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Background: Few large population-based studies have compared the incidence of bleeding of gastroduodenal ulcers between patients with and without end-stage renal disease. We investigated the association between ulcer bleeding and end-stage renal disease in patients receiving hemodialysis, and we sought to identify risk factors for ulcer bleeding.Methods: We performed a nationwide seven-year population study using data from the National Health Insurance Research Database in Taiwan. We identified 36 474 patients with end-stage renal disease who were receiving hemodialysis, 6320 patients with chronic kidney disease and 36 034 controls matched for age, sex and medication use. We performed log-rank testing to analyze differences in survival time without ulcer bleeding among the three groups. We performed Cox proportional hazard regressions to evaluate the risk factors for ulcer bleeding among the three groups and to identify risk factors in patients receiving hemodialysis.Results: Patients receiving hemodialysis and those with chronic kidney disease had a significantly higher incidence of ulcer bleeding than controls had (p<0.001). Hemodialysis (hazard ratio [HR] 5.24, 95% confidence interval [CI] 4.67-5.86) and chronic kidney disease (HR 1.95, 95% CI 1.62-2.35) were independently associated with an increased risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and use of nonsteroidal anti-inflammatory drugs were risk factors for ulcer bleeding in patients with end-stage renal disease who were receiving hemodialysisInterpretation: Patients with end-stage renal disease who are receiving hemodialysis had a high risk of ulcer bleeding. Diabetes mellitus, coronary artery disease, cirrhosis and the use of nonsteroidal anti-inflammatory drugs were important risk factors for ulcer bleeding in these patients. [ABSTRACT FROM AUTHOR]

Background: Surgical resection (SR) is the main treatment for small bowel adenocarcinoma (SBA), but it increases metabolic demand, systemic inflammation, and digestive dysfunction, resulting in major impacts on the postoperative outcomes of patients. In this study, we aimed to investigate the role of the postoperative prognostic nutritional index (PNI), a surrogate marker of inflammation and nutrition, in patients with SBA after resection., Methods: From June 2014 to March 2022, 44 consecutive patients who underwent SR for SBA in Taipei Veterans General Hospital were retrospectively reviewed. Factors associated with survival including PNI were analyzed., Results: PNI decreased in patients after SR for SBA (median change: -1.82), particularly in those who underwent Whipple operation or developed postoperative pancreatic fistula. Postoperative PNI <45.2 best predicted overall survival (OS) (area under the receiver operating characteristic curve [AUROC]: 0.826, p = 0.001). Patients with lower postoperative PNI had significantly worse OS compared to those with higher postoperative values (median OS: 19.3 months vs not reached, p < 0.001). Low postoperative PNI (hazard ratio [HR]: 11.404, p = 0.002), tumoral lymphovascular invasion (HR: 8.023, p = 0.012), and adjuvant chemotherapy (HR: 0.055, p = 0.002) were independent risk factors for OS. Postoperative PNI also significantly predicted recurrence-free survival independent of lymphovascular invasion and adjuvant chemotherapy (HR: 6.705, p = 0.001)., Conclusion: PNI commonly decreases in patients with SBA who undergo Whipple surgery or develop postoperative pancreatic fistula. Postoperative PNI independently predicts survival and may serve as a clinical marker to optimize patient outcomes., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: The benefits of HCV eradication on distinct recurrence patterns and long-term hepatic outcomes in patients with hepatocellular carcinoma (HCC) undergoing radiofrequency ablation (RFA) remain uncertain. This study aims to assess the impact of HCV eradication on HCC recurrence patterns and long-term hepatic outcomes after RFA and to identify predictors of recurrence in patients achieving sustained virological response (SVR)., Methods: We retrospectively enrolled 274 patients receiving RFA for HCV-related HCC, including 73 and 88 patients treated with interferon-based (IFN) and direct-acting antivirals (DAA) therapy, respectively. We analysed factors associated with local tumour progression (LTP), distant recurrence, overall survival, and hepatic decompensation., Results: SVR was achieved in 49.3% of patients undergoing IFN therapy and 93.2% of patients undergoing DAA therapy. HCV eradication was not associated with LTP but significantly correlated with reduced risk of distant recurrence (by DAA: hazard ratio (HR) = 0.449, p = 0.006), overall survival (by IFN: HR = 0.242, p < 0.001; by DAA: HR = 0.274, p < 0.001) and hepatic decompensation (by IFN: HR = 0.313, p = 0.004; by DAA: HR = 0.281, p < 0.001). The benefits of achieving SVR in terms of overall survival and hepatic decompensation remained significant in subgroups of patients with and without recurrence. Patients with SVR showed a significant decline in FIB-4 score and a higher proportion of ALBI grade improvement. Among SVR patients, the IMbrave050 criteria predicted LTP but not distant recurrence, whereas the FIB-4 score after SVR, rather than the baseline FIB-4, predicted distant recurrence., Conclusions: HCV eradication was associated with a significant reduction in distant recurrence, mortality and hepatic decompensation following RFA in patients with HCV-related HCC., (© 2024 John Wiley & Sons Ltd.)

Background: Portal hypertension affects hepatic, splanchnic and portosystemic collateral systems. Although alcohol is a well-known risk factor for liver cirrhosis, it also affects vascular contractility. However, the relevant effects on portal hypertension have not been evaluated in non-alcoholic cirrhosis. The present study aimed to investigate the impacts of low-dose alcohol on portal hypertension-related derangements in non-alcoholic cirrhotic rats., Methods: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The chronic or acute effects of low-dose alcohol (2.4 g/kg/day, oral gavage, approximately 1.3 drinks/day in humans) were evaluated., Results: The chronic administration of low-dose alcohol did not precipitate liver fibrosis in the sham or cirrhotic rats; however, it significantly increased splanchnic blood inflow (P=0.034) and portosystemic collaterals (P=0.001). Mesenteric angiogenesis and pro-angiogenic proteins were up-regulated in the alcohol-treated cirrhotic rats, and poorer collateral vasoresponsiveness to vasoconstrictors (P<0.001) was noted. Consistently, acute alcohol administration reduced splenorenal shunt resistance. Collateral vasoresponsiveness to vasoconstrictors also significantly decreased (P=0.003)., Conclusions: In non-alcoholic cirrhosis rats, a single dose of alcohol adversely affected portosystemic collateral vessels due to vasodilatation. Long-term alcohol use precipitated splanchnic hyperdynamic circulation, in which mesenteric angiogenesis played a role. Further studies are warranted to evaluate the benefits of avoiding low-dose alcohol consumption in patients with non-alcoholic cirrhosis., (© 2024 The Author(s).)

Background & Aims: Immune checkpoint inhibitors (ICIs) can restore exhausted T cell immunity not only for cancer treatment but also potentially for curing chronic hepatitis B (CHB). The impact of ICIs on Hepatitis B surface antigen (HBsAg) seroclearance in cancer patients was unclear., Methods: Consecutive cancer patients from 2016 to 2020 (Cohort 1, n=118), and hepatocellular carcinoma (HCC) patients from 2020 to 2022 (Cohort 2, n=44, as validation) receiving ICIs and positive for HBsAg were retrospectively recruited. An additional hepatitis B virus (HBV)-HCC cohort (Cohort 3, n=85) without ICI served as a control group. Factors associated with HBsAg loss or combining HBsAg decline >1 log were analyzed., Results: With median follow-up of 17.5 months, 8 (6.8%) in cohort 1 and 4 (9.1%) in cohort 2 achieved HBsAg seroclearance, and additional 4 in cohort 1 and 1 in cohort 2 had HBsAg decline >1 log. In multivariate analysis, HBsAg <100 IU/mL was associated with HBsAg seroclearance (HR=6.274, p=0.028). In the validation cohort, the cumulative incidence of HBsAg loss at months 12 and 24 was 13.0% and 38.4% for baseline HBsAg <100 IU/ml, which were significantly higher than those in the control group (p=0.0267). While no case in cohort 3 achieved HBsAg within 24 months. Of the 17 cases achieved HBsAg loss and decline >1 log, 16 (94.1%) had nucleos(t)ide analogs treatment. The median time to HBsAg loss or HBsAg decline was 16.5 months (ranged 9.6 to 27.5)., Conclusions: ICIs may accelerate HBsAg seroclearance in cancer patients with baseline HBsAg <100 IU/ml. This finding provides important information for the design of future ICI trials to achieve functional cure in patients with CHB., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interests. Please refer to the accompanying ICMJE disclosure forms for further details., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Portal hypertension leads to lethal complications in liver cirrhosis. Oxidative stress induced hepatic vascular dysfunction, which exaggerated vasoconstriction and increases hepatic vascular resistance (HVR). Gut dysbiosis further exacerbates portal hypertension. Fructooligosaccharides are prebiotics with potent antioxidant effect. This study aimed to evaluate the roles of fructooligosaccharides in portal hypertension-related vascular dysregulation and gut microbiome., Methods: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as controls. The rats then randomly received fructooligosaccharides or vehicle for 4 weeks. Experiments were performed on the 29th day after operations., Results: Fructooligosaccharides did not affect portal pressure. Interestingly, fructooligosaccharides significantly attenuated HVR (p = .03). Malondialdehyde, an oxidative stress marker, reduced significantly in the liver in fructooligosaccharides-treated group. In addition, superoxide dismutase and trolox equivalent antioxidant capacity increased in the treatment group. On the other hand, vasodilatation-related protein expressions, GTPCH and phospho-eNOS, enhanced significantly. Fructooligosaccharides had no adverse vasodilatation effects on splanchnic vascular system or porto-systemic collateral systems. Locomotor function was not affected by fructooligosaccharides. Faecal microbiota analysis showed that Negativicutes, Selenomonadales and Lactobacillus salivarius reduced in the fructooligosaccharides-treated group., Conclusion: In conclusion, fructooligosaccharides attenuate hepatic vascular dysfunction in cirrhotic rats via at least partly, ameliorate of dysbiosis and oxidative stress., (© 2024 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)

Background/aims: The performance of machine learning (ML) in predicting the outcomes of patients with hepatocellular carcinoma (HCC) remains uncertain. We aimed to develop risk scores using conventional methods and ML to categorize early-stage HCC patients into distinct prognostic groups., Methods: The study retrospectively enrolled 1,411 consecutive treatment-naïve patients with the Barcelona Clinic Liver Cancer (BCLC) stage 0 to A HCC from 2012 to 2021. The patients were randomly divided into a training cohort (n=988) and validation cohort (n=423). Two risk scores (CATS-IF and CATS-INF) were developed to predict overall survival (OS) in the training cohort using the conventional methods (Cox proportional hazards model) and ML-based methods (LASSO Cox regression), respectively. They were then validated and compared in the validation cohort., Results: In the training cohort, factors for the CATS-IF score were selected by the conventional method, including age, curative treatment, single large HCC, serum creatinine and alpha-fetoprotein levels, fibrosis-4 score, lymphocyte-tomonocyte ratio, and albumin-bilirubin grade. The CATS-INF score, determined by ML-based methods, included the above factors and two additional ones (aspartate aminotransferase and prognostic nutritional index). In the validation cohort, both CATS-IF score and CATS-INF score outperformed other modern prognostic scores in predicting OS, with the CATSINF score having the lowest Akaike information criterion value. A calibration plot exhibited good correlation between predicted and observed outcomes for both scores., Conclusion: Both the conventional Cox-based CATS-IF score and ML-based CATS-INF score effectively stratified patients with early-stage HCC into distinct prognostic groups, with the CATS-INF score showing slightly superior performance.

Background: Links have been reported between the airflow limitation and both metabolic syndrome (MetS) and fatty liver (FL). Additionally, associations between genetic factors and risks of MetS, FL, and airflow limitation have been identified separately in different studies. Our study aims to simultaneously explore the association between specific single nucleotide polymorphisms (SNPs) of certain genes and the risk of the three associated diseases., Methods: In this retrospective cross-sectional nationwide study, 150,709 participants from the Taiwan Biobank (TWB) were enrolled. We conducted a genotype-phenotype association analysis of nine SNPs on seven genes (ApoE-rs429358, MBOAT7-rs641738, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, TM6SF2-rs58542926, and IFNL4-rs368234815) using data from the TWB1.0 and TWB2.0 genotype dataset. Participants underwent a series of assessments including questionnaires, blood examinations, abdominal ultrasounds, and spirometry examinations., Results: MetS was associated with FL and airflow limitation. ApoE-rs429358, LEPR-rs1805096, APOC3-rs2854116, APOC3-rs2854117, PPP1R3B-rs4240624, PPP1R3B-rs4841132, and TM6SF2-rs58542926 were significantly associated with the risk of MetS. The cumulative impact of T alleles of ApoE-rs429358 and TM6SF2-rs58542926 on the risk of FL was observed (p-value for trend < 0.001). Individuals without MetS and airflow limitation carrying LEPR-rs1805096 G&#95;G genotype exhibited a reduction in the forced expiratory volume in 1 s percentage prediction (Coefficient -35, 95 % confidence interval (CI) -69.7- -0.4), low forced vital capacity percentage prediction (Coefficient -41.6, 95 % CI -82.6- -0.6), and low vital capacity percentage prediction (Coefficient -42.2, 95 % CI -84.2- -0.1)., Conclusions: MetS significantly correlated with FL and airflow limitation. Multiple SNPs were notably associated with MetS. Specifically, T alleles of ApoE-rs429358 and TM6SF2-rs58542926 cumulatively increased the risk of FL. LEPR-rs1805096 shows a trend-wise association with pulmonary function, which is significant in patients without MetS or airflow limitation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Infection-related lipopolysaccharide (LPS) release causes cytokine storm and acute lung injury. Emerging data show that the interleukin 6 (IL-6) inhibitor tocilizumab can improve lung damage in patients with sepsis. This study aimed to investigate the therapeutic effect of tocilizumab on acute lung injury in cirrhotic rats. Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Tocilizumab was administered on post-operative day 21, and LPS was injected intraperitoneally on day 29. Three hours after LPS injection, hemodynamic parameters, biochemistry data, and arterial blood gas analysis were evaluated, along with measurements of IL-6 and tumor necrosis factor-α (TNF-α). Liver and lung histology was examined, and protein levels were analyzed. LPS administration reduced portal pressure, portal venous flow and cardiac index in the BDL rats. In addition, LPS administration induced acute lung injury, hypoxia and elevated TNF-α and IL-6 levels. Pre-treatment with tocilizumab did not affect hemodynamic and biochemistry data, but it ameliorated lung injury and decreased TNF-α, IL-6, and CD68-positive macrophage infiltration. Moreover, tocilizumab administration improved hypoxia and gas exchange in the BDL rats, and downregulated hepatic and pulmonary inflammatory protein expression. In conclusion, LPS administration induced acute lung injury in biliary cirrhotic rats. Pre-treatment with tocilizumab reduces lung damage and hypoxia, possibly by downregulating inflammatory proteins and reducing IL-6, TNF-α and CD68-positive macrophage recruitment in the lung., Competing Interests: Declaration of competing interest The authors would like to acknowledge the Clinical Research Core Laboratory of Taipei Veterans General Hospital for providing the experimental space and facilities. This work was supported by grants from the Taipei Veterans General Hospital (V112D-65-003-MY2-1) and the Szu-Zuan Research Foundation of Internal Medicine (grant nos. 111025), Taipei, Taiwan. The funders played no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Although the link between hepatic steatosis and lung function has been confirmed, the focus has largely been on central airways. The association between hepatic steatosis and increased peripheral airway resistance has not yet been explored. Hepatic steatosis and increased peripheral resistance are connected with immunity dysregulation. High neutrophil-to-lymphocyte ratio (NLR) and low lymphocyte-to-monocyte ratio (LMR) have been recognized as indicators of immunity dysregulation. In this study, the association between hepatic steatosis and increased peripheral airway resistance was evaluated, and the effect of immunity dysregulation (high NLR/low LMR) on the increased peripheral airway resistance among patients with hepatic steatosis was explored. In this retrospective study, chest or abdomen CT scans and spirometry/impulse oscillometry (IOS) from 2018 to 2019 were used to identify hepatic steatosis and increased central/peripheral airway resistance in patients. Among 1391 enrolled patients, 169 (12.1%) had hepatic steatosis. After 1:1 age and abnormal ALT matching was conducted, clinical data were compared between patients with and without hepatic steatosis. A higher proportion of patients with hepatic steatosis had increased peripheral airway resistance than those without hepatic steatosis (52.7% vs 40.2%, P = .025). Old age, high body mass index, history of diabetes, and high NLR/low LMR were significantly correlated with increased peripheral airway resistance. The presence of hepatic steatosis is associated with increased peripheral airway. High NLR/low LMR is an independent associated factor of increased peripheral airway resistance in patients with hepatic steatosis. It is advisable for patients with hepatic steatosis to regularly monitor their complete blood count/differential count and undergo pulmonary function tests including IOS., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aim: The association between long-term proton-pump inhibitors (PPIs) use and malignancies had long been discussed, but it still lacks consensus. Our study investigated the association between PPI use and hepatocellular carcinoma (HCC) recurrence following curative surgery., Methods: We retrospectively enrolled 6037 patients with HCC who underwent hepatectomy. Patients were divided into four groups according to their PPI usage. (non-users: < 28 cumulative defined daily dose [cDDD]; short-term users: 28-89 cDDD; mid-term users: 90-179 cDDD, and long-term users: ≥ 180 cDDD, respectively). Recurrence-free survival (RFS) and overall survival (OS) were analyzed using Kaplan-Meier method and Cox proportional hazard models., Results: Among the 6037 HCC patients, 2043 (33.84%) were PPI users. PPI users demonstrated better median RFS (3.10 years, interquartile range [IQR] 1.49-5.01) compared with non-users (2.73 years, IQR 1.20-4.74; with an adjusted hazard ratio [aHR] of 0.57, 95% confidence interval [CI] 0.44-0.74, P < 0.001). When considering the cumulative dosage of PPI, only long-term PPI users had significant lower risk of HCC recurrence than non-PPI group (adj-HR: 0.50; 95% CI: 0.35-0.70; P < 0.001). Moreover, the impact of long-term PPIs use on improving RFS was significant in most of the subgroup analysis, except in patients with advanced tumor stages, with non-cirrhosis, or with a history of chronic kidney disease. However, there were no significant differences in median OS between PPI users and non-users (4.23 years, IQR 2.73-5.86 vs 4.04 years, IQR 2.51-5.82, P = 0.369)., Conclusion: Long-term PPI use (≥ 180 cDDD) may be associated with a better RFS in HCC patients after hepatectomy., (© 2024 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: Nutritional administration in acute pancreatitis (AP) management has sparked widespread discussion, yet contradictory mortality results across meta-analyses necessitate clarification. The optimal nutritional route in AP remains uncertain. Therefore, this study aimed to compare mortality among nutritional administration routes in patients with AP using consistency model., Methods: This study searched four major databases for relevant randomized controlled trials (RCTs). Two authors independently extracted and checked data and quality. Network meta-analysis was conducted for estimating risk ratios (RRs) with 95% confidence interval (CI) based on random-effects model. Subgroup analyses accounted for AP severity and nutrition support initiation., Results: A meticulous search yielded 1185 references, with 30 records meeting inclusion criteria from 27 RCTs (n = 1594). Pooled analyses showed the mortality risk reduction associated with nasogastric (NG) (RR = 0.34; 95%CI: 0.16-0.73) and nasojejunal (NJ) feeding (RR = 0.46; 95%CI: 0.25-0.84) in comparison to nil per os. Similarly, NG (RR = 0.45; 95%CI: 0.24-0.83) and NJ (RR = 0.60; 95%CI: 0.40-0.90) feeding also showed lower mortality risk than total parenteral nutrition. Subgroup analyses, stratified by severity, supported these findings. Notably, the timing of nutritional support initiation emerged as a significant factor, with NJ feeding demonstrating notable mortality reduction within 24 and 48 h, particularly in severe cases., Conclusion: For severe AP, both NG and NJ feeding appear optimal, with variations in initiation timings. NG feeding does not appear to merit recommendation within the initial 24 h, whereas NJ feeding is advisable within the corresponding timeframe following admission. These findings offer valuable insights for optimizing nutritional interventions in AP., (© 2024 The Association for the Publication of the Journal of Internal Medicine.)

Background and Aims: Liver cirrhosis is often associated with type 2 diabetes (T2D), but research on treatment of T2D in cirrhotic patients is scarce. We investigated the long-term outcomes of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with T2D and cirrhosis., Methods: Using propensity score matching, we selected 467 matched pairs of GLP-1 RA users and nonusers from the National Health Insurance Research Database of Taiwan from January 1, 2008, to December 31, 2019. Multivariable-adjusted Cox proportional hazards models were used to compare the outcomes between GLP-1 RA users and nonusers., Results: The mean follow-up time was 3.28 and 3.06 years for GLP-1 RA users and nonusers, respectively. The rates of death were 27.46 and 55.90 per 1000 person-years for GLP-1 RA users and nonusers, respectively. The multivariable-adjusted models showed that GLP-1 RA users had lower risks of mortality (adjusted hazard ratio [aHR], 0.47; 95% confidence interval [CI], 0.32-0.69), cardiovascular events (aHR, 0.6; 95% CI, 0.41-0.87), decompensated cirrhosis (aHR, 0.7; 95% CI, 0.49-0.99), hepatic encephalopathy (aHR, 0.59; 95% CI, 0.36-0.97), and liver failure (aHR, 0.54; 95% CI, 0.34-0.85) than nonusers. A longer cumulative duration of GLP-1 RA use had a lower risk of these outcomes than GLP-1 RA nonuse., Conclusions: This population-based cohort study showed that GLP-1 RA users exhibited a significantly lower risk of death, cardiovascular events, decompensated cirrhosis, hepatic encephalopathy, and liver failure in patients with T2D and compensated liver cirrhosis. Additional studies are needed to confirm our results., (Copyright © 2024 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Background: Gallstone disease is a common health problem worldwide. The role of the gut microbiota in gallstone pathogenesis remains obscure. Our aim was to evaluate the association and crosstalk between gut microbiota, gut metabolomic, and metabolic parameters in cholesterol gallstone patients, pigmented gallstone patients, and controls., Methods: We collected stool samples from healthy individuals and patients with gallstones in our hospital from March 2019 to February 2021. 16s rRNA sequencing was performed, followed by differential abundance analyses. Measurement of bile acids and short-chain fatty acids was conducted via targeted metabolomics., Result: Thirty healthy individuals and 20 gallstone patients were recruited. The intergroup difference of microbial composition was significant between control and gallstone patients. The control group had more abundant Faecalibacterium , Prevotella 9 , and Bacteroides plebeius DSM 17135 . The cholesterol stones group had higher Desulfovibrionaceae and Bacteroides uniformis than the other two groups, while the pigment stone group had more abundant Escherichia-Shigella . In the analysis of metabolites, only n-butyric acid had a significantly higher concentration in the controls than in the gallstone group ( p < 0.01). The level of 3α-hydroxy-12 ketolithocholic acid, deoxycholic acid, and cholic acid showed no intergroup differences but was correlated to the serum cholesterol level and bacterial richness and evenness., Conclusion: Our study revealed the key taxa that can discriminate between individuals with or without gallstones. We also identified metabolites that are possibly associated with metabolic parameter and bacterial diversity. However, the correlation of the metabolites to certain clusters of bacteria should be analyzed in a larger cohort., Competing Interests: Conflicts of interest: Dr. Yi-Hsiang Huang and Dr. Ming Hou, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Objective: Previous studies have suggested that body mass index (BMI) should be considered when assessing the relationship between fatty liver (FL) and osteoporosis. The aim of this study was to investigate future fracture events in people with FL, focusing on the effect of BMI in both sexes., Methods: This retrospective cohort study from 2011 to 2019 enrolled 941 people, including 441 women and 500 men, aged 50 years or older who underwent liver imaging (ultrasound, computed tomography, or magnetic resonance image) and dual-energy X-ray absorptiometry (DXA, for bone mineral density measurements). The study examined predictors of osteoporosis in both sexes, and the effect of different ranges of BMI (18.5-24, 24-27, and ≥27 kg/m2 in women; 18.5-24, 24-27, 27-30 and ≥30 kg/m2 in men) on the risk of future fractures in FL patients., Results: The average follow-up period was 5.3 years for women and 4.2 years for men. Multivariate analysis identified age and BMI as independent risk factors for osteoporosis in both sexes. Each unit increase in BMI decreased the risk of osteoporosis by ≥10%. In both women and men with FL, a BMI of 24-27 kg/m2 offered protection against future fractures, compared to those without FL and with a BMI of 18.5-24 kg/m2., Conclusion: The protective effect of a higher BMI against future fractures in middle-aged and elderly women and men with FL is not uniform and decreases beyond certain BMI ranges.

Background: In liver cirrhosis, chronic inflammation is associated with an increase in oxidative stress, and subsequently an increase in the concentration of oxidized low-density lipoprotein (ox-LDL). Ezetimibe is a lipid-lowering agent with anti-inflammation and anti-oxidative stress activities. This study aimed to investigate the effect of ezetimibe treatment on ox-LDL in cirrhotic rats., Methods: Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. Ezetimibe (10 mg/kg/d) or vehicle was administered in the sham-operated or BDL rats for 4 weeks, after which hemodynamic parameters, biochemistry data, and oxidative stress were evaluated. Plasma and intrahepatic ox-LDL levels were also examined, and hepatic proteins were analyzed to explore the mechanism of ezetimibe treatment., Results: The BDL rats had typical features of cirrhosis including jaundice, impaired liver function, hyperlipidemia, and elevated ox-LDL levels compared to the sham-operated rats. Ezetimibe treatment did not affect hemodynamics, liver biochemistry, or plasma lipid levels. However, it significantly reduced oxidative stress, plasma levels of ox-LDL, and tumor necrosis factor α. In addition, ezetimibe upregulated the hepatic protein expression of an ox-LDL scavenger (lectin-like ox-LDL rececptor-1), which resulted in reductions in intrahepatic ox-LDL and fat accumulation in the BDL rats. Nevertheless, ezetimibe treatment did not ameliorate hepatic inflammation or liver fibrosis., Conclusion: Ezetimibe reduced plasma and intrahepatic ox-LDL levels in the cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, ezetimibe did not alleviate hepatic fibrosis or inflammation in the biliary cirrhotic rats., Competing Interests: Conflicts of interest: Dr. Ching-Chih Chang, Dr. Hui-Chun Huang, Dr. Ming-Chih Hou, and Dr. Fa-Yauh Lee, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Introduction: Field factors play more important roles in predicting the outcomes of patients compared with tumor factors in early-stage hepatocellular carcinoma (HCC). However, the prognostic ability of noninvasive serum marker scores for hepatic fibrosis and liver functional reserve on very early-stage HCC is still not yet determined. We aimed to investigate the performance of these serum marker scores in predicting the prognoses of patients with very early-stage HCC., Methods: A total of 446 patients with very early-stage HCC from 2012 to 2022 were retrospectively enrolled. Serum biomarkers and prognostic scores determining overall survival (OS) were analyzed by Cox proportional hazards model. We compared the Akaike information criterion among the prognostic nutritional index (PNI), aspartate aminotransferase-to-platelet ratio index, albumin-bilirubin (ALBI) score, EZ (easy)-ALBI score, modified ALBI score, fibrosis-4 score, and lymphocyte-to-monocyte ratio to determine the predictability on the OS., Results: After a median follow-up of 41.0 months (interquartile range 36.9-45.1 months), 81 patients died, with a 5-year OS rate of 71.0%. Among the noninvasive serum marker scores, PNI had the best performance in predicting the OS with the lowest Akaike information criterion (846.407) compared with other scores. Moreover, we stratified the patients into high-risk (PNI <45) and low-risk (PNI ≥45) groups. It showed that the 5-year OS rates were 83.4% and 60.8% in the low-risk and high-risk PNI groups, respectively ( P < 0.001)., Discussion: PNI had the best performance in predicting the OS for patients with very early-stage HCC., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: Device-assisted enteroscopy has been used for over 20 years for the management of patients with suspected small bowel bleeding. Unlike esophagogastroduodenoscopy and colonoscopy, the appropriate timing of enteroscopy is still unknown. In recent guidelines, early enteroscopy is suggested to maximize diagnostic yield and therapeutic yield in patients with suspected small bowel bleeding. However, few studies have identified its influence on clinical outcomes, including mortality or rebleeding rate. We conducted this study to evaluate the influence of the timing of double-balloon enteroscopy on clinical outcomes in patients with suspected small bowel bleeding., Methods: Patients with overt small bowel bleeding who underwent double-balloon enteroscopy from January 2013 to February 2021 were retrospectively reviewed. Patients were categorized into an early enteroscopy group (≤14 days) and a nonearly enteroscopy group (>14 days). Clinical outcomes, including short-term mortality and rebleeding rate, long-term mortality and rebleeding rate, diagnostic yield, and therapeutic yield, were analyzed., Results: A total of 100 patients (mean age, 66.2 years; 53% male) were included, and 44 patients were stratified into the early enteroscopy group. The diagnostic yield, therapeutic yield, mortality, and rebleeding rate were similar between two groups. In multivariate conditional logistic regression analysis, there were no significant differences between two groups regarding the 30-day rebleeding rate (adjusted odds ratio [aOR], 1.43; 95% CI, 0.47-4.33), 90-day rebleeding rate (aOR, 1.18; 95% CI, 0.47-2.94), 30-day mortality rate (aOR, 1.29; 95% CI, 0.21-8.13), 90-day mortality rate (aOR, 1.94; 95% CI, 0.48-7.87), and 90-day bleeding-related mortality (aOR, 2.18; 95% CI, 0.24-19.52). The Kaplan-Meier survival curve analysis showed that the timing of DBE was not associated with the long-term rebleeding rate or mortality rate ( p = 0.57 and 0.83, respectively)., Conclusion: The timing of enteroscopy did not influence the clinical outcomes, including the short-term mortality rate, short-term rebleeding rate, long-term mortality rate, and rebleeding rate, in patients with suspected overt small bowel bleeding., Competing Interests: Conflicts of interest: Dr. Ming-Chih Hou, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: The introduction of direct-acting antiviral agents (DAAs) has revolutionized the therapeutic landscape of chronic hepatitis C (CHC), however real-world data on the risk factors of hepatocellular carcinoma (HCC) recurrence following DAA treatment in CHC-HCC patients are limited in Taiwan. We aimed to evaluate the therapeutic efficacy of DAAs in Taiwanese patients with prior hepatitis C virus (HCV)-induced HCC and identify the posttreatment risk factors for HCC recurrence., Methods: Between January 2017 and August 2021, 208 CHC-HCC patients underwent DAA treatment at Taipei Veterans General Hospital. Among them, 94 patients met the inclusion criteria (Barcelona clinic liver cancer [BCLC] stage 0/A after treatment with complete radiological response) for analysis. Comprehensive demographic, clinical, and laboratory data were collected before and after DAA treatment. The primary outcome was HCC recurrence post-DAA treatment, and independent variables were assessed using multivariate Cox proportional hazards models., Results: The mean age of the enrolled patients was 75.9 ± 8.9 years; 44.7% were male, and 94.7% were Child-Pugh class A. Before DAA treatment, 31.9% experienced HCC recurrence. The median follow-up after DAA treatment was 22.1 months (interquartile range, 8.6-35.9 months). After treatment, 95.7% of the patients achieved a sustained virological response (SVR 12 ), but HCC recurrence occurred in 54.3%. Cumulative HCC recurrence rates after treatment were 31.1% at 1 year, 57.3% at 3 years, and 68.5% at up to 5.69 years. Multivariate analysis revealed that prior HCC recurrence before DAA treatment (hazard ratio [HR] = 3.15, p = 0.001), no SVR 12 after treatment (HR = 6.829, p = 0.016), 12-week posttreatment alpha-fetoprotein (AFP) level >10 ng/mL (HR = 2.34, p = 0.036), and BCLC A3 lesions (two or three nodules without any tumor exceeding 3 cm) (HR = 2.31, p = 0.039) were independent risk factors for HCC recurrence. We further developed a risk stratification system based on these significant independent factors., Conclusion: This investigation underscores the critical influence of factors such as prior HCC recurrence, successful attainment of SVR 12 , posttreatment AFP level, and specific tumor characteristics in determining the risk of HCC recurrence after treatment with DAAs. Our proposed innovative risk stratification system may not only contribute to enhanced personalized care but also holds the potential to optimize treatment outcomes., Competing Interests: Conflicts of interest: Dr. Chien-Wei Su, Dr. Fa-Yauh Lee, Dr. Yi-Hsiang Huang, and Dr. Ming-Chih Hou, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2024, the Chinese Medical Association.)

Background: Esophageal squamous cell neoplasms (ESCNs) are common second primary tumors in patients with head and neck cancer. Image-enhanced endoscopy (IEE) with Lugol chromoendoscopy or magnifying narrow-band imaging both increase the detection of early ESCNs. No evidence-based ESCN surveillance program for head and neck cancer patients without a history of synchronous ESCNs exists. We aimed to evaluate the performance of an IEE surveillance program with magnifying narrow-band imaging endoscopy and Lugol chromoendoscopy., Methods: From April 2016, we routinely used IEE with magnifying narrow-band imaging and Lugol chromoendoscopy to evaluate patients with head and neck cancer history. All patients who were negative for ESCNs at the first surveillance endoscopy and received at least 2 IEEs through December 2019 were included. Demographic profiles, clinical data, cancer characteristics, IEE results and pathology reports were analyzed., Results: A total of 178 patients were included. Only 4 patients (2.2%) developed metachronous ESCNs during follow-up, all of whom received curative resection treatment. The interval for the development of metachronous ESCNs was 477 to 717 days. In multivariate Firth logistic regression and Kaplan‒Meier survival curve analysis, Lugol's voiding lesion type C had an increased risk of esophageal cancer development (adjusted odds ratio = 15.71; 95% confidence interval, 1.33-185.87, p = 0.029). Eight patients died during the study period, and none of them had metachronous ESCNs., Conclusions: IEE with magnifying narrow-band imaging and Lugol chromoendoscopy is an effective surveillance program in head and neck cancer patients without a history of ESCNs. Annual surveillance can timely detect early ESCNs with low ESCN-related mortality., (© 2024. The Author(s) under exclusive licence to The Japan Esophageal Society.)

Objective: This randomised trial aimed to address whether endoscopic variceal ligation (EVL) or propranolol (PPL) is more effective at preventing initial oesophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC)., Design: Patients with HCC and medium-to-large oesophageal varices (EVs) but without previous EVB were randomised to receive EVL (every 3-4 weeks until variceal eradication) or PPL (up to 320 mg daily) at a 1:1 ratio. Long-term follow-up data on EVB, other upper gastrointestinal bleeding (UGIB), non-bleeding liver decompensation, overall survival (OS) and adverse events (AEs) were analysed using competing risk regression., Results: Between June 2011 and April 2021, 144 patients were randomised to receive EVL (n=72) or PPL (n=72). In the EVL group, 7 patients experienced EVB, and 30 died; in the PPL group, 19 patients had EVB, and 40 died. The EVL group had a lower cumulative incidence of EVB (Gray's test, p=0.009) than its counterpart, with no mortality difference (Gray's test, p=0.085). For patients with Barcelona Clinic Liver Cancer (BCLC) stage A/B, EVL was better than PPL in reducing EVB (p<0.001) and mortality (p=0.003). For patients beyond BCLC stage B, between-group outcomes were similar. Other UGIB, non-bleeding liver decompensation and AEs did not differ between groups. A competing risk regression model confirmed the prognostic value of EVL., Conclusion: EVL is superior to PPL in preventing initial EVB in patients with HCC. The benefits of EVL on EVB and OS may be limited to patients with BCLC stage A/B and not to those with BCLC stage C/D., Trial Registration Number: NCT01970748., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

HCV NS5A is a dimeric phosphoprotein involved in HCV replication. NS5A inhibitors are among direct-acting antivirals (DAA) for HCV therapy. The Y93H mutant of NS5A is resistant to NS5A inhibitors, but the precise mechanism remains unclear. In this report, we proposed a Ser38-His93-Asn91 triad to dissect the mechanism. Using pymol 1.3 software, the homology structure of JFH1 NS5A was determined based on the dimer structure of genotype 1b extracted from the database Protein DataBank (www.ebi.ac.uk/pdbsum) with codes 1ZH1 and 3FQM/3FQQ. FLAG-NS5A-WT failed to form dimer in the absence of nonstructural proteins from subgenomic replicon (NS3-5A); however, FLAG-NS5A-Y93H was able to form dimer without the aid of NS3-5A. The Ser38-His93-Asn91 triad in the dimer of the Y93H variant predicts a structural crash of the cleft receiving the NS5A inhibitor daclatasvir. The dimerization assay revealed that the existence of JFH1-NS5A-1ZH1 and -3FQM homology dimers depended on each other for existence and that both NS5A-WT 1ZH1 and 3FQM dimers cooperated to facilitate RNA replication. However, NS5A-Y93H 1ZH1 alone could form dimer and conduct RNA replication in the absence of the 3FQM structure. In conclusion, this study provides novel insight into the functional significance of the Ser38-His93-Asn91 triad in resistance of the Y93H variant to NS5A inhibitors., (© 2023 Federation of European Biochemical Societies.)

Hepatic encephalopathy (HE) is one of the major complications of liver disease and significantly affects the quality of life (QOL) of patients. HE is common and frequently relapses in cirrhotic patients. The management of HE is supportive, and precipitating conditions should be eliminated. Most drugs used to treat HE are conventional and include nonabsorbable disaccharides such as lactulose, and antibiotics such as rifaximin. However, their therapeutic efficacy is still suboptimal, and novel therapeutic agents are urgently needed. In addition, the optimal management and diagnosis of minimal HE/covert HE are under debate. In this review, we focus on novel pathogenetic mechanisms such as central nervous system clearance, and emerging therapeutic targets of HE, such as fecal material transplantation. We also discuss different classifications and etiologies of HE., Competing Interests: Conflicts of interest: Dr. Hui-Chun Huang, Dr. Ching-Chih Chang, Dr. Yi-Hsiang Huang, Dr. Ming-Chih Hou, and Dr. Fa-Yauh Lee, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: Performance status (PS) is associated with the severity of liver cirrhosis and is also an important survival determinant in hepatocellular carcinoma (HCC). Albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade have been proposed to evaluate liver dysfunction in HCC, but their role in patients with different PS is unclear. We aimed to investigate the prognostic role of ALBI and EZ-ALBI grade in a large HCC cohort with variable PS., Methods: A total of 3355 newly diagnosed HCC patients between 2002 and 2018 were identified and retrospectively analyzed. Independent prognostic predictors associated with survival were investigated using the Cox proportional hazards model., Results: Patients with poor PS had decreased survival compared with those with good PS. In the Cox model, creatinine ≥1.2 mg/dL, α-fetoprotein (AFP) ≥20 ng/mL, vascular invasion, distant metastasis, total tumor volume >100 cm 3 , presence of ascites, ALBI grades 2 and 3, EZ-ALBI grade 2 and grade 3, PS 1-4, and noncurative treatment were independently associated with higher mortality in the entire cohort (all p < 0.001). ALBI grade and EZ-ALBI grade can well stratify overall survival in subgroup patients with PS 0, PS 1-2, and PS 3-4 (all p < 0.001)., Conclusion: Patients with good PS have better long-term survival compared with those with poor PS. ALBI and EZ-ALBI grade can discriminate long-term outcome in the entire cohort as well as in patients with different PS. ALBI and EZ-ALBI are objective and feasible prognostic models to evaluate liver dysfunction in HCC patients independent of PS., Competing Interests: Conflicts of interest: Dr Teh-Ia Huo, an editorial board member at Journal of the Chinese Medical Association , had no role in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Introduction: Endoscopic variceal ligation (EVL) plus nonselective β-blockers (NSBB) is the standard of care for secondary prophylaxis of esophageal variceal bleeding (EVB). This trial aimed to compare the rebleeding rates between EVL plus NSBB till eradication of esophageal varices (EEV) and EVL plus long-term NSBB., Methods: After control of acute EVB, patients with cirrhosis were randomized into 2 groups, with group A patients receiving EVL plus propranolol till EEV, while group B patients received standard of care with continuation of propranolol. Recurrent varices were ligated at follow-up endoscopy in both groups., Results: The median follow-up period was 23.0 months in group A (n = 106) and 23.6 months in group B (n = 106). Twelve patients (11.3%) in group A and 11 (10.4%) in group B had recurrent EVB. The difference in rebleeding rates and the 95% confidence interval (CI) was 0.9% (-7.5% to 9.3%). The upper 95% CI bound of the difference was within the margin of 13.2%, and the noninferiority of group A to group B was established. Thirty-eight patients (35.8%) in group A and 40 (37.7%) in group B had further decompensation, with the difference (95% CI) of -1.9% (-14.9% to 11.1%). Twenty-four patients (22.6%) in group A and 26 (24.5%) in group B expired, with the difference (95% CI) in mortality rates of -1.9% (-13.3% to 9.5%)., Discussion: EVL plus propranolol till EEV was noninferior to EVL plus continuing propranolol in secondary prophylaxis of EVB, but the impact on further decompensation and transplantation-free survival deserved further investigation., (Copyright © 2023 by The American College of Gastroenterology.)

Aims: Hepatitis C virus (HCV) relies on the viral and host factors to complete its life cycle. It has evolved to profit from Akt activation at some stage in its life cycle through various mechanisms, notably by activating lipogenesis, which is crucial for infectious virions production., Materials and Methods: By employing an Akt-specific inhibitor, the impact of Akt on intracellular and extracellular infectivity was investigated. To ascertain the role of Akt in the HCV life cycle, the two-part cell culture-derived HCV infection protocol utilizing Akt1 small interfering RNAs (siRNAs) was implemented. The impact of Akt1 on intracellular HCV transition was determined using membrane flotation assay and proximity ligation assay coupled with Anti-Rab7 immunoprecipitation and immunofluorescence., Key Findings: Akt1 silencing reduced infectious virions release to a degree comparable to that of ApoE, a host component involved in the HCV assembly and release, suggesting Akt1 was critical in the late stage of the HCV life cycle. Extracellular infectivity of HCV was inhibited by brefeldin A, and the inhibitory effect was augmented by Akt1 silencing and partially restored by ectopic Akt1 expression. Immunofluorescence revealed that Akt1 inhibition suppressed the interaction between HCV core protein and lipid droplet. Akt1 silencing impeded the transition of HCV from the endoplasmic reticulum to the endosome and hence inhibited the secretion of HCV infectious virions from the late endosome., Significance: Our study demonstrates that Akt1 has an impact on the lipogenesis pathway and plays a critical role in the assembly and secretion of infectious HCV., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Hepatitis C virus (HCV) infection is recognized as a major causative agent of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. HCV non-structural protein 5A (NS5A) is a dimeric phosphoprotein with a hyperphosphorylated form to act as a switch that regulates HCV replication and assembly. NS5A inhibitors have been utilized as the scaffold for combination therapy of direct-acting antiviral agents (DAA). However, the mode of action of NS5A inhibitors is still unclear due to the lack of mechanistic detail regarding NS5A phosphorylation and dimerization in the HCV life cycle. It has been demonstrated that phosphorylation of NS5A at Ser235 is essential for RNA replication of the JFH1 strain. In this report, we found that NS5A phosphomimetic Ser235 substitution (Ser-to-Asp mutation) formed a dimer that was resistant to disruption by NS5A inhibitors as was the NS5A resistance-associated substitution Y93H. Phosphorylation of NS5A at Ser235 residue was required for the interaction of two NS5A-WT molecules in JFH1-based cell culture system but not absolutely required for dimerization of the NS5A-Y93H mutant. Interestingly, HCV nonstructural proteins from the subgenomic replicon NS3-5A was required for NS5A-WT dimerization but not required for NS5A-Y93H dimerization. Our data suggest that spontaneous Ser235 phosphorylation of NS5A and ensuing dimerization account for resistance of the JFH1/NS5A-Y93H mutant to NS5A inhibitors., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Patients with type 2 diabetes (T2D) tend to have nonalcoholic fatty liver disease (NAFLD) with poorer prognosis. We performed this research to compare the risks of cardiovascular diseases, cirrhosis, liver-related mortality, and cardiovascular mortality between glucagon-like peptide-1 receptor agonist (GLP-1 RA) use and no-use in patients with T2D without viral hepatitis., Methods: From January 1, 2008, to December 31, 2018, we used propensity-score matching to identify 31,183 pairs of GLP-1 RA users and nonusers from Taiwan's National Health Insurance Research Database. Multivariable-adjusted Cox proportional hazards models were used to examine the outcomes between the study and control groups., Results: The median (Q1, Q3) follow-up time for GLP-1 RA users and nonusers were 2.19 (1.35, 3.52) and 2.14 (1.19, 3.68) years, respectively. The all-cause mortality incidence rate was 5.67 and 13.06 per 1000 person-years for GLP-1 RA users and nonusers, respectively. Multivariable-adjusted analysis showed that GLP-1 RA use had significantly lower risks of all-cause mortality (aHR 0.48, 95%CI 0.43-0.53), cardiovascular events (aHR 0.92, 95%CI 0.86-0.99), cardiovascular death (aHR 0.57, 95%CI 0.45-0.72), and liver-related death (aHR 0.32, 95%CI 0.13-0.75). However, there was no significant difference in the risk of liver cirrhosis development, hepatic failure, and hepatocellular carcinoma compared to GLP-1 RA no-use., Conclusions: This nationwide cohort study showed that GLP-1 RA use was associated with a significantly lower risk of all-cause mortality, cardiovascular events, and cardiovascular death in patients with T2D among Taiwan population. More prospective studies are warranted to verify our results., (© 2023. The Author(s).)

Introduction: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel biomarker for liver fibrosis, but little is known about its role in cirrhosis-associated clinical outcomes. This study aimed to investigate the predictive role of M2BPGi in cirrhosis-associated complications., Methods: One hundred and forty-nine cirrhotic patients were retrospectively enrolled. Patients were followed up for 1 year, and cirrhosis-associated clinical events were recorded. Receiver operating characteristic curve (ROC) analysis was used to establish the values of the predictive models for cirrhotic outcomes, and Cox proportional hazards regression models were used to identify predictors of clinical outcomes., Results: Sixty (40.3%) patients experienced cirrhosis-associated clinical events and had higher M2BPGi levels compared to those without events (8.7 vs. 5.1 cutoff index, p &lt; 0.001). The most common cirrhosis-associated complications were bacterial infections (24.2%). On ROC analysis, M2BPGi to albumin ratio (M2BPGi/albumin) had comparable discriminant abilities for all cirrhosis-associated events (area under the ROC curve [AUC] = 0.74) compared with M2BPGi, Child-Pugh, model for end-stage liver disease, albumin-bilirubin scores, and neutrophil-to-lymphocyte ratio and was superior to M2BPGi alone for all bacterial infectious events (AUC = 0.80). Cox regression analysis revealed that the M2BPGi/albumin, but not M2BPGi alone, independently predicted all cirrhosis-associated events (hazard ratio [HR] = 1.34, p = 0.038) and all bacterial infectious events (HR = 1.51, p = 0.011) within 1 year. However, M2BPGi/albumin did not predict other cirrhotic complications and transplant-free survival., Discussion/conclusion: M2BPGi/albumin might serve as a potential prognostic indicator for patients with cirrhosis, particularly for predicting bacterial infections., (© 2024 S. Karger AG, Basel.)

The severity of liver functional reserve is an important prognostic predictor in hepatocellular carcinoma (HCC). The albumin-bilirubin (ALBI), easy (EZ)-ALBI, platelet-albumin-bilirubin (PALBI), platelet-albumin (PAL) score, and MELD 3.0 score are used to evaluate the severity of liver dysfunction. However, their prognostic role in HCC patients, specifically with renal insufficiency (RI), is unclear. We aimed to investigate the predictive accuracy of the five models in these patients. A total of 1120 newly diagnosed HCC patients with RI were enrolled. A multivariate Cox proportional analysis was used to identify independent predictors associated with survival. In the Cox model, older age, an α-fetoprotein ≥20 ng/mL, vascular invasion, a medium and high tumor burden score, poor performance status, a higher ALBI grade, an EZ-ALBI grade, a PALBI grade, a PAL grade, and MELD 3.0 score were all independently associated with decreased overall survival (all p < 0.001). Among the five liver reserve models, the ALBI grade is the best surrogate marker to represent liver functional reserve in terms of outcome prediction. The albumin-based liver reserve models (ALBI, EZ-ALBI, PALBI, and PAL) and MELD 3.0 are all feasible prognostic markers to indicate liver injury, specifically in HCC patients with RI. Among them, the ALBI grade is the most robust tool for survival prediction in these patients.

Background and Aim: Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal-oral route. In addition, the exclusion of multidrug-resistant organisms (MDROs) has been recommended since 2018. This task has become more complicated in the era of the coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is crucial to commence screening for SARS-CoV-2, alongside other traditional tests. Our aim was to investigate whether hidden carriers of SARS-CoV-2 were enrolled for stool donation, and the status of the presence or incidence of MDRO during fecal donation in Taiwan., Methods: Fecal products collected from March 2019 to December 2022 were tested for MDRO and nucleic acid amplification tests for SARS-CoV-2 using the pooling method. The period of fecal product collection crossed the time before and during the COVID pandemic in Taiwan., Results: A total of 151 fecal samples were collected. The fecal products were tested using polymerase chain reaction (PCR) to detect SARS-CoV-2. The results were negative for all stocks. This was similar to the results of MDRO testing. The safety of FMT products has been guaranteed during the pandemic., Conclusion: Our FMT center produced MDRO-free and COVID-19-free products before and during the COVID-19 outbreak in Taiwan. Our protocol was effective for ensuring the safety of FMT products., (© 2023 The Authors. JGH Open published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Background: The Child-Turcotte-Pugh (CTP) score is widely used for assessing the liver's functional reserve in patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). This study aims to explore the outcomes of patients with HCC and CTP class B and to investigate the prognostic accuracy of prediction models for ACLD in these patients., Methods: We retrospectively enrolled 1143 patients with HCC and CTP class B between 2007 and 2022. We divided the patients into three subgroups based on their CTP scores: CTP-B7, CTP-B8, and CTP-B9. We compared the corrected Akaike information criterion among each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD), and MELD 3.0., Results: Among the enrolled patients, 576 (50.3%) were in the CTP-B7 group, 363 (31.8%) were in the CTP-B8 group, and 204 (17.9%) were in the CTP-B9 group. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients died, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6%, and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS ( p = 0.089), both of which were better than those in the CTP-B9 group ( p < 0.001). Furthermore, the MELD 3.0 score had the lowest corrected akaike information criteria value and provided a more accurate mortality prediction than the MELD score, ALBI grade, modified ALBI grade, and CTP score., Conclusion: Patients in the CTP-B7 and CTP-B8 groups had comparable OS, both of which were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the most accurate mortality prediction in patients with HCC and CTP class B., Competing Interests: Conflicts of interest: Dr. Teh-Ia Huo, Dr. Yi-Hsiang Huang and Dr. Ming-Chih Hou, editorial board membesr at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

The safety of fecal microbiota transplantation (FMT) has been highlighted by extended-spectrum β-lactamase (ESBL)-producing Escherichia coli bacteremia transmitted from donors and acquisition of diarrheagenic E. coli (Shiga toxin-producing E. coli (STEC) and enteropathogenic E. coli (EPEC)) via FMT. The use of donor screening criteria to lower the risk of pathogen transmission via FMT is essential. This study aimed to demonstrate the outcomes of our strict donor screening program. This study was conducted at our FMT center between January 2019 and June 2022. Our donor screening program included an initial questionnaire and subsequent blood and stool testing. We further used selective culture for third-generation cephalosporin-resistant (3GCR) Enterobacterales and multiplex PCR to detect diarrheagenic E. coli in stools. The resistance mechanisms and sequence type of 3GCR Enterobacterales were determined. A total of 742 individuals were assessed, and 583 participants (78.6%) were excluded after questionnaire. Of the remaining 159 participants undergoing stool and blood tests, 37 participants were finally qualified (5.0%, 37/742). A high fecal carriage rate of ESBL-producing Enterobacterales (35.2%, 56/159), including E. coli (n=53) and Klebsiella pneumoniae (n=5), and diarrheagenic E. coli (31.4%, 50/159), including EPEC (n=41), enteroaggregative E. coli (n=11), enterotoxigenic E. coli (n=4), and STEC (n=1), was noted. CTX-M-79 and CTX-M-15 were dominant in E. coli and K. pneumoniae, respectively. The sequence types of the ESBL-producing strains were diverse. The screening for 3GCR Enterobacterales and diarrheagenic E. coli in stool is necessary. Our findings also support the effectiveness of multiplex PCR panels in FMT donor screening programs., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Portal hypertension develops along with the progression of liver cirrhosis. Natriuretic peptides have been shown to reduce portal pressure but concomitantly activate the renin-angiotensin-aldosterone system (RAAS). Angiotensin receptor-neprilysin inhibitors (ARNIs) upregulate natriuretic peptides and avoid the adverse effects of RAAS activation. ARNIs have been shown to reduce portal pressure in rats with pre-hepatic portal hypertension, which involves relatively little liver injury. This study aimed to evaluate the relevant effects of an ARNI in rats with both liver cirrhosis and portal hypertension., Methods: Male Sprague-Dawley rats received common bile duct ligation to induce liver cirrhosis and portal hypertension. Sham-operated rats served as surgical controls. All rats were randomly allocated into three groups to receive distilled water (vehicle), LCZ696 (an ARNI), or valsartan for 4 weeks. Portal hypertension and relevant derangements were assessed after treatment., Results: Portal hypertension and hyperdynamic circulation developed in the cirrhotic rats. In the rats with cirrhosis and portal hypertension, both LCZ696 and valsartan reduced portal hypertension, mean arterial pressure, and systemic vascular resistance. The decrease in portal pressure was highly associated with the reduction in arterial pressure and systemic vascular resistance. Blood flow in hepatic, splanchnic, and portosystemic collateral systems was not altered. LCZ696 did not significantly influence liver injury or plasma cytokine levels. Liver fibrosis and splanchnic angiogenesis were not affected., Conclusion: ARNI treatment exerted portal pressure lowering effects via peripheral vasodilatation and decreasing systemic arterial pressure in the rats with liver cirrhosis and portal hypertension. Caution should be taken when using ARNIs in liver cirrhosis., Competing Interests: Conflicts of interest: Dr. Yi-Hsiang Huang, Dr. Ming-Chih Hou and Dr. Fa-Yauh Lee, editorial board members at Journal of the Chinese Medical Association, have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Background: The treatment of chronic hepatitis C (CHC) infection underwent a significant transformation with the introduction of all-oral direct-acting anti-virals (DAAs). These medications offered a high success rate in treatment, shorter duration, good tolerability, and expanded treatment options. However, a residual risk of hepatocellular carcinoma (HCC) development remained for a few patients even after achieving sustained virological response (SVR). To date, there is a lack of real-world data on evaluating risk factors associated with de novo HCC in CHC patients post-SVR, particularly in Taiwan., Methods: Between January 2017 and December 2019, a total of 671 consecutive CHC patients who achieved SVR after receiving DAAs were included for analysis. Patients with a history of HCC or liver transplantation prior to DAAs, a short follow-up period (<1 year), or treatment failure with DAAs were excluded. The primary outcome was the development of HCC following the initiation of DAAs. Variables associated with the primary outcome were assessed using multivariate Cox proportional hazards models., Results: The mean age of the enrolled patients was 65.1 ± 12.8 years, with 39.6% of them being male. Among the patients, 30.6% had advanced (F3-4) fibrosis, and the median follow-up period was 2.90 years. The cumulative incidence of HCC in CHC patients post-SVR12 was 1.6% at 1 year, 4.4% at 2 years, 4.8% at 3 years, 5.3% at 4 years, and 6.1% at 4.8 years, respectively. Variables independently associated with de novo HCC were advanced liver fibrosis (hazard ratio [HR] = 6.745; 95% CI = 1.960-23.218; p = 0.002), end-of-treatment 12 weeks (EOT 12 ) alpha-fetoprotein (AFP) >7 ng/mL (HR = 3.059; 95% CI = 1.215-7.669; p = 0.018), EOT 12 albumin-bilirubin (ALBI) grade ≥ 2 (HR = 2.664; 95% CI = 1.158-6.128; p = 0.021), and body mass index (BMI) ≥ 25 kg/m 2 (HR = 2.214; 95% CI = 1.011-4.852; p = 0.047)., Conclusion: Despite achieving viral clearance with DAAs, CHC patients still face a residual risk of de novo HCC. Establishing a risk stratification model based on independent variables could facilitate the prediction of future HCC development and enhance screening strategies., Competing Interests: Conflicts of interest: Dr. Fa-Yauh Lee, Dr. Yi-Hsiang Huang and Dr. Ming-Chih Hou, editorial board members at Journal of the Chinese Medical Association , have no roles in the peer review process of or decision to publish this article. The other authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Tumor burden score (TBS) has been recently introduced to indicate the extent of tumor burden in different cancers, but its role in advanced hepatocellular carcinoma (HCC) is unclear. We aimed to determine the prognostic role of TBS in patients with HCC beyond the Milan criteria receiving surgical resection (SR) or transarterial chemoembolization (TACE). A total of 1303 newly diagnosed HCC patients beyond Milan criteria receiving SR or TACE as the primary therapy were retrospectively analyzed. Independent prognostic predictors were examined by the multivariate Cox proportional hazards model. SR was associated with better overall survival compared with TACE in these patients. Multivariate Cox analysis of the entire cohort revealed that age > 66 years (hazard ratio [HR]: 1.145, 95% confidence interval [CI]: 1.004-1.305, p = 0.043), serum α-fetoprotein > 200 ng/mL (HR: 1.602, 95% CI: 1.402-1.831, p < 0.001), performance status 2-4 (HR: 1.316, 95% CI: 1.115-1.553, p < 0.001), medium TBS (HR: 1.225, 95% CI:1.045-1.436, p = 0.012), high TBS (HR: 1.976, 95% CI: 1.637-2.384, p < 0.001), albumin-bilirubin (ALBI) grade 2-3 (HR: 1.529, 95% CI: 1.342-1.743, p < 0.001), presence of vascular invasion (HR: 1.568, 95% CI: 1.354-1.816, p < 0.001), and TACE (HR: 2.396, 95% CI: 2.082-2.759, p < 0.001) were linked with decreased survival. SR consistently predicted a significantly better survival in different TBS subgroups. TBS is a feasible and independent prognostic predictor in HCC beyond the Milan criteria. SR provides better long-term outcome compared with TACE in these patients independent of TBS grade, and should be considered as the primary treatment modality in this special patient group., (© 2023. Springer Nature Limited.)

The development of acute kidney injury (AKI) and hepatorenal syndrome-acute kidney injury (HRS-AKI) in cirrhosis has been associated with intestinal barrier dysfunction and gut-kidney crosstalk. We use the related markers such as zonulin, lipopolysaccharides (LPS), and lipopolysaccharide-binding protein (LBP) to predict AKI and HRS-AKI in cirrhotic patients and evaluate their in vitro effects on intestinal (Caco-2) cells and renal tubular (HK-2) cells. From 2013 to 2020, we enrolled 70 cirrhotic patients and developed prediction models for AKI and HRS-AKI over a six-month period. There were 13 (18.6%) and 8 (11.4%) cirrhotic patients developed AKI and HRS-AKI. The prediction models incorporated zonulin, LPS, LBP, C-reactive protein, age, and history of hepatitis B for AKI, and zonulin, LPS, LBP, total bilirubin, and Child-Pugh score for HRS-AKI. The area under curve (AUC) for the prediction of AKI and HRS-AKI was 0.94 and 0.95, respectively. Furthermore, the conditioned medium of LPS+hrLBP pre-treated Caco-2 cells induced apoptosis, necrosis, and zonulin release in HK-2 cells, demonstrating the communication between them. This study found that zonulin, LPS, and LBP are potential practical markers for predicting AKI and HRS-AKI in cirrhotic patients, which may serve as potential targets for renal outcomes in cirrhotic patients., (© 2023. Springer Nature Limited.)

Background & Aims: During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended. We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic., Methods: Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. One experienced gastroenterologist reviewed the prior-scheduled list of patients for the EVL prophylaxisprogram. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020., Results: Of the 124 patients receiving EVL, a higher percentage of esophageal variceal bleeding (EVB) was noted (9/32, 28.1% vs. 8/92, 8.7%, p = 0.006) during the lockdown period, with a higher percentage of EVB in the referrals (7/9, 77.8% vs. 2/14, 14.2%, p = 0.007). Among patients who received prophylactic EVL, 6 of 78 (7.7%) experienced EVB during the normal period, which is no different to 2 of 23 (8.7%) during the lockdown period. Twenty-three patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB during the lockdown period. Child-Turcotte-Pugh (CTP) class C was predictive of EVB (relative risk 8.400, P = 0.033), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.016, P = 0.002)., Conclusion: Entrance into the prophylaxis program does not only decreases risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period., (© 2023. The Author(s).)

Background: Alpha fetoprotein (AFP) is the most widely used tumor marker for hepatocellular carcinoma (HCC). Nevertheless, few studies have investigated the prognostic factors of HCC patients with normal serum AFP levels., Methods: We retrospectively enrolled 2198 patients with HCC and normal serum AFP levels (<20 ng/mL) from 2007 to 2020. Overall survival (OS) rates were calculated by the Kaplan-Meier method, and analyses of the prognostic factors were performed using a Cox proportional hazard model., Results: Among the enrolled patients, 1385 (63%) patients were in the low-normal AFP group (serum AFP levels ≤7 ng/mL), and 813 (37%) patients were in the high-normal AFP group (serum AFP levels between 7 and 20 ng/mL). The high-normal AFP group had poorer liver functional reserve, more multiple tumors, and smaller tumor size compared to those in the low-normal AFP group. After a median follow-up of 32.4 months, 942 patients died, and the 5-year OS rate was 54.4%. The 5-year OS rates were 57.4% and 49.8% in the low-normal AFP group and high-normal AFP group, respectively (p = 0.001). A multivariate analysis showed the independent prognostic factors of poor OS were no anti-viral therapy, advanced albumin-bilirubin grades, the presence of vascular invasion, tumor size ≥5 cm, and non-curative treatment modalities. Serum AFP levels were not associated with OS according to the multivariate analysis., Conclusion: Liver functional reserve, anti-viral therapy, tumor size, vascular invasion, and treatment modalities, determined the outcomes of HCC patients with normal serum AFP levels, but serum AFP levels did not., Competing Interests: Declaration of competing interest There are no potential conflicts of financial and non-financial interests in the study., (Copyright © 2022. Published by Elsevier B.V.)

Introduction: Chemotherapy and radiation therapy for breast cancer cause side effects, such as cardiovascular changes, which can be monitored with echocardiography. However, more convenient methods are always encouraged. Radial arterial waves that are used to detect cardiovascular changes can be used to assist in confirming cardiovascular changes., Aim: This retrospective study aimed to analyze the frequency and time domains of the radial artery pulse wave in patients with breast cancer to understand its effectiveness in identifying cardiovascular changes., Methods: Patients with breast cancer were screened from the pulse examination records in Changhua Christian Hospital and divided into the treatment and remission groups. After unlinking the data, the pulse data were analyzed for the breast cancer treatment and remission group, including the average value of the parameters of four consecutive pulse diagnosis records in four consecutive months to test the difference in pulse waves due to breast cancer treatment between the two groups. Additionally, the pulse wave stability of the two groups was compared using the coefficient of variation., Results and Conclusion: The comparison of the pulse wave data between 19 patients in the treatment group and 40 patients in the remission group revealed 45 parameters in time and 50 in frequency domains. D3, ND3, NA1, and NT1 are the four parameters with significant differences (p < 0.05), which are all related to heart function, and mainly related to cardiac output and peripheral resistance, indicating that patients in the treatment period have poor heart function. No difference was found in the degree of data dispersion between the two groups. Cardiovascular side effects caused by breast cancer treatment can mainly be shown in the pulse wave time domain., Competing Interests: Conflict of interest Authors have no conflict of interest., (© the Author(s).)

Background: There is still controversy about whether tenofovir disoproxil fumarate (TDF) and entecavir (ETV) have different effects on the outcomes of patients with hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC)., Aims: The aim of this study was to compare the prognoses between ETV and TDF treatment among patients with HBV-related HCC after hepatectomy., Methods: An analysis was done on data from the Taiwan Cancer Registry, which was linked to Taiwan National Health Insurance Research Database, for the years 2011-2016. We identified 7107 patients with HBV-related HCC after curative hepatectomy, and 25.3% of them used ETV or TDF after surgery. After propensity score overlap weighting, 1797 patients treated with ETV (n = 1365) or TDF (n = 432) were included for analyses. Cox proportional hazards models were used to compare the efficacy of ETV and TDF for recurrence and overall survival (OS)., Results: After hepatectomy, the recurrence rate per 100 person-years was 14.87 for the ETV group and 9.25 for the TDF group. The risk of recurrence was similar in the TDF group and the ETV group (HR [95% CI]: 0.91 [0.69-1.19; p = 0.479]), as was the risk of all-cause mortality (HR [95% CI]: 0.67 [0.42-1.07]; p = 0.091). When considering early recurrence (<2 years) and late recurrence (≧2 years), the TDF and ETV groups showed no significant differences. Subgroup analyses and sensitivity analyses demonstrated consistent results., Conclusion: Both TDF and ETV showed similar health benefits in terms of recurrence and OS in patients with HBV-related HCC patients after hepatectomy., (© 2023 John Wiley & Sons Ltd.)

Introduction: Outcomes of transarterial chemoembolization (TACE) for intermediate-stage hepatocellular carcinoma (HCC) are diverse because of the heterogeneity of tumor burden. Radiologic pattern is one criterion for determining whether TACE is unsuitable. However, additional evidence is required. This study determined the influence of radiologic morphology on the outcomes of initial and subsequent TACE., Methods: From January 2007 to September 2021, 633 treatment-naive patients with HCC with intermediate-stage HCC undergoing TACE were retrospectively enrolled. Of these patients, 386 patients received repeated TACE. The radiological features of HCC were evaluated by two radiologists and classified into encapsulated nodular type, simple nodular type with extranodular growth, confluent multinodular type, and infiltrative type. The objective response rate (ORR) and survival rate after initial and subsequent TACE among various radiologic morphologies were compared., Results: After initial TACE, encapsulated nodular type HCC had the highest ORR (58%), followed by extranodular type (45.8%), confluent multinodular type (29%), and infiltrative type (19.5%). Notably, radiologic pattern was highly associated with tumor burden. Tumor burden and radiologic morphology were significantly associated with ORR and overall survival (OS) in the multivariate analysis. In 386 patients with subsequent TACE, encapsulated nodular type HCC had the highest ORR (48.7%), followed by extranodular type (37.3%), confluent multinodular type (26.2%), and infiltrative type (10%). In the multivariate analysis, radiologic features were significant independent predictors of ORR and OS after receiving subsequent TACE., Conclusion: Radiologic patterns determine the outcomes of initial and subsequent TACE. Systemic therapy should be considered for patients with intermediate-stage HCC with unfavorable radiologic patterns., Competing Interests: Y.-H.H. has received research grants from Gilead Sciences and Bristol-Meyers Squibb and honoraria from Abbvie, Gilead Sciences, Bristol-Meyers Squibb, Ono Pharmaceutical, Merck Sharp and Dohme, Eisai, Eli Lilly, Ipsen, and Roche, and has served in an advisory role for Abbvie, Gilead Sciences, Bristol-Meyers Squibb, Ono Pharmaceuticals, Eisai, Eli Lilly, Ipsen, Merck Sharp and Dohme, and Roche. Other authors declare no conflicts of interest., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Background: Peristomal wound infection is a common complication in patients receiving percutaneous endoscopic gastrostomy (PEG). The main reason for peristomal infection might be the oral microbes coating the gastrostomy tube during implantation. Povidone-iodine solution can be applied for skin and oral decontamination. We designed a randomized controlled trial to test the effectiveness of a Betadine® (povidone-iodine) coated gastrostomy tube to reduce peristomal infection after percutaneous endoscopic gastrostomy., Methods: A total of 50 patients were randomized to Betadine and control groups (25 patients in each group) from April 2014 to August 2021 at a tertiary medical center. All patients received the pull method for PEG implantation using a 24-french gastrostomy tube. The primary endpoint was peristomal wound infection rate 2 weeks after the procedure., Results: Changes in Neutrophil/Lymphocyte ratio (N/L ratio) and C-Reative protein (Delta CRP) at 24 h after PEG were higher in the control group than in the Betadine group (N/L ratio, 3.1 vs. 1.2, p = 0.047; CRP, 2.68 vs.1.16, p = 0.009). The two groups did not differ in post-PEG fever, peristomal infection, pneumonia, or all-cause infection. Delta CRP could predict peristomal infection and all-cause infection within 2 weeks (AUROC 0.712 vs. 0.748; p = 0.039 vs. 0.008). The best cut-off-point of Delta CRP for the diagnosis of peristomal wound infection was 3 mg/dl., Conclusion: The betadine coating gastrostomy tube method could not reduce peristomal infection after percutaneous endoscopic gastrostomy. CRP elevation of less than 3 mg/dl may be used to exclude the potential peristomal wound infection., Trial Registration: NCT04249570 ( https://clinicaltrials.gov/ct2/show/NCT04249570 )., (© 2023. The Author(s).)

Cirrhosis-related hepatic and renal endothelial dysfunction is characterized by macrophage-endothelium adhesion-mediated inflammation, glycocalyx/barrier damage, and impaired vasodilation. Activation of adenosine A2A receptor (A 2A R) protects cirrhotic rats from impairment of hepatic microcirculation post hepatectomy. This study evaluates the effects of A 2A R activation on the cirrhosis-related hepatic and renal endothelial dysfunction in biliary cirrhotic rats receiving two weeks of A 2A R agonist PSB0777 [bile duct ligated (BDL)+PSB0777] treatment. Endothelial dysfunction in cirrhotic liver, renal vessels, and kidney is characterized by downregulation of the A 2A R expressions, decreased vascular endothelial vasodilatory (p-eNOS)/anti-inflammatory (IL-10/IL-10R)/barrier [VE-cadherin (CDH5) and β-catenin (CTNNB1)]/glycocalyx [syndecan-1 (SDC1) and hyaluronan synthase-2 (HAS2)] markers, and increased leukocyte-endothelium adhesion molecules (F4/80, CD68, ICAM-1, and VCAM-1). In BDL rats, PSB0777 treatment improves hepatic and renal endothelial dysfunction, ameliorates portal hypertension, and attenuates renal hypoperfusion by restoring of the vascular endothelial anti-inflammatory, barrier, glycocalyx markers and vasodilatory response as well as inhibiting the leukocyte-endothelium adhesion. In an in vitro study, conditioned medium (CM) of bone marrow-derived macrophage (BMDM) of BDL rats [BMDM-CM (BDL)] induced barrier/glycocalyx damage, which was reversed by the PSB0777 pre-treatment. The A 2A R agonist is a potential agent that can simultaneously correct cirrhosis-related hepatic and renal endothelial dysfunction, portal hypertension, renal hypoperfusion, and renal dysfunction., (Copyright © 2023 The Authors. Production and hosting by Elsevier B.V. All rights reserved.)

Objective: Ultrasound (US) detection acupuncture (UDA) is an innovative acupuncture technique that uses ultrasonography (USG) to detect the depth of the lung before performing acupuncture on the points around the chest to avoid puncturing the lungs. For acupuncturists to use UDA appropriately, it is crucial to have a good operating method to identify the pleura with USG. This study compared 2 US operating methods through active learning in a "flipped classroom" setting for acupuncture students., Materials and Methods: Students and interns were recruited to complete the UDA flipped classroom course and evaluate the operations of 2 US methods on either of 2 simulation models: (1) a single B-mode or (2) a combined M-mode + B-mode. Participants were interviewed and satisfaction surveys were administered to obtain feedback., Results: A total of 37 participants completed the course and evaluations. The combined mode had better measurement accuracy, acupuncture safety, and operating time ( P  < 0.05), and no pneumothoraxes occurred. Among both participant groups, the combined mode allowed the student group to learn quickly and the intern group to become more proficient. Both interviews and satisfaction surveys yielded positive feedback., Conclusions: Using a combined mode for UDA can improve its performance greatly. The combined mode is definitely helpful for learning and promotion of UDA., Competing Interests: No financial conflicts of interests exist., (Copyright 2023, Mary Ann Liebert, Inc., publishers.)

A series of ten cationic complexes of the general formula [(C^C)Au(P^P)]X, where C^C = 4,4'-di- tert -butyl-1,1'-biphenyl, P^P is a diphosphine ligand, and X is a noncoordinating counteranion, have been synthesized and fully characterized by means of chemical and X-ray structural methods. All the complexes display a remarkable switch-on of the emission properties when going from a fluid solution to a solid state. In the latter, long-lived emission with lifetime τ = 1.8-83.0 μs and maximum in the green-yellow region is achieved with moderate to high photoluminescence quantum yield (PLQY). This emission is ascribed to an excited state with a mainly triplet ligand-centered ( 3 LC) nature. This effect strongly indicates that rigidification of the environment helps to suppress nonradiative decay, which is mainly attributed to the large molecular distortion in the excited state, as supported by density functional theory (DFT) and time-dependent DFT (TD-DFT) computation. In addition, quenching intermolecular interactions of the emitter are avoided thanks to the steric hindrance of the substituents. Emissive properties are therefore restored efficiently. The influence of both diphosphine and anion has been investigated and rationalized as well. Using two complexes as examples and owing to their enhanced optical properties in the solid state, the first proof-of-concept of the use of gold(III) complexes as electroactive materials for the fabrication of light-emitting electrochemical cell (LEC) devices is herein demonstrated. The LECs achieve peak external quantum efficiency, current efficiency, and power efficiency up to ca. 1%, 2.6 cd A -1 , and 1.1 lm W -1 for complex 1PF 6 and 0.9%, 2.5 cd A -1 , and 0.7 lm W -1 for complex 3 , showing the potential use of these novel emitters as electroactive compounds in LEC devices.

(1) Background: The severity of liver functional reserve plays an important role in the management of hepatocellular carcinoma (HCC). Noninvasive models such as the model for end-stage liver disease (MELD), albumin-bilirubin (ALBI) grade and easy (EZ)-ALBI grade, platelet-albumin-bilirubin (PALBI) and platelet-albumin (PAL) are used to evaluate liver dysfunction. We aimed to compare the prognostic performance of these four albumin-based models against MELD in HCC patients undergoing transarterial chemoembolization (TACE). (2) Methods: A total of 1038 treatment naïve HCC patients who received TACE as the primary treatment were enrolled. A multivariate Cox model was used to determine independent survival predictors. (3) Results: Multivariate analysis revealed that higher serum creatinine and α-fetoprotein level, vascular invasion, large tumor size, ALBI grades 2-3, EZ-ALBI grades 2-3, PALBI grades 2-3, PAL grades 2-3, but not the MELD score, were independent predictors associated with decreased survival in different Cox models. Among these models, the PALBI grade had the highest homogeneity and lowest corrected Akaike information criteria value, followed by EZ-ALBI, PAL, ALBI and, lastly, MELD. (4) Conclusions: All four albumin-based liver reserve models are better prognostic tools than MELD score in HCC patients undergoing TACE. Of these, the PALBI score is the best model to evaluate the liver reserve and should be considered a surrogate marker in these patients.