Τρίτη 19 Σεπτεμβρίου 2017

Surveying the Literature: Synopsis of Recent Key Publications

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Preoxygenation Before Extubation: A Road to Patient Safety Less Traveled!

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Postoperative High-Sensitivity Troponin and Its Association With 30-Day and 12-Month, All-Cause Mortality in Patients Undergoing On-Pump Cardiac Surgery

imageBACKGROUND: Troponin T is a predictor of cardiac morbidity and mortality after cardiac surgery with most data examining fourth generational troponin T assays. We hypothesize that postoperative high-sensitivity troponin T (hsTnT) measured in increments of the upper limit of the norm independently predicts 30-day all-cause mortality. METHODS: We included consecutive patients undergoing on-pump cardiac surgery from February 2010 to March 2012 in a prospective cohort that measured hsTnT at 0600 of the first and second postoperative day. Our primary end point was 30-day, all-cause mortality. The secondary end point was 12-month, all-cause mortality in patients surviving the first 30 days. We divided hsTnT into 5 predetermined categorizes based on the upper limit of the norm (ULN). We used Cox regression to examine an association of hsTnT independent of the EuroSCORE II at both 30 days as well as at 12 months in patients surviving the first 30 days. We assessed the area under the receiver operating characteristics curve and the net reassignment improvement for examining the benefit of adding of hsTnT to the EuroSCORE II for prognostication and restratification of 30-day, all-cause mortality. RESULTS: We included 1122 of 1155 eligible patients (75% male; mean age 66 ± 11 years). We observed 58 (5.2%) deaths at 30 days and another 35 (3.4%) deaths at 12 months in patients surviving 30 days. HsTnT categorized by ULN exhibited a graded response for the mortality. Furthermore, hsTnT remained an independent predictor of all-cause mortality at 30 days (adjusted hazard ratio 1.019 [1.014–1.024] per 10-fold increase in ULN) as well as at 12 months (adjusted hazard ratio 1.019 [1.007–1.032]) in patients surviving the first 30 days. The addition of hsTnT to the EuroSCORE II significantly increased the area under the receiver operating characteristics curve (area under curve: 0.816 [95% confidence interval, 0.754–0.878] versus area under curve: 0.870 [95% confidence interval, 0.822–0.917], respectively; P = .012). Finally, adding hsTnT to the EuroSCORE II improved restratification by the net reassignment improvement, primarily by improving rule-out of events. CONCLUSIONS: This analysis suggests that, similar to previous assays, higher postoperative concentrations of hsTnT are independently associated with all-cause mortality in patients undergoing on-pump cardiac surgery.

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Paravertebral Block Does Not Reduce Cancer Recurrence, but Is Related to Higher Overall Survival in Lung Cancer Surgery: A Retrospective Cohort Study

imageBACKGROUND: Postoperative analgesic methods are suggested to have an impact on long-term prognosis after cancer surgery through opioid-induced immune suppression. We hypothesized that regional analgesia that reduces the systemic opioid requirement would be related to lower cancer recurrence and higher overall survival compared to intravenous patient-controlled analgesia (PCA) for lung cancer surgery. METHODS: Records for all patients who underwent open thoracotomy for curative resection of primary lung cancer between 2009 and 2013 in a tertiary care hospital were retrospectively analyzed. Patients were divided by postoperative analgesic methods: PCA (n = 574), thoracic epidural analgesia (TEA, n = 619), or paravertebral block (PVB, n = 536). Overall and recurrence-free survivals were compared among 3 analgesic methods via a multivariable Cox proportional hazard model and a log-rank test after adjusting confounding factors using propensity score matching (PSM). RESULTS: Analgesic method was associated with overall survival (P= .0015; hazard ratio against TEA [95% confidence intervals]: 0.58 [0.39–0.87] for PCA, 0.60 [0.45–0.79] for PVB). After confounder adjustment using PSM, PVB showed higher overall survival than PCA (log-rank P= .0229) and TEA (log-rank P= .0063) while PCA and TEA showed no difference (log-rank P= .6). Hazard ratio for PVB was 0.66 [0.46–0.94] against PCA and 0.65 [0.48–0.89] against TEA after PSM. However, there was no significant association between the analgesic methods and recurrence-free survival (P= .5; log-rank P with PSM = .5 between PCA and TEA, .5 between PCA and PVB, .1 between TEA and PVB). CONCLUSIONS: Pain-control methods are not related to cancer recurrence. However, PVB may have a beneficial effect on overall survival of patients with lung cancer.

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Xenon as an Adjuvant to Propofol Anesthesia in Patients Undergoing Off-Pump Coronary Artery Bypass Graft Surgery: A Pragmatic Randomized Controlled Clinical Trial

imageBACKGROUND: Xenon was shown to cause less hemodynamic instability and reduce vasopressor needs during off-pump coronary artery bypass (OPCAB) surgery when compared with conventionally used anesthetics. As xenon exerts its organ protective properties even in subanesthetic concentrations, we hypothesized that in patients undergoing OPCAB surgery, 30% xenon added to general anesthesia with propofol results in superior hemodynamic stability when compared to anesthesia with propofol alone. METHODS: Fifty patients undergoing elective OPCAB surgery were randomized to receive general anesthesia with 30% xenon adjuvant to a target-controlled infusion of propofol or with propofol alone. The primary end point was the total intraoperative dose of norepinephrine required to maintain an intraoperative mean arterial pressure >70 mm Hg. Secondary outcomes included the perioperative cardiorespiratory profile and the incidence of adverse and serious adverse events. RESULTS: Adding xenon to propofol anesthesia resulted in a significant reduction of norepinephrine required to attain the predefined hemodynamic goals (cumulative intraoperative dose: median [interquartile range]: 370 [116–570] vs 840 [335–1710] µg, P = .001). In the xenon-propofol group, significantly less propofol was required to obtain a similar depth of anesthesia as judged by clinical signs and the bispectral index (propofol effect site concentration [mean ± SD]: 1.8 ± 0.5 vs 2.8 ± 0.3 mg, P≤ .0001). Moreover, the xenon-propofol group required significantly less norepinephrine during the first 24 hours on the intensive care unit (median [interquartile range]: 1.5 [0.1–7] vs 5 [2–8] mg, P = .048). Other outcomes and safety parameters were similar in both groups. CONCLUSIONS: Thirty percent xenon added to propofol anesthesia improves hemodynamic stability by decreasing norepinephrine requirements in patients undergoing OPCAB surgery.

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Δευτέρα 18 Σεπτεμβρίου 2017

Localization of Cdc7 Protein Kinase During DNA Replication in Saccharomyces cerevisiae

DDK, a conserved serine-threonine protein kinase composed of a regulatory subunit, Dbf4, and a catalytic subunit, Cdc7, is essential for DNA replication initiation during S phase of the cell cycle through MCM2-7 helicase phosphorylation. The biological significance of DDK is well characterized, but the full mechanism of how DDK associates with substrates remains unclear. Cdc7 is bound to chromatin in the Saccharomyces cerevisiae genome throughout the cell cycle, but there is little empirical evidence as to specific Cdc7 binding locations. Using biochemical and genetic techniques, this study investigated the specific localization of Cdc7 on chromatin. The Calling Cards method, using Ty5 retrotransposons as a marker for DNA-protein binding, suggests Cdc7 kinase is preferentially bound to genomic DNA known to replicate early in S phase, including centromeres and origins of replication. We also discovered Cdc7 binding throughout the genome, which may be necessary to initiate other cellular processes, including meiotic recombination and translesion synthesis. A kinase-dead Cdc7 point mutation increases the Ty5 retrotransposon integration efficiency and a 55 amino acid C-terminal truncation of Cdc7, unable to bind Dbf4, reduces Cdc7 binding suggesting a requirement for Dbf4 to stabilize Cdc7 on chromatin during S phase. Chromatin immunoprecipitation demonstrates that Cdc7 binding near specific origins changes during S phase. Our results suggest a model where Cdc7 is loosely bound to chromatin during G1. At the G1/S transition, Cdc7 binding to chromatin is increased and stabilized, preferentially at sites that may become origins, in order to carry out a variety of cellular processes.



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U isotopes distribution in the Lower Rhone River and its implication on radionuclides disequilibrium within the decay series

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Publication date: November 2017
Source:Journal of Environmental Radioactivity, Volumes 178–179
Author(s): Mathilde Zebracki, Xavier Cagnat, Stéphanie Gairoard, Nicolas Cariou, Frédérique Eyrolle-Boyer, Béatrice Boulet, Christelle Antonelli
The large rivers are main pathways for the delivery of suspended sediments into coastal environments, affecting the biogeochemical fluxes and the ecosystem functioning. The radionuclides from 238U and 232Th—series can be used to understand the dynamic processes affecting both catchment soil erosion and sediment delivery to oceans. Based on annual water discharge the Rhone River represents the largest river of the Mediterranean Sea. The Rhone valley also represents the largest concentration in nuclear power plants in Europe. A radioactive disequilibrium between particulate 226Ra(p) and 238U(p) was observed in the suspended sediment discharged by the Lower Rhone River (Eyrolle et al. 2012), and a fraction of particulate 234Th was shown to derive from dissolved 238U(d) (Zebracki et al. 2013). This extensive study has investigated the dissolved U isotopes distribution in the Lower Rhone River and its implication on particulate radionuclides disequilibrium within the decay series. The suspended sediment and filtered river waters were collected at low and high water discharges. During the 4—months of the study, two flood events generated by the Rhone southern tributaries were monitored. In river waters, the total U(d) concentration and U isotopes distribution were obtained through Q-ICP-MS measurements. The Lower Rhone River has displayed non-conservative U—behavior, and the variations in U(d) concentration between southern tributaries were related to the differences in bedrock lithology. The artificially occurring 236U was detected in the Rhone River at low water discharges, and was attributed to the liquid releases from nuclear industries located along the river. The (235U/238U)(d) activity ratio (=AR) in river waters was representative of the 235U natural abundance on Earth. The (226Ra/238U)(p) AR in suspended sediment has indicated a radioactive disequilibrium (average 1.3 ± 0.1). The excess of 234Th in suspended sediment =(234Thxs(p)) was apparent solely at low water discharges. The activity of 234Thxs(p) was calculated through gamma measurements and ranged from unquantifiable to 56 ± 14 Bq kg−1. The possibility of using 234Th as a tracer for the suspended sediment dynamics in large Mediterranean river was then discussed.



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