Endotoxemia related to cardiopulmonary bypass is associated with increased risk of infection after cardiac surgery: a prospective observational study

Abstract Introduction Previous studies have documented a high frequency of endotoxemia associated with cardiopulmonary bypass (CPB). Endotoxemia may be responsible for some of the complications associated with cardiac surgery. The purpose of the study was to examine the prevalence of endotoxemia during cardiopulmonary bypass supported aortocoronary bypass grafting surgery (ACB) using a new assay, the Endotoxin Activity Assay (EAA), and explore the association between endotoxemia and post-operative infection. Methods The study was a single center prospective observational study measuring EAA during the perioperative period for elective ACB. Blood samples were drawn at induction of anesthesia (T1), immediately prior to release of the aortic cross-clamp (T2), and on the first post-operative morning (T3). The primary outcome was the prevalence of endotoxemia. Secondary outcomes assessed included infection rates, intensive care unit (ICU) and hospital length of stay. An EAA of < 0.40 units was interpreted as "low", 0.41 to 0.59 units as "intermediate", and ≥0.60 units as "high". Results A total of 57 patients were enrolled and 54 patients were analyzable. The mean EAA at T1 was 0.38 +/- 0.14, at T2 0.39 +/- 0.18, and at T3 0.33 +/- 0.18. At T2 only 13.5% (7/52) of patients had an EAA in the high range. There was a positive correlation between EAA and duration of surgery (P = 0.02). In patients with EAA ≥0.40 at T2, 26.1% (6/23) of patients developed post-operative infections compared to 3.5% (1/29) of those that had a normal EAA (P = 0.0354). Maximum EAA over the first 24 hours was also strongly correlated with risk of post-operative infection (P = 0.0276). Conclusions High levels of endotoxin occur less frequently during ACB than previously documented. However, endotoxemia is associated with a significantly increased risk of the development of post-operative infection. Measuring endotoxin levels during ACB may provide a mechanism to identify and target a high risk patient population

A bias correction method for fast fuel-to-air ratio estimation in diesel engines

l probes in turbocharged diesel engines are usually located downstream of the turbine, exhibiting a good dynamic response but a significant delay because of the exhaust line transport and the hardware itself. With the introduction of after-treatment systems, new sensors that can measure the exhaust concentrations are required for optimal control and diagnosis. Zirconia-based potentiometric sensors permit the measurement of nitrogen oxides and oxygen with the same hardware. However, their dynamic response is slower and more filtered than that of traditional l probes and, in addition, the sensor location downstream of the after-treatment systems increases this problem. The paper uses a Kalman filter for online dynamic estimation of the relative fuel-to-air ratio l21 in a turbocharged diesel engine. The combination of a fast drifted fuel-to-air ratio model with a slow but accurate zirconia sensor permits the model bias to be corrected. This bias is modelled with a look-up table depending on the engine operating point and is integrated online on the basis of the Kalman filter output. The calculation burden is alleviated by using the converged gain of the steady-state Kalman filter, precalculated offline. Finally, robustness conditions for stopping the bias updating are included in order to account for the sensor and model uncertainties. The proposed algorithm and sensor layout are successfully proved in a turbocharged diesel engine. Experimental and simulation results are included to support validation of the algorithm.This work was partially supported through project HIREFIRE (grant number: IPT-370000-2010-022).Guardiola, C.; Plá Moreno, B.; Blanco-Rodriguez, D.; Mazer, A.; Hayat, O. (2013). A bias correction method for fast fuel-to-air ratio estimation in diesel engines. Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering. 227(8):1099-1111. https://doi.org/10.1177/0954407012473415S109911112278Lu, X., Han, D., & Huang, Z. (2011). Fuel design and management for the control of advanced compression-ignition combustion modes. Progress in Energy and Combustion Science, 37(6), 741-783. doi:10.1016/j.pecs.2011.03.003Chiang, C.-J., Stefanopoulou, A. G., & Jankovic, M. (2007). Nonlinear Observer-Based Control of Load Transitions in Homogeneous Charge Compression Ignition Engines. IEEE Transactions on Control Systems Technology, 15(3), 438-448. doi:10.1109/tcst.2007.894637Riegel, J. (2002). Exhaust gas sensors for automotive emission control. Solid State Ionics, 152-153, 783-800. doi:10.1016/s0167-2738(02)00329-6ZHUIYKOV, S., & MIURA, N. (2007). Development of zirconia-based potentiometric NOx sensors for automotive and energy industries in the early 21st century: What are the prospects for sensors? Sensors and Actuators B: Chemical, 121(2), 639-651. doi:10.1016/j.snb.2006.03.044Schilling, A., Amstutz, A., & Guzzella, L. (2008). Model-based detection and isolation of faults due to ageing in the air and fuel paths of common-rail direct injection diesel engines equipped with a λ and a nitrogen oxides sensor. Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering, 222(1), 101-117. doi:10.1243/09544070jauto659Kalman, R. E. (1960). A New Approach to Linear Filtering and Prediction Problems. Journal of Basic Engineering, 82(1), 35-45. doi:10.1115/1.3662552Jones, V. K., Ault, B. A., Franklin, G. F., & Powell, J. D. (1995). Identification and air-fuel ratio control of a spark ignition engine. IEEE Transactions on Control Systems Technology, 3(1), 14-21. doi:10.1109/87.370705Chen-Fang Chang, Fekete, N. P., Amstutz, A., & Powell, J. D. (1995). Air-fuel ratio control in spark-ignition engines using estimation theory. IEEE Transactions on Control Systems Technology, 3(1), 22-31. doi:10.1109/87.370706Wagner, J. R., Dawson, D. M., & Liu Zeyu. (2003). Nonlinear air-to-fuel ratio and engine speed control for hybrid vehicles. IEEE Transactions on Vehicular Technology, 52(1), 184-195. doi:10.1109/tvt.2002.807156Muske, K. R., Jones, J. C. P., & Franceschi, E. M. (2008). Adaptive Analytical Model-Based Control for SI Engine Air–Fuel Ratio. IEEE Transactions on Control Systems Technology, 16(4), 763-768. doi:10.1109/tcst.2007.912243Regitz, S., & Collings, N. (2008). Fast response air-to-fuel ratio measurements using a novel device based on a wide band lambda sensor. Measurement Science and Technology, 19(7), 075201. doi:10.1088/0957-0233/19/7/075201Galindo, J., Serrano, J. R., Guardiola, C., Blanco-Rodriguez, D., & Cuadrado, I. G. (2011). An on-engine method for dynamic characterisation of NOx concentration sensors. Experimental Thermal and Fluid Science, 35(3), 470-476. doi:10.1016/j.expthermflusci.2010.11.010Ljung, L. (1979). Asymptotic behavior of the extended Kalman filter as a parameter estimator for linear systems. IEEE Transactions on Automatic Control, 24(1), 36-50. doi:10.1109/tac.1979.1101943Nyberg, M., & Stutte, T. (2004). Model based diagnosis of the air path of an automotive diesel engine. Control Engineering Practice, 12(5), 513-525. doi:10.1016/s0967-0661(03)00120-5Macian, V., Lujan, J. M., Guardiola, C., & Yuste, P. (2006). DFT-based controller for fuel injection unevenness correction in turbocharged diesel engines. IEEE Transactions on Control Systems Technology, 14(5), 819-827. doi:10.1109/tcst.2006.876924Macián, V., Luján, J. M., Guardiola, C., & Perles, A. (2006). A comparison of different methods for fuel delivery unevenness detection in Diesel engines. Mechanical Systems and Signal Processing, 20(8), 2219-2231. doi:10.1016/j.ymssp.2005.04.001Payri, F., Luján, J. M., Guardiola, C., & Rizzoni, G. (2006). Injection diagnosis through common-rail pressure measurement. Proceedings of the Institution of Mechanical Engineers, Part D: Journal of Automobile Engineering, 220(3), 347-357. doi:10.1243/09544070jauto34Desantes, J. M., Galindo, J., Guardiola, C., & Dolz, V. (2010). Air mass flow estimation in turbocharged diesel engines from in-cylinder pressure measurement. Experimental Thermal and Fluid Science, 34(1), 37-47. doi:10.1016/j.expthermflusci.2009.08.009Galindo, J., Climent, H., Guardiola, C., & Doménech, J. (2009). Strategies for improving the mode transition in a sequential parallel turbocharged automotive diesel engine. International Journal of Automotive Technology, 10(2), 141-149. doi:10.1007/s12239-009-0017-1Kalman, R. E., & Bucy, R. S. (1961). New Results in Linear Filtering and Prediction Theory. Journal of Basic Engineering, 83(1), 95-108. doi:10.1115/1.3658902Rajamani, M. R., & Rawlings, J. B. (2009). Estimation of the disturbance structure from data using semidefinite programming and optimal weighting. Automatica, 45(1), 142-148. doi:10.1016/j.automatica.2008.05.032Höckerdal, E., Frisk, E., & Eriksson, L. (2011). EKF-based adaptation of look-up tables with an air mass-flow sensor application. Control Engineering Practice, 19(5), 442-453. doi:10.1016/j.conengprac.2011.01.006Peyton Jones, J. C., & Muske, K. R. (2009). Identification and adaptation of linear look-up table parameters using an efficient recursive least-squares technique. ISA Transactions, 48(4), 476-483. doi:10.1016/j.isatra.2009.04.00

Magnesium Depletion in Patients Treated with Therapeutic Hypothermia After Cardiac Arrest

Magnesium (Mg2+) depletion can have detrimental effects in postcardiac arrest patients through multiple potential mechanisms. Therapeutic hypothermia (TH) produces a Mg2+ diuresis, but the effects of postcardiac arrest TH on serum Mg2+ levels in patients with postcardiac arrest syndrome (PCAS) are yet to be systematically quantified. We conducted a retrospective chart review of 119 consecutive comatose PCAS patients treated with TH between 2005 and 2010 and compared them to 33 matched historic controls (HCs) seen at the same institution between 2002 and 2005 who were not treated with TH. We abstracted data from the first 96 hours postarrest, including date, time, and value of serum Mg2+ levels and date, time, and amount of Mg2+ repletion, along with outcomes at discharge. The median Mg2+ level of TH patients was 2.0?mg/dL [interquartile range (IQR), 1.9?2.2?mg/dL] (0.82 mmol/L [IQR, 0.78?0.90 mmol/L]) versus 2.2?mg/dL [IQR, 1.9?2.4?mg/dL] (0.90 mmol/L [IQR, 0.82?0.99 mmol/L]) (p=0.2) in HCs. In addition, 42.9% (520/1214) of Mg2+ levels in TH patients versus 31.9% (43/135) (p=0.014) in HC patients were below 2.0?mg/dL [0.82 mmol/L]. The average number of times the Mg2+ level was checked in TH patients was 10.2 (range 1?18) versus 4.1 (range 1?10) in HCs. The TH patients were more likely to receive supplemental Mg2+ than HCs (81.5% [97/119] vs. 27.3% [9/33] [p<0.01]). The mean supplemental Mg2+ dose was 1.9?g for TH patients versus 0.5?g for HC patients. Mortality in patients treated with TH was 53.1% (60/113) versus 78.6% (22/28) (p=0.014) in HCs. Low serum Mg2+ levels with subsequent Mg2+ supplementation were more common in comatose patients with PCAS treated with TH compared to normothermic HC patients. The effect of untreated hypomagnesemia on postcardiac arrest outcomes remains to be determined.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/140255/1/ther.2014.0012.pd

Improving the Diagnosis of Acute Heart Failure Using a Validated Prediction Model

ObjectivesWe sought to derive and validate a prediction model by using N-terminal pro–B-type natriuretic peptide (NT-proBNP) and clinical variables to improve the diagnosis of acute heart failure (AHF).BackgroundThe optimal way of using natriuretic peptides to enhance the diagnosis of AHF remains uncertain.MethodsPhysician estimates of probability of AHF in 500 patients treated in the emergency department from the multicenter IMPROVE CHF (Improved Management of Patients With Congestive Heart Failure) trial recruited between December 2004 and December 2005 were classified into low (0% to 20%), intermediate (21% to 79%), or high (80% to 100%) probability for AHF and then compared with the blinded adjudicated AHF diagnosis. Likelihood ratios were calculated and multiple logistic regression incorporated covariates into an AHF prediction model that was validated internally by the use of bootstrapping and externally by applying the model to another 573 patients from the separate PRIDE (N-Terminal Pro-BNP Investigation of Dyspnea in the Emergency Department) study of the use of NT-proBNP in patients with dyspnea.ResultsLikelihood ratios for AHF with NT-proBNP were 0.11 (95% confidence interval [CI]: 0.06 to 0.19) for cut-point values <300 pg/ml; increasing to 3.43 (95% CI: 2.34 to 5.03) for values 2,700 to 8,099 pg/ml, and 12.80 (95% CI: 5.21 to 31.45) for values ≥8,100 pg/ml. Variables used to predict AHF were age, pre-test probability, and log NT-proBNP. When applied to the external data by use of its adjudicated final diagnosis as the gold standard, the model appropriately reclassified 44% of patients by intermediate clinical probability to either low or high probability of AHF with negligible (<2%) inappropriate redirection.ConclusionsA diagnostic prediction model for AHF that incorporates both clinical assessment and NT-proBNP has been derived and validated and has excellent diagnostic accuracy, especially in cases with indeterminate likelihood for AHF

Corrigendum: Semaphorin 4C: A Novel Component of B-Cell Polarization in Th2-Driven Immune Responses

Background: Semaphorins are important molecules in embryonic development and multiple semaphorins have been identified as having key roles in immune regulation. To date, there is little known about Semaphorin 4C (Sema4C) in immune biology. We report for the first time that Sema4C is inducible in human and murine B-cells and may be important for normal B-cell development. Methods: Human Tonsillar B-cells were studied following activation via anti-CD40 antibodies in the presence or absence of representative Th1, Th2, and regulatory cytokines. Murine B-cells from WT and Sema4C-/- mice were similarly stimulated. B-cell phenotyping in WT and Sema4C mutant mice was performed by flow cytometry and lymphoid architecture was studied by immunohistochemistry. Sema4C expression and synapse formation was analyzed by confocal microscopy. Results: Gene Array studies performed on human tonsillar B-cells stimulated to produce IgE revealed that Sema4C was among the top genes expressed at 24 hours, and the only semaphorin to be increased under Th2 conditions. Validation studies demonstrated that human and murine B-cells expressed Sema4C under similar conditions. Sema4C-/- mice had impaired maturation of B-cell follicles in spleens and associated decreases in follicular and marginal zone B-cells as well as impaired IgG and IgA production. In keeping with a potential role in maturation of B-cells, Sema4C was expressed predominantly on CD27+ Human B-cells. Within 72 hours of B-cell activation, Sema4C was localized to one pole in a synapse-like structure, in association with F-Actin, BCR, and Plexin-B2. Cell polarization was impaired in Sema4C-/- mice. Conclusion: We have identified a novel immune semaphorin induced in human and murine B-cells under Th2 conditions. Sema4C appears to be a marker for human memory B-cells. It may be important for B-cell polarization and for the formation of normal splenic follicles

Flowering Date of Taxonomic Families Predicts Phenological Sensitivity to Temperature: Implications for Forecasting the Effects of Climate Change on Unstudied Taxa

Premise of the study: Numerous long-term studies in seasonal habitats have tracked interannual variation in fi rst fl owering date (FFD) in relation to climate, documenting the effect of warming on the FFD of many species. Despite these efforts, long-term phenological observations are still lacking for many species. If we could forecast responses based on taxonomic affi nity, however, then we could leverage existing data to predict the climate-related phenological shifts of many taxa not yet studied; Methods: We examined phenological time series of 1226 species occurrences (1031 unique species in 119 families) across seven sites in North America and England to determine whether family membership (or family mean FFD) predicts the sensitivity of FFD to standardized interannual changes in temperature and precipitation during seasonal periods before fl owering and whether families differ signifi cantly in the direction of their phenological shifts; Key results: Patterns observed among species within and across sites are mirrored among family means across sites; earlyfl owering families advance their FFD in response to warming more than late-fl owering families. By contrast, we found no consistent relationships among taxa between mean FFD and sensitivity to precipitation as measured here; Conclusions: Family membership can be used to identify taxa of high and low sensitivity to temperature within the seasonal, temperate zone plant communities analyzed here. The high sensitivity of early-fl owering families (and the absence of earlyfl owering families not sensitive to temperature) may refl ect plasticity in fl owering time, which may be adaptive in environments where early-season conditions are highly variable among years

C. elegans SIRT6/7 Homolog SIR-2.4 Promotes DAF-16 Relocalization and Function during Stress

FoxO transcription factors and sirtuin family deacetylases regulate diverse biological processes, including stress responses and longevity. Here we show that the Caenorhabditis elegans sirtuin SIR-2.4—homolog of mammalian SIRT6 and SIRT7 proteins—promotes DAF-16–dependent transcription and stress-induced DAF-16 nuclear localization. SIR-2.4 is required for resistance to multiple stressors: heat shock, oxidative insult, and proteotoxicity. By contrast, SIR-2.4 is largely dispensable for DAF-16 nuclear localization and function in response to reduced insulin/IGF-1-like signaling. Although acetylation is known to regulate localization and activity of mammalian FoxO proteins, this modification has not been previously described on DAF-16. We find that DAF-16 is hyperacetylated in sir-2.4 mutants. Conversely, DAF-16 is acetylated by the acetyltransferase CBP-1, and DAF-16 is hypoacetylated and constitutively nuclear in response to cbp-1 inhibition. Surprisingly, a SIR-2.4 catalytic mutant efficiently rescues the DAF-16 localization defect in sir-2.4 null animals. Acetylation of DAF-16 by CBP-1 in vitro is inhibited by either wild-type or mutant SIR-2.4, suggesting that SIR-2.4 regulates DAF-16 acetylation indirectly, by preventing CBP-1-mediated acetylation under stress conditions. Taken together, our results identify SIR-2.4 as a critical regulator of DAF-16 specifically in the context of stress responses. Furthermore, they reveal a novel role for acetylation, modulated by the antagonistic activities of CBP-1 and SIR-2.4, in modulating DAF-16 localization and function

In vitro Liver Zonation of Primary Rat Hepatocytes

The ability of the liver to simultaneously carry out multiple functions is dependent on the metabolic heterogeneity of hepatocytes spatially located within a liver lobule spanning from the portal triad to the central vein. This complex zonal architecture of the liver, however, makes accurate in vitro modeling a challenge and often standard culture systems assume a homogenous model which may lead to inaccurate translatability of results. Here, we use a combination of mathematical modeling and experimental data to demonstrate a readily constructible in vitro flow system capable of liver zonation in primary rat hepatocytes. We show the differential expression of zonation markers, enhanced functionality when compared to standard static cultures and zone-specific metabolism and cell damage in the presence of paracetamol, a known zone-specific toxin. This type of advanced system provides a more in-depth and essential understanding of liver physiology and pathophysiology as well as the accurate evaluation of pharmacological interventions at a zone-specific level

The On-Orbit Performance of the Galaxy Evolution Explorer

We report the first year on-orbit performance results for the Galaxy Evolution Explorer (GALEX), a NASA Small Explorer that is performing a survey of the sky in two ultraviolet bands. The instrument comprises a 50 cm diameter modified Ritchey-Chretien telescope with a 1.25 degree field of view, selectable imaging and objective grism spectroscopic modes, and an innovative optical system with a thin-film multilayer dichroic beam splitter that enables simultaneous imaging by a pair of photon counting, microchannel plate, delay line readout detectors. Initial measurements demonstrate that GALEX is performing well, meeting its requirements for resolution, efficiency, astrometry, bandpass definition and survey sensitivity.Comment: This paper will be published as part of the Galaxy Evolution Explorer (GALEX) Astrophysical Journal Letters Special Issu

Sternal plating for primary and secondary sternal closure; can it improve sternal stability?

<p>Abstract</p> <p>Background</p> <p>Sternal instability with mediastinitis is a very serious complication after median sternotomy. Biomechanical studies have suggested superiority of rigid plate fixation over wire cerclage for sternal fixation. This study tests the hypothesis that sternal closure stability can be improved by adding plate fixation in a human cadaver model.</p> <p>Methods</p> <p>Midline sternotomy was performed in 18 human cadavers. Four sternal closure techniques were tested: (1) approximation with six interrupted steel wires; (2) approximation with six interrupted cables; (3) closure 1 (wires) or 2 (cables) reinforced with a transverse sternal plate at the sixth rib; (4) Closure using 4 sternal plates alone. Intrathoracic pressure was increased in all techniques while sternal separation was measured by three pairs of sonomicrometry crystals fixed at the upper, middle and lower parts of the sternum until 2.0 mm separation was detected. Differences in displacement pressures were analyzed using repeated measures ANOVA and Regression Coefficients.</p> <p>Results</p> <p>Intrathoracic pressure required to cause 2.0 mm separation increased significantly from 183.3 ± 123.9 to 301.4 ± 204.5 in wires/cables alone vs. wires/cables plus one plate respectively, and to 355.0 ± 210.4 in the 4 plates group (p < 0.05). Regression Coefficients (95% CI) were 120 (47–194) and 142 (66–219) respectively for the plate groups.</p> <p>Conclusion</p> <p>Transverse sternal plating with 1 or 4 plates significantly improves sternal stability closure in human cadaver model. Adding a single sternal plate to primary closure improves the strength of sternal closure with traditional wiring potentially reducing the risk of sternal dehiscence and could be considered in high risk patients.</p