Since 2015, Society of Critical Care Medicine/American Society for Parenteral and Enteral Nutrition and Canadian critical care nutrition support guidelines have both been updated. Despite a similar evidentiary basis, there remain key differences between guideline recommendations. These differences in recommendations may pose confusion for the clinician and may encumber widespread applicability.
View Article and Find Full Text PDFNutrition support is a necessary therapy for critically ill cardiac surgery patients. However, conclusive evidence for this population, consisting of well-conducted clinical trials is lacking. To clarify optimal strategies to improve outcomes, an international multidisciplinary group of 25 experts from different clinical specialties from Germany, Canada, Greece, USA and Russia discussed potential approaches to identify patients who may benefit from nutrition support, when best to initiate nutrition support, and the potential use of pharmaco-nutrition to modulate the inflammatory response to cardiopulmonary bypass.
View Article and Find Full Text PDFBackground: Critically ill patients are at increased risk of developing malnutrition-related complications because of physiological changes, suboptimal delivery, and reduced intake. Strategies to improve nutrition during critical illness recovery are required to prevent iatrogenic underfeeding and risk of malnutrition. The purpose of this study was to assess the feasibility and acceptability of a novel family-centered intervention to improve nutrition in critically ill patients.
View Article and Find Full Text PDFBackground: The purpose of this study was to determine what was "best achievable practice" with the implementation of a novel enteral feeding protocol (Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol [PEP uP protocol]).
Methods: This study was a multicenter quality improvement collaborative wherein we describe nutrition practices and outcomes within PEP uP sites. We report the minimum, average, and maximal site-level performance on aspects related to nutrition practices and outcomes.
Background: Selenium (Se) is an essential trace element with antioxidant, anti-inflammatory, and immunomodulatory effects. So far, several randomized clinical trials (RCTs) have demonstrated that parenteral Se may improve clinical outcomes in intensive care unit (ICU) patients. Since publication of our previous systematic review and meta-analysis on antioxidants in the ICU, reports of several trials have been published, including the largest RCT on Se therapy.
View Article and Find Full Text PDFCritical illness is hypothesized to associate with loss of "health-promoting" commensal microbes and overgrowth of pathogenic bacteria (dysbiosis). This dysbiosis is believed to increase susceptibility to nosocomial infections, sepsis, and organ failure. A trial with prospective monitoring of the intensive care unit (ICU) patient microbiome using culture-independent techniques to confirm and characterize this dysbiosis is thus urgently needed.
View Article and Find Full Text PDFBackground: Enteral nutrition (EN) is recommended as the preferred route for early nutrition therapy in critically ill adults over parenteral nutrition (PN). A recent large randomized controlled trial (RCT) showed no outcome differences between the two routes. The objective of this systematic review was to evaluate the effect of the route of nutrition (EN versus PN) on clinical outcomes of critically ill patients.
View Article and Find Full Text PDFIntroduction: Intravenous fish oil (FO) lipid emulsions (LEs) are rich in ω-3 polyunsaturated fatty acids, which exhibit anti-inflammatory and immunomodulatory effects. We previously demonstrated that FO-containing LEs may be able to decrease mortality and ventilation days in patients who are critically ill. Since 2014, several additional randomized controlled trials (RCTs) of FO-containing LEs have been published.
View Article and Find Full Text PDFBackground: Critical illness is characterized by a loss of commensal flora and an overgrowth of potentially pathogenic bacteria, leading to a high susceptibility to nosocomial infections. Probiotics are living non-pathogenic microorganisms, which may protect the gut barrier, attenuate pathogen overgrowth, decrease bacterial translocation and prevent infection. The purpose of this updated systematic review is to evaluate the overall efficacy of probiotics and synbiotic mixtures on clinical outcomes in critical illness.
View Article and Find Full Text PDFBackground: Previous studies have documented widespread iatrogenic underfeeding in intensive care unit (ICU) patients. In an experimental setting, we demonstrated the safety and efficacy of a novel enteral feeding protocol designed to overcome the main barriers to adequate delivery of enteral nutrition (EN), the Enhanced Protein-Energy Provision via the Enteral Route Feeding Protocol (PEP uP protocol). The purpose of this article is to describe our experience with implementing this feeding protocol under "real-world" settings in Canada.
View Article and Find Full Text PDFClinical practice guidelines (CPGs) are systematically developed statements to assist practitioners and patient decisions about appropriate healthcare for specific clinical circumstances, and are designed to minimize practice variation, improve costs, and improve clinical outcomes. The Canadian Critical Care Practice Guidelines (CCPGs) were first published in 2003 and most recently updated in 2013. A total of 68 new randomized controlled trials were identified since the last version in 2009, 50 of them published between 2009 and 2013.
View Article and Find Full Text PDFHox genes encode transcription factors that play essential roles during embryo morphogenesis and organogenesis. Expression of several Hox members persists at the adult age, indicating a wide spectrum of action from embryonic to postnatal life. In the present study, we reported that in adult mice, the Hoxa5 gene shows a dynamic expression profile in the ovary that depends on the estrous cycle, the gestational status, and the age of the female, suggesting that Hoxa5 may have distinct physiological functions in the ovary.
View Article and Find Full Text PDFCre-expressing mouse lines constitute an important asset to mammalian genetics, allowing the deletion of genes in a spatio-temporal specific manner. Our study on Hox gene function in lung development has led us to use a lung endoderm-specific deletion with the Sftpc-cre mouse line expressing the Cre recombinase gene under the control of human surfactant protein C regulatory sequences. In control experiments, the Cre recombinase faithfully activated the Rosa26-lacZ reporter gene in lung epithelium.
View Article and Find Full Text PDFBackground: The genomic organization of Hox clusters is fundamental for the precise spatio-temporal regulation and the function of each Hox gene, and hence for correct embryo patterning. Multiple overlapping transcriptional units exist at the Hoxa5 locus reflecting the complexity of Hox clustering: a major form of 1.8 kb corresponding to the two characterized exons of the gene and polyadenylated RNA species of 5.
View Article and Find Full Text PDFHox genes encode transcription factors of crucial importance in the pattern formation of a large spectrum of species. Several studies have now proposed a role for these developmental genes in cancer biology. It has been suggested that HOXA5 possesses growth-suppressive properties through activation of p53 expression in human breast tissue.
View Article and Find Full Text PDFAnalysis of the Hoxa5(-/-) mutants has revealed the critical role of Hoxa5 in survival, specification of axial identity, and ontogeny of organs, including the respiratory tract. The presence of the selection cassette in the original Hoxa5(-/-) mutation may interfere with the interpretation of the phenotypes. To circumvent this aspect and to bypass the lethality of the Hoxa5 mutation, we have designed a conditional approach and generated Hoxa5 allelic variants.
View Article and Find Full Text PDFChromosomal translocation is a common cause of leukaemia and the most common chromosome translocations found in leukaemia patients involve the mixed lineage leukaemia (MLL) gene. AF10 is one of more than 30 MLL fusion partners in leukaemia. We have recently demonstrated that the H3K79 methyltransferase hDOT1L contributes to MLL-AF10-mediated leukaemogenesis through its interaction with AF10 (ref.
View Article and Find Full Text PDFRecent progress has enlightened the involvement of Hox genes in organogenesis. Several Hox genes are expressed in normal and neoplastic mammary glands. Using Hoxa5 mutant mice, we showed that Hoxa5-/- females present nursing defects.
View Article and Find Full Text PDFThe Hoxa5 mutation is associated with a high perinatal mortality rate caused by a severe obstruction of the laryngotracheal airways, pulmonary dysmorphogenesis, and a decreased production of surfactant proteins. Surviving Hoxa5(-/-) mutant mice also display lung anomalies with deficient alveolar septation and areas of collapsed tissue, thus demonstrating the importance of Hoxa5 throughout lung development and maturation. Here, we address the functional consequences of the Hoxa5 mutation on respiration and chemoreflexes by comparing the breathing pattern of Hoxa5(-/-) mice to that of wild-type animals under resting conditions and during exposure to moderate ventilatory stimuli such as hypoxia and hypercapnia.
View Article and Find Full Text PDFThe genetic control of gut regionalization relies on a hierarchy of molecular events in which the Hox gene family of transcription factors is suspected to be key participant. We have examined the role of Hox genes in gut patterning using the Hoxa5(-/-) mice as a model. Hoxa5 is expressed in a dynamic fashion in the mesenchymal component of the developing gut.
View Article and Find Full Text PDFHox and Pax transcription factors are master regulators of skeletal and organ morphogenesis. Some skeletal malformations encountered in Hoxa5 mutants are shared by the undulated (un) mice, which bear a point mutation in the Pax1 gene. To investigate whether Hoxa5 and Pax1 act in common pathways during skeletal development, we analyzed Hoxa5;un compound mutants.
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