The association between trajectory of serum cholesterol, statin dosage, and the risk of recurrent biliary stone diseases.

BACKGROUND: Statins may reduce the risk of recurrent gallstone disease by decreasing bile cholesterol saturation and pathogenicity. However, limited studies have investigated this issue. This study aimed to assess whether statin doses and serum cholesterol levels were associated with a decreased risk of recurrent biliary stone diseases after the first event index, with a follow-up time of 15 years. METHODS: Based on the Chang Gung Research Database (CGRD) between January 1, 2001, and December 31, 2020, we enrolled 68,384 patients with the International Classification of Diseases, Ninth and Tenth Revision codes of choledocholithiasis. After exclusions, 32,696 patients were divided into non-statin (<28 cDDD, cumulative defined daily doses) (n = 27,929) and statin (≥28 cDDD) (n = 4767) user groups for analysis. Serum cholesterol trajectories were estimated using group-based trajectory modeling (n = 8410). RESULTS: The statin users had higher Charlson Comorbidity Index (CCI) scores than the non-statin users. Time-dependent Cox regression analysis showed that statin use >365 cDDD was associated with a significantly lower risk of recurrent biliary stones (adjusted hazard ratio [aHR] = 0.28, 95% CI, 0.24-0.34; p < 00.0001), acute pancreatitis (aHR = 0.24, 95% CI, 0.17-0.32, p < 00.0001), and cholangitis (aHR = 0.28, 95% CI, 0.25-0.32, p < 00.0001). Cholecystectomy was also a protective factor for recurrent biliary stones (aHR = 0.41, 95% CI, 0.37-0.46; p < 00.0001). The higher trajectory serum cholesterol group (Group 3) had a lower risk trend for recurrent biliary stones (aHR = 0.79, p = 0.0700) and a lower risk of cholangitis (aHR = 0.79, p = 0.0071). CONCLUSION: This study supports the potential benefits of statin use and the role of cholecystectomy in reducing the risk of recurrent biliary stone diseases.

The multicenter real-world report of the efficacies of 14-day esomeprazole-based and rabeprazole-based high-dose dual therapy in first-line Helicobacter pylori eradication in Taiwan.

BACKGROUND: High-dose dual therapy (HDDT) using proton-pump inhibitors (PPI) and amoxicillin attracted attention for its simplicity and lower adverse event profile. Besides, vonoprazan is not available worldwide. This real-world study aims to compare the efficacy of esomeprazole-based and rabeprazole-based HDDT regimens and to identify clinical factors influencing outcomes. METHODS: A retrospective study enrolled 346 Helicobacter pylori-infected naïve patients from January 2016 to August 2023. Patients were assigned to either a 14-day esomeprazole-based HDDT (EA-14; esomeprazole 40 mg t.i.d. and amoxicillin 750 mg q.i.d. for 14 days, n = 173) or a 14-day rabeprazole-based HDDT (RA-14; rabeprazole 20 mg and amoxicillin 750 mg q.i.d. for 14 days, n = 173). RESULTS: Five patients from the EA-14 group and 10 from the RA-14 group were lost to follow-up, resulting in 168 and 163 patients for the per-protocol (PP) analysis, respectively. Eradication rates for the EA-14 and RA-14 groups were 90.2% and 80.9% (P = 0.014) in intention-to-treat (ITT) analysis; and 92.9% and 85.9% (P = 0.039) in PP analysis. Adverse event rates were similar between the two groups (11.9% vs 11.7%, P = 0.944). In multiple logistic regression analysis, age≧60 was associated with eradication failure (P = 0.046) and a trend of significance for smoking (P = 0.060) in the EA-14 group but not in the RA-14 group. A trend of significance was also observed for eradication regimens (EA-14 vs RA-14) (P = 0.071). The antibiotic resistance rates were amoxicillin (2.3%), clarithromycin (14.7%), metronidazole (40.3%), and dual resistance to clarithromycin and metronidazole (7.0%). CONCLUSIONS: Esomeprazole-based HDDT achieved over 90% eradication rates but rabeprazole-based HDDT, which failed.

ChemMORT: an automatic ADMET optimization platform using deep learning and multi-objective particle swarm optimization.

Drug discovery and development constitute a laborious and costly undertaking. The success of a drug hinges not only good efficacy but also acceptable absorption, distribution, metabolism, elimination, and toxicity (ADMET) properties. Overall, up to 50% of drug development failures have been contributed from undesirable ADMET profiles. As a multiple parameter objective, the optimization of the ADMET properties is extremely challenging owing to the vast chemical space and limited human expert knowledge. In this study, a freely available platform called Chemical Molecular Optimization, Representation and Translation (ChemMORT) is developed for the optimization of multiple ADMET endpoints without the loss of potency (https://cadd.nscc-tj.cn/deploy/chemmort/). ChemMORT contains three modules: Simplified Molecular Input Line Entry System (SMILES) Encoder, Descriptor Decoder and Molecular Optimizer. The SMILES Encoder can generate the molecular representation with a 512-dimensional vector, and the Descriptor Decoder is able to translate the above representation to the corresponding molecular structure with high accuracy. Based on reversible molecular representation and particle swarm optimization strategy, the Molecular Optimizer can be used to effectively optimize undesirable ADMET properties without the loss of bioactivity, which essentially accomplishes the design of inverse QSAR. The constrained multi-objective optimization of the poly (ADP-ribose) polymerase-1 inhibitor is provided as the case to explore the utility of ChemMORT.

The Clinical Presentations of Liver Abscess Development After Endoscopic Retrograde Cholangiopancreatography with Choledocholithiasis: A 17-Year Follow-Up.

Background: Endoscopic Retrograde Cholangiopancreatography (ERCP), used for choledocholithiasis treatment, carries a risk of pyogenic liver abscess (PLA) due to communication between the biliary system and bowel contents. However, limited data exists on this issue. This study aims to identify the risk factors pertaining to liver abscesses following ERCP lithotomy. Methods: We conducted a retrospective case series across multiple centers to evaluate patients who developed PLA after ERCP for choledocholithiasis. Data was obtained from the Chung Gung Research Database (January 2001 to December 2018). Out of 220 enrolled patients, 195 were categorized in the endoscopic sphincterotomy (ES) group, while 25 were in the non-ES group for further analysis. Results: The non-ES group had significantly higher total bilirubin levels compared to the ES group (4.3 ± 5.8 vs 1.9 ± 2.0, p<0.001). Abscess size, location, and distribution (single or multiple) were similar between the two groups. The most common pathogens were Klebsiella pneumoniae and Escherichia coli. Pseudomonas infection was significantly less prevalent in the ES group compared to the non-ES group (3.6% vs 16.7%, p=0.007). Patients with concurrent malignancies (HR: 9.529, 95% CI: 2.667-34.048, p=0.001), elevated total bilirubin levels (HR: 1.246, 95% CI: 1.062-1.461, p=0.007), multiple abscess lesions (HR: 5.146, 95% CI: 1.777-14.903, p=0.003), and growth of enterococcus pathogens (HR: 4.518, 95% CI: 1.290-15.823, p=0.001) faced a significantly higher risk of in-hospital mortality. Conclusion: PLA incidence was higher in the ES group compared to the non-ES group following ERCP for choledocholithiasis. Attention should be given to significant risk factors, including concurrent malignancies, elevated total bilirubin levels, multiple abscess lesions, and growth of enterococcus pathogens, to reduce in-hospital mortality.

The Efficacy and Safety of 14-day Rabeprazole Plus Amoxicillin High Dose Dual Therapy by Comparing to 14-day Rabeprazole-Containing Hybrid Therapy for the Naïve Helicobacter pylori Infection in Taiwan: A Randomized Controlled Trial.

INTRODUCTION: High-dose dual therapy (HDDT) can attain acceptable eradication rates provided that the optimal doses, timing and treatment duration are applied. The existing evidence still shows inconsistent reports (< 90%) on HDDT therapy except in some Asian countries. We aimed to assess and compare the efficacy of 14-day HDDT by comparing it to 14-day rabeprazole-containing hybrid therapy (HT) and to investigate the host and bacterial factors predicting the treatment outcomes of eradication therapies. METHODS: In this open-label, randomized controlled trial, we recruited 243 naïve Helicobacter pylori-infected patients from September 1, 2018, to November 30, 2021. They were randomly allocated (1:1) to the HDDT group (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days, n = 122) and the HT group (rabeprazole 20 mg and amoxicillin 1 g b.i.d. for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg and metronidazole 500 mg b.i.d. for 7 days, n = 121). Twelve patients were absent during follow-up in the HDDT group and 4 in the HT group, resulting in 110 for the HDDT group and 117 for HT group in the per protocol (PP) study. The outcome was determined by urea breath tests 8 weeks later. RESULTS: The eradication rates for the HDDT and HT groups were 77.0% (95% confidence interval [CI]: 68.5% to 84.1%) and 94.2% (95% CI: 88.4% to 97.6%) (P < 0.001) in intention-to-treat analysis; 85.5% (95% CI: 77.5% to 91.5%) and 97.4% [95% CI: 92.6% to 99.5%] (P = 0.001) in per protocol analysis. The adverse event rates were 7.3% in the HDDT group and 14.5% in the HT group (P = 0.081). The habit of coffee drinking was the dependent factor for eradication failure in the HDDT group (88.2% vs. 68.8%, P = 0.040), but had no influence in the HT group (97.9% versus 95.0%, P = 0.449) in the univariate analysis. CONCLUSION: This study demonstrated that 14-day rabeprazole-containing HDDT did not achieve > 90% eradication rates for first-line H. pylori eradication as 14-day rabeprazole-containing HT did. HDDT is a potentially beneficial combination, which involves only two drugs with mild adverse effects; more precise studies are urged to find answers regarding these failures. This clinical trial was registered retrospectively on 28 November, 2021, as ClinicalTrials.gov identifier: NCT05152004.

Early and Direct Endoscopic Stone Removal in the Moderate Grade of Acute Cholangitis with Choledocholithiasis Was Safe and Effective: A Prospective Study.

BACKGROUND: Evidence supporting the feasibility of single-stage stone removal in patients with a moderate grade of acute cholangitis remains insufficient. The maximal size of a common bile-duct stone suitable for removal during a single-stage ERCP in a moderate grade of acute cholangitis is unknown. METHODS: We prospectively enrolled 196 endoscopic retrograde cholangiopancreatography (ERCP)-naïve patients diagnosed with acute cholangitis and choledocholithiasis. For eligible patients, single-stage treatment involved stone removal at initial ERCP. RESULTS: A total of 123 patients were included in the final analysis. The success rate of complete stone extraction was similar between patients with mild and moderate grades of acute cholangitis (89.2% vs. 95.9%; p = 0. 181). Complication rates were comparable between the two groups. In the moderate grade of the cholangitis group, among patients who underwent early single-stage ERCP, the length of hospitalization declined as short as the patients in the mild grade of cholangitis (10.6 ± 6.2 vs. 10.1 ± 5.1 days; p = 0.408). In the multivariate analysis, early ERCP indicated shorter hospitalization times (≤10 days) (odds ratio (OR), 3.981; p = 0.001). A stone size less than 1.5 cm presented a high success rate (98.0%) for complete stone removal. CONCLUSIONS: Single-stage retrograde endoscopic stone removal in mild and moderate grades of acute cholangitis may be safe and effective, which can obviate the requirement for a second session, thus reducing medical expenses. CLINICALTRIALS: gov: NCT03754491.

ABC-Net: a divide-and-conquer based deep learning architecture for SMILES recognition from molecular images.

Structural information for chemical compounds is often described by pictorial images in most scientific documents, which cannot be easily understood and manipulated by computers. This dilemma makes optical chemical structure recognition (OCSR) an essential tool for automatically mining knowledge from an enormous amount of literature. However, existing OCSR methods fall far short of our expectations for realistic requirements due to their poor recovery accuracy. In this paper, we developed a deep neural network model named ABC-Net (Atom and Bond Center Network) to predict graph structures directly. Based on the divide-and-conquer principle, we propose to model an atom or a bond as a single point in the center. In this way, we can leverage a fully convolutional neural network (CNN) to generate a series of heat-maps to identify these points and predict relevant properties, such as atom types, atom charges, bond types and other properties. Thus, the molecular structure can be recovered by assembling the detected atoms and bonds. Our approach integrates all the detection and property prediction tasks into a single fully CNN, which is scalable and capable of processing molecular images quite efficiently. Experimental results demonstrate that our method could achieve a significant improvement in recognition performance compared with publicly available tools. The proposed method could be considered as a promising solution to OCSR problems and a starting point for the acquisition of molecular information in the literature.

The Novel Finding of Dynamic Change in eGFR Up to One Year after End of Treatment in HCV-Infected Patients Receiving Sofosbuvir and Velpatasvir.

Background: The results of long-term renal evolution in HCV-infected patients using sofosbuvir and velpatasvir (SOF/VEL), with or without ribavirin (RBV), are lacking. Aims: We evaluated the renal safety for HCV-infected patients receiving SOF/VEL. Methods: Between 1 June 2019 and 6 July 2020, we included 594 HCV-infected patients receiving SOF/VEL +/- RBV for 12 weeks in Taiwan. Viral eradication rate (defined by sustained virological response at week 12 post-treatment; SVR12) and changes to renal function were considered. Results: SVR12 was achieved in 99.3% (590/594) upon per-protocol analysis. Patients saw improved hepatobiliary function and fibrosis after the start of SOF/VEL therapy. For renal function, those with baseline estimated glomerular filtration rate (eGFR) ≥ 60 (mL/min/1.73 m2) experienced transient on-treatment reduction in renal function that improved upon ending treatment, but recurrent eGFR degradation during one-year follow-up. The use of RBV (OR = 5.200, 95% CI: 1.983-13.634, p = 0.001) was a significant risk factor at SVR24, while diabetes mellitus (OR = 2.765, 95% CI: 1.104-6.922, p = 0.030) and the use of RBV (OR = 3.143, 95% CI: 1.047-9.435, p = 0.041) were identified as significant risk factors of worsening renal function at SVR48. SOF/VEL did not worsen renal function among those with stage 4-5 chronic kidney disease (CKD) who were not receiving dialysis. Conclusions: A trend of decline in eGFR at 1 year after SOF/VEL treatment was observed among diabetic patients with baseline eGFR ≥ 60 (mL/min/1.73 m2) and concomitant use of RBV. The close monitoring of renal function is warranted. Further study should be conducted in order to weigh the risks and benefit of RBV.

BioNet: a large-scale and heterogeneous biological network model for interaction prediction with graph convolution.

MOTIVATION: Understanding chemical-gene interactions (CGIs) is crucial for screening drugs. Wet experiments are usually costly and laborious, which limits relevant studies to a small scale. On the contrary, computational studies enable efficient in-silico exploration. For the CGI prediction problem, a common method is to perform systematic analyses on a heterogeneous network involving various biomedical entities. Recently, graph neural networks become popular in the field of relation prediction. However, the inherent heterogeneous complexity of biological interaction networks and the massive amount of data pose enormous challenges. This paper aims to develop a data-driven model that is capable of learning latent information from the interaction network and making correct predictions. RESULTS: We developed BioNet, a deep biological networkmodel with a graph encoder-decoder architecture. The graph encoder utilizes graph convolution to learn latent information embedded in complex interactions among chemicals, genes, diseases and biological pathways. The learning process is featured by two consecutive steps. Then, embedded information learnt by the encoder is then employed to make multi-type interaction predictions between chemicals and genes with a tensor decomposition decoder based on the RESCAL algorithm. BioNet includes 79 325 entities as nodes, and 34 005 501 relations as edges. To train such a massive deep graph model, BioNet introduces a parallel training algorithm utilizing multiple Graphics Processing Unit (GPUs). The evaluation experiments indicated that BioNet exhibits outstanding prediction performance with a best area under Receiver Operating Characteristic (ROC) curve of 0.952, which significantly surpasses state-of-theart methods. For further validation, top predicted CGIs of cancer and COVID-19 by BioNet were verified by external curated data and published literature.

Correction: Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase.

Correction for 'Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase' by Jin-Zheng Wang et al., Food Funct., 2021, 12, 6240-6253, DOI: 10.1039/D1FO00913C.

Learning to SMILES: BAN-based strategies to improve latent representation learning from molecules.

Computational methods have become indispensable tools to accelerate the drug discovery process and alleviate the excessive dependence on time-consuming and labor-intensive experiments. Traditional feature-engineering approaches heavily rely on expert knowledge to devise useful features, which could be costly and sometimes biased. The emerging deep learning (DL) methods deliver a data-driven method to automatically learn expressive representations from complex raw data. Inspired by this, researchers have attempted to apply various deep neural network models to simplified molecular input line entry specification (SMILES) strings, which contain all the composition and structure information of molecules. However, current models usually suffer from the scarcity of labeled data. This results in a low generalization ability of SMILES-based DL models, which prevents them from competing with the state-of-the-art computational methods. In this study, we utilized the BiLSTM (bidirectional long short term merory) attention network (BAN) in which we employed a novel multi-step attention mechanism to facilitate the extracting of key features from the SMILES strings. Meanwhile, SMILES enumeration was utilized as a data augmentation method in the training phase to substantially increase the number of labeled data and enlarge the probability of mining more patterns from complex SMILES. We again took advantage of SMILES enumeration in the prediction phase to rectify model prediction bias and provide a more accurate prediction. Combined with the BAN model, our strategies can greatly improve the performance of latent features learned from SMILES strings. In 11 canonical absorption, distribution, metabolism, excretion and toxicity-related tasks, our method outperformed the state-of-the-art approaches.

Increased Risk of Pyogenic Liver Abscess after Endoscopic Sphincterotomy for Treatment of Choledocholithiasis.

BACKGROUND AND AIM: Endoscopic sphincterotomy (ES) abolished the barrier between the hepatobiliary system and duodenum and might be at risk of pyogenic liver abscess (PLA). We aimed to identify the association factors of PLA in patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) procedures for treatment of choledocholithiasis. METHODS: This study was based on the Chung Gung Research Database (CGRD) between January 1, 2001 and December 31, 2018. Those who had an International Classification of Diseases, Ninth and Tenth Revision (ICD9 and ICD10) codes of choledocholithiasis and received ERCP were enrolled. After strict exclusions, 11,697 patients were further divided into the endoscopic sphincterotomy (ES) group (n=7,111) and other ERCP group (n=4,586) for analysis. RESULTS: Patients receiving ES had significantly higher rates of PLA than those of the other ERCP group (5-year cumulative incidence 2.4% versus 1.7%; 10-year cumulative incidence 3.9% versus 3.2%, log-rank p=0.0177). Aging, male gender, surgery for hepato-pancreato-biliary system and hepatobiliary malignancy were significant association factors of PLA. On multivariate analysis, the ES increased the risk of PLA (adjusted hazard ratio [aHR]=1.49; 95% CI=1.12-1.98; p=0.0058) but decreased the risks for acute pancreatitis (aHR=0.72; 95% CI=0.60-0.85; p=0.0002) and cholangitis (aHR= 0.91; 95% CI=0.84-0.99; p=0.0259). There was no significant difference about recurrent choledocholithiasis between groups. CONCLUSION: This study demonstrated a significant risk of PLA after patients receiving ES compared with the other ERCP group. We should also carefully monitor the association factors of PLA after ERCP treatment of choledocholithiasis including aging, male gender, surgery for the hepato-pancreato-biliary system and hepatobiliary malignancy.

Nutritional targeting modification of silkworm pupae oil catalyzed by a smart hydrogel immobilized lipase.

To prepare a nutritional supplement using silkworm pupae oil (SPO) as a feedstock, a microfluidic reactor with a smart hydrogel immobilized lipase was first constructed to reduce the relative content of palmitic acid at sn-1,3 and improve the nutritional function. The effects of flow rate, reaction temperature, and substrate molar ratio were investigated. In vitro digestion and pH-stat models were employed to analyze the digestion feature after the modification of SPO, while HPLC-ELSD, zeta potential, DSC, and TGA were used to evaluate the nutritional function. The relative content of "OOO" and "OPO" type triglycerides was increased by 49.48% and 107.67%, and that of palmitic acid at sn-1,3 was decreased by 49.61% in 10 s. After the verification of the in vitro digestion model, the fatty acid release rate of the modified SPO was significantly improved by 22.07%, indicating the nutritional function improvement of SPO. Therefore, the nutritional function of SPO has been improved successfully by the application of a microchannel reactor with photo-immobilized lipase, which could set a reference for the utilization of insect oil resources.

MG-BERT: leveraging unsupervised atomic representation learning for molecular property prediction.

MOTIVATION: Accurate and efficient prediction of molecular properties is one of the fundamental issues in drug design and discovery pipelines. Traditional feature engineering-based approaches require extensive expertise in the feature design and selection process. With the development of artificial intelligence (AI) technologies, data-driven methods exhibit unparalleled advantages over the feature engineering-based methods in various domains. Nevertheless, when applied to molecular property prediction, AI models usually suffer from the scarcity of labeled data and show poor generalization ability. RESULTS: In this study, we proposed molecular graph BERT (MG-BERT), which integrates the local message passing mechanism of graph neural networks (GNNs) into the powerful BERT model to facilitate learning from molecular graphs. Furthermore, an effective self-supervised learning strategy named masked atoms prediction was proposed to pretrain the MG-BERT model on a large amount of unlabeled data to mine context information in molecules. We found the MG-BERT model can generate context-sensitive atomic representations after pretraining and transfer the learned knowledge to the prediction of a variety of molecular properties. The experimental results show that the pretrained MG-BERT model with a little extra fine-tuning can consistently outperform the state-of-the-art methods on all 11 ADMET datasets. Moreover, the MG-BERT model leverages attention mechanisms to focus on atomic features essential to the target property, providing excellent interpretability for the trained model. The MG-BERT model does not require any hand-crafted feature as input and is more reliable due to its excellent interpretability, providing a novel framework to develop state-of-the-art models for a wide range of drug discovery tasks.

Eradication Rates for Esomeprazole and Lansoprazole-Based 7-Day Non-Bismuth Concomitant Quadruple Therapy for First-Line Anti-Helicobacter pylori Treatment in Real World Clinical Practice.

PURPOSE: Non-bismuth concomitant quadruple therapy is commonly administered in Taiwan, achieving an acceptable efficacy as a first-line anti-Helicobacter pylori treatment. This study compared the eradication rates between esomeprazole- and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line anti-H. pylori treatment. PATIENTS AND METHODS: This study included 206 H. pylori-infected naïve patients between July 2016 and February 2019. The patients were prescribed with either a 7-day non-bismuth containing quadruple therapy (esomeprazole, 40 mg twice daily; amoxicillin, 1 g twice daily; and metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily for 7 days [EACM group]; lansoprazole, 30 mg twice daily; amoxicillin, 1 g twice daily; metronidazole, 500 mg twice daily; and clarithromycin, 500 mg twice daily [LACM group]). Then, the patients were asked to perform urea breath tests 8 weeks later. RESULTS: The eradication rates in the EACM group were 86.1% (95% confidence interval [CI], 77.8%-92.2%) and 90.6% (95% CI, 82.9%-95.6%) in the intention-to-treat (ITT) and the per-protocol (PP) analyses, respectively. Moreover, the eradication rates in the LACM group were 90.1% (95% CI, 82.6%-95.2%) and 92.6% (95% CI, 85.5%-96.9%) in the ITT and the PP analyses, respectively. Consequently, the LACM group exhibited more diarrhea patients than the EACM group (7.1% versus 1.0%, p = 0.029), but all symptoms were mild. Univariate analysis in this study showed that metronidazole-resistant strains were the clinical factor affecting the eradications (95.3% versus 78.9%, p = 0.044). Moreover, a trend was observed in dual clarithromycin- and metronidazole-resistant strains (91.5% versus 66.7%, p = 0.155). CONCLUSION: The eradication rates between esomeprazole and lansoprazole-based non-bismuth concomitant quadruple therapy for first-line H. pylori treatment were similar in this study. Both could achieve a > 90% report card in the PP analysis.

The efficacies of non-bismuth containing quadruple therapies in the treatment of first-line anti-Helicobacter pylori across 4-year time interval with changing antibiotics resistance.

BACKGROUND: Non-bismuth containing quadruple therapy (concomitant therapy) is an alternative treatment for Helicobacter pylori (H. pylori) eradication with increasing clarithromycin-resistant strains over times. This study compared the efficacies of non-bismuth containing quadruple therapy (concomitant therapy) in the treatment of first-line anti-Helicobacter Pylori between two time intervals (January 2013 to June 2014 and June 2016 to December 2017). METHODS: H. pylori-infected patients were recruited in the intention-to-treat (ITT analysis) and divided into EACM-A group (enrolled from January 2013 to June 2014, N = 98) and EACM-B group (enrolled from June 2016 to December 2017, N = 99). Patients were prescribed with 7-day esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. Ninety patients and 93 patients were analyzed in the per protocol (PP) analysis (8 and 6 patients lost follow-up in each group). Urea breath tests were performed 4-8 weeks thereafter. RESULTS: The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.7%-93.5%) and 84.8% (95% CI = 76.2%-91.2%) (p = 0.55) in intention-to-treat (ITT) analysis; 95.6% (95% CI = 89.1%-98.8%) and 90.3% (95% CI = 82.4%-95.5%) (p = 0.17) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. 0.24). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.46); metronidazole (32.4% vs. 33.3%, p = 0.93) and levofloxacin (14.7% vs. 37.8%, p = 0.02). CONCLUSION: The success rate of 7-days concomitant therapy encountered an approximately 5% decrease across 4-year time interval (2013-2017) with the changes of clarithromycin resistance from 11.8% to 17.8% in Taiwan.

Comparison of tenofovir and entecavir in the development of acute kidney injury in cirrhotic chronic hepatitis B patients with refractory ascites.

BACKGROUND AND AIM: Tenofovir disoproxil fumarate (TDF) and entecavir are effective antiviral medications that are recommended as first-line monotherapies for the treatment of chronic hepatitis B (CHB) infection, including decompensated liver cirrhosis with ascites. Acute kidney injury (AKI) commonly occurs in patients with cirrhosis and ascites. The aim of this study was to compare the development of AKI during TDF and entecavir treatment of CHB patients with cirrhotic refractory ascites. METHODS: From January 2011 to April 2017, we identified patients who were diagnosed with cirrhosis with refractory ascites and received TDF or entecavir treatments at Kaohsiung Chang Gung Memorial Hospital. AKI was defined as an increase in serum creatinine of more than 0.3 mg/dL or 1.5-fold from baseline. All episodes of AKI were recorded and compared between those who received TDF and entecavir. RESULTS: A total of 111 patients were enrolled in this retrospective study, of which 22 patients were treated with TDF and 89 were treated with entecavir. Patients with AKI episodes had a higher proportion of TDF treatment (P = 0.01), male (P = 0.023), hepatocellular carcinoma (P = 0.007), admission (P = 0.045), and mortality (P = 0.018). Logistic regression analysis illustrated that TDF treatment of patients with comorbidity was an independent risk factor for the development of AKI [odds ratio (OR), 3.756; 95% confidence interval (CI), 1.293-10.912; P = 0.015] and hepatorenal syndrome (OR, 7.651; 95% CI, 1.697-34.508; P = 0.008). CONCLUSIONS: TDF treatment is a risk factor for AKI and HRS development in cirrhotic patients with refractory ascites in comparison with entecavir treatment, especially in patients with comorbidity.

Risks of adverse events for users of proton-pump inhibitors plus aspirin or clopidogrel in patients with aspirin-related ulcer bleeding.

BACKGROUND AND AIM: Clopidogrel is widely prescribed for patients with of aspirin-related upper gastrointestinal bleeding (UGIB) history. This study aimed to compare the risk of a major adverse cardiovascular event (MACE), UGIB, and mortality between aspirin and clopidogrel in patients at risk of bleeding. METHODS: We analyzed adult patients at high risk of UGIB following aspirin-related bleeding for secondary MACE prevention between 2000 and 2012. Secondary prevention was for those patients who had ever been hospitalized for cardiovascular disease and reused aspirin or changed to clopidogrel after discharge. Study endpoints were recurrence of MACE, UGIB, and death in 90 days of follow-up. The associations between study outcomes and the use of clopidogrel (vs aspirin) were analyzed. RESULTS: Among 947 eligible patients, 653 reused aspirin (in combination with a proton-pump inhibitor), and 294 were treated with clopidogrel (in combination with a proton-pump inhibitor) after discharge for UGIB. Compared with aspirin treatment, clopidogrel showed an increased risk of MACE (adjusted hazard ratio [aHR] 1.65; 95% confidence interval [CI] 0.87-3.12) and UGIB (aHR 1.25; 95% CI 0.66-2.36), but without statistical significance in 90 days' follow-up. Clopidogrel use was associated with greater than four times the risk of any cause of mortality (aHR 4.84; 95% CI 1.59-14.75), but the significance did not hold in propensity score-matched cohort analysis (P = 0.06). CONCLUSIONS: A nonsignificant difference between clopidogrel and aspirin for short-term MACE prevention as well as UGIB recurrence was found in the present study. Further research to assess 90-day mortality would assist clinical decision making.

The impact of aspirin on Klebsiella pneumoniae liver abscess in diabetic patients.

In this study, we aimed to investigate the impact of aspirin on the risk of pyogenic liver abscess caused by Klebsiella pneumoniae (KP-PLA) and invasive KP-PLA syndrome (IKPS) in diabetic patients. Diabetic patients who were propensity-score matched were retrospectively included from hospital-based database. Kaplan-Meier approach with a log-rank test was used to compare the cumulative incidences of KP-PLA including IKPS between aspirin users and non-users. Totally, 63,500 patients were analyzed after propensity-score matching (1:1). Compared with that of non-users, the incidence of KP-PLA was significantly reduced in aspirin users (0.31% vs. 0.50%, p < 0.01), but not for that of IKPS (0.02% vs. 0.03%, p = 0.29). Patients taking aspirin for ≥ 90 days had a significantly lower risk for KP-PLA (hazard ratio, 0.67; 95%CI, 0.50-0.90). Females, taking clopidogrel or metformin for ≥ 90 days, and taking H2-blockers or proton pump inhibitors (PPIs) for ≥ 5 days were also associated with a lower risk of KP-PLA. However, cholangitis and a glycated hemoglobin ≥ 8.5% were associated with an increased risk of KP-PLA.

Incidence and risk factors of colonoscopic post-polypectomy bleeding and perforation in patients with end-stage renal disease.

BACKGROUND AND AIMS: Colonoscopic polypectomy in end-stage renal disease (ESRD) patients are at risks of post-polypectomy bleeding and perforation, but evidences are limited. This study aimed to determine the incident polypectomy complications among ESRD patients. METHODS: In the nationwide ESRD cohort, a propensity score matched case-control study design was conducted to assess risk associated with post-polypectomy bleeding and perforation using the Taiwanese National Health Insurance Research Database from 1997 to 2013 for adults aged 40 years and older; 7011 ESRD and 19 118 non-ESRD patients met the study criteria. A total of 5302 patients in each group were matched for further analyses. The primary endpoint was post-polypectomy bleeding or bowel perforation in 30 days. The secondary endpoint was mortality and length of hospital stay for the bleeding complications requiring hospitalization. RESULTS: Overall incidences of post-polypectomy bleeding or perforation in patients with ESRD was higher than the non-ESRD group (5.83% vs 1.78%, P < 0.0001) in the matched cohort. High risk of adverse outcomes was associated with ESRD (adjusted odds ratio [aOR], 2.38, 95% confidence interval [CI], 1.85-3.05), female patient (aOR, 1.7, 95% CI, 1.37-2.11), history of acute myocardial infarction (aOR, 1.91, 95% CI, 1.1-3.32), liver disease (aOR, 1.79, 95% CI, 1.37-2.34), diabetes (aOR, 1.45, 95% CI, 1.16-1.82), cancer (aOR, 1.4, 95% CI, 1.09-1.81), inpatient setting (aOR, 13.19, 95% CI, 9.73-17.88), and prior use of clopidogrel (aOR, 1.61, 95% CI, 1.03-2.52) and warfarin (aOR, 2.03, 95% CI, 1.21-3.41). CONCLUSIONS: End-stage renal disease was associated with approximately twofold higher risk of colonoscopic post-polypectomy bleeding or perforation and should be cautiously performed in this special population cohort.