Very early changes in serum creatinine are associated with 30-day mortality after cardiac surgery: A cohort study.

BACKGROUND: Acute kidney injury predicts adverse outcomes after cardiac surgery. OBJECTIVES: To determine whether ultra-short-term changes (within 120 min) in serum creatinine (SCrea) levels after cardiac surgery predict clinical outcomes (30-day mortality). DESIGN: Observational cohort study. SETTING: Austrian tertiary referral centre. PATIENTS: A total of 7651 patients scheduled to undergo elective cardiac surgery. MAIN OUTCOME MEASURES: We analysed SCrea levels measured pre-operatively (baseline) and within 120 min after surgery. We also adjusted the postoperative SCrea levels for fluid balance. Patients were grouped according to the difference between the pre and postoperative SCrea levels (ΔSCreaAdmICU). We performed univariable and multivariable analyses to determine the association between changes in SCrea levels and 30-day mortality. RESULTS: After cardiac surgery, the SCrea level decreased in 5923 patients and increased in 1728 patients. Increased SCrea levels were associated with a 21% increase in 30-day mortality. Even minimal increases in SCrea (0 to <26.5 µmol l) were significantly associated with 30-day mortality [hazard ratio (HR), 1.98; 95% confidence interval (CI), 1.54 to 2.55; P < 0.001]. Adjustments for fluid balance strengthened the above association (increases of 0 to <26.5 µmol l: HR, 1.78; 95% CI, 1.40 to 2.26; P < 0.001; increases of at least 26.5 µmol l: HR, 2.40; 95% CI, 1.68 to 3.42; P < 0.001). CONCLUSION: Even minimal, ultra-short-term increases in SCrea levels after cardiac surgery are associated with increased 30-day mortality. Adjustment for fluid balance strengthens this association. The change in SCrea between baseline and after admission to the Intensive Care Unit (ΔSCreaAdmICU) can serve as a simple, cheap and widely available marker for very early risk stratification after cardiac surgery.

Laser desorption vs. electrospray of polyyne-threaded rotaxanes: Preventing covalent cross-linking and promoting noncovalent aggregation.

Laser-induced cross-linking of polyynes is successfully hindered when the polyyne is encapsulated as part of a rotaxane and therefore protected by a surrounding macrocycle. When the rotaxane is electrosprayed, however, noncovalent aggregate ions are efficiently formed. Aggregates of considerable size (including more than 50 rotaxane molecules with masses beyond 100k Da) and charge states (up to 13 charges and beyond) have been observed. Either protons or sodium cations act as the charge carriers. These aggregates are not formed when the individual components of the rotaxane, i.e., the macrocycle or the polyyne, are separately electrosprayed. This underlines the structural importance of the rotaxane for the aggregate formation. Straightforward force field calculations indicate that the polyyne thread hinders the folding of the macrocycles, which facilitates the bonding interaction between the two components.

Sterol Composition of Clinically Relevant Mucorales and Changes Resulting from Posaconazole Treatment.

Mucorales are fungi with increasing importance in the clinics. Infections take a rapidly progressive course resulting in high mortality rates. The ergosterol biosynthesis pathway and sterol composition are of interest, since they are targeted by currently applied antifungal drugs. Nevertheless, Mucorales often exhibit resistance to these drugs, resulting in therapeutic failure. Here, sterol patterns of six clinically relevant Mucorales (Lichtheimia corymbifera, Lichtheimia ramosa, Mucor circinelloides, Rhizomucor pusillus, Rhizopus arrhizus, and Rhizopus microsporus) were analysed in a targeted metabolomics fashion after derivatization by gas chromatography-mass spectrometry. Additionally, the effect of posaconazole (POS) treatment on the sterol pattern of R. arrhizus was evaluated. Overall, fifteen different sterols were detected with species dependent variations in the total and relative sterol amount. Sterol analysis from R. arrhizus hyphae confronted with sublethal concentrations of posaconazole revealed the accumulation of 14-methylergosta-8,24-diene-3,6-diol, which is a toxic sterol that was previously only detected in yeasts. Sterol content and composition were further compared to the well-characterized pathogenic mold Aspergillus fumigatus. This work contributes to a better understanding of the ergosterol biosynthesis pathway of Mucorales, which is essential to improve antifungal efficacy, the identification of targets for novel drug design, and to investigate the combinatorial effects of drugs targeting this pathway.

The Resonant Excitation Process in Commercial Quadrupole Ion Traps Revisited.

The collision-induced resonant excitation process in real quadrupole ion traps is revisited theoretically and experimentally by explicitly including in the discussion the influence of higher order potential impurities. This includes mainly the dependence of the secular oscillation frequency fion on the ion's oscillation amplitude zmax. Due to frequency calibration, commercial ion traps use excitation frequencies fexc that are higher than the theoretical secular oscillation frequency fion. This may lead to switching in frequency order between fexc and fion that can allow ions to stay longer in on-resonance. It is also found that there is a most efficient but also a harshest excitation frequency, which are not identical. These phenomena are explained and described with a simple harmonic oscillator model and precise numerical calculations, using the trajectory simulation program ITSIM 5.0. Experimental MS2 have been performed with the thermometer ion leucine-enkephalin, which are then in line with expectations from the trajectory calculations. The important difference to the existing literature is that, here, overexcitation is characterized by the observed a4/b4 fragment-ion ratio, while the fragmentation efficiency was kept constant. By slightly increasing the excitation frequency one can obtain drastically different effective collisional temperatures. This knowledge gives even commercial ion traps, without instrument adjustments, the possibility of producing energetically versatile fragment ion spectra. It is also shown that the damped driven harmonic oscillator cannot be used as a simplified model of the motion during the resonant excitation process in real ion traps.

The effect of acute ventilation-perfusion mismatch on respiratory heat exchange in a porcine model.

BACKGROUND: Respiratory heat exchange is an important physiological process occurring in the upper and lower respiratory tract and is usually completed when inspired gases reach the alveoli. Animal and human studies demonstrated that heat exchange can be modulated by altering pulmonary ventilation and perfusion. The purpose of this study was to examine the effect of acute ventilation-perfusion (V/Q) mismatch on respiratory heat exchange. In clinical practice, monitoring respiratory heat exchange might offer the possibility of real-time tracking of acute V/Q-mismatch. METHODS: In 11 anesthetized, mechanically ventilated pigs, V/Q-mismatch was established by means of four interventions: single lung ventilation, high cardiac output, occlusion of the left pulmonary artery and repeated whole-lung lavage. V/Q-distributions were determined by the multiple inert gas elimination technique (MIGET). Respiratory heat exchange was measured as respiratory enthalpy using the novel, pre-commercial VQm™ monitor (development stage, Rostrum Medical Innovations, Vancouver, CA). According to MIGET, shunt perfusion of low V/Q compartments increased during single lung ventilation, high cardiac output and whole-lung lavage, whereas dead space and ventilation of high V/Q compartments increased during occlusion of the left pulmonary artery and whole-lung lavage. RESULTS: Bohr dead space increased after pulmonary artery occlusion and whole-lung lavage, venous admixture increased during single lung ventilation and whole-lung lavage, PaO2/FiO2 was decreased during all interventions. MIGET confirmed acute V/Q-mismatch. Respiratory enthalpy did not change significantly despite significant acute V/Q-mismatch. CONCLUSION: Clinically relevant V/Q-mismatch does not impair respiratory heat exchange in the absence of additional thermal stressors and may not have clinical utility in the detection of acute changes.

Serum Creatinine Back-Estimation in Cardiac Surgery Patients: Misclassification of AKI Using Existing Formulae and a Data-Driven Model.

BACKGROUND AND OBJECTIVES: A knowledge of baseline serum creatinine (bSCr) is mandatory for diagnosing and staging AKI. With often missing values, bSCr is estimated by back-calculation using several equations designed for the estimation of GFR, assuming a "true" GFR of 75 ml/min per 1.73 m(2). Using a data set from a large cardiac surgery cohort, we tested the appropriateness of such an approach and compared estimated and measured bSCr. Moreover, we designed a novel data-driven model (estimated serum creatinine [eSCr]) for estimating bSCr. Finally, we analyzed the extent of AKI and mortality rate misclassifications. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Data for 8024 patients (2833 women) in our cardiac surgery center were included from 1997 to 2008. Measured and estimated bSCr were plotted against age for men and women. Patients were classified to AKI stages defined by the Kidney Disease Improving Global Outcomes (KDIGO) group. Results were compared with data from another cardiac surgery center in Zurich, Switzerland. RESULTS: The Modification of Diet in Renal Disease and the Chronic Kidney Disease Epidemiology Collaboration formulae describe higher estimated bSCr values in younger patients, but lower values in older patients compared with the measured bSCr values in both centers. The Pittsburgh Linear Three Variables formula correctly describes the increasing bSCr with age, however, it underestimates the overall bSCr level, being in the range of the 25% quantile of the measured values. Our eSCr model estimated measured bSCr best. AKI stage 1 classification using all formulae, including our eSCr model, was incorrect in 53%-80% of patients in Vienna and in 74%-91% in Zurich; AKI severity (according to KDIGO stages) and also mortality were overestimated. Mortality rate was higher among patients falsely classified into higher KDIGO stages by estimated bSCr. CONCLUSIONS: bSCr values back-estimated using currently available eGFR formulae are inaccurate and cannot correctly classify AKI stages. Our model eSCr improves the prediction of AKI but to a still inadequate extent.