The growing disparity between the number of liver transplant candidates and the supply of deceased donor organs has motivated the development of living donor liver transplantation (LDLT). Over the ...last two decades, the operation has been markedly improved by innovations rendering modern results comparable with those of deceased donor liver transplantation (DDLT). However, there remains room for further innovation, particularly in adult living donor liver transplantation (ALDLT). Unlike whole‐size DDLT and pediatric LDLT, size‐mismatching between ALDLT graft and recipient body weight and changing dynamics of posttransplant allograft regeneration have remained major challenges. A better understanding of the complex surgical anatomy and physiologic differences of ALDLT helps avoid small‐for‐size graft syndrome, graft congestion from outflow obstruction and graft hypoperfusion from portal flow steal. ALDLT for high‐urgency patients (Model for End‐Stage Liver Disease score >30) can achieve results comparable to DDLT in high volume centers. Size limitations of partial grafts and donor safety issues can be overcome with dual grafts and modified right‐lobe grafts that preserve the donor's middle hepatic vein trunk. Extended application of LDLT for unresectable hepatocellular carcinoma above Milan criteria is an optional strategy at the cost of slightly compromised survival. ABO‐blood group incompatibility obstacles have been broken down by introducing a paired donor exchange program and refined peri‐operative management of ABO‐incompatible ALDLT. This review focuses on recent innovations of surgical techniques, safe donor selection, current strategies to expand ALDLT with broadened patient selection criteria and important aspects of teamwork required for success.
Expanding a successful adult living donor liver transplantation program requires a better understanding of the physiologic differences between living donor and deceased donor liver transplantation, technical innovation, broadened recipient acceptance criteria, and consistently safe donor selection criteria. Companion videos demonstrating the techniques described in this comprehensive review can be found in the AJT Video Library at amjtransplant.com.
Edge localized modes (ELMs) in high-confinement mode plasmas were completely suppressed in KSTAR by applying n=1 nonaxisymmetric magnetic perturbations. Initially, the ELMs were intensified with a ...reduction of frequency, but completely suppressed later. The electron density had an initial 10% decrease followed by a gradual increase as ELMs were suppressed. Interesting phenomena such as a saturated evolution of edge T(e) and broadband changes of magnetic fluctuations were observed, suggesting the change of edge transport by the applied magnetic perturbations.
Merons which are topologically equivalent to one-half of skyrmions can exist only in pairs or groups in two-dimensional (2D) ferromagnetic (FM) systems. The recent discovery of meron lattice in ...chiral magnet Co
Zn
Mn
raises the immediate challenging question that whether a single meron pair, which is the most fundamental topological structure in any 2D meron systems, can be created and stabilized in a continuous FM film? Utilizing winding number conservation, we develop a new method to create and stabilize a single pair of merons in a continuous Py film by local vortex imprinting from a Co disk. By observing the created meron pair directly within a magnetic field, we determine its topological structure unambiguously and explore the topological effect in its creation and annihilation processes. Our work opens a pathway towards developing and controlling topological structures in general magnetic systems without the restriction of perpendicular anisotropy and Dzyaloshinskii-Moriya interaction.
Coronary computed tomographic angiography (coronary CT) is a non-invasive test for diagnosis of cardiac function. Coronary calcium scores determined by coronary CT are associated with cardiovascular ...risk factors. However, no studies have investigated the association between coronary calcium scores and cardiovascular complications after liver transplantation (LT). We therefore evaluated the utility of preoperative coronary calcium scores for predicting early postoperative cardiovascular complications in LT recipients.
Between 2010 and 2012, 443 LT recipients were analysed retrospectively. Preoperative cardiovascular assessments, including coronary CT, were performed. A coronary calcium score >400 was defined as a positive finding. Predictive factors of early postoperative cardiovascular complications were evaluated by univariate and multivariate analyses. Major cardiovascular complications occurring during a period of 1 month after LT were noted.
Of the 443 patients, 38 (8.6%) experienced one or more cardiovascular complications. Positive coronary CT findings were seen in 11 (2.5%) patients. In the multivariate analysis, a coronary calcium score >400 {odds ratio (OR)=4.62 95% confidence interval (CI): 1.14–18.72, P=0.032} and female sex OR=2.76 (1.37–5.57), P=0.005 were predictive of cardiovascular complications.
A preoperative coronary calcium score of >400 predicted cardiovascular complications occurring 1 month after LT, suggesting that preoperative evaluation of coronary calcium scores could help predict early postoperative cardiovascular complications in LT recipients.
XIAP-associated factor 1 (XAF1) is a new candidate tumor suppressor, which has been known to exert proapoptotic effects by interfering with the caspase-inhibiting activity of XIAP. To explore the ...XAF1's candidacy for a suppressor in urogenital tumorigenesis, we investigated the XAF1 status in a series of cancer cell lines and primary tumors derived from the bladder, kidney and prostate. Expression of XAF1 transcript was undetectable or extremely low in 60% (3/5) of bladder, 66% (10/15) of kidney, and 100% (3/3) prostate cancer cell lines. Abnormal reduction of XAF1 was also found in 33% (18/55) of primary bladder and 40% (8/20) of primary kidney tumors, and showed a correlation with advanced stage and high grade of bladder tumor. Hypermethylation at 14 CpG sites in the 5' proximal region of the XAF1 promoter was highly prevalent in cancers versus adjacent normal or benign tissues and tightly associated with reduced gene expression. XAF1 expression enhanced the apoptotic response of tumor cells to chemotherapeutic agents, such as etoposide or 5-FU. While XAF1 expression did not influence the subcellular distribution or expression of XIAP, it elevated the protein stability of p53 and its target gene expression. Moreover, the apoptosis-sensitizing and growth suppression function of XAF1 was markedly impeded by blockade of p53 function. Collectively, our study demonstrates that epigenetic alteration of XAF1 is frequent in human urogenital cancers and may contribute to the malignant progression of tumors by rendering tumor cells a survival advantage partially through the attenuated p53 response to apoptotic stresses.
Background
This study aimed to investigate whether radiofrequency ablation (RFA) is an alternative to surgical resection for hepatocellular carcinoma (HCC) within the context of current guidelines.
...Methods
This retrospective study included patients with normal portal pressure and serum bilirubin level who initially underwent liver resection or RFA for a single HCC of maximum size 3 cm. Between‐group differences in cumulative rates of survival and recurrence specific for HCC were analysed in the entire cohort and in a propensity score‐matched cohort.
Results
A total of 604 patients were enrolled, 273 in the liver resection group and 331 in the RFA group. The 5‐ and 10‐year HCC‐specific survival rates for the resection and RFA groups were 87·6 versus 82·1 per cent and 59·0 versus 61·2 per cent respectively (P = 0·214), whereas overall 5‐ and 10‐year recurrence‐free survival rates for the corresponding groups were 60·6 versus 39·4 per cent and 37·5 versus 25·1 per cent respectively (P < 0·001). In the propensity score‐matched cohort (152 pairs), there were no differences in HCC‐specific survival (hazard ratio (HR) 1·03 for RFA versus resection; P = 0·899), whereas recurrence‐free survival again differed between the treatment groups (HR 1·75; P < 0·001). RFA was independently associated with poorer outcomes in terms of treatment‐site recurrence‐free survival (adjusted HR 1·66; P = 0·026), but not non‐treatment‐site recurrence‐free survival (adjusted HR 1·15; P = 0·354).
Conclusion
Although RFA carries a higher risk of treatment‐site recurrence than hepatic resection, it provides comparable overall survival in patients with a single small HCC without portal hypertension or a raised bilirubin level.
Good alternative in small hepatocellular carcinoma
Uncovering the mechanisms that govern the maintenance of stem-like cancer cells is critical for developing therapeutic strategies for targeting these cells. Constitutive activation of c-Jun ...N-terminal kinase (JNK) has been reported in gliomas and correlates with histological grade. Here, we found that JNK signaling is crucial for the maintenance of 'stemness' in glioma cells. Sphere-cultured glioma cells showed more phosphorylation of JNK compared with serum-containing monolayer cultures. Importantly, blockade of JNK signaling with SP600125 or small interfering RNAs targeting JNK1 or JNK2 significantly reduced the CD133(+)/Nestin(+) population and suppressed sphere formation, colony formation in soft agar, and expression of stem cell markers in sphere-cultured glioma cells. Intriguingly, sphere-cultured glioma cells exhibited enhanced expression of Notch-2, but not Notch-1, -3 or -4, and JNK inhibition almost completely abrogated this increase. Blocking the phosphoinoside 3-kinase (PI3K)/Akt pathway with LY294002 or si-Akt also suppressed the self-renewal of sphere-cultured glioma cells. PI3K, but not Akt, had a role as an upstream kinase in JNK1/2 activation. In addition, treatment with si-JNK greatly increased etoposide- and ionizing radiation (IR)-induced cell death in glioma spheres. Consistent with glioma cell lines, glioma stem-like cells isolated from primary patient glioma cells also had a higher activity of JNK and Notch-2 expression. Importantly, inhibition of JNK2 led to a decrease of Notch-2 expression and suppressed the CD133(+)/Nestin(+) cell population in patient-derived primary glioma cells. Finally, downregulation of JNK2 almost completely suppressed intracranial tumor formation by glioma cells in nude mice. Taken together, these data demonstrate that JNK signaling is crucial for the maintenance of self-renewal and tumorigenicity of glioma stem-like cells and drug/IR resistance, and can be considered a promising target for eliminating stem-like cancer cells in gliomas.
WHO grade II gliomas are divided into three classes:
-wildtype,
-mutant and no 1p/19q codeletion, and
-mutant and 1p/19q-codeleted. Different molecular subtypes have been reported to have prognostic ...differences and different chemosensitivity. Our aim was to evaluate the predictive value of imaging phenotypes assessed with the Visually AcceSAble Rembrandt Images lexicon for molecular classification of lower grade gliomas.
MR imaging scans of 175 patients with lower grade gliomas with known
mutation and 1p/19q-codeletion status were included (78 grade II and 97 grade III) in the discovery set. MR imaging features were reviewed by using Visually AcceSAble Rembrandt Images (VASARI); their associations with molecular markers were assessed. The predictive power of imaging features for
-wild type tumors was evaluated using the Least Absolute Shrinkage and Selection Operator. We tested the model in a validation set (40 subjects).
Various imaging features were significantly different according to
mutation. Nonlobar location, larger proportion of enhancing tumors, multifocal/multicentric distribution, and poor definition of nonenhancing margins were independent predictors of an
wild type according to the Least Absolute Shrinkage and Selection Operator. The areas under the curve for the prediction model were 0.859 and 0.778 in the discovery and validation sets, respectively. The
-mutant, 1p/19q-codeleted group frequently had mixed/restricted diffusion characteristics and showed more pial invasion compared with the
-mutant, no codeletion group.
Preoperative MR imaging phenotypes are different according to the molecular markers of lower grade gliomas, and they may be helpful in predicting the
mutation status.
Summary
Background
Asthma is a chronic inflammatory disease caused by complex interactions of genetic, epigenetic, and environmental factors. For this reason, new approaches are required to clarify ...the pathogenesis of asthma by systemic review.
Objective
We applied a 1H‐NMR metabolomics approach to investigate the altered metabolic pattern in sera from patients with asthma and sought to identify the mechanism underlying asthma and potential biomarkers.
Method
A global profile of sera from patients with asthma (n = 39) and controls (n = 26) was generated using 1H‐NMR spectroscopy coupled with multivariate statistical analysis. Endogenous metabolites in serum were rapidly measured using the target‐profiling procedure.
Results
Multivariate statistical analysis showed a clear distinction between patients with asthma and healthy subjects. Sera of asthma patients were characterized by increased levels of methionine, glutamine, and histidine and by decreased levels of formate, methanol, acetate, choline, O‐phosphocholine, arginine, and glucose. The metabolites detected in the sera of patients with asthma are involved in hypermethylation, response to hypoxia, and immune reaction. Furthermore, the levels of serum metabolites from patients with asthma correlated with asthma severity; in particular, lipid metabolism was altered in patients with lower forced expiratory volume in 1 s percentage (FEV1%) predicted values. In addition, potential biomarkers showed strong predictive power in ROC analysis, and the presence of asthma in external validation models was predicted with high accuracy (90.9% for asthma and 100% for control subjects).
Conclusion & Clinical Relevance
These data showed that 1H‐NMR‐based metabolite profiling of serum may be useful for the effective diagnosis of asthma and a further understanding of its pathogenesis.
We present new constraints on the dark matter-induced annual modulation signal using 1.7 years of COSINE-100 data with a total exposure of 97.7 kg yr. The COSINE-100 experiment, consisting of 106 kg ...of NaI(Tl) target material, is designed to carry out a model-independent test of DAMA/LIBRA's claim of WIMP discovery by searching for the same annual modulation signal using the same NaI(Tl) target. The crystal data show a 2.7 cpd/kg/keV background rate on average in the 2-6 keV energy region of interest. Using a χ-squared minimization method we observe best fit values for modulation amplitude and phase of 0.0092±0.0067 cpd/kg/keV and 127.2±45.9 d, respectively.
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