Background
ABO‐incompatible (ABO‐I) living donor liver transplantation (LDLT) has a high success rate. There are few detailed comparisons regarding biliary complications, infective complications and ...patient survival between ABO‐compatible (ABO‐C) and ABO‐I LDLT. The aim was to compare the outcomes of ABO‐I LDLT with those of ABO‐C LDLT using the matched‐pairs method.
Methods
Patients who underwent ABO‐I LDLT procedures between 2010 and 2013 were studied. They were matched for significant variables with patients who had ABO‐C LDLT (1 : 2 matching).
Results
Forty‐seven ABO‐I LDLT procedures were included. Ninety‐four patients who had ABO‐C LDLT were selected as a comparator group. The incidence of cytomegalovirus, bacterial and fungal infections during the first 3 months was similar after ABO‐I LDLT and ABO‐C LDLT (85 versus 76 per cent, 28 versus 37 per cent, and 13 versus 20 per cent, respectively). Antibody‐mediated rejection occurred after two procedures within 2 weeks of transplantation, but liver function improved with plasma exchange in both patients. There were no differences in the rate of acute rejection and biliary complications between ABO‐I and ABO‐C groups (P = 0·478 and P = 0·511 respectively). Three patients who had ABO‐I LDLT developed diffuse intrahepatic biliary complications and progressed to graft failure. The 1‐, 2‐ and 3‐year patient survival rates after ABO‐I LDLT and ABO‐C LDLT were 89 versus 87 per cent, 85 versus 83 per cent, and 85 versus 79 per cent, respectively.
Conclusion
The short‐term outcomes of ABO‐I LDLT were comparable to those of ABO‐C LDLT in this study. ABO‐I LDLT is an effective and safe transplant option with the potential to expand the pool of live donors.
Similar short‐term outcomes
The large volume of adult living donor liver transplantations (ALDLTs) at our center affords a unique opportunity to examine the impact of acute‐on‐chronic liver failure (ACLF) among high–Model for ...End‐Stage Liver Disease MELD score patients. From February 1998 to March 2010, 1958 cirrhotic recipients were analyzed to study the relationship between MELD scores and ALDLT outcomes. A total of 327 high‐MELD score recipients were categorized into ACLF and non‐ACLF groups, and their outcomes were compared. The 5‐year graft and patient survival in the high‐MELD group were 75.2% and 76.4%, respectively, which were significantly worse than the low and intermediate MELD groups. The presence of ACLF associated with higher MELD scores appeared to be the dominant factor responsible for the inferior results of patients with MELD score of 30–34 points. The 5‐year graft survivals in the ACLF group was 70.5% and in the non‐ACLF group it was 81.0% (p = 0.035). Therefore, ALDLT should be performed as soon as possible in high‐MELD score patients prior to ACLF development. Moreover, ACLF patients should be separately categorized when analyzing the outcomes of ALDLT. ALDLT for ACLF patients should not be discouraged because favorable outcomes can be expected through timely ALDLT and comprehensive management.
While adult living donor liver transplantation should be performed as soon as possible before acute‐on‐chronic liver failure develops, it should not be discouraged for patients with acute‐on‐chronic liver failure since timely transplantation and comprehensive management can bring a favorable outcome.
Purpose
Prior studies identified high variability in prevalence of withdrawal of life-sustaining treatment in the ICU. Variability in end-of-life decision-making has been reported at many levels: ...between countries, ICUs, and individual intensivists. We performed a systematic review examining regional, national, inter-hospital, and inter-physician variability in withdrawal of life-sustaining treatment in the ICU.
Methods
Using a predefined search strategy, we queried three electronic databases for peer-reviewed articles addressing withdrawal of life-sustaining treatment in adult patients in the ICU. Data were analyzed for variability in prevalence of withdrawal of life-sustaining treatment. Withholding of life-sustaining treatment was also examined where information was provided. An assessment tool was developed to quantify the risk of bias in the included articles.
Results
We identified 1284 studies, with 56 included after review. Most studies had unclear or high risk of bias, primarily due to unclear case definitions or potential confounding. The mean prevalence of withdrawal of life-sustaining treatment for patients who died varied from 0 to 84.1 % between studies, with standard deviation of 23.7 %. Sensitivity analysis of general ICU patients yielded similar results. Withholding also varied between 5.3 and 67.3 % (mean 27.3, SD 18.5 %). Substantial variability was found between world regions, countries, individual ICUs within a country, and individual intensivists within one ICU.
Conclusions
We identified substantial variability in the withdrawal of life-sustaining treatment across world regions and countries. Similar variability existed between ICUs within countries and even between providers within the same ICU. Further study is necessary, and could lead to interventions to improve end-of-life care in the ICU.
Machine learning (ML) is a burgeoning field of medicine with huge resources being applied to fuse computer science and statistics to medical problems. Proponents of ML extol its ability to deal with ...large, complex and disparate data, often found within medicine and feel that ML is the future for biomedical research, personalized medicine, computer‐aided diagnosis to significantly advance global health care. However, the concepts of ML are unfamiliar to many medical professionals and there is untapped potential in the use of ML as a research tool. In this article, we provide an overview of the theory behind ML, explore the common ML algorithms used in medicine including their pitfalls and discuss the potential future of ML in medicine.
Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM®) provides the earliest parameter of clot amplitudes at 5 min ...(A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT).
A total of 3446 retrospective ROTEM® measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib.
The median PLT was 47 000 mm−3 and the median Fib was 100 mg dl−1 during LDLT. The A5 parameters of EXTEM (A5EXTEM) and INTEM (A5INTEM) were highly correlated with MCF (r=0.96 and r=0.95, respectively), PLT (r=0.76 and r=0.77, respectively), and Fib (r=0.63 and r=0.64, respectively). A5 of FIBTEM (A5FIBTEM) was also correlated with MCF (r=0.91) and Fib (r=0.75). A5EXTEM thresholds of 15 and 19 mm predicted PLT<30 000 mm−3 (AUC=0.90) and <50 000 mm−3 (AUC=0.87), respectively, whereas A5FIBTEM 4 mm predicted Fib<100 mg dl−1 (AUC=0.86). Biases from A5EXTEM and A5FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively.
A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.
A Korean fusion energy development promotion law (FEDPL) was enacted in 2007. As a following step, a conceptual design study for a steady-state Korean fusion demonstration reactor (K-DEMO) was ...initiated in 2012. After the thorough 0D system analysis, the parameters of the main machine characterized by the major and minor radii of 6.8 and 2.1 m, respectively, were chosen for further study. The analyses of heating and current drives were performed for the development of the plasma operation scenarios. Preliminary results on lower hybrid and neutral beam current drive are included herein. A high performance Nb3Sn-based superconducting conductor is adopted, providing a peak magnetic field approaching 16 T with the magnetic field at the plasma centre above 7 T. Pressurized water is the prominent choice for the main coolant of K-DEMO when the balance of plant development details is considered. The blanket system adopts a ceramic pebble type breeder. Considering plasma performance, a double-null divertor is the reference configuration choice of K-DEMO. For a high availability operation, K-DEMO incorporates a design with vertical maintenance. A design concept for K-DEMO is presented together with the preliminary design parameters.
The folding of genomic DNA from the beads-on-a-string-like structure of nucleosomes into higher-order assemblies is crucially linked to nuclear processes. Here we calculate 3D structures of entire ...mammalian genomes using data from a new chromosome conformation capture procedure that allows us to first image and then process single cells. The technique enables genome folding to be examined at a scale of less than 100 kb, and chromosome structures to be validated. The structures of individual topological-associated domains and loops vary substantially from cell to cell. By contrast, A and B compartments, lamina-associated domains and active enhancers and promoters are organized in a consistent way on a genome-wide basis in every cell, suggesting that they could drive chromosome and genome folding. By studying genes regulated by pluripotency factor and nucleosome remodelling deacetylase (NuRD), we illustrate how the determination of single-cell genome structure provides a new approach for investigating biological processes.
Despite ionizing radiation (IR) is being widely used as a standard treatment for lung cancer, many evidences suggest that IR paradoxically promotes cancer malignancy. However, its molecular ...mechanisms underlying radiation-induced cancer progression remain obscure. Here, we report that exposure to fractionated radiation (2 Gy per day for 3 days) induces the secretion of granulocyte-colony-stimulating factor (G-CSF) that has been commonly used in cancer therapies to ameliorate neutropenia. Intriguingly, radiation-induced G-CSF promoted the migratory and invasive properties by triggering the epithelial-mesenchymal cell transition (EMT) in non-small-cell lung cancer cells (NSCLCs). By irradiation, G-CSF was upregulated transcriptionally by β-catenin/TCF4 complex that binds to the promoter region of G-CSF as a transcription factor. Importantly, irradiation increased the stability of β-catenin through the activation of PI3K/AKT (phosphatidylinositol 3-kinase/AKT), thereby upregulating the expression of G-CSF. Radiation-induced G-CSF is recognized by G-CSFR and transduced its intracellular signaling JAK/STAT3 (Janus kinase/signal transducers and activators of transcription), thereby triggering EMT program in NSCLCs. Taken together, our findings suggest that the application of G-CSF in cancer therapies to ameliorate neutropenia should be reconsidered owing to its effect on cancer progression, and G-CSF could be a novel therapeutic target to mitigate the harmful effect of radiotherapy for the treatment of NSCLC.
Claudins (CLDNs) are a family of integral membrane proteins central to the formation of tight junctions, structures that are involved in paracellular transport and cellular growth and ...differentiation, and are critical for the maintenance of cellular polarity. Recent studies have provided evidence that CLDNs are aberrantly expressed in diverse types of human cancers, including hepatocellular carcinomas (HCCs). However, little is known about how CLDN expression is involved in cancer progression. In this study, we show that CLDN1 has a causal role in the epithelial-mesenchymal transition (EMT) in human liver cells, and that the c-Abl-Ras-Raf-1-ERK1/2 signaling axis is critical for the induction of malignant progression by CLDN1. Overexpression of CLDN1 induced expression of the EMT-regulating transcription factors Slug and Zeb1, and thereby led to repression of E-cadherin, β-catenin expression, enhanced expression of N-cadherin and Vimentin, a loss of cell adhesion, and increased cell motility in normal liver cells and HCC cells. In line with these findings, inhibition of either c-Abl or ERK clearly attenuated CLDN1-induced EMT, as evidenced by a reversal of N-cadherin and E-cadherin expression patterns, and restored normal motility. Collectively, these results indicate that CLDN1 is necessary for the induction of EMT in human liver cells, and that activation of the c-Abl-Ras-Raf-1-ERK1/2 signaling pathway is required for CLDN1-induced acquisition of the malignant phenotype. The present observations suggest that CLDN1 could be exploited as a biomarker for liver cancer metastasis and might provide a pivotal point for therapeutic intervention in HCC.
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