The Characteristics of Postoperative Mediastinitis During the Changing Phases of Cardiac Surgery.

BACKGROUND: Mediastinitis is a serious complication of open heart surgery associated with high mortality, considerable health care costs, and prolonged hospital stay. We examined characteristics and incidence of mediastinitis during 29 years when indications and patient material have been in a process of change. METHODS: This was a retrospective population-based study comprising all mediastinitis patients more than 16 years of age after open heart surgery between 1990 and 2018 from a population of 1.7 million. Patient records of 50 mediastinitis patients from 2004 to 2014 were reviewed and compared with 120 patients from 1990 to 1999. RESULTS: Annual mediastinitis rate varied 0% to 1.5% with a decreasing trend-from a level exceeding 1.2% to approximately 0.3%-over the study period. In 2004 to 2014 patients with mediastinitis were older, more often smokers, and more often had diabetes mellitus and renal insufficiency than in 1990 to 1999. No difference in length of hospital treatment, antibiotic prophylaxis or treatment, intensive care unit treatment, or mortality was observed between 1990 to 1999 and 2004 to 2014. Coronary artery bypass graft surgery became less common and valve replacement and hybrid operations more common among operations leading to mediastinitis. Staphylococcus aureus increased (from 25% to 56%, p = .005) whereas coagulase-negative staphylococci (46% to 23%, P < .001) and gram-negative bacteria (18% to 12%, P = .033) decreased as causative agents. Surgery for mediastinitis remained similar except introduction of vacuum-assisted closure treatment. CONCLUSIONS: The rate of mediastinitis decreased during these 29 years. No difference in 30-day mortality in mediastinitis was seen: 0.9% in 1990 to 1999 and 2% in 2004 to 2014.

Experimental and theoretical analysis of asymmetric induction in heterogeneous catalysis: diastereoselective hydrogenation of chiral alpha-hydroxyketones over Pt catalyst.

Assessing the origin of asymmetric induction in heterogeneously catalyzed hydrogenation is a challenging task. In this work, hydrogenation of a chiral compound, (R)-1-hydroxy-1-phenyl-2-propanone [(R)-PAC], in toluene over cinchonidine modified and unmodified Pt/Al(2)O(3) was studied. To reveal the detailed reaction mechanism and the origin of stereoselectivity in the Pt-catalyzed hydrogenation of the CO double bond, the structures and energies of several adsorption modes of (R)-PAC as well as whole reaction paths for hydrogenation were investigated on Pt(111) by density functional theory (DFT). In agreement with experimental results, the theoretically obtained potential energy profiles for the studied hydrogenation mechanisms implied that (1R,2S)-1-phenyl-1,2-propanediol is formed in excess with respect to the other diastereomeric product diol, (1R,2R)-1-phenyl-1,2-propanediol. Generally, if the elementary hydrogen addition step was thermodynamically more favorable on one of the two diastereotopic faces, it was also kinetically preferred on the same face, and vice versa. Pairwise addition of hydrogen was the most energetically favorable mechanism. Adsorption and hydrogenation of other structurally similar chiral alpha-hydroxyketones, (R)-3-hydroxy-2-butanone and (R)-2-hydroxy-1-cyclohexanone, were also studied computationally on Pt(111). The results showed that cluster model DFT calculations can be used to assess (dia)stereoselectivity in metal-catalyzed hydrogenation of even such complex organic molecules as studied here.

NMR and molecular modeling of the dimeric self-association of the enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in the solution state and their relevance to enantiomer self-disproportionation on achiral-phase chromatography (ESDAC).

Molecular modeling of the homo- and heterochiral dimeric self-associates of the enantiomers of 1,1'-bi-2-naphthol and 1-phenyl-2,2,2-trifluoroethanol in solution has been performed in order to understand their NMR behavior and in light of the phenomenon of "enantiomer self-disproportionation on achiral-phase chromatography" (ESDAC). For 1,1'-bi-2-naphthol in C(6)D(6), distinct NMR signals for each enantiomer arise for some spins in non-racemic mixtures-the phenomenon of self-induced diastereomeric anisochronism (SIDA). The linear divergence of these split signals across an enantiomeric titration (a series of samples in which the percentage of one enantiomer is varied from 50-100% whilst maintaining a constant total concentration), as well as the near linear migration of certain signals in CDCl(3) across a similar enantiomeric titration, where signals were not observed to be split, is consistent with the calculated small energy differences between the homo- and heterochiral associates. For an enantiomeric titration of 1-phenyl-2,2,2-trifluoroethanol in n-hexane, NMR signals also remained unsplit but the noticeable migration of some revealed a skew indicative of a preference for the heterochiral associate. This was duly reflected in the calculations which provided a DeltaG value favoring the heterochiral associate by 2.4 kJ mol(-1). The relevance of these results to evaluating the likely occurrence of ESDAC is considered.

A combined NMR, DFT, and X-ray investigation of some cinchona alkaloid O-ethers.

Structures and conformational behavior of several cinchona alkaloid O-ethers in the solid state (X-ray), in solution (NMR and DFT), and in the gas phase (DFT) were investigated. In the crystal, O-phenylcinchonidine adopts the Open(3) conformation similar to cinchonidine, whereas the O-methyl ether derivatives of both cinchonidine and cinchonine are packed in the Closed(1) conformation. Dynamic equilibria in solutions of the alkaloids were revealed by combined experimental-theoretical spin simulation/iteration techniques for the first time. In the (1)H NMR spectra in CDCl3 and toluene-d8 at room temperature, Closed(1) conformation was observed for the O-silyl ethers as a separate set of signals. For O-methyl ether derivatives Closed(1) could be separated only at -30 degrees C in CDCl3 or toluene-d8 and for O-phenylcinchonidine at -70 degrees C in CDCl3/CD2Cl2. The ratio between the Closed(2) and Open(3) conformers was estimated by analyzing the vicinal coupling constant (3)J(H9,H8) at ambient and low temperatures. The observed conformational equilibria of O-(tert-butyldimethylsilyl)cinchonidine in CDCl 3 and toluene-d8 are in good agreement with the theoretically estimated equilibrium populations of the conformations according to Boltzmann statistics. The conformational equilibria of four cinchona alkaloid O-ether solutes in CDCl3 and toluene-d8 are discussed in the light of their relevance to the mechanism of 1-phenyl-1,2-propanedione (PPD) hydrogenation over cinchona alkaloid modified heterogeneous platinum catalysts. It was demonstrated that the conformation found to be abundant in the liquid phase has no direct correlation with the enantioselectivity of the PPD hydrogenation reaction.

Synthesis and NMR characterization of the cis and trans isomers of [Pt(II)(N9-adeH)2(pz)2] and X-ray crystallography of the trans isomer.

The reaction of tetrapyrazine Pt(II) with adenine under basic conditions yielded two products both disubstituted by adenine and bound in all cases to the N-9 nitrogen of adenine. Crystals amenable to X-crystallographic analysis were obtained for one product which was consequently identified as trans-[Pt(II)(N9-adeH)2(pz)2](NO3)(4).H2O. The other product, though, was identified as the cis isomer based on extensive and comparative NMR structural studies whereby the two compounds were examined as both neutral and tetraprotonated species in solution. The major product of the reaction was unexpectedly the cis isomer, thus obtained in contrast to the trans effect, and the reason for this result is speculated on. Computational calculations using DFT at the B3LYP/TZVP-MARI-J level of theory provided the head-to-tail conformer as the overwhelmingly more stable species over the head-to-head conformer for both compounds whilst the trans product was found to be more stable than the cis. Thus the reaction does not follow a thermodynamic course and rather is kinetically controlled in concert with the speculated mode of reaction.

1H, (13)C, and (15)N NMR stereochemical study of cis-fused 7a(8a)-methyl and 6-phenyl octa(hexa)hydrocyclopenta[d][1,3]oxazines and [3,1]benzoxazines.

Four 7a-methyl octa(or hexa)hydrocyclopenta[d][1,3]oxazines, five 8a-methyl octa(or hexa)hydro[3,1]benzoxazines, two 6-phenyl hexahydro[3,1]benzoxazinones, and 8a-methyl hexahydro[1,3]benzoxazinone, all cis-fused, were prepared and their stereostructures studied by various one- and two-dimensional (1)H, (13)C, and (15)N NMR spectroscopic methods. In solution, the cyclopentane-fused 2-oxo derivatives and the 1,3-benzoxazinone were found to attain exclusively the N-in/O-in conformation, whereas the 6-phenyl 2-oxo/thioxo derivatives were found to be present predominantly in the N-out conformation. The C-2 unsubstituted and the 2-oxo/thioxo 7a/8a-methyl derivatives were all present in solution as a rapidly interconverting equilibrium of the N-in and N-out conformations. The C-2 methyl derivatives were each found to be interconvertable mixtures of epimers (at C-2) with the N-in conformer predominating for one epimer and the N-out conformer predominating for the other, with both predominating conformers having the C-2 methyl group equatorially orientated. The substituent on the nitrogen (H or Me) was found to be always predominantly equatorial with respect to the heteroring, except for the epimeric 2-methyl derivatives with N-out conformations where steric constraints and the generalized anomeric effect resulted in the axial orientation of the C-2 methyl being favored.