The Efficacy of Proton Pump Inhibitor in Cirrhotics with Variceal Bleeding: A Systemic Review and Meta-Analysis.

BACKGROUND AND AIMS: Proton pump inhibitor (PPI) was widely used in cirrhotic patients with variceal bleeding empirically rather than evidence-based practice. We aimed to evaluate the plausible indication of PPI use in variceal bleeding cirrhotic patients and figure out whether it can decrease the re-bleeding rate after endoscopic therapy. Furthermore, we also investigated the association between PPI and bleeding-related mortality in these patients. METHODS: We have searched in PubMed, Medline, Web of Science, Google Scholar, Cochrane and Embase prior to May 2019. Pooled OR and 95% CI were calculated by random-effects model. RESULTS: A total of 11 original articles including 1,818 cirrhotic patients were analyzed. The overall meta-analysis highlighted that PPI use may decrease the re-bleeding rate after endoscopic therapy (OR 0.52, 95% CI 0.35-0.77). The conclusion was irrespective of study methods, endoscopic purpose and hemorrhage sites. However, the conclusion speculated that PPI should be prescribed >1 month. Meanwhile, PPI use may not impact the bleeding-related mortality. CONCLUSIONS: PPI, used for >1 month, can decrease re-bleeding rate after endoscopic therapy in cirrhotic patients for prophylaxis or emergency treatment purpose. No matter how long it takes, PPI use is not associated with bleeding-related mortality.

Prognostic impact of neutrophil-to-lymphocyte ratio in cirrhosis: A propensity score matching analysis with a prespecified cut-point.

BACKGROUND & AIMS: An elevated neutrophil-to-lymphocyte ratio (NLR) has received attention as a prognostic surrogate across chronic liver diseases. However, an exact threshold has not been fully elucidated. METHODS: A total number of 589 patients with cirrhosis (LC) were included. The value of NLR was calculated and its optimal cut-off was initially determined by X-tile program. Independent predictors of 90-day mortality were identified with Cox regression model. The Kaplan-Meier method was used to generate survival curves. To reduce influences of selection bias and possible confounders, a 1:2 propensity score matching (PSM) was performed. RESULTS: The X-tile indicated that the difference in survival was most significant for NLR more than 8.9. Serum NLR > 8.9 was an independent indicator in the entire cohort and PSM subset (HR 4.268, 95% CI 2.211-8.238, P < .001; HR 4.209, 95% CI 1.448-12.238, P = .008 respectively). Subgroup analysis showed that NLR > 8.9 was an independent risk factor of 90-day mortality regardless of age, gender, CTP or MELD score. CONCLUSIONS: The value of NLR more than 8.9 is a feasible cut-off across clinical settings among applicable population. The adding of NLR to other conventional predictive systems has the potential to provide incremental value without extra economic cost.

External validation and improvement of LiFe score as a prediction tool in critically ill cirrhosis patients.

AIM: The LiFe (liver, injury, failure, evaluation) score, calculated according to arterial lactate, total bilirubin, and international normalized ratio (INR), is a novel score for risk prediction in intensive care unit (ICU) patients with cirrhosis. The present study aimed to externally validate and optimize the LiFe score for predicting outcomes in critically ill cirrhosis patients. METHODS: The study used the single-center database Medical Information Mart for Intensive Care-III (MIMIC-III) for analysis. A total of 536 critically ill cirrhosis patients from the MIMIC-III database were analyzed. Routine clinical and laboratory variables were included to compare survivors with non-survivors. The LiFe score was then regraded into three groups to calculate the optimal cut-off values. RESULTS: In-ICU mortality occurred in 169 (31.5%) of the patients. Survivor and non-survivor cohorts were similar in age, gender, and etiology of cirrhosis. Multivariate analyses of in-ICU mortality identified four independent variables: total bilirubin, creatinine, INR, and arterial lactate. An external validation of the LiFe score showed good accuracy for predicting in-ICU mortality with an area under the receiver operating characteristic curve of 0.708. In addition, a significant positive correlation exists between LiFe score and acute-on-chronic liver failure grade (r = 0.393, P < 0.001). A log-rank test comparing the strata of simplified LiFe scores found that in-ICU mortality rates were 16.8%, 27.7%, and 51.7%, respectively, among patients in the three simplified risk categories. CONCLUSIONS: The LiFe score, based on laboratory tests, can be useful as a preliminary and convenient scoring tool in a broad cohort of critically ill cirrhosis patients. Simplified risk categories to stratify patients into three groups improves its feasibility and generalizability for clinical application.

Increasing Diverticulosis in an Aging Population: A Colonoscopy-Based Study of 5-Year Trends in 26 463 Patients in Northern China.

BACKGROUND Because such data are scarce in northern China, the purpose of this study was to determine trends in diverticulosis over the past 5 years. MATERIAL AND METHODS A total of 26 463 patients (27 558 examinations, including 1095 repeated colonoscopies) performed between January 2011 and December 2015 were reviewed respectively. The distributions of diverticulosis were recorded, which were classified as right-sided, left-sided, and bilateral type. The trends in diverticulosis were analyzed in terms of aging and yearly increase. Additionally, associations of the occurrence of diverticulosis with age (≤39, 40-59, and ≥60 years) and sex were determined using a logistic regression model. RESULTS We identified 1045 patients with colonic diverticulosis, with an overall prevalence of 3.8% (1045/27 558). A preponderance of right-sided diverticulosis was demonstrated, accounting for 72.9% (693/951) of included subjects. The proportion of colonic diverticulosis increased significantly (P<0.001 for trend), from 2.78% (112/4028) in 2011 to 4.98% (309/6208) in 2015. The proportion of patients of all age groups with diverticulosis increased significantly (P<0.001 for trend) in correlation with yearly increase. There was a greater proportion of diverticulosis, regardless of the distribution, in patients aged ³60 than in younger age groups (P<0.001 for trend). Multivariate analysis showed older age and male sex (P<0.001) were independent risk factor for diverticulosis. CONCLUSIONS Colonic diverticulosis has been increasing in northern China, where rapid aging is ongoing.

Red blood cell distribution width to platelet ratio levels in assessment of histologic severity in patients with primary biliary cholangitis.

We aimed to investigate the relationship between the histologic severity and red blood cell distribution width to platelet ratio (RPR) in patients with primary biliary cholangitis (PBC). One hundred and seven consecutive patients with liver biopsy-proven and as yet treatment-naïve PBC were enrolled as the primary and validation cohort. The histologic stages were divided into early stage (Scheuer's stage 1 & 2) and late stage (Scheuer's stage 3 & 4). The overall patient demographics, clinical manifestations, hematological tests and biochemical profile were retrospectively collected from our database. Both groups were compared in terms of RPR, aspartate aminotransferase-to-platelet ratio index (APRI), fibrosis index based on the 4 factors (FIB-4) and AST/ALT ratio (AAR). Of the 77 patients in the primary cohort, a total of 24 (31.2%) had early stage PBC, whereas 53 (68.8%) represented late stage. Patients with late stage PBC showed significantly higher red blood cell distribution width (15.5 vs. 14.1%, p = .016), RPR (0.15 vs. 0.09, p < .001), direct bilirubin (32.4 vs. 12.9 µmol/L, p = .041), FIB-4 (3.41 vs. 6.34, p = .001) and significantly lower platelet (132.8 vs. 185.8 × 109/L, p = .002). The area under the curve, cut-off value, sensitivity, specificity, positive predictive value, negative predictive value for determining late stage were 0.74, 0.14, 49.1%, 95.8%, 96.3% and 46.0%, respectively. Additionally, high RPR may also serve as a prognostic indicator for 18-month mortality. In conclusion, RPR can be used as a non-invasive and effective predictor of histologic severity in patients with PBC.

Analysis of the learning curve for peroral endoscopic myotomy for esophageal achalasia: Single-center, two-operator experience.

BACKGROUND AND AIM: Peroral endoscopic myotomy (POEM) has emerged as an advanced technique for the treatment of achalasia, and defining the learning curve is mandatory. METHODS: From August 2011 to June 2014, two operators in our institution (A&B) carried out POEM on 35 and 33 consecutive patients, respectively. Moving average and cumulative sum (CUSUM) methods were used to analyze the POEM learning curve for corrected operative time (cOT), referring to duration of per centimeter myotomy. Additionally, perioperative outcomes were compared among distinct learning curve phases. RESULTS: Using the moving average method, cOT reached a plateau at the 29th case and at the 24th case for operators A and B, respectively. CUSUM analysis identified three phases: initial learning period (Phase 1), efficiency period (Phase 2) and mastery period (Phase 3). The relatively smooth state in the CUSUM graph occurred at the 26th case and at the 24th case for operators A and B, respectively. Mean cOT of distinct phases for operator A were 8.32, 5.20 and 3.97 min, whereas they were 5.99, 3.06 and 3.75 min for operator B, respectively. Eckardt score and lower esophageal sphincter pressure significantly decreased during the 1-year follow-up period. Data were comparable regarding patient characteristics and perioperative outcomes. CONCLUSION: This single-center study demonstrated that expert endoscopists with experience in esophageal endoscopic submucosal dissection reached a plateau in learning of POEM after approximately 25 cases.

Electroless deposition of copper nanoparticles integrates polydopamine coating on reverse osmosis membranes for efficient biofouling mitigation.

In this study, highly antimicrobial CuNPs were integrated into a hydrophilic polydopamine (PDA) coating and immobilized on a RO TFC membrane via a mild and facile reduction approach to form a stable and durable dual-functional layer. Based on the XDLVO analysis, the introduction of PDA increased the membrane-foulant total interaction energy (ΔGmwf) to 14.13 mJ/m2, resulting in improved anti-adhesive properties as demonstrated by a 37% decrease in BSA adsorption for the modified membranes. The well dispersed and high loadings of CuNPs induced by PDA conferred strong bacterial toxicity to the modified membranes, reducing the viability of E. coli by 76%. Furthermore, the presence of catechol groups on PDA favors the formation of covalent bond with CuNPs, thus prolonging the durability of the copper-based anti-biofouling membranes. The combination of PDA coating and CuNPs functionalization imparts the membrane with simultaneous anti-adhesive and anti-microbial properties, leading to a substantial reduction in biofouling propensity in dynamic biofouling experiments. Specifically, the flux decline due to biofouling observed for the modified membranes significantly decreased from 65% to 39%, and biofilm thickness and TOC biomass were 58%, and 55% lower, respectively. This study provides a facile and versatile strategy to construct high performance RO membranes with excellent anti-biofouling functionality.

Antifouling lipid membrane coupled with silver nanoparticles for electrochemical detection of nucleic acids in biological fluids.

Electrochemical method capable of detecting specific nucleic acids in complex fluid will undoubtedly advance the diagnosis of many kinds of diseases. Herein, by coupling lipid membrane with silver nanoparticles (AgNPs), we develop a new electrochemical method for sensitive and reliable detection of nucleic acids in biological fluids. The advantages of lipid membrane especially its excellent antifouling ability is employed to enhance the applicability of the method in complex environment; while the significant solid-state Ag/AgCl response of AgNPs is used to ensure the detection sensitivity of the method. The core of this method's workflow is the target-induced Y-shape structure formation, which results in the recruitment of AgNPs to the electrode surface, producing considerable electrochemical responses used for target nucleic acid detection. Taking highly upregulated in liver cancer (HULC), a liver cancer-related long non-coding RNA as a model target, the method exhibits high sensitivity, specificity, and reproducibility with a detection limit of 0.42 fM. Moreover, the method displays desirable usability in biological fluids such as serum, which will be of great potential in clinical diagnosis.

Identification of programmed death ligand-1 positive exosomes in breast cancer based on DNA amplification-responsive metal-organic frameworks.

Cancer-derived exosomes have recently emerged as potent candidates for diagnosis and prognosis of breast cancer. As an example, programmed death ligand-1 positive (PD-L1+) exosomes are found to be correlated with the progression and immunotherapy response of breast cancer, and therefore show great potential in liquid biopsy. Herein, we propose an electrochemical biosensing method for accurate identification of PD-L1+ exosomes by using DNA amplification-responsive metal-organic frameworks, PVP@HRP@ZIF-8. Specially, PD-L1+ exosomes are captured by anti-CD63 functionalized magnetic beads and bound with anti-PD-L1-linked capture probe. Then, in situ hyperbranched rolling circle amplification, a typical DNA amplification reaction, is conducted using the surface-attached capture probes as primers, which lows environmental pH. As a result, disassembly of PVP@HRP@ZIF-8 takes place, leading to the release of enzymes, which can arouse amplified electrochemical responses for the identification of target exosomes. Experimental results reveal that the biosensing method displays a linear range for PD-L1+ exosomes identification from 1 × 103 to 1 × 1010 particles/mL and the detection limit reaches 334 particles/mL. What is more, by using the method, elevated level of circulating PD-L1+ exosomes is found in the undiluted serum samples from patients with breast cancer, particularly for metastatic breast cancer, revealing a positive correlation of the PD-L1+ exosome level with the tumor staging and disease progression of breast cancer. Therefore, the biosensing method may be valuable for not only exosome identification but also providing reference information for diagnosis and real-time monitoring of breast cancer in the future.

Prognostic nomogram for acute pancreatitis patients: An analysis of publicly electronic healthcare records in intensive care unit.

PURPOSE: The mortality rate of severe acute pancreatitis (AP) is 20-30% even after admission to intensive care unit (ICU). Thus we aimed to develop a laboratory-based nomogram to identify AP patients at high risk for mortality. MATERIALS AND METHODS: The primary and validation cohorts were extracted from the Medical Information Mart for Intensive Care III database (MIMIC-III). Independent predictors were determined using multiple Cox analysis and then assembled to predict survival. The performance of proposed nomogram was evaluated by Harrell's concordance index (C-index) and area under the receiver operating characteristic (AUC) analysis, and subsequently compared with conventional scoring systems. RESULTS: A total of 342 AP patients admitted to ICU were enrolled, with 30-day, 180-day and 1-year mortality rate of 10.8%, 16.1% and 17.5%, respectively. Independent factors from multivariate Cox model to prognosticate 30-day and 1-year mortality were retrieved. The C-index of 1-year prediction nomogram (0.758, 95%CI: 0.676-0.840) were superior to several prediction approaches, and these findings were further confirmed by applying time-specific AUC analysis. Decision curve analysis indicated our nomogram was feasible in clinical practice. Similar results were observed in the validation cohort. CONCLUSIONS: The proposed nomogram gives rise to accurately prognostic prediction for critically AP patients admitted to ICU.

Prognostic nomogram incorporating neutrophil-to-lymphocyte ratio for early mortality in decompensated liver cirrhosis.

BACKGROUND: Neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation. However, its predictive utility of 30-day mortality remains elusive in decompensated cirrhotics. AIMS: We aimed to combine NLR and other variables associated with early mortality of cirrhotics with acute insults in to a predictive nomogram. METHODS: We retrospectively analyzed 352 decompensated cirrhotics. The 30-day mortality was regarded as primary outcome. Multivariate Cox analysis was performed, and a NLR-based nomogram was developed. The performance of nomogram was determined in terms of its calibration, discrimination and clinical usefulness. Serum cytokines were evaluated by Milliplex cytokine assay. RESULTS: On multiple analysis, independent factors for early mortality were albumin, MELD and NLR, which were all selected into the nomogram. The nomogram showed good discrimination, with a concordance index of 0.88. Calibration of the nomogram predicted survival corresponding optimally with the actual outcomes. Decision curve analysis indicated our nomogram was useful in clinical practice. Among circulating cytokines we investigated, IL-6 and IL-8 were substantially elevated in cirrhotics compared to healthy subjects. High NLR was positively correlated with the expression of IL-6 and IL-8. CONCLUSION: The proposed nomogram incorporating NLR offered an individualized predictive tool for 30-day mortality in decompensated cirrhotics. The escalating value of NLR likely implicated excessive inflammatory response.

Sex differences in risk factors of uncomplicated colonic diverticulosis in a metropolitan area from Northern China.

As the world's most populated and rapidly aging country, there is limited information on sex-related differences in factors regarding uncomplicated colonic diverticulosis in China. We aimed to investigate sex differences in individual risk factor in a northern metropolis. Patients with colonic diverticulosis who underwent indicated colonoscopy were queried with respect to medical history and demographic features. Demographic information, life style factors and co-morbidities were retrieved from a prospective dataset. Multiple regression analyses were performed to determine precipitating factors of diverticula. Of 4,386 enrolled patients, colonic diverticulosis were detected in 218 cases (4.97%). Multiple logistic regression analysis implicated increasing age (OR = 1.05, 95%CI 1.03-1.06, P < 0.001), red meat ≥100 g/d (OR = 2.53, 95%CI 1.72-3.70, P < 0.001), smoking (OR = 2.14, 95%CI 1.05-4.33, P = 0.035), rheumatologic diseases (OR = 3.38, 95%CI 1.09-10.5, P = 0.035) and NSAIDs (OR = 2.11, 95%CI 1.12-3.97, P = 0.020) were significantly associated with diverticulosis in men, whilst advancing age (OR = 1.03, 95%CI 1.01-1.05, P = 0.013), BMI (OR = 1.12, 95%CI 1.04-1.19, P = 0.001), smoking (OR = 10.2, 95%CI 2.81-37.4, P < 0.001), rheumatologic diseases (OR = 8.04, 95%CI 3.05-21.2, P < 0.001), hypertension (OR = 1.76, 95%CI 1.01-3.06, P = 0.047), colonic polyps (OR = 3.12, 95%CI 1.82-5.36, P < 0.001) and antihypertensive medications (OR = 2.99, 95%CI 1.66-5.39, P < 0.001) in women. In conclusion, it is pivotal to take account of differentially sex-related factors in regard to the development of uncomplicated colonic diverticulosis.

Does neutrophil-to-lymphocyte ratio predict 1-year mortality in patients with primary biliary cholangitis? Results from a retrospective study with validation cohort.

OBJECTIVES: Neutrophil-to-lymphocyte ratio (NLR) has been used to predict prognosis in various liver diseases, but its role in primary biliary cholangitis (PBC) is not clarified. We aimed to investigate the prognostic usefulness of NLR for 1-year mortality in PBC. METHODS: The study recruited a retrospective cohort with 88 patients with PBC and a prospective validation cohort with 63 participants who were followed-up for 1 year. NLR and other laboratory measurements were analysed by multivariate regression model for identifying independent factors for early mortality. The cut-off threshold of NLR was determined by calculating the area under the receiver operating characteristics curve (AUROC) and used in a subsequent Kaplan-Meier survival analysis. RESULTS: Univariate and multivariate analyses showed that Mayo Risk Score (MRS), serum creatinine and NLR were independent indicators for mortality. NLR yielded significantly higher AUROC (0.86) than those of platelet-to-lymphocyte ratio (0.58, p=0.03), but comparable with MRS (0.87, p=0.88). Spearman's correlation analysis represented a positive correlation between escalating NLR and aggravating Child-Pugh grade (r=0.44, p<0.001). Patients with NLR <2.18 exhibited higher survival (with 100% sensitivity and 67.1% specificity) within 1 year follow-up duration, and NLR ≥2.18 was indicative of higher mortality (log-rank test, p<0.001). In addition, these results were internally confirmed by a validation cohort. CONCLUSION: NLR is closely related to short-term mortality in patients with PBC.