.4%) had NASH. The controlled attenuation parameter (CAP) and liver stiffness (LS) were significantly correlated with the degrees of steatosis (r = 0.656, P<0.001) and fibrosis (r = 0.714, P<0.001), respectively. The optimal cut-off values for steatosis were 247 dB/m for S1, 280 dB/m for S2, and 300 dB/m for S3. Based on the independent predictors derived from multivariate analysis [P = 0.044, odds ratio (OR) 4.133, 95% confidence interval (CI) 1.037–16.470 for AP>250 dB/m; P = 0.013, OR 3.399, 95% CI 1.295–8.291 for S>7.0 kPa; and P<0.001, OR 7.557, 95% CI 2.997–19.059 for lanine aminotransferase>60 IU/L], we developed a novel CLA model for discriminating patients with NASH. The CLA model showed good discriminatory capability, with an area under the receiver operating characteristic curve (AUROC) of 0.812 (95% CI 0.724–0.880). To assess discriminatory power, the AUROCs, as determined by the bootstrap method, remained largely unchanged between iterations, with an average value of 0.833 (95% CI 0.740–0.893). Conclusion: This novel TE-based CLA model showed acceptable accuracy in discriminating NASH from simple steatosis. However, further studies are required for external validation. [ABSTRACT FROM AUTHOR]

Background & Aim: To investigate the prevalence, mortalities, and patient characteristics of Acute-on-chronic liver failure (ACLF) according to the AARC (Asian Pacific Association for the Study of the Liver ACLF Research Consortium) and European Association for the Study of the Liver CLIF-C (Chronic Liver Failure Consortium) definitions. Methods: We collected retrospective data for 1470 hospitalized patients with chronic liver disease (CLD) and acute deterioration between January 2013 and December 2013 from 21 university hospitals in Korea. Results: Of the patients assessed, the prevalence of ACLF based on the AARC and CLIF-C definitions was 9.5% and 18.6%, respectively. The 28-day and 90-day mortality rates were higher in patients with ACLF than in those without ACLF. Patients who only met the CLIF-C definition had significantly lower 28-day and 90-day survival rates than those who only met the AARC definition (68.0% vs. 93.9%, P<0.001; 55.1% vs. 92.4%, P<0.001). Among the patients who had non-cirrhotic CLD, the 90-day mortality of the patients with ACLF was higher than of those without ACLF, although not significant (33.3% vs. 6.0%, P = 0.192). Patients with previous acute decompensation (AD) within 1- year had a lower 90-day survival rate than those with AD more than 1 year prior or without previous AD (81.0% vs. 91.9% or 89.4%, respectively, all P<0.001). Patients who had extra-hepatic organ failure without liver failure had a similar 90-day survival rate to those who had liver failure as a prerequisite (57.0% vs. 60.6%, P = 0.391). Conclusions: The two ACLF definitions result in differences in mortality and patient characteristics among ACLF patients. We suggest that non-cirrhotic CLD, previous AD within 1 year, and extra-hepatic organ failure should be included in the ACLF diagnostic criteria. In addition, further studies are necessary to develop a universal definition of ACLF. [ABSTRACT FROM AUTHOR]

Background/Aims Transient elastography ( TE) has become an alternative to liver biopsy ( LB). This study investigated the diagnostic performance of liver stiffness ( LS) measurement using TE in Korean patients with chronic hepatitis B and C ( CHB and CHC). Methods From April 2006 to June 2014, 916 patients (567 CHB and 349 CHC) who underwent LB and TE at 15 centres were analyzed. The Batts and Ludwig scoring system was used for histologic assessment. Aspartate aminotransferase ( AST)-to-platelet ratio indexes ( APRI) were calculated. Area under the receiver operating characteristic curve ( AUROC) was used. Results The median age, LS value, and APRI score were 45 years, 8.8 kPa, and 0.61, respectively, in CHB patients vs. 51 years, 6.8 kPa and 0.55, respectively, in CHC patients. TE was significantly superior to APRI in CHB patients (AUROC 0.774 vs. 0.72 for ≥F2, 0.849 vs. 0.812 for ≥F3, and 0.902 vs. 0.707 for F4, respectively; all P < 0.05). Furthermore, TE was significantly superior for predicting ≥ F3 stage (AUROC 0.865 vs. 0.840, P = 0.009) whereas it was similar for predicting ≥ F2 and F4 stage (AUROC 0.822 vs. 0.796; 0.910 vs. 0.884; all P > 0.05) in CHC patients. In CHB patients, optimal cut-off LS values were 7.8 kPa for ≥F2, 8.2 kPa for ≥ F3, and 11.6 kPa for F4, vs. 6.8 kPa, 8.6 kPa, and 14.5 kPa, respectively, in CHC patients. Conclusions TE can accurately assess the degree of liver fibrosis in Korean patients with CVH. TE was superior to APRI for predicting each fibrosis stage. [ABSTRACT FROM AUTHOR]

A subsequent attempt to cut the trichobezoar using argon plasma coagulation and a polypectomy snare also failed to fragment it efficiently (Fig. 1968, 63, 339 - 343 2 Benatta M. A. Endoscopic retrieval of gastric trichobezoar after fragmentation with electrocautery using polypectomy snare and argon plasma coagulation in a pediatric patient. [Extracted from the article]