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.
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.
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.
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.
ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
A large change in albedo has a significant effect on glacier ablation. Atmospheric aerosols – e.g. black carbon (BC) and dust – can reduce the albedo of glaciers and thus contribute to their melting. ...In this study, two main themes were explored: (1) the decrease in albedo of the Zhadang glacier on Mt. Nyainqentanglha between 2001 and 2012, as observed by the Moderate Resolution Imaging Spectroradiometer (MODIS) on-board the Terra satellite, and the correlation of this albedo with mass balance; and (2) the concentrations of BC and dust in the glacier measured during 2012, and the associated impacts of these impurities on albedo and radiative forcings (RF). The average albedo of the Zhadang glacier from the MODIS increased with the altitude and fluctuated but had a decreasing trend (−0.003 a−1) during the period 2001–2012, with the highest (0.722) in 2003 and the lowest (0.597) in 2009 and 2010. The mass balance of the glacier has a positively significant correlation with its surface albedo derived from MODIS. Snow samples were collected on the Zhadang glacier to measure the BC and dust in the summer of 2012. The impacts of BC and dust on albedo reduction in different melting conditions were identified with the SNow ICe Aerosol Radiative (SNICAR) model initiated by in situ observation data. The sensitivity analysis showed that BC was a major factor in albedo reduction when the glacier was covered by newly fallen snow. Nevertheless, the contribution of dust to albedo reduction can reach as high as 56%, much exceeding that of BC (28%), when the glacier experiences strong surficial melting and its surface is almost bare ice. The average RF caused by dust could increase from 1.1 to 8.6 W m−2, exceeding the RF caused by BC after snow was deposited and surface melting occurred in the Zhadang glacier. This implies that it may be dust that primarily dominates the melting of some glaciers in the inner Tibetan Plateau during melting seasons, rather than BC.
Prediction of the
(IDH1)-mutation and 1p/19q-codeletion status of World Health Organization grade ll gliomas preoperatively may assist in predicting prognosis and planning treatment strategies. Our ...aim was to characterize the histogram and texture analyses of apparent diffusion coefficient and fractional anisotropy maps to determine
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
Ninety-three patients with World Health Organization grade II gliomas with known
mutation and 1p/19q-codeletion status (18
wild-type, 45
mutant and no 1p/19q codeletion, 30
mutant and 1p/19q codeleted tumors) underwent DTI. ROIs were drawn on every section of the T2-weighted images and transferred to the ADC and the fractional anisotropy maps to derive volume-based data of the entire tumor. Histogram and texture analyses were correlated with the
-mutation and 1p/19q-codeletion status. The predictive powers of imaging features for
wild-type tumors and 1p/19q-codeletion status in
-mutant subgroups were evaluated using the least absolute shrinkage and selection operator.
Various histogram and texture parameters differed significantly according to
-mutation and 1p/19q-codeletion status. The skewness and energy of ADC, 10th and 25th percentiles, and correlation of fractional anisotropy were independent predictors of an
wild-type in the least absolute shrinkage and selection operator. The area under the receiver operating curve for the prediction model was 0.853. The skewness and cluster shade of ADC, energy, and correlation of fractional anisotropy were independent predictors of a 1p/19q codeletion in
-mutant tumors in the least absolute shrinkage and selection operator. The area under the receiver operating curve was 0.807.
Whole-tumor histogram and texture features of the ADC and fractional anisotropy maps are useful for predicting the
-mutation and 1p/19q-codeletion status in World Health Organization grade II gliomas.
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
There is a growing body of research on the neural control of immunity and inflammation. However, it is not known whether the nervous system can regulate the production of inflammatory myeloid cells ...from hematopoietic progenitor cells in disease conditions. Myeloid cell numbers in diabetic patients were strongly correlated with plasma concentrations of norepinephrine, suggesting the role of sympathetic neuronal activation in myeloid cell production. The spleens of diabetic patients and mice contained higher numbers of tyrosine hydroxylase (TH)-expressing leukocytes that produced catecholamines. Granulocyte macrophage progenitors (GMPs) expressed the β2 adrenergic receptor, a target of catecholamines. Ablation of splenic sympathetic neuronal signaling using surgical, chemical, and genetic approaches diminished GMP proliferation and myeloid cell development. Finally, mice lacking TH-producing leukocytes had reduced GMP proliferation, resulting in diminished myelopoiesis. Taken together, our study demonstrates that catecholamines produced by leukocytes and sympathetic nerve termini promote GMP proliferation and myeloid cell development.
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•Sympathetic nervous system (SNS) mediates differentiation of myeloid progenitors•TH+ leukocytes express high amounts of neuropeptide Y receptors (NPYRs)•TH+ cells are required for myeloid cell generation during “emergency” hematopoiesis•Regulation of myelopoiesis by the β2 adrenergic receptor expressed by GMPs
Neural control of immunity and inflammation has been reported. Vasamsetti and colleagues demonstrate that the sympathetic nervous system controls the development of inflammatory myeloid cells from their progenitors in inflammatory conditions.
Microbial metabolites, such as short-chain fatty acids (SCFAs), are highly produced in the intestine and potentially regulate the immune system. We studied the function of SCFAs in the regulation of ...T-cell differentiation into effector and regulatory T cells. We report that SCFAs can directly promote T-cell differentiation into T cells producing interleukin-17 (IL-17), interferon-γ, and/or IL-10 depending on cytokine milieu. This effect of SCFAs on T cells is independent of GPR41 or GPR43, but dependent on direct histone deacetylase (HDAC) inhibitor activity. Inhibition of HDACs in T cells by SCFAs increased the acetylation of p70 S6 kinase and phosphorylation rS6, regulating the mTOR pathway required for generation of Th17 (T helper type 17), Th1, and IL-10(+) T cells. Acetate (C2) administration enhanced the induction of Th1 and Th17 cells during Citrobacter rodentium infection, but decreased anti-CD3-induced inflammation in an IL-10-dependent manner. Our results indicate that SCFAs promote T-cell differentiation into both effector and regulatory T cells to promote either immunity or immune tolerance depending on immunological milieu.
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