Cutaneous metastases: From epidemiology to therapy.

Cutaneous metastases are seen in up to 10% of all oncology patients and can occur in different locations depending on the entity. Cutaneous metastases are often associated with a high psychological burden and, especially in the case of exulceration, with shame and social withdrawal. This review discusses the diagnostic and therapeutic options. The most common tumor entities in which cutaneous metastases are observed are discussed, and local and systemic treatment options are presented according to the current state of research.

Uric acid is associated with long-term adverse cardiovascular outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND AND AIMS: Evidence links uric acid (UA) with the promotion of cardiovascular disease. We assessed the prognostic value of UA on long-term major adverse outcomes (MACE) in patients with acute coronary syndrome (ACS), undergoing percutaneous coronary intervention (PCI). METHODS: As primary endpoint, we assessed the association of UA (continuous and dichotomized) with MACE, including cardiovascular death, myocardial infarction (MI) and stroke, using Cox regression and propensity matching. As secondary endpoints, the influence of hyperuricemia (defined as UA levels > 6.0 mg/dl in women, and >7.0 mg/dl in men) was analysed separately for cardiovascular death, MI, and stroke. The incremental prognostic value of UA was tested using the net reclassification improvement (NRI), and the integrated discrimination improvement (IDI). RESULTS: We included 1215 patients. Hyperuricemia was present in 356 (29.3%) patients. Mean follow-up was 5.5 years. UA (HR 1.091 [1.035-1.150]; p = 0.001) and hyperuricemia (HR 1.750 [1.388-2.207]; p < 0.001) were significantly associated with MACE. Results were consistent between Cox regression and propensity matched analysis. Patients with hyperuricemia had a 1.6-fold increased relative risk for cardiovascular death (p = 0.005) and a 1.5-fold increased risk for MI (p = 0.032). For stroke, hyperuricemia only constituted a confounder (HR 1.104; p = 0.970). The prognostic accuracy of an established risk prediction model was significantly increased by adding UA (continuous NRI p = 0.004; categorical NRI p = 0.029; IDI p = 0.002). CONCLUSIONS: Our data suggest an independent association of elevated UA with long-term MACE in ACS patients undergoing PCI. Whether lowering UA might be beneficial remains to be elucidated in large clinical trials.

Epicardial adipose tissue and cardiovascular outcome in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

AIMS: We investigated the association between epicardial adipose tissue (EAT) thickness and cardiovascular outcomes in a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention. METHODS: Of 1198 patients undergoing percutaneous coronary intervention, transthoracic echocardiography was performed in 438 patients during the index hospitalization. EAT thickness was measured in the parasternal long-axis view perpendicularly on the free wall of the right ventricle at end-systole in three consecutive cardiac cycles and then averaged. As the primary outcome measure, a composite of major adverse cardiovascular events - including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke - was investigated after three years of follow-up. RESULTS: Patients were included between 2004 and 2012 and 293 (66.9%) were men. The median EAT thickness was 2.65 mm (interquartile range 2.00-3.00). EAT was correlated with body mass index ( R=0.404; p<0.001), weight ( R=0.314; p<0.001), baseline creatinine ( R=0.118; p=0.014) and baseline glucose ( R=0.129; p=0.007). After a follow-up period of three years, a major adverse cardiovascular event occurred in 64 patients (14.6%) corresponding to 36 (8.2%) with cardiovascular death, 21 (4.8%) with myocardial infarction and seven (1.6%) with stroke. Regarding the primary endpoint, EAT thickness revealed a significant predictive effect on univariate Cox regression (hazards ratio 1.479, 95% CI 1.192-1.953; p=0.006) and multivariate Cox regression analysis (hazards ratio 1.524, 95% CI 1.011-2.267; p=0.038) after adjusting for established cardiovascular confounders. CONCLUSIONS: In a cohort of high-risk patients with acute coronary syndrome undergoing percutaneous coronary intervention, EAT was associated with established markers of cardiovascular death and had a predictive value for the three-year cardiovascular outcome.

Charge control of the inverse trans-influence.

The synthesis and characterization of uranium(VI) mono(imido) complexes, by the oxidation of corresponding uranium(V) species, are presented. These experimental results, paired with DFT analyses, allow for the comparison of the electronic structure of uranium(VI) mono(oxo) and mono(imido) ligands within a conserved ligand framework and demonstrate that the magnitude of the ground state stabilization derived from the inverse trans-influence (ITI) is governed by the relative charge localization on the multiply bonded atom or group.

A new tripodal ligand system with steric and electronic modularity for uranium coordination chemistry.

The synthesis of a potentially redox active tripodal ligand containing a tris(aryloxide) functionalized mesitylene anchor, (((tBu)ArOH)(3)mes) (1), and its metalation with low-valent uranium to form [(((tBu)ArO)(3)mes)U] (1-U) is reported. The results from characterization by X-ray crystallography, spectroscopic studies, and computational analysis, as well as initial reactivity studies, support a +3 uranium oxidation state. Comparison to the previously synthesized complex, [(((tBu)ArO)(3)tacn)U] (2-U), featuring the redox-innocent triazacyclononane anchor reveals that changing the anchor from the flexible triazacyclononane to a rigid mesityl fragment increases the structural flexibility of the aryloxide substituents in complexes of 1. The synthesis and crystal structures of uranium(IV) amide complexes of 1-U and 2-U are discussed.

A hexahistidine-Zn2+-dye label reveals STIM1 surface exposure.

Site-specific fluorescent labeling of proteins in vivo remains one of the most powerful techniques for imaging complex processes in live cells. Although fluorescent proteins in many colors are useful tools for tracking expression and localization of fusion proteins in cells, these relatively large tags (>220 aa) can perturb protein folding, trafficking and function. Much smaller genetically encodable domains (<15 aa) offer complementary advantages. We introduce a small fluorescent chelator whose membrane-impermeant complex with nontoxic Zn(2+) ions binds tightly but reversibly to hexahistidine (His(6)) motifs on surface-exposed proteins. This live-cell label helps to resolve a current controversy concerning externalization of the stromal interaction molecule STIM1 upon depletion of Ca(2+) from the endoplasmic reticulum. Whereas N-terminal fluorescent protein fusions interfere with surface exposure of STIM1, short His(6) tags are accessible to the dye or antibodies, demonstrating externalization.

Single- and double-cubane clusters in the multiple oxidation states [VFe(3)S(4)](3+,2+,1+).

A new series of cubane-type [VFe(3)S(4)](z)() clusters (z = 1+, 2+, 3+) has been prepared as possible precursor species for clusters related to those present in vanadium-containing nitrogenase. Treatment of [(HBpz(3))VFe(3)S(4)Cl(3)](2)(-) (2, z = 2+), protected from further reaction at the vanadium site by the tris(pyrazolyl)hydroborate ligand, with ferrocenium ion affords the oxidized cluster [(HBpz(3))VFe(3)S(4)Cl(3)](1)(-) (3, z = 3+). Reaction of 2 with Et(3)P results in chloride substitution to give [(HBpz(3))VFe(3)S(4)(PEt(3))(3)](1+) (4, z = 2+). Reaction of 4 with cobaltocene reduced the cluster with formation of the edge-bridged double-cubane [(HBpz(3))(2)V(2)Fe(6)S(8)(PEt(3))(4)] (5, z = 1+, 1+), which with excess chloride underwent ligand substitution to afford [(HBpz(3))(2)V(2)Fe(6)S(8)Cl(4)](4)(-) (6, z = 1+, 1+). X-ray structures of (Me(4)N)[3], [4](PF(6)), 5, and (Et(4)N)(4)[6] x 2MeCN are described. Cluster 5 is isostructural with previously reported [(Cl(4)cat)(2)(Et(3)P)(2)Mo(2)Fe(6)S(8)(PEt(3))(4)] and contains two VFe(3)S(4) cubanes connected across edges by a Fe(2)S(2) rhomb in which the bridging Fe-S distances are shorter than intracubane Fe-S distances. Mössbauer (2-5), magnetic (2-5), and EPR (2, 4) data are reported and demonstrate an S = 3/2 ground state for 2 and 4 and a diamagnetic ground state for 3. Analysis of (57)Fe isomer shifts based on an empirical correlation between shift and oxidation state and appropriate reference shifts results in two conclusions. (i) The oxidation 2 --> 3 + e(-) results in a change in electron density localized largely or completely on the Fe(3) subcluster and associated sulfur atoms. (ii) The most appropriate charge distributions are [V(3+)Fe(3+)Fe(2+)(2)S(4)](2+) (Fe(2.33+)) for 1, 2, and 4 and [V(3+)Fe(3+)(2)Fe(2+)S(4)](3+) (Fe(2.67+)) for 3 and [V(2)Fe(6)S(8)(SEt)(9)](3+). Conclusion i applies to every MFe(3)S(4) cubane-type cluster thus far examined in different redox states at parity of cluster ligation. The formalistic charge distributions are regarded as the best current approximations to electron distributions in these delocalized species. The isomer shifts require that iron atoms are mixed-valence in each cluster.