The impact of a reduced dose of dexamethasone on glucose control after coronary artery bypass surgery

<p>Abstract</p> <p>Background</p> <p>Intensive insulin therapy to maintain normoglycemia after cardiac surgery reduces morbidity and mortality. We investigated the magnitude and duration of hyperglycemia caused by dexamethasone administered after cardiopulmonary bypass.</p> <p>Methods</p> <p>A single-center before-after cohort study was performed. All consecutive patients undergoing coronary artery bypass grafting with cardiopulmonary bypass during a 6-month period were included. Insulin administration was guided by a sliding scale protocol. Halfway the observation period, the dexamethasone protocol was changed. The single dose (1D) group received a pre-operative dose of dexamethasone of 1 mg/kg. The double dose group (2D) received an additional dose of 0.5 mg/kg of dexamethasone post-operatively at ICU admission.</p> <p>Results</p> <p>We included 116 patients in the 1D group and 158 patients in the 2D group. There were no significant baseline differences between the groups. Median Euroscore was 5. In univariable analysis, the glucose level was different between groups 1D and 2D at 4, 6, 9, 12 and 24 hours after ICU admission (all p < 0.001). Insulin infusion was higher in the 1D group. Corrected for insulin dose in multivariable linear analysis, the difference in glucose between the 1D and 2D groups was 1.5 mmol/L (95% confidence interval 1.0–2.0, p < 0.001) 12 hours after ICU admission.</p> <p>Conclusion</p> <p>Dexamethasone exerts a hyperglycemic effect in cardiac surgery patients. Patients receiving high-dose corticosteroid therapy should be monitored and treated more intensively for hyperglycemic episodes.</p

Implementation and evaluation of a nurse-centered computerized potassium regulation protocol in the intensive care unit - a before and after analysis

<p>Abstract</p> <p>Background</p> <p>Potassium disorders can cause major complications and must be avoided in critically ill patients. Regulation of potassium in the intensive care unit (ICU) requires potassium administration with frequent blood potassium measurements and subsequent adjustments of the amount of potassium administrated. The use of a potassium replacement protocol can improve potassium regulation. For safety and efficiency, computerized protocols appear to be superior over paper protocols. The aim of this study was to evaluate if a computerized potassium regulation protocol in the ICU improved potassium regulation.</p> <p>Methods</p> <p>In our surgical ICU (12 beds) and cardiothoracic ICU (14 beds) at a tertiary academic center, we implemented a nurse-centered computerized potassium protocol integrated with the pre-existent glucose control program called GRIP (Glucose Regulation in Intensive Care patients). Before implementation of the computerized protocol, potassium replacement was physician-driven. Potassium was delivered continuously either by central venous catheter or by gastric, duodenal or jejunal tube. After every potassium measurement, nurses received a recommendation for the potassium administration rate and the time to the next measurement. In this before-after study we evaluated potassium regulation with GRIP. The attitude of the nursing staff towards potassium regulation with computer support was measured with questionnaires.</p> <p>Results</p> <p>The patient cohort consisted of 775 patients before and 1435 after the implementation of computerized potassium control. The number of patients with hypokalemia (<3.5 mmol/L) and hyperkalemia (>5.0 mmol/L) were recorded, as well as the time course of potassium levels after ICU admission. The incidence of hypokalemia and hyperkalemia was calculated. Median potassium-levels were similar in both study periods, but the level of potassium control improved: the incidence of hypokalemia decreased from 2.4% to 1.7% (P < 0.001) and hyperkalemia from 7.4% to 4.8% (P < 0.001). Nurses indicated that they considered computerized potassium control an improvement over previous practice.</p> <p>Conclusions</p> <p>Computerized potassium control, integrated with the nurse-centered GRIP program for glucose regulation, is effective and reduces the prevalence of hypo- and hyperkalemia in the ICU compared with physician-driven potassium regulation.</p

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Inter-individual variability in habituation of anxiety-related responses within three mouse inbred strains

Inter-individual variability in behavioral and physiological response has become a well-established phenomenon in animal models of anxiety and other disorders. Such variability is even demonstrated within mouse inbred strains. A recent study showed that adaptive and non-adaptive anxiety phenotypes (measured as habituation and/or sensitization of anxiety responses) may differ within cohorts of 129 mice. This variability was expressed across both anxiety- and activity-related behavioral dimensions. These findings were based however on re-analysis of previously published data. The present study therefore aimed to empirically validate these findings in 129 mice. In addition, we assessed such inter-individuality in two other strains: BALB/c and C57BL/6. Males of three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, 4 consecutive trials). Behavioral observations were supplemented with assessment of circulating corticosterone levels. Clustering the individual response trajectories of behavioral and endocrine responses yielded two multidimensional response types of different adaptive value. Interestingly, these response types were displayed by individuals of all three strains. The response types differed significantly on anxiety and activity related behavioral dimensions but not on corticosterone concentrations. This study empirically confirms that adaptive capacities may differ within 129 cohorts. In addition, it extends this inter-individual variability in behavioral profiles to BALB/c and C57BL/6. Whether these two sub-types constitute differential anxiety phenotypes may differ per strain and requires further study

Inter-individual variability in habituation of anxiety-related responses within three mouse inbred strains

Inter-individual variability in behavioral and physiological response has become a well-established phenomenon in animal models of anxiety and other disorders. Such variability is even demonstrated within mouse inbred strains. A recent study showed that adaptive and non-adaptive anxiety phenotypes (measured as habituation and/or sensitization of anxiety responses) may differ within cohorts of 129 mice. This variability was expressed across both anxiety- and activity-related behavioral dimensions. These findings were based however on re-analysis of previously published data. The present study therefore aimed to empirically validate these findings in 129 mice. In addition, we assessed such inter-individuality in two other strains: BALB/c and C57BL/6. Males of three mouse inbred strains (BALB/c, C57BL/6 and 129S2) were behaviorally characterized through repeated exposure to a mild aversive stimulus (modified Hole Board, 4 consecutive trials). Behavioral observations were supplemented with assessment of circulating corticosterone levels. Clustering the individual response trajectories of behavioral and endocrine responses yielded two multidimensional response types of different adaptive value. Interestingly, these response types were displayed by individuals of all three strains. The response types differed significantly on anxiety and activity related behavioral dimensions but not on corticosterone concentrations. This study empirically confirms that adaptive capacities may differ within 129 cohorts. In addition, it extends this inter-individual variability in behavioral profiles to BALB/c and C57BL/6. Whether these two sub-types constitute differential anxiety phenotypes may differ per strain and requires further study

Comprehensive Mutation Analysis of PMS2 in a Large Cohort of Probands Suspected of Lynch Syndrome or Constitutional Mismatch Repair Deficiency (CMMRD) Syndrome

Monoallelic PMS2 germline mutations cause 5-15% of Lynch syndrome, a midlife cancer predisposition, whereas biallelic PMS2 mutations cause approximately 60% of constitutional MMR deficiency (CMMRD), a rare childhood cancer syndrome. Recently improved DNA and RNA-based strategies are applied to overcome problematic PMS2 mutation analysis due to the presence of pseudogenes and frequent gene conversion events. Here, we determined PMS2 mutation detection yield and mutation spectrum in a nationwide cohort of 396 probands. Furthermore, we studied concordance between tumor IHC/ MSI (immunohistochemistry/ microsatellite-instability) profile and mutation carrier state. Overall, we found 52 different pathogenic PMS2 variants explaining 121 Lynch syndrome and nine CMMRD patients. In vitro MMR assays suggested pathogenicity for three missense variants. Ninety-one PMS2 mutation carriers (70%) showed isolated loss of PMS2 in their tumors, for 31 (24%) no or inconclusive IHC was available, and eight carriers (6%) showed discordant IHC (presence of PMS2 or loss of both MLH1 and PMS2). Ten cases with isolated PMS2 loss (10%; 10/97) harbored MLH1 mutations. We confirmed that recently improved mutation analysis provides a high yield of PMS2 mutations in patients with isolated loss of PMS2 expression. Application of universal tumor pre-screening methods will however miss some PMS2 germline mutation carriers. This article is protected by copyright. All rights reserved