Many studies have been conducted to identify the causative organisms in colorectal cancer (CRC) and compare the microbiota of healthy individuals and those with CRC. The pathways by which the microbiota promotes CRC development are not yet fully understood. The hypothesized mechanisms include damage to the DNA, production of carcinogenic metabolites, and promotion of chronic inflammation. In a state of dysbiosis, the gut loses protective bacteria and is enriched with pathogenic and cancer-promoting bacteria, which promotes functions associated with cancer such as angiogenesis, loss of apoptosis, and cell proliferation. We have established a strong link between microbiota dysbiosis and certain species of bacteria and even viruses involved in tumorigenesis. In this review, we look at some of the major identified species and how they are related to CRC. Future research should include and even focus on mycobiome and virome on CRC development. Due to the diversity of the gut microbiome, there is a high possibility that the gain and loss of bacteria and their metabolic functions lead to CRC.
We introduce GPflux, a Python library for Bayesian deep learning with a strong emphasis on deep Gaussian processes (DGPs). Implementing DGPs is a challenging endeavour due to the various mathematical subtleties that arise when dealing with multivariate Gaussian distributions and the complex bookkeeping of indices. To date, there are no actively maintained, open-sourced and extendable libraries available that support research activities in this area. GPflux aims to fill this gap by providing a library with state-of-the-art DGP algorithms, as well as building blocks for implementing novel Bayesian and GP-based hierarchical models and inference schemes. GPflux is compatible with and built on top of the Keras deep learning eco-system. This enables practitioners to leverage tools from the deep learning community for building and training customised Bayesian models, and create hierarchical models that consist of Bayesian and standard neural network layers in a single coherent framework. GPflux relies on GPflow for most of its GP objects and operations, which makes it an efficient, modular and extensible library, while having a lean codebase.
Rationale: Adult-to-adult right lobe living donor liver transplantation is a viable alternative to whole liver transplantation from a deceased donor. The key aspect of the surgical procedure is the restoration of adequate graft blood flow and maintenance of sufficient volume of well vascularized parenchyma in the donor. Specific features of vascular anatomy in the donor and the recipient can be eventual cause for significant technical difficulties during transplantation. They can also increase the risk of complications and deteriorate graft functioning.Aim: To identify the incidence of various types of afferent and efferent vascularization of right lobe of the liver, potential techniques of vascular reconstructive procedures, rates and types of postoperative complications, as well as immediate surgical results.Materials and methods: We retrospectively analyzed the data on 220 right lobe liver transplantations adult patients, consecutively performed from 2010 to 2017 in one center. Specific characteristics of liver vascularization in donors and recipients were determined by pre-operative computed tomography and intra-operatively. The information on the types of vascular reconstruction, complications and results of surgical procedures was obtained from patients' medical files.Results: The following variants of blood supply to the right liver lobe were seen most frequently: portal vein trifurcation 22%, shortened trunk of the right portal vein branch 13%, supplementary v. hepatica from SgVIII with a diameter of > 5 mm 22%, supplementary lower right v. hepatica 17%, isolated venous outflow from all right lobe segments 2%, two arteries 2%. In addition, 17% of the recipients had portal vein thrombosis and 1% portal vein fibrosis. During the follow-up all donors remained alive. The rate of surgical complications was 12.5%, among them bile pocket or biloma 8.5%, intra-abdominal bleeding 2.5%, wound complications 1.5%. The rate of early post-operative complications in the recipients was 31.5%, with 4.5% of them being vascular and 15.5% biliary. The 6-months and 4-years survival of the recipients (Kaplan-Meier) was 98% and 95%, respectively.Conclusion: Immediate and longterm survival of the recipients of living donor right lobe live grafts, as well as absence of fatalities among their donors, confirm high effectiveness and expedience of this type of intervention. The observed anatomic variety of blood supply to the right liver lobe stipulates stringent requirements to the quality of preoperative diagnostics, deliberate donor selection, thorough planning of the procedure and high qualification of the surgical team. A relatively high rate of postoperative complications warrants the necessity of an intensive diagnostic monitoring in the early post-operative period and active strategies of their correction.
Assessing the viability and monitoring the function of liver graft in the early postoperative period are critical clinical tasks. One possible solution is to determine the changes in concentration of blood glucose, its metabolites and glycerol in the graft using interstitial microdialysis. Objective: to study the dynamics of interstitial glucose, lactate, pyruvate and glycerol in the early post-liver transplant period – depending on the initial graft function (IGF) – and to compare with the results of standard laboratory blood tests. Materials and methods. Four selected clinical observations of deceased donor liver transplantation are presented. Two of the observations showed normal IGF, one observation – early allograft dysfunction (EAD), complicated by hepatic artery thrombosis (HAT), while one observation demonstrated primary non-function (PNF). Collection of microdialysis samples began after arterial reperfusion of the liver graft and continued continuously for 7 days or until death. Standard blood biochemistry and coagulation tests were performed at least once a day. Results. With normal IGF and a smooth postoperative period, interstitial concentrations of glucose, lactate, pyruvate and glycerol remained stable throughout the observation period, ranging from 5 to 20 mmol/L, 1.1 to 7.5 mmol/L, 90 to 380 μmol/L, and 10–100 μmol/L, respectively. EAD was associated with initially higher levels of glucose, lactate, and pyruvate. With HAT development, there was a rapid (within 2–4 hours) five-fold increase in interstitial concentration of lactate with simultaneous decrease in glucose and pyruvate levels to 0.1 mmol/L and 11 μmol/L, respectively. In the case of PNF, there was an initially high concentration of interstitial lactate – 16.4 mmol/L, which increased further to 35.5 mmol/L. Glucose concentration was close to 0. Changes in interstitial glucose, its metabolites and glycerol concentrations chronologically preceded the corresponding changes in peripheral blood composition by 3–5 hours. Conclusion. Microdialysis measurement of interstitial glucose, lactate, pyruvate and glycerol concentrations facilitates real-time monitoring of liver graft viability and function. The high sensitivity of the method could help in accelerating diagnosis of vascular complications (HAT in particular), as well as graft dysfunction with other causes. Therefore, the method is feasible in clinical practice.
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