Sarcopenia and survival in patients undergoing pancreatic resection.

BACKGROUND: Recent studies have suggested that lean core muscle area may predict outcomes from major abdominal surgeries. Pancreatic resections have been independently analyzed less frequently. METHODS: Pancreatic resections from 2005 to 2012 were reviewed. Sarcopenia was defined as the lowest tertile for lean psoas muscle area (LPMA). Preoperative risk factors, including comorbidities, albumin, weight loss, age and gender, were analyzed with a primary endpoint of overall survival. Secondary endpoints included complications, discharge destination and readmission. RESULTS: The study sample of 270 patients had complications in 42% of patients, with 26% developing serious complication. The majority (80%) were discharged home, and 1.9% died in the peri-operative period. The mean length of follow up was 31.2 months (range 0-94), and 37% required at least one readmission. LPMA was predictive of discharge destination for females (p = 0.038). Sarcopenia was predictive of readmission in males, compared to subjects in the second LPMA tertile (HR 0.3; 95% CI: 0.1-0.9). In all male subjects, including a subset with adenocarcinoma, patients with sarcopenia were more likely to die than males in the highest LPMA tertile (HR: 2.6; 95% CI: 1.4-4.8 and HR: 2.4; 95% CI: 1.2-4.9, respectively). In all patients with pancreatic ductal adenocarcinoma, transfusion (HR: 1.9; 95% CI: 1.1-3.4) and positive margins (HR: 2.0; 95% CI: 1.2-3.3) were the only factors predictive of overall survival. CONCLUSIONS: Sarcopenia appears to be a predictor of overall survival in male patients undergoing pancreatic resections, but not specifically for patients with pancreatic ductal adenocarcinoma. As prospective data in future studies are identified, sarcopenia may become a useful tool in predicting outcomes.

Synthesis of functional "top-half" partial structures of azinomycin a and B.

The design and synthesis of a detailed series of functional "top-half" substructures of azinomycin A and B is described.

Probing the electronic structure of platinum(II) chromophores: crystal structures, NMR structures, and photophysical properties of six new bis- and di- phenolate/thiolate Pt(II)diimine chromophores.

A general route for synthesis of six structurally similar Pt(II) diimine thiolate/phenolates chromophores possessing bulky phenolate or thiolate ligands is reported. The Pt chromophores were characterized using an array of techniques including 1H, 13C, and 195Pt NMR, absorption, emission, (spectro)electrochemistry, and EPR spectroscopy. Systematic variation of the electronic structure of the Pt(II) chromophores studied was achieved by (i) changing solvent polarity; (ii) substituting oxygen for sulfur in the donor ligand; (iii) alternating donor ligands from bis- to di-coordination; and (iv) changing the electron donating/withdrawing properties of the ligand(s). The lowest excited state in these new chromophores was assigned to a [charge-transfer-to-diimine] transition from the HOMO of mixed Pt/S (or Pt/O) character on the basis of absorption and emission spectroscopy, UV/vis (spectro)electrochemistry, and EPR spectroscopy. One of the chromophores, Pt(dpphen)(3,5-di-tert-butyl-catecholate) represents an example of a Pt(II) diimine phenolate chromophore that possesses a reversible oxidation centered predominantly on the donor ligand. Results from EPR spectroscopy indicate participation of the Pt(II) orbitals in the HOMO. There is a dramatic difference in the photophysical properties of carborane complexes compared to other mixed-ligand Pt(II) compounds, which includes room-temperature emission and photostability. The charge-transfer character of the lowest excited state in this series of chromophores is maintained throughout. Moreover, the absorption and emission energies and the redox properties of the excited state can be significantly tuned.

Intramolecular electrocatalysis of 8-oxo-guanine oxidation: secondary structure control of electron transfer in osmium-labeled oligonucleotides.

A phosphoramidite containing Os(bpy)(3)(2+) (Os; bpy, 2,2'-bipyridine) with a three-carbon linker was synthesized and used to prepare oligonucleotides with the Os redox catalyst appended to the 5'-end. The electrogenerated Os(III) is capable of oxidizing 7,8-dihydro-8-oxo-guanine (8G), but 8G is not electrochemically reactive at indium tin oxide electrodes because of poor electrode kinetics for the direct reaction. The hairpin-forming oligonucleotide Os-5'-ATG TCA GAT TAG CAG GCC TGA CAT 8G was synthesized and characterized by thermal denaturation and native gel electrophoresis both in the hairpin form and when hybridized to its Watson-Crick complement. The redox potential in both forms of the appended Os(III/II) couple was 0.63 V (all potentials vs Ag/AgCl), which is identical to that for the free complex. The diffusion coefficients of the hairpin form (10.2 x 10(-)(7) cm(2)/s) and the duplex form (8.7 x 10(-)(7) cm(2)/s) were consistent with values expected from studies of noncovalently bound redox labels, which suggest that the measured diffusion coefficient should be that of the appended DNA molecule. The oligonucleotide was designed such that in the duplex form, the 8G is far from the Os(III/II) couple, but in the hairpin form, the 8G is situated close to the redox center. For the duplex form, cyclic voltammetry studies showed that mediated oxidation of the 8G nucleobase occurred only through bimolecular reaction of the electrogenerated Os(III) of one duplex with the 8G of another duplex. However, in the hairpin form, intramolecular electron transfer from 8G to Os(III) in the same molecule was apparent in both chronoamperometry and cyclic voltammetry.

Synthesis and characterization of phenothiazine labeled oligodeoxynucleotides: novel 2'-deoxyadenosine and thymidine probes for labeling DNA.

A facile procedure for the incorporation of phenothiazine at the terminus of oligodeoxynucleotides is reported. Phenothiazine is covalently linked to the 5'-position of 2'-deoxyadenosine and thymidine. Next, the corresponding phosphoramidites are prepared, and then the labeled nucleosides are incorporated in DNA using an automated DNA solid-phase synthesizer. Phenothiazine labeled oligodeoxynucleotides form stable B-form duplexes with similar melting temperatures, CD spectra, and DSC traces compared to unlabeled DNA duplexes. The favorable photophysical properties of phenothiazine are also retained after covalent attachment to the oligodeoxynucleotide.

Solid-Phase Synthesis and Photophysical Properties of DNA Labeled at the Nucleobase with Ru(bpy)(2)(4-m-4'-pa-bpy)(2+).

A facile procedure for incorporating a Ru(diimine)(3)(2+) complex at the nucleobase in an oligonucleotide is reported that combines the advantages of Pd(0) cross-coupling and solid-phase DNA chemistries. These ruthenium-modified oligonucleotides form stable duplexes, and the favorable photophysical properties associated with the Ru(diimine)(3)(2+) complex are retained after site-specific covalent attachment.