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Nasogastric tube placement is frequently performed in various medical settings. While generally deemed safe in patients without risk factors, complications may occur due to malposition, justifying the need of systematic confirmation of position with chest radiographs. We present the case of a critically ill male adult patient for whom the tube position was initially deemed very unusual on postinsertion radiographs, prompting further workup which ultimately confirmed an oropharyngeal perforation with a left parapharyngeal, left visceral, retrotracheal, and right retrodiaphragmatic course, and resulting in a recurrent pneumothorax and empyema treated by surgical decortication., (© 2024 The Authors. Published by Elsevier Inc. on behalf of University of Washington.)

Werner syndrome (WS) is a progeroid disorder caused by mutations in a protein containing both a DNA exonuclease and DNA helicase domains. Previous studies indicated that males lacking the helicase domain of the Wrn protein orthologue exhibited hepatic transcriptomic and metabolic alterations. In this study, we used a label-free liquid chromatography-tandem mass spectrometry approach to uncover proteins abundance associated with specific biological processes that differed depending on the age (four or ten months) and/or the genotype (wild type or Wrn mutant) in the serum and liver of mice. Principal component analysis of the proteomic data from both serum and hepatic tissue revealed a sexual dimorphism regardless of the age and the genotype of the mice. Moreover, although all Wrn mutant mice exhibited fatty liver by the age of ten months, a significant age and genotype dependent enrichment of proteins involved in lipid and fatty acid metabolic processes were uncovered only in males. Also, a genotype dependent increase in serum oxidant detoxification processes was observed in the serum of Wrn mutant males. Despite these sexual differences, several aspects of the immune system were affected in both females and males. Finally, an increase of specific immunoglobulin molecules was common in the liver and serum of both older Wrn mutant females and males. Such results suggest that specific immunoglobulin variants maybe associated with fatty liver progression in WS.

The development of Metabolic Syndrome (MetS) affects a large number of people around the world and represents a major issue in the field of health. Thus, it is important to implement new strategies to reduce its prevalence, and various approaches are currently under development. Recently, an eco-friendly technology named electrodialysis with ultrafiltration membrane (EDUF) was used successfully for the first time at a semi-industrial scale to produce three fractions concentrated in bioactive peptides (BPs) from an enzymatically hydrolyzed whey protein concentrate (WPC): the initial (F1), the final (F2) and the recovery fraction (F3), and it was demonstrated in vitro that F3 exhibited interesting DPP-IV inhibitory effects. Therefore, the present study aimed to evaluate the effect of each fraction on in vivo models of obesity. A daily dose of 312.5 mg/kg was administered to High Fat/High Sucrose diet (HFHS) induced C57BL6/J mice for eight weeks. The physiological parameters of each group and alterations of their gut microbiota by the fractions were assessed. Little effect of the different fractions was demonstrated on the physiological state of the mice, probably due to the digestion process of the BP content. However, there were changes in the gut microbiota composition and functions of mice treated with F3.

Antimicrobial resistance (AMR) is continuing to grow across the world. Though often thought of as a mostly public health issue, AMR is also a major agricultural and environmental problem. As such, many researchers refer to it as the preeminent One Health issue. Aerial transport of antimicrobial-resistant bacteria via bioaerosols is still poorly understood. Recent work has highlighted the presence of antibiotic resistance genes in bioaerosols. Emissions of AMR bacteria and genes have been detected from various sources, including wastewater treatment plants, hospitals, and agricultural practices; however, their impacts on the broader environment are poorly understood. Contextualizing the roles of bioaerosols in the dissemination of AMR necessitates a multidisciplinary approach. Environmental factors, industrial and medical practices, as well as ecological principles influence the aerial dissemination of resistant bacteria. This article introduces an ongoing project assessing the presence and fate of AMR in bioaerosols across Canada. Its various sub-studies include the assessment of the emissions of antibiotic resistance genes from many agricultural practices, their long-distance transport, new integrative methods of assessment, and the creation of dissemination models over short and long distances. Results from sub-studies are beginning to be published. Consequently, this paper explains the background behind the development of the various sub-studies and highlight their shared aspects.

Meta-analyses suggest that yogurt consumption reduces type 2 diabetes incidence in humans, but the molecular basis of these observations remains unknown. Here we show that dietary yogurt intake preserves whole-body glucose homeostasis and prevents hepatic insulin resistance and liver steatosis in a dietary mouse model of obesity-linked type 2 diabetes. Fecal microbiota transplantation studies reveal that these effects are partly linked to the gut microbiota. We further show that yogurt intake impacts the hepatic metabolome, notably maintaining the levels of branched chain hydroxy acids (BCHA) which correlate with improved metabolic parameters. These metabolites are generated upon milk fermentation and concentrated in yogurt. Remarkably, diet-induced obesity reduces plasma and tissue BCHA levels, and this is partly prevented by dietary yogurt intake. We further show that BCHA improve insulin action on glucose metabolism in liver and muscle cells, identifying BCHA as cell-autonomous metabolic regulators and potential mediators of yogurt's health effects., (© 2022. The Author(s).)

Over the past years, promising results from studies have shown that herring milt hydrolysates (HMH) can counter immune-metabolic disorders associated with obesity. However, more studies must corroborate these results. Thus, three commercial hydrolysates (HMH1, HMH2, and HMH3) as well as the fractions of two of them (HMH4 and HMH5) obtained by electrodialysis with ultrafiltration membranes (EDUF) were evaluated in vivo at higher doses compared to a previous study. To achieve this, seven groups of mice were fed for 8 weeks with either a control Chow diet or an obesogenic diet rich in fat and sucrose (HFHS) and supplemented by daily gavage with water or 312.5 mg/kg of one of the five HMH products. In summary, HMH supplements had no impact on weight gain. In the insulin tolerance test (ITT), HMH2 and its HMH5 fraction significantly reduced the blood sugar variation ( p < 0.05). However, during the glucose tolerance (OGTT), HMH2 supplement increased the hyperinsulinemia variation ( p < 0.05) induced by the HFHS diet. HMH1, HMH2, and HMH5 supplements generated potentially beneficial changes for health in the gut microbiota. These results reveal that HMH do not counteract obesity effects but may decrease certain physiological effects induced by obesity.

Consumption of polyphenol-rich food is associated with better metabolic health. Tucum-do-Pantanal (Bactris setosa Mart) and taruma-do-cerrado (Vitex cymosa Bertero ex Spreng) are underexploited native Brazilian fruits with an important source of phytochemicals. In this study, we assessed the effects of 100 mg kg-1 tucum (TPE) and taruma (TCE) extracts on diet-induced obesity (DIO) C57BL/6J mice. After 8 weeks of daily treatment, TPE and TCE were found to significantly prevented the diet-induced body weight gain and fully protected against hepatic steatosis associated with a tendency to stimulate hepatic AMPK phosphorylation. TPE reduced visceral obesity and improved glucose metabolism as revealed by an improvement of the insulin tolerance test, a reduction in the insulin fasting level, and a decreased glucose-induced hyperinsulinemia during an oral glucose tolerance test. TPE and TCE showed promising effects on the treatment of obesity and NAFLD, furthermore, TPE on insulin resistance.

Background: Recent meta-analyses suggest that the consumption of fermented dairy products reduces type 2 diabetes and cardiovascular disease (CVD) risk, although the underlying mechanisms remain unclear., Objective: We evaluated whether dairy protein products modulated gut microbiota and cardiometabolic features in mouse models of diet-induced obesity and CVD., Methods: Eight-week-old C57BL/6J wild-type (WT) and LDLr-/-ApoB100/100 (LRKO) male mice were fed for 12 and 24 wk, respectively, with a high-fat/high-sucrose diet [66% kcal lipids, 22% kcal carbohydrates (100% sucrose), 12% kcal proteins]. The protein sources of the 4 diets were 100% nondairy protein (NDP), or 50% of the NDP energy replaced by milk (MP), milk fermented by Lactobacillus helveticus (FMP), or Greek-style yogurt (YP) protein. Fecal 16S rRNA gene-based amplicon sequencing, intestinal gene expression, and glucose tolerance test were conducted. Hepatic inflammation and circulating adhesion molecules were measured by multiplex assays., Results: Feeding WT mice for 12 wk led to a 74% increase in body weight, whereas after 24 wk the LRKO mice had a 101.5% increase compared with initial body weight. Compared with NDP and MP, the consumption of FMP and YP modulated the gut microbiota composition in a similar clustering pattern, upregulating the Streptococcus genus in both genotypes. In WT mice, feeding YP compared with NDP increased the expression of genes involved in jejunal (Reg3b, 7.3-fold, P = 0.049) and ileal (Ocln, 1.7-fold, P = 0.047; Il1-β,1.7-fold, P = 0.038; Nos2, 3.8-fold, P = 0.018) immunity and integrity. In LRKO mice, feeding YP compared with MP improved insulin sensitivity by 65% (P = 0.039). In LRKO mice, feeding with FMP versus NDP attenuated hepatic inflammation (monocyte chemoattractant protein 1, 2.1-fold, P ˂ 0.0001; IL1-β, 5.7-fold, P = 0.0003; INF-γ, 1.7-fold, P = 0.002) whereas both FMP [vascular adhesion molecule 1 (VCAM1), 1.3-fold, P = 0.0003] and YP (VCAM1, 1.04-fold, P = 0.013; intracellular adhesion molecule 1, 1.4-fold, P = 0.028) decreased circulating adhesion molecules., Conclusion: Both fermented dairy protein products reduce cardiometabolic risk factors in diet-induced obese mice, possibly by modulating the gut microbiota., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter lifespan. Yet, little is known about the impact of WRN mutations on the central nervous system in both humans and mouse models of WS. In the current study, we have performed a longitudinal behavioral assessment on mice bearing a Wrn helicase deletion. Behavioral tests demonstrated a loss of motor activity and coordination, reduction in perception, increase in repetitive behavior, and deficits in both spatial and social novelty memories in Wrn mutant mice compared to age-matched wild type mice. These neurological deficits were associated with biochemical and histological changes in the brain of aged Wrn mutant mice. Microglia, resident immune cells that regulate neuronal plasticity and function in the brain, were hyper-ramified in multiple regions involved with the behavioral deficits of Wrn mutant mice. Furthermore, western analyses indicated that Wrn mutant mice exhibited an increase of oxidative stress markers in the prefrontal cortex. Supporting these findings, electron microscopy studies revealed increased cellular aging and oxidative stress features, among microglia and neurons respectively, in the prefrontal cortex of aged Wrn mutant mice. In addition, multiplex immunoassay of serum identified significant changes in the expression levels of several pro- and anti-inflammatory cytokines. Taken together, these findings indicate that microglial dysfunction and neuronal oxidative stress, associated with peripheral immune system alterations, might be important driving forces leading to abnormal neurological symptoms in WS thus suggesting potential therapeutic targets for interventions., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase (WRN). Mice lacking part of the helicase domain of the WRN ortholog exhibit several phenotypic features of WS. In this study, we generated a Wrn mutant line that, like humans, relies entirely on dietary sources of vitamin C (ascorbate) to survive, by crossing them to mice that lack the gulonolactone oxidase enzyme required for ascorbate synthesis. In the presence of 0.01% ascorbate (w/v) in drinking water, double-mutant mice exhibited a severe reduction in lifespan, small size, sterility, osteopenia, and metabolic profiles different from wild-type (WT) mice. Although increasing the dose of ascorbate to 0.4% improved dramatically the phenotypes of double-mutant mice, the metabolic and cytokine profiles were different from age-matched WT mice. Finally, double-mutant mice treated with 0.01% ascorbate revealed a permanent activation of all the 3 branches of the ER stress response pathways due to a severe chronic oxidative stress in the ER compartment. In addition, markers associated with the ubiquitin-proteasome-dependent ER-associated degradation pathway were increased. Augmenting the dose of ascorbate reversed the activation of this pathway to WT levels rendering this pathway a potential therapeutic target in WS.-Aumailley, L., Dubois, M. J., Brennan, T. A., Garand, C., Paquet, E. R., Pignolo, R. J., Marette, A., Lebel, M. Serum vitamin C levels modulate the lifespan and endoplasmic reticulum stress response pathways in mice synthesizing a nonfunctional mutant WRN protein.

Objective: The objective was to systematically review the literature summarizing the effect on mortality of albumin compared to non-albumin solutions during the fluid resuscitation phase of burn injured patients., Data Sources: We searched MEDLINE, EMBASE and CENTRAL and the content of two leading journals in burn care, Burns and Journal of Burn Care and Research., Study Selection: Two reviewers independently selected randomized controlled trials comparing albumin vs. non-albumin solutions for the acute resuscitation of patients with >20% body surface area involvement., Data Extraction: Reviewers abstracted data independently and assessed methodological quality of the included trials using predefined criteria., Data Synthesis: A random effects model was used to assess mortality. We identified 164 trials of which, 4 trials involving 140 patients met our inclusion criteria. Overall, the methodological quality of the included trials was fair. We did not find a significant benefit of albumin solutions as resuscitation fluid on mortality in burn patients (relative risk (RR) 1.6; 95% confidence interval (CI), 0.63-4.08). Total volume of fluid infusion during the phase of resuscitation was lower in patients receiving albumin containing solution -1.00ml/kg/%TBSA (total body surface area) (95% CI, -1.42 to -0.58)., Conclusion: The pooled estimate demonstrated a neutral effect on mortality in burn patients resuscitated acutely with albumin solutions. Due to limited evidence and uncertainty, an adequately powered, high quality trial could be required to assess the impact of albumin solutions on mortality in burn patients., (Copyright © 2016 Elsevier Ltd and ISBI. All rights reserved.)

Adiposopathy, or sick fat, refers to adipose tissue dysfunction that can lead to several complications such as dyslipidemia, insulin resistance, and hyperglycemia. The relative contribution of adiposopathy in predicting insulin resistance remains unclear. We investigated the relationship between adiposopathy, as assessed as a low plasma adiponectin/leptin ratio, with anthropometry, body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), inflammation, and fitness level (ergocycle VO2max, mL/kgFFM/min) in 53 men (aged 34-53 years) from four groups: sedentary controls without obesity (body mass index [BMI] <25 kg/m(2)), sedentary with obesity (BMI > 30 kg/m(2)), sedentary with obesity and glucose intolerance, and endurance trained active without obesity. The adiponectin/leptin ratio was the highest in trained men (4.75 ± 0.82) and the lowest in glucose intolerant subjects with obesity (0.27 ± 0.06; ANOVA p < 0.0001) indicating increased adiposopathy in those with obesity. The ratio was negatively associated with adiposity (e.g., waist circumference, r = -0.59, p < 0.01) and positively associated with VO2max (r = 0.67, p < 0.01) and insulin sensitivity (M/I, r = 0.73, p < 0.01). Multiple regression analysis revealed fitness as the strongest independent predictor of insulin sensitivity (partial R (2) = 0.61). While adiposopathy was also an independent and significant contributor (partial R (2) = 0.10), waist circumference added little power to the model (partial R (2) = 0.024). All three variables remained significant independent predictors when trained subjects were excluded from the model. Plasma lipids were not retained in the model. We conclude that low fitness, adiposopathy, as well as adiposity (and in particular abdominal obesity) are independent contributors to insulin resistance in men without diabetes.

Suboptimal intake of dietary vitamin C (ascorbate) increases the risk of several chronic diseases but the exact metabolic pathways affected are still unknown. In this study, we examined the metabolic profile of mice lacking the enzyme gulonolactone oxidase (Gulo) required for the biosynthesis of ascorbate. Gulo-/- mice were supplemented with 0%, 0.01%, and 0.4% ascorbate (w/v) in drinking water and serum was collected for metabolite measurements by targeted mass spectrometry. We also quantified 42 serum cytokines and examined the levels of different stress markers in liver. The metabolic profiles of Gulo-/- mice treated with ascorbate were different from untreated Gulo-/- and normal wild type mice. The cytokine profiles of Gulo-/-mice, in return, overlapped the profile of wild type animals upon 0.01% or 0.4% vitamin C supplementation. The life span of Gulo-/- mice increased with the amount of ascorbate in drinking water. It also correlated significantly with the ratios of serum arginine/lysine, tyrosine/phenylalanine, and the ratio of specific species of saturated/unsaturated phosphatidylcholines. Finally, levels of hepatic phosphorylated endoplasmic reticulum associated stress markers IRE1α and eIF2α correlated inversely with serum ascorbate and life span suggesting that vitamin C modulates endoplasmic reticulum stress response and longevity in Gulo-/- mice.

Werner syndrome (WS) is a premature aging disorder caused by mutations in a DNA helicase/exonuclease. Mice lacking the helicase domain of this protein exhibit metabolic abnormalities that are reversed by vitamin C. In this study, we used a targeted metabolomic approach to identify serum metabolites significantly altered in young mutant mice treated with or without vitamin C. We also measured several serum inflammatory and cardiometabolic factors. We show that young mutant mice exhibit an increase in serum hydroxyproline and plasminogen activator inhibitor-1 (PAI-1), markers of cardiovascular diseases and inflammation, before they exhibit morphological anomalies in different tissues. We also observed an increase in three very long chain lysophosphatidylcholines underlying peroxisome perturbation. Vitamin C reversed the concentrations of these metabolites and PAI-1 to wild type values. Transcriptomic analyses on the liver of mutant mice revealed a decrease in the expression of genes involved in fatty acid degradation compared to wild type animals. Vitamin C treatment increased the expression of genes involved in glutathione metabolism and the synthesis of unsaturated fatty acids in these mice. These results show that changes at the transcriptomic level concord with the alterations of several serum metabolites in these mice. Finally, we found that a mislocalization of the Wrn mutant protein in the liver endoplasmic reticulum fraction increased oxidative stress in that cellular compartment. Vitamin C reversed this oxidative stress. To conclude, this study provides novel potential predictive cardiometabolic biomarkers in WS that will allow the assessment of the impact of vitamin C on patients with WS., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-family DNA helicase, WRN. Mice lacking part of the helicase domain of the WRN orthologue exhibit many phenotypic features of WS, including metabolic abnormalities and a shorter mean life span. In contrast, mice lacking the entire Wrn protein (i.e. Wrn null mice) do not exhibit a premature aging phenotype. In this study, we used a targeted mass spectrometry-based metabolomic approach to identify serum metabolites that are differentially altered in young Wrn helicase mutant and Wrn null mice. An antibody-based quantification of 43 serum cytokines and markers of cardiovascular disease risk complemented this study. We found that Wrn helicase mutants exhibited elevated and decreased levels, respectively, of the anti-inflammatory cytokine IL-10 and the pro-inflammatory cytokine IL-18. Wrn helicase mutants also exhibited an increase in serum hydroxyproline and plasminogen activator inhibitor-1, markers of extracellular matrix remodeling of the vascular system and inflammation in aging. We also observed an abnormal increase in the ratio of very long chain to short chain lysophosphatidylcholines in the Wrn helicase mutants underlying a peroxisome perturbation in these mice. Remarkably, the Wrn mutant helicase protein was mislocalized to the endoplasmic reticulum and the peroxisomal fractions in liver tissues. Additional analyses with mouse embryonic fibroblasts indicated a severe defect of the autophagy flux in cells derived from Wrn helicase mutants compared to wild type and Wrn null animals. These results indicate that the deleterious effects of the helicase-deficient Wrn protein are mediated by the dysfunction of several cellular organelles.

Numerous controversies surround the peptide hormone irisin. Although implicated as a myokine promoting the browning of adipose tissue in rodents, its roles in humans remain unclear. Contradictory results have also been found with respect to the relationships between adiposity or metabolic health and plasma irisin levels in humans. We investigated the relationship between irisin levels and body composition (hydrostatic weighing), insulin sensitivity (hyperinsulinemic-euglycemic clamp), fitness level (ergocycle VO2max) and skeletal muscle metabolic profile in 53 men (aged 34-53 years) from four groups: sedentary non-obese controls (body mass index [BMI] <25 kg/m(2)), sedentary obese (BMI >30 kg/m(2)), sedentary obese glucose-intolerant, and non-obese highly trained endurance active. Baseline plasma irisin levels were significantly different between groups, being lowest in trained men (140.6 ± 38.2 ng/mL) and highest in metabolically deteriorated glucose-intolerant subjects (204.0 ± 50.5 ng/mL; ANOVA p = 0.01). Including all subjects, irisin levels were positively associated with adiposity (e.g. fat mass, r = 0.430, p < 0.01) and negatively associated with fitness (r = -0.369, p < 0.01), insulin sensitivity (M/I, r = -0.355, p < 0.01) and muscle citrate synthase (CS) activity (r = -0.482, p < 0.01). Most correlations lost statistical significance when excluding active individuals, except for insulin resistance (r = -0.413, p < 0.01) and CS (r = -0.462, p < 0.01). Multiple regression analyses reveal CS as the strongest independent predictor of irisin levels (r(2) range 0.214 to 0.237). We conclude that muscle oxidative potential is an important factor linked to circulating irisin levels.

Objectives: Intraoperative assessment of coronary artery bypass grafts (CABG) anastomotic quality can be performed using transit-time flowmetry (TTF). The aim of this study was to compare on- versus off-pump coronary graft TTF and early postoperative outcomes., Materials and Methods: Between January 2009 and January 2010, 521 distal graft flows were assessed using TTF measurements in 253 consecutive patients undergoing primary isolated CABG surgery. Data were analyzed using multilevel models accounting for clustering among surgeons and grafts performed in the same patient., Results: Mean age was 66 ± 10 years and 22% were female (n = 55) with 34% diabetics (n = 86) and 40% preoperative myocardial infarction (MI) (n = 101). The surgeries were performed off-pump in 67% (n = 170) with sequential vein grafts in 57% (n = 144) of patients. Off-pump patients had higher pre-operative left ventricular ejection fractions (LVEF), fewer urgent surgeries, fewer distal anastomoses, and fewer sequential vein grafts (all p<0.001). Intra-operative coronary graft TTF measurements were lower in sequential vein grafts performed off-pump versus on-pump. More patients in the on-pump group needed milrinone or dobutamine 24-48 h postoperatively (p = 0.005). Independent predictors of lower TTF included female gender and off-pump surgery, whereas predictors of better TTF were preoperative MI, larger coronary diameter at the site of the distal anastomosis, and sequential vein grafting., Conclusions: Lower intra-operative TTF measurements were found in sequential vein grafts in off-pump CABG. However, off-pump patients experienced similar short-term outcomes compared to on-pump patients.

Objective: Hypoalbuminemia is a common finding in burned patients, but its association with increased morbidity and mortality has not been well established. We assessed whether hypoalbuminemia in the first 24h of admission is associated with organ dysfunction in patients with severe burns., Methods: For a two year period (2008-2009), we reviewed the records of burn adult patients with a total body surface area 20% admitted in our unit within the first 24h of injury. A multiple linear regression analysis was conducted to assess hypoalbuminemia as an independent predictor of organ dysfunction., Results: 56 subjects were analyzed. Multiple linear regression analysis showed that hypoalbuminemia in the first 24h of admission was an independent predictor of organ dysfunction. Serum albumin concentration ≤ 30 g/L was associated with a two-fold increase in organ dysfunction [SOFA scores at day 0 (p=0.005), day 1 (p=0.005) and first week mean values (p=0.004)], but not with mortality (p=0.061)., Conclusion: Hypoalbuminemia is associated with organ dysfunction in burned patients. Unlike unmodifiable predictors such as age, burn surface and inhalation burn, correction of hypoalbuminemia might represent a goal for a future trial in burn patients., (Copyright © 2012 Elsevier Ltd and ISBI. All rights reserved.)

The protein tyrosine phosphatase (PTPase) Src-homology 2-domain-containing phosphatase (SHP)-1 was recently reported to be a novel regulator of insulin's metabolic action. In order to examine the role of this PTPase in skeletal muscle, we used adenovirus (AdV)-mediated gene transfer to express an interfering mutant of SHP-1 [dominant negative (DN)SHP-1; mutation C453S] in L6 myocytes. Expression of DNSHP-1 increased insulin-induced Akt serine-threonine kinase phosphorylation and augmented glucose uptake and glycogen synthesis. Pharmacological inhibition of glucose transporter type 4 (GLUT4) activity using indinavir and GLUT4 translocation assays revealed an important role for this transporter in the increased insulin-induced glucose uptake in DNSHP-1-expressing myocytes. Both GLUT4 mRNA and protein expression were also found to be increased by DNSHP-1 expression. Furthermore, AdV-mediated delivery of DNSHP-1 in skeletal muscle of transgenic mice overexpressing Coxsackie and AdV receptor also enhanced GLUT4 protein expression. Together, these findings confirm that SHP-1 regulates muscle insulin action in a cell-autonomous manner and further suggest that the PTPase negatively modulates insulin action through down-regulation of both insulin signaling to Akt and GLUT4 translocation, as well as GLUT4 expression.

Background: Heterogeneity in microvascular perfusion is associated with impaired tissue oxygenation. We hypothesized that cardiac surgery with or without cardiopulmonary bypass (CPB) could induce microvascular alterations., Methods: We used an orthogonal polarization spectral imaging technique to evaluate the sublingual microcirculation in patients undergoing cardiac surgery with (n = 9) or without (n = 6) CPB. We also included, as a control group, 7 patients undergoing thyroidectomy with the same anesthetic procedure. Hemodynamic and microcirculatory variables were obtained the day before surgery, after induction of anesthesia, during CPB, on admission to the intensive care unit or the recovery room, and 6 and 24 hours after the end of the surgical procedure. Data are presented as median (25th to 75th percentile)., Results: No differences in hemodynamic variables were observed between the two cardiac surgery groups. The proportion of perfused vessels was similar in all three groups at baseline (89% [87% to 90%]), and decreased similarly after induction of anesthesia to 71% (69% to 74%). It decreased further during CPB to 53% (50% to 56%). On admission to the intensive care unit or recovery room, alterations were more severe in CPB than in off-pump patients (60% [59% to 62%] versus 64% [61% to 65%]; p = 0.03), whereas they had already normalized in thyroidectomy patients (89% [86% to 90%]; p = 0.0005 versus cardiac surgery). In both cardiac surgery groups these microcirculatory alterations decreased with time, but persisted at 24 hours. The severity of microvascular alterations correlated with peak lactate levels after cardiac surgery (y = 11.5 - 0.15x; r(2) = 0.65; p < 0.05)., Conclusions: Microcirculatory alterations are observed in cardiac surgery patients whether or not CPB is used. Anesthesia contributes to these alterations, but its effects are transient.

Carcinoembryonic antigen-related cell adhesion molecule 1 (CC1) is a cell adhesion molecule within the Ig superfamily. The Tyr-phosphorylated isoform of CC1 (CC1-L) plays an important metabolic role in the regulation of hepatic insulin clearance. In this report, we show that CC1-deficient (Cc1(-/-)) mice are prone to hepatic steatosis, as revealed by significantly elevated hepatic triglyceride and both total and esterified cholesterol levels compared with age-matched wild-type controls. Cc1(-/-) mice were also predisposed to lipid-induced hepatic steatosis and dysfunction as indicated by their greater susceptibility to store lipids and express elevated levels of enzymatic markers of liver damage after chronic feeding of a high-fat diet. Hepatic steatosis in the Cc1(-/-) mice was linked to a significant increase in the expression of key lipogenic (fatty acid synthase, acetyl CoA carboxylase) and cholesterol synthetic (3-hydroxy-3-methylglutaryl-coenzyme A reductase) enzymes under the control of sterol regulatory element binding proteins-1c and -2 transcription factors. Cc1(-/-) mice also exhibited impaired insulin clearance, glucose intolerance, liver insulin resistance, and elevated hepatic expression of the key gluconeogenic transcriptional activators peroxisome proliferator-activated receptor-gamma coactivator-1 and Forkhead box O1. Lack of CC1 also exacerbated both glucose intolerance and hepatic insulin resistance induced by high-fat feeding, but insulin clearance was not further deteriorated in the high-fat-fed Cc1(-/-) mice. In conclusion, our data indicate that CC1 is a key regulator of hepatic lipogenesis and that Cc1(-/-) mice are predisposed to liver steatosis, leading to hepatic insulin resistance and liver damage, particularly when chronically exposed to dietary fat.

Background: Percutaneous catheterization is a frequently-used technique to gain access to the central venous circulation. Inadvertent arterial puncture is often without consequence, but can lead to devastating complications if it goes unrecognized and a large-bore dilator or catheter is inserted. The present study reviews our experience with these complications and the literature to determine the safest way to manage catheter-related cervicothoracic arterial injury (CRCAI)., Methods: We retrospectively identified all cases of iatrogenic carotid or subclavian injury following central venous catheterization at three large institutions in Montreal. We reviewed the French and English literature published from 1980 to 2006, in PubMed, and selected studies with the following criteria: arterial misplacement of a large-caliber cannula (>/=7F), adult patients (>18 years old), description of the method for managing arterial trauma, reference population (denominator) to estimate the success rate of the therapeutic option chosen. A consensus panel of vascular surgeons, anesthetists and intensivists reviewed this information and proposed a treatment algorithm., Results: Thirteen patients were treated for CRCAI in participating institutions. Five of them underwent immediate catheter removal and compression, and all had severe complications resulting in major stroke and death in one patient, with the other four undergoing further intervention for a false aneurysm or massive bleeding. The remaining eight patients were treated by immediate open repair (six) or through an endovascular approach (two) for subclavian artery trauma without complications. Five articles met all our inclusion criteria, for a total of 30 patients with iatrogenic arterial cannulation: 17 were treated by immediate catheter removal and direct external pressure; eight (47%) had major complications requiring further interventions; and two died. The remaining 13 patients submitted to immediate surgical exploration, catheter removal and artery repair under direct vision, without any complications (47% vs 0%, P = .004)., Conclusion: During central venous placement, prevention of arterial puncture and cannulation is essential to minimize serious sequelae. If arterial trauma with a large-caliber catheter occurs, prompt surgical or endovascular treatment seems to be the safest approach. The pull/pressure technique is associated with a significant risk of hematoma, airway obstruction, stroke, and false aneurysm. Endovascular treatment appears to be safe for the management of arterial injuries that are difficult to expose surgically, such as those below or behind the clavicle. After arterial repair, prompt neurological evaluation should be performed, even if it requires postponing elective intervention. Imaging is suggested to exclude arterial complications, especially if arterial trauma site was not examined and repaired.

Background: Aminoglycosides are mandatory in the treatment of severe infections in burns. However, their pharmacokinetics are difficult to predict in critically ill patients. Our objective was to describe the pharmacokinetic parameters of high doses of tobramycin administered at extended intervals in severely burned patients., Methods: We prospectively enrolled 23 burned patients receiving tobramycin in combination therapy for Pseudomonas species infections in a burn ICU over 2 years in a therapeutic drug monitoring program. Trough and post peak tobramycin levels were measured to adjust drug dosage. Pharmacokinetic parameters were derived from two points first order kinetics., Results: Tobramycin peak concentration was 7.4 (3.1-19.6)microg/ml and Cmax/MIC ratio 14.8 (2.8-39.2). Half-life was 6.9 (range 1.8-24.6)h with a distribution volume of 0.4 (0.2-1.0)l/kg. Clearance was 35 (14-121)ml/min and was weakly but significantly correlated with creatinine clearance., Conclusion: Tobramycin had a normal clearance, but an increased volume of distribution and a prolonged half-life in burned patients. However, the pharmacokinetic parameters of tobramycin are highly variable in burned patients. These data support extended interval administration and strongly suggest that aminoglycosides should only be used within a structured pharmacokinetic monitoring program.

Objectives: Microvascular alterations may play a role in the development of multiple organ failure in severe sepsis. The effects of red blood cell transfusions on microvascular perfusion are not well defined. We investigated the effects of red blood cell transfusion on sublingual microvascular perfusion in patients with sepsis., Design: Prospective, observational study., Setting: A 31-bed, medical-surgical intensive care unit of a university hospital., Patients: Thirty-five patients with severe sepsis requiring red blood cell transfusions., Interventions: Transfusion of one to two units of leukocyte-reduced red blood cells., Measurements and Main Results: The sublingual microcirculation was assessed with an Orthogonal Polarization Spectral device before and 1 hr after red blood cell transfusion. Red blood cell transfusions increased hemoglobin concentration from 7.1 (25th-75th percentile, 6.7-7.6) to 8.1 (7.5-8.6) g/dL (p < .01), mean arterial pressure from 75 (69-89) to 82 (75-90) mm Hg (p < .01), and oxygen delivery from 349 (278-392) to 391 (273-473) mL/min.M (p < .001). Microvascular perfusion was not significantly altered by transfusion, but there was considerable interindividual variation. The change in capillary perfusion after transfusion correlated with baseline capillary perfusion (Spearman-rho = -.49; p = .003). Capillary perfusion was significantly lower at baseline in patients who increased their capillary perfusion by >8% compared with those who did not (57 [52-64] vs. 75 [70-79]; p < .01), while hemodynamic and global oxygen transport variables were similar in the two groups. Red blood cell storage time had no influence on the microvascular response to red blood cell transfusion., Conclusions: The sublingual microcirculation is globally unaltered by red blood cell transfusion in septic patients; however, it can improve in patients with altered capillary perfusion at baseline.

Objective: Nosocomial infections remain a major problem in intensive care units. Several authorities have recommended housing patients in single rooms to prevent cross-transmission of potential pathogens, but this issue is currently debated. The aim of the present study was to compare the rate of nosocomial cross-contamination between patients hosted in single rooms versus bay rooms., Design: Prospective observational data acquisition over 2.5 years., Setting: A 14-bed medico-surgical ICU, composed of six single-bed rooms plus a six-bed and a two-bed bay room served by the same staff., Patients and Participants: All patients admitted from 1 July 2002 to 31 December 2004., Interventions: None., Measurements and Results: Prevalence of methicillin-resistant Staphylococcus aureus (MRSA) in admitted patients was 1.1% and acquisition rate 2.4%. The incidence density of MRSA acquisition was 4.1 [95% CI 2.7-6.3]/1,000 patient-days in bay rooms versus 1.3 [0.5-3.4]/1,000 patient-days in single rooms (p<0.001). Pseudomonas spp. acquisition rate was 3.9 [2.5-6.1]/1,000 patient-days in bay rooms versus 0.7 [0.2-2.4]/1,000 patient-days in single rooms (p<0.001), and Candida spp. colonization was 38.4 [33.3-44.1]/1,000 patient-days in bay rooms versus 13.8 [10.2-18.6]/1,000 patient-days (p<0.001). By multivariate analysis, the relative risk of MRSA, Pseudomonas aeruginosa and Candida spp. acquisition in single rooms or cubicles versus bay rooms was 0.65, 0.61 and 0.75 respectively., Conclusions: These data suggest that in an institution where MRSA is not hyperendemic, infection control measures may be more effective to prevent cross-transmission of microorganisms in patients housed in single rooms.

Background and Objectives: Multiple blood transfusions are considered a common cause of acute respiratory distress syndrome (ARDS). We hypothesized that ARDS is more a consequence of ARDS risk factors (in particular circulatory shock) requiring transfusions than a result of the transfusions themselves., Methods: This retrospective study included 103 patients admitted during a 10-month period to an 858-bed university hospital who received multiple transfusions (more than six units of packed red blood cells in 24 h)., Results: Ten patients developed ARDS; they were more commonly admitted with circulatory shock (36 (38.7%) vs. 8 (80%), P = 0.01), polytrauma (7 (7.5%) vs. 4 (40%), P = 0.01) or thoracic trauma (3 (3.2%) vs. 4 (40%), P = 0.01). The sequential organ-failure assessment (SOFA) score at admission was higher in patients who developed ARDS than in those who did not (9.0 +/- 3.1 vs. 5.6 +/- 3.4, P < 0.005). The total amount of transfusion in the first 24 h was 14.0 +/- 6.8 U in the ARDS patients and 10.6 +/- 7.3 U in the other patients (P = 0.17); the differences remained non-significant in the following days. During the first 24 h, patients who developed ARDS received more fresh frozen plasma than those who did not (21.8 +/- 10.6 U vs. 10.7 +/- 14.7 U, P = 0.02). Patients who developed ARDS had lower PaO2/FiO2 ratios (114 +/- 61 mmHg vs. 276 +/- 108 mmHg, P = 0.01), lower arterial pH (7.27 +/- 0.10 vs. 7.34 +/- 0.11, P = 0.06) and higher minute volume (10.6 +/- 2.8 L min(-1) vs. 7.9 +/- 1.8 L min(-1), P = 0.03) than patients without ARDS. Multivariable analysis retained thoracic trauma and hypoxaemia during the first 24 h (but not multiple transfusions) as independent risk factors for ARDS., Conclusions: In this retrospective study, the development of ARDS in massively transfused patients was less related to poly-transfusion than to other factors related to circulatory shock, polytrauma or thoracic trauma. Thoracic trauma and a low PaO2 during the first 24 h were identified as independent risk factors for ARDS.

Thoracic epidural anesthesia (TEA) combined with general anesthesia in cardiac surgery has the potential to initiate earlier spontaneous ventilation and extubation, improved hemodynamics, less arrhythmia or myocardial ischemia, and an attenuated neurohormonal response. The aim of the current study was to characterize the correlation between TEA and postoperative resource use or outcome in a consecutive-patient cohort. The study was performed in a tertiary care, 3-surgeon, university-affiliated hospital that performs 350 to 400 cardiac surgeries per year. All 1293 adult patients who underwent cardiac surgery between July 1, 2002, and February 1, 2006, were included. Patients were assigned to anesthesiologists practicing TEA (TEA group, n = 506) or not (control group, n = 787) for cardiac surgery. The preoperative parameter values and Parsonnet scores for the 2 groups were similar. The 2 groups had the same distribution of surgery types. The TEA group presented with fewer intensive care unit (ICU) complications, such as delirium, pneumonia, and acute renal failure, and presented with better myocardial protection. The TEA group presented with a higher proportion of immediately postoperative extubations and with shorter ventilation times and ICU stays. Total ICU costs decreased from US $18,700 to $9900 per patient. Combining TEA and general anesthesia for cardiac surgery allows a significant change in anesthesia strategy. This change improves immediate postoperative outcomes and reduces the use and costs of ICU resources.

Objective: To test the hypothesis that administration of albumin to correct hypoalbuminemia might have beneficial effects on organ function in a mixed population of critically ill patients., Design: : Prospective, controlled, randomized study., Setting: Thirty-one-bed, mixed medicosurgical department of intensive care., Patients: All adult patients with a serum albumin concentration < or =30 g/L were assessed for eligibility. Principal exclusion criteria were expected length of stay <72 hrs, life expectancy <3 months or a do-not-resuscitate order, albumin administration in the preceding 24 hrs, or evidence of fluid overload., Interventions: The 100 patients were randomized to receive 300 mL of 20% albumin solution on the first day, then 200 mL/day provided their serum albumin concentration was <31 g/dL (albumin group), or to receive no albumin (control group)., Measurements and Main Results: The primary outcome was the effect of albumin administration on organ function as assessed by a delta Sequential Organ Failure Assessment score from day 1 to day 7 (or the day of intensive care discharge or death, whichever came first). The two groups of 50 patients were comparable at baseline for age, gender, albumin concentration, and Acute Physiology and Chronic Health Evaluation II score. Albumin concentration did not change over time in the control group but increased consistently in the albumin group (p < .001). Organ function improved more in the albumin than in the control group (p = .026), mainly due to a difference in respiratory, cardiovascular, and central nervous system components of the Sequential Organ Failure Assessment score. Diuretic use was identical in both groups, but mean fluid gain was almost three times higher in the control group (1679 +/- 1156 vs. 658 +/- 1101 mL, p = .04). Median daily calorie intake was higher in the albumin than in the control group (1122 [935-1158] vs. 760 [571-1077] kcal, p = .05)., Conclusions: Albumin administration may improve organ function in hypoalbuminemic critically ill patients. It results in a less positive fluid balance and a better tolerance to enteral feeding.

The protein tyrosine phosphatase SHP-1 is a well-known inhibitor of activation-promoting signaling cascades in hematopoietic cells but its potential role in insulin target tissues is unknown. Here we show that Ptpn6(me-v/me-v) (also known as viable motheaten) mice bearing a functionally deficient SHP-1 protein are markedly glucose tolerant and insulin sensitive as compared to wild-type littermates, as a result of enhanced insulin receptor signaling to IRS-PI3K-Akt in liver and muscle. Downregulation of SHP-1 activity in liver of normal mice by adenoviral expression of a catalytically inert mutant of SHP-1, or after small hairpin RNA-mediated SHP-1 silencing, further confirmed this phenotype. Tyrosine phosphorylation of CEACAM1, a modulator of hepatic insulin clearance, and clearance of serum [125I]-insulin were markedly increased in SHP-1-deficient mice or SHP-1-deficient hepatic cells in vitro. These findings show a novel role for SHP-1 in the regulation of glucose homeostasis through modulation of insulin signaling in liver and muscle as well as hepatic insulin clearance.

Objective: To evaluate the effects of dobutamine on microcirculatory blood flow alterations in patients with septic shock., Design: Prospective, open-label study., Setting: A 31-bed, medico-surgical intensive care unit of a university hospital., Patients: Twenty-two patients with septic shock., Interventions: Intravenous administration of dobutamine (5 mug/kg.min) for 2 hrs (n = 22) followed by the addition of 10 M acetylcholine (topically applied, n = 10)., Measurements and Main Results: Complete hemodynamic measurements were obtained before and after dobutamine administration. In addition, the sublingual microcirculation was investigated with an orthogonal polarization spectral imaging technique before and after dobutamine administration and after topical application of acetylcholine. Dobutamine significantly improved capillary perfusion (from 48 +/- 15 to 67 +/- 11%, p = .001), but with large individual variation, whereas capillary density remained stable. The addition of topical acetylcholine completely restored capillary perfusion (98 +/- 1%, p = .001) and capillary density. The changes in capillary perfusion during dobutamine administration were not related to changes in cardiac index (p = .45) or arterial pressure (p = .29). Interestingly, the decrease in lactate levels was proportional to the improvement in capillary perfusion (y = 0.07 - 0.02x, r = .46, p = .005) but not to changes in cardiac index (p = .55)., Conclusions: The administration of 5 mug/kg.min dobutamine can improve but not restore capillary perfusion in patients with septic shock. These changes are independent of changes in systemic hemodynamic variables.

We studied the manipulative activity of five wedge-capped capuchins (Cebus olivaceus) confronted with different types of unfamiliar and portable objects: wooden blocks, plastic rings, spoons, and coconuts. Combinatorial manipulations involving two portable objects of the same type were quite frequent. The lately introduced objects, whatever their kind, appeared as the most attractive. Nevertheless, some objects remained very attractive throughout the overall experiment, especially the wooden blocks which elicited more combinatorial and striking behaviors than the other objects. Concerning space, we observed that the individuals choose specific locations to perform their manipulative acts. The spatial distributions of these acts were more concentrated, and less concordant between individuals, in the present study than in two others conducted with the same group but involving the manipulation of familiar objects. This suggests that individual differences were more marked when the subjects manipulated unfamiliar objects than when they manipulated familiar ones. This finding may have applications when the members of a group have to benefit from an enrichment of their environment.

Objective: To characterize the time course of microcirculatory alterations and their relation to outcome in patients with septic shock., Design: Prospective, observational study., Setting: Thirty-one-bed, medico-surgical intensive care unit in a university hospital., Patients: Forty-nine patients with septic shock., Interventions: The sublingual microcirculation was investigated with an orthogonal polarization spectral imaging device on the day of onset of septic shock (baseline) and each day until resolution of shock., Measurements and Main Results: Five sequences of 20 secs each were recorded and analyzed off-line by a semiquantitative method. Data were analyzed with nonparametric tests and presented as median (25th-75th percentiles). Three patients died after the resolution of shock from unrelated causes and were excluded. Of the other 46 patients, 26 survived and 20 died: 13 due to unresolving shock and seven due to persistent multiple organ failure after resolution of shock. At the onset of shock, survivors and nonsurvivors had similar vascular density (5.6 [4.7-7.0] vs. 6.2 [5.4-7.0]/mL; p = nonsignificant) and percentage of perfused small vessels (65.0 [53.1-68.9] vs. 58.4 [47.5-69.1]%; p = nonsignificant). Small vessel perfusion improved over time in survivors (analysis of variance, p <.05 between survivors and nonsurvivors) but not in nonsurvivors. Despite similar hemodynamic and oxygenation profiles and use of vasopressors at the end of shock, patients dying after the resolution of shock in multiple organ failure had a lower percentage of perfused small vessels than survivors (57.4 [46.6-64.9] vs. 79.3 [67.2-83.2]%; p =.02)., Conclusions: Microcirculatory alterations improve rapidly in septic shock survivors but not in patients dying with multiple organ failure, regardless of whether shock has resolved.

Background: Microvascular blood flow alterations may impair tissue oxygenation and may participate in the development of multiple organ failure in patients with severe heart failure. We hypothesized that microvascular blood flow alterations are present in patients with severe heart failure and cardiogenic shock., Methods: We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 40 patients with acute severe heart failure, including 31 patients with cardiogenic shock, and in a control group of 15 patients who were examined the day before cardiac surgery. The effects of topical application of acetylcholine (10-2M) were also tested in 5 patients with cardiogenic shock. Five sublingual areas were recorded, allocated a random number, and later analyzed semiquantitatively. Data were analyzed with non-parametric tests and presented as medians (percentiles 25-75)., Results: The density of all the vessels was similar in the 3 groups. The proportion of perfused small (<20 microm) vessels was lower in patients with cardiac failure and cardiogenic shock than in control patients (63% [46%-65%] and 49% [38%-64%] vs 92% [90%-93%], P <.001). The perfusion of large vessels was preserved in all groups. The proportion of perfused vessels was higher in patients who survived than in patients who did not survive in all vessels (90% [84%-93%] vs 81% [74%-87%], P <.05) and in small vessels (64% [49%-68%] vs 43% [37%-62%], P <.05). The topical application of acetylcholine totally reversed these alterations, Conclusions: Microvascular blood flow alterations are frequently observed in patients with severe heart failure and are more severe in patients who do not survive.

Study Objectives: To characterize the hemodynamic course of cardiogenic shock and to relate the cause of death to ongoing cardiac failure or multiple organ dysfunction., Design: Retrospective study., Setting: A 31-bed department of intensive care in a university hospital., Patients: All patients admitted for cardiogenic shock from January 1999 to December 2000., Interventions: None., Measurements and Results: Charts were reviewed for demographic, clinical, hemodynamic, oxygen transport, inflammation, and organ dysfunction data. Of 62 patients with cardiogenic shock, 40 (65%) did not survive. Eight patients (20%) died from fatal arrhythmia, 14 patients (35%) died with low cardiac index (CI) [ie, < 2.2 L/min/m(2)], and 18 patients (45%) died with normalized CI (ie, > 2.2 L/min/m(2)) and a higher CI/oxygen extraction ratio. Of these 18 patients, 9 had evidence of infection. The patients with normalized CI were younger and stayed longer in the ICU than patients with low CI., Conclusion: A substantial number of patients with cardiogenic shock die with a normalized CI, suggesting a distributive defect, in the absence of obvious infection. These patients are younger and have a longer ICU course. The release of mediators may be secondary to gut hypoperfusion.

Glucose transport across the cell surface is a key regulatory step for glucose metabolism in skeletal muscle. Both insulin and exercise increase glucose transport into myofibers through glucose transporter (GLUT) proteins. Skeletal muscle expresses several members of the GLUT family but the GLUT4 glucose transporter is considered the main "regulatable" isoform that is modulated by insulin and contraction. Glucose transport rate can be stimulated either by recruitment of GLUT4 units from intracellular storage vesicles or through activation of cell surface transporters. Insulin activates GLUT4 translocation through a complex signaling cascade involving both the lipid kinase phosphatidylinositol 3-kinase and the proto-oncoprotein c-Cbl. Contraction, on the other hand, appears to trigger GLUT4 translocation at least in part through activation of the metabolite-sensing 5'-AMP-activated protein kinase. Furthermore, recent studies suggest that p38 MAP kinase activation represents a point of convergence of the signaling pathways utilized by insulin and contraction to increase GLUT4 activation at the cell surface. This review will summarize our current knowledge of these alternative pathways of GLUT4 regulation in skeletal muscle.

Objective: To assess the sublingual microcirculation in a patient during vasopressin administration for a distributive shock after cardiopulmonary bypass., Design and Setting: Case-report in the Department of Intensive Care of a university hospital., Patient: A 53 year-old man developed severe distributive shock after cardiac transplant, requiring massive doses of vasopressor agents., Methods: Vasopressin administered twice at a dose of 0.02 U/min increased mean blood pressure and allowed partial weaning of other vasopressor drugs. Microcirculatory alterations were assessed by orthogonal polarization spectral technique: 50% and 60% of capillaries were perfused at baseline, and these proportions did not worsen when vasopressin was administered., Conclusions: Despite its strong vasopressor effects vasopressin infusion did not worsen microcirculatory alterations in this patient with distributive shock following cardiac surgery.

Objective: To determine whether hypoalbuminemia is an independent risk factor for poor outcome in the acutely ill, and to assess the potential of exogenous albumin administration for improving outcomes in hypoalbuminemic patients., Summary Background Data: Hypoalbuminemia is associated with poor outcomes in acutely ill patients, but whether this association is causal has remained unclear. Trials investigating albumin therapy to correct hypoalbuminemia have proven inconclusive., Methods: A meta-analysis was conducted of 90 cohort studies with 291,433 total patients evaluating hypoalbuminemia as an outcome predictor by multivariate analysis and, separately, of nine prospective controlled trials with 535 total patients on correcting hypoalbuminemia., Results: Hypoalbuminemia was a potent, dose-dependent independent predictor of poor outcome. Each 10-g/L decline in serum albumin concentration significantly raised the odds of mortality by 137%, morbidity by 89%, prolonged intensive care unit and hospital stay respectively by 28% and 71%, and increased resource utilization by 66%. The association between hypoalbuminemia and poor outcome appeared to be independent of both nutritional status and inflammation. Analysis of dose-dependency in controlled trials of albumin therapy suggested that complication rates may be reduced when the serum albumin level attained during albumin administration exceeds 30 g/L., Conclusions: Hypoalbuminemia is strongly associated with poor clinical outcomes. Further well-designed trials are needed to characterize the effects of albumin therapy in hypoalbuminemic patients. In the interim, there is no compelling basis to withhold albumin therapy if it is judged clinically appropriate.

Microvascular blood flow alterations are frequent in animal models of sepsis and may impair tissue oxygenation. We hypothesized that alterations of the microcirculation are present in patients with sepsis. We used an orthogonal polarization spectral imaging technique to investigate the sublingual microcirculation in 10 healthy volunteers, 16 patients before cardiac surgery, 10 acutely ill patients without sepsis (intensive care unit control subjects), and 50 patients with severe sepsis. The effects of topical application of acetylcholine (10(-2) M) were tested in 11 patients with sepsis. In each subject, five to seven sublingual areas were recorded and analyzed semiquantitatively. Data were analyzed with nonparametric tests and are presented as medians (25th-75th percentiles). No significant difference in microvascular blood flow was observed between healthy volunteers and patients before cardiac surgery or intensive care unit control subjects. The density of all vessels was significantly reduced in patients with severe sepsis (4.5 [4.2-5.2] versus 5.4 [5.4-6.3]/mm in volunteers, p < 0.01). The proportion of perfused small (< 20 microm) vessels was reduced in patients with sepsis (48 [33-61] versus 90 [89-92]% in volunteers, p < 0.001). These alterations were more severe in nonsurvivors. The topical application of acetylcholine totally reversed these alterations. In conclusion, microvascular blood flow alterations are frequent in patients with sepsis and are more severe in patients with a worse outcome.

Delirium in the intensive care unit is a serious problem that has recently attracted much attention. User-friendly and reliable tools, such as the Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), offer the clinician the opportunity to identify delirium in patients better. Diagnosis of delirium in a critical care population is often a difficult task because classical psychiatric evaluation is impossible for a number of reasons. The CAM-ICU makes use of nonverbal assessments to evaluate the cardinal features of delirium (i.e. acute or fluctuating onset, inattention, disorganized thinking and altered level of consciousness). Its development for use in the critical care setting represents a significant advance that could lead to better care for such patients.