Monitoring Hepatocyte Dysfunction and Biliary Complication After Liver Transplantation Using Quantitative Hepatobiliary Scintigraphy

The significance of hepatobiliary scintigraphy (HBS) for hepatic graft function assessment was established mostly on retrospective studies and was not widely recognized due to the lack of quantitative data and variation in accuracy. This prospective study was performed to investigate the effectiveness of quantitative HBS for assessing hepatocyte dysfunction and biliary complication in liver transplant recipients.In 57 recipients who had undergone orthotopic liver transplantation, a total of 67 dynamic ^99mTc-EHIDA scans were performed and quantitative parameters including the hepatocyte extraction fraction (HEF), time to maximum hepatic radioactivity (T_max), and time for peak activity to decrease by 50% (T_1/2) were calculated. The scintigraphic results based on the 3 parameters were compared against the final diagnosis. A ROC curve analysis was carried out to identify the cutoff value of T_max for diagnosis of biliary stricture. Correlation between the parameters of postoperative HBS and conventional biochemical liver function indices were also analyzed.Quantitative ^99mTc-EHIDA HBS had an overall sensitivity of 94.12% (16/17), specificity of 93.33% (42/45), and diagnostic accuracy of 93.55% (58/62) for detecting hepatocyte dysfunction and biliary complication in liver transplant recipients. The recommended cutoff value of T_max for diagnosis of post-transplant biliary stricture was set at 15.75 min with a sensitivity of 100.0% and a specificity of 94.0%. The scintigraphic parameters (HEF, T_max) were statistically significantly associated with the conventional liver function parameters.Quantitative ^99mTc-EHIDA HBS offers a noninvasive imaging modality with high sensitivity and specificity to diagnose hepatocyte dysfunction as well as distinguish between patients with or without biliary stricture following liver transplantation. Furthermore, HEF and T_max values obtained from dynamic HBS show good correlation with conventional liver function parameters.     

Genetic toxicity assessment using liver cell models: past,present, and future

ABSTRACT

Genotoxic compounds may be detoxified to non-genotoxic metabolites while many pro-carcinogens require metabolic activation to exert their genotoxicity in vivo. Standard genotoxicity assays were developed and utilized for risk assessment for over 40 years. Most of these assays are conducted in metabolically incompetent rodent or human cell lines. Deficient in normal metabolism and relying on exogenous metabolic activation systems, the current in vitro genotoxicity assays often have yielded high false positive rates, which trigger unnecessary and costly in vivo studies. Metabolically active cells such as hepatocytes have been recognized as a promising cell model in predicting genotoxicity of carcinogens in vivo. In recent years, significant advances in tissue culture and biological technologies provided new opportunities for using hepatocytes in genetic toxicology. This review encompasses published studies (both in vitro and in vivo) using hepatocytes for genotoxicity assessment. Findings from both standard and newly developed genotoxicity assays are summarized. Various liver cell models used for genotoxicity assessment are described, including the potential application of advanced liver cell models such as 3D spheroids, organoids, and engineered hepatocytes. An integrated strategy, that includes the use of human-based cells with enhanced biological relevance and throughput, and applying the quantitative analysis of data, may provide an approach for future genotoxicity risk assessment.     

Learning to Discretize: Solving 1D Scalar Conservation Laws via Deep Reinforcement Learning

Conservation laws are considered to be fundamental laws of nature. It has broad applications in many fields, including physics, chemistry, biology, geology, and engineering. Solving the differential equations associated with conservation laws is a major branch in computational mathematics. The recent success of machine learning, especially deep learning in areas such as computer vision and natural language processing, has attracted a lot of attention from the community of computational mathematics and inspired many intriguing works in combining machine learning with traditional methods. In this paper, we are the first to view numerical PDE solvers as an MDP and to use (deep) RL to learn new solvers. As proof of concept, we focus on 1-dimensional scalar conservation laws. We deploy the machinery of deep reinforcement learning to train a policy network that can decide on how the numerical solutions should be approximated in a sequential and spatial-temporal adaptive manner. We will show that the problem of solving conservation laws can be naturally viewed as a sequential decision-making process, and the numerical schemes learned in such a way can easily enforce long-term accuracy. Furthermore, the learned policy network is carefully designed to determine a good local discrete approximation based on the current state of the solution, which essentially makes the proposed method a meta-learning approach. In other words, the proposed method is capable of learning how to discretize for a given situation mimicking human experts. Finally, we will provide details on how the policy network is trained, how well it performs compared with some state-of-the-art numerical solvers such as WENO schemes, and supervised learning based approach L3D and PINN, and how well it generalizes.     

Cefoperazone-sulbactam and risk of coagulation disorders or bleeding: a retrospective cohort study

ABSTRACT

Objectives: Limited evidence has suggested that cefoperazone-sulbactam causes coagulation disorders and bleeding.

Methods: The authors conducted a retrospective study to compare patients receiving cefoperazone-sulbactam versus those treated with cefoperazone-tazobactam or ceftazidime. Propensity-score matching was used to explore whether treatment with cefoperazone-sulbactam increased the risk of prothrombin time (PT) prolongation, coagulation disorders, and bleeding, or decreased platelets (PLT).

Results: The cohort included 23,242 patients. Among patients receiving cefoperazone-sulbactam, the risk of PT prolongation, coagulation disorders, decreased PLT, and bleeding was 5.3%, 9.2%, 15.7%, and 4.2%, respectively. Propensity-score matching analyses suggested that cefoperazone-sulbactam increased the risk of PT prolongation (aOR 2.26, 95% CI 1.61–3.18), coagulation disorders (aOR 1.81, 95% CI 1.43–2.30), and decreased PLT (aOR 1.46, 95% CI 1.25–1.72), but not increase bleeding (aOR 1.05, 95% CI 0.79–1.40) compared with ceftazidime. Patients receiving cefoperazone-sulbactam had higher risk of PT prolongation (aOR 1.53, 95% CI 1.11–2.10), coagulation disorders (aOR 1.53, 95% CI 1.21–1.95), but not decreased PLT (aOR 0.93, 95% CI 0.81–1.07) or bleeding (aOR 1.11, 95% CI 0.87–1.42), compared with those receiving cefoperazone-tazobactam.

Conclusion: Cefoperazone-sulbactam may be associated with a higher risk of PT prolongation and coagulation disorders compared with cefoperazone-tazobactam and ceftazidime.     

Double-balloon enteroscopy for retrieving retained small-bowel video capsule endoscopes: a systematic review

Abstract

Background and aim: Capsule retention is the most common adverse event associated with video capsule endoscopy. The use of double-balloon enteroscopy-assisted capsule endoscope retrieval has been increasingly reported in recent years. However, evidence is limited regarding its success rate, associated factors, and subsequent clinical outcomes.

Methods: A systematic review of relevant studies published before January 2019 was performed. Successful retrieval rate and associated factors, rate of endoscopic balloon dilation, and outcomes after double-balloon enteroscopy were summarized and pooled.

Results: Within 154 associated original articles, 12 including 150 cases of capsule retrieval by double-balloon enteroscopy were included. The estimated pooled successful retrieval rate was 86.5% (95% confidence interval, 75.6–95.1%). Anterograde approach and capsules retained in the jejunum or trapped by malignant strictures were associated with a higher successful retrieval rate than the retrograde approach (62/83 [74.7%] vs. 10/38 [26.3%], p?<?.001) and capsules retained in the ileum (41/41 [100.0%] vs. 43/58 [74.1%], p?<?.001) or trapped by benign strictures (21/21 [100.0%] vs. 65/83 [78.3%], p?=?.043). Endoscopic balloon dilation was performed in 38.8% (95% confidence interval, 22.3–56.3%) of patients with benign strictures. Two perforations (1.3%) were reported as severe adverse events after double-balloon enteroscopy. A significantly lower surgery rate was found among cases with successful video capsule removal compared with unsuccessful cases (7.2% vs. 38.5%, p?=?.002).

Conclusions: Double-balloon enteroscopy is feasible and safe for removing retained video capsule endoscopes, and its use could decrease the need for surgery in patients with benign strictures and facilitate subsequent surgery in patients with malignant strictures.     

从形气神谈溃疡性结肠炎的中西医认识

溃疡性结肠炎(Ulcerative colitis,UC)是一种病情反复、迁延难愈的炎症肠病,已被世界卫生组织列为现代难治病之一[1]。本病病因及发病机制尚不明确,西药治疗效果欠佳。近年来中医药的介入,临床取得显著疗效。西医学认为疾病是机体在一定致病因素的作用下自稳调节紊乱,经过机体内损伤和抗损伤反应的相互斗争,表现出的一系列功能。