Role of the microbiome, probiotics, and 'dysbiosis therapy' in critical illness.

Purpose of reviewLoss of 'health-promoting' microbes and overgrowth of pathogenic bacteria (dysbiosis) in ICU is believed to contribute to nosocomial infections, sepsis, and organ failure (multiple organ dysfunction syndrome). This review discusses new understanding of ICU dysbiosis, new data for probiotics and fecal transplantation in ICU, and new data characterizing the ICU microbiome.Recent findingsICU dysbiosis results from many factors, including ubiquitous antibiotic use and overuse. Despite advances in antibiotic therapy, infections and mortality from often multidrug-resistant organisms (i.e., Clostridium difficile) are increasing. This raises the question of whether restoration of a healthy microbiome via probiotics or other 'dysbiosis therapies' would be an optimal alternative, or parallel treatment option, to antibiotics. Recent clinical data demonstrate probiotics can reduce ICU infections and probiotics or fecal microbial transplant (FMT) can treat Clostridium difficile. This contributes to recommendations that probiotics should be considered to prevent infection in ICU. Unfortunately, significant clinical variability limits the strength of current recommendations and further large clinical trials of probiotics and FMT are needed. Before larger trials of 'dysbiosis therapy' can be thoughtfully undertaken, further characterization of ICU dysbiosis is needed. To addressing this, we conducted an initial analysis demonstrating a rapid and marked change from a 'healthy' microbiome to an often pathogen-dominant microbiota (dysbiosis) in a broad ICU population.SummaryA growing body of evidence suggests critical illness and ubiquitous antibiotic use leads to ICU dysbiosis that is associated with increased ICU infection, sepsis, and multiple organ dysfunction syndrome. Probiotics and FMT show promise as ICU therapies for infection. We hope future-targeted therapies using microbiome signatures can be developed to correct 'illness-promoting' dysbiosis to restore a healthy microbiome post-ICU to improve patient outcomes

Flight test and evaluation of Omega navigation in a general aviation aircraft. Volume 2: Appendices

Detailed documentation for each flight of the Omega Flight Evaluation study is presented, including flight test description sheets and actual flight data plots. Computer programs used for data processing and flight planning are explained and the data formats utilized by the Custom Interface Unit are summarized

Extreme Dysbiosis of the Microbiome in Critical Illness.

Critical 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. Characterizing ICU patient microbiome changes may provide first steps toward the development of diagnostic and therapeutic interventions using microbiome signatures. To characterize the ICU patient microbiome, we collected fecal, oral, and skin samples from 115 mixed ICU patients across four centers in the United States and Canada. Samples were collected at two time points: within 48 h of ICU admission, and at ICU discharge or on ICU day 10. Sample collection and processing were performed according to Earth Microbiome Project protocols. We applied SourceTracker to assess the source composition of ICU patient samples by using Qiita, including samples from the American Gut Project (AGP), mammalian corpse decomposition samples, childhood (Global Gut study), and house surfaces. Our results demonstrate that critical illness leads to significant and rapid dysbiosis. Many taxons significantly depleted from ICU patients versus AGP healthy controls are key "health-promoting" organisms, and overgrowth of known pathogens was frequent. Source compositions of ICU patient samples are largely uncharacteristic of the expected community type. Between time points and within a patient, the source composition changed dramatically. Our initial results show great promise for microbiome signatures as diagnostic markers and guides to therapeutic interventions in the ICU to repopulate the normal, "health-promoting" microbiome and thereby improve patient outcomes. IMPORTANCE Critical illness may be associated with the loss of normal, "health promoting" bacteria, allowing overgrowth of disease-promoting pathogenic bacteria (dysbiosis), which, in turn, makes patients susceptible to hospital-acquired infections, sepsis, and organ failure. This has significant world health implications, because sepsis is becoming a leading cause of death worldwide, and hospital-acquired infections contribute to significant illness and increased costs. Thus, a trial that monitors the ICU patient microbiome to confirm and characterize this hypothesis is urgently needed. Our study analyzed the microbiomes of 115 critically ill subjects and demonstrated rapid dysbiosis from unexpected environmental sources after ICU admission. These data may provide the first steps toward defining targeted therapies that correct potentially "illness-promoting" dysbiosis with probiotics or with targeted, multimicrobe synthetic "stool pills" that restore a healthy microbiome in the ICU setting to improve patient outcomes

A randomized trial of glutamine and antioxidants in critically ill patients.

BACKGROUND: Critically ill patients have considerable oxidative stress. Glutamine and antioxidant supplementation may offer therapeutic benefit, although current data are conflicting. METHODS: In this blinded 2-by-2 factorial trial, we randomly assigned 1223 critically ill adults in 40 intensive care units (ICUs) in Canada, the United States, and Europe who had multiorgan failure and were receiving mechanical ventilation to receive supplements of glutamine, antioxidants, both, or placebo. Supplements were started within 24 hours after admission to the ICU and were provided both intravenously and enterally. The primary outcome was 28-day mortality. Because of the interim-analysis plan, a P value of less than 0.044 at the final analysis was considered to indicate statistical significance. RESULTS: There was a trend toward increased mortality at 28 days among patients who received glutamine as compared with those who did not receive glutamine (32.4% vs. 27.2%; adjusted odds ratio, 1.28; 95% confidence interval [CI], 1.00 to 1.64; P=0.05). In-hospital mortality and mortality at 6 months were significantly higher among those who received glutamine than among those who did not. Glutamine had no effect on rates of organ failure or infectious complications. Antioxidants had no effect on 28-day mortality (30.8%, vs. 28.8% with no antioxidants; adjusted odds ratio, 1.09; 95% CI, 0.86 to 1.40; P=0.48) or any other secondary end point. There were no differences among the groups with respect to serious adverse events (P=0.83). CONCLUSIONS: Early provision of glutamine or antioxidants did not improve clinical outcomes, and glutamine was associated with an increase in mortality among critically ill patients with multiorgan failure. (Funded by the Canadian Institutes of Health Research; ClinicalTrials.gov number, NCT00133978.)

Glutamine supplementation in cystic fibrosis: a randomized placebo-controlled trial

Rationale: Pulmonary infection and malnutrition in cystic fibrosis are associated with decreased survival. Glutamine has a possible anti-microbial effect, with a specific impact against Pseudomonas aeruginosa. We aimed to test the hypothesis that oral glutamine supplementation (21 g/day) for 8 weeks in adults with cystic fibrosis would decrease pulmonary inflammation and improve clinical status. Methods: The study design was a randomized double-blind placebo-controlled study design with an iso-nitrogenous placebo. The primary analysis was intention to treat, and the primary outcome was change in induced sputum neutrophils. Results: Thirty-nine individuals were recruited and thirty-six completed the study. Glutamine supplementation had no impact on any of the outcome measures in the intention-to-treat analysis. In the per protocol analysis, glutamine supplementation was associated with an increase in induced sputum neutrophils (P = 0.046), total cells (P = 0.03), and in Pseudomonas isolation agar colony forming units (P = 0.04) compared to placebo. Conclusions: There was no effect of glutamine supplementation on markers of pulmonary inflammation in the intention-to-treat analysis

In Search of Collegiate Flight “Education”

The goal of most college flight programs is not to produce general aviation pilots, but rather professional pilots who also attain AA/BS degree-related life skills, wrote one professor [emphases his]. A central thesis of this paper is that before college flight graduates can compete for professional jobs, they will need post-graduation flight experience, i.e., general aviation experience, and to get those general aviation jobs, graduates will also need excellent general aviation skills - which flight collegiate programs commonly do not provide. The professor\u27s comment is explicitly condescending in its differentiation between general aviation and professional flying. This hubris is part of the collegiate aviation problem -training to professional standards in general aviation aircraft, and using a college\u27s own graduates to perpetuate a limited, tightly constrained, incestuous training program in general aviation aircraft does not mean that those graduates are exposed to or qualified for the real world of general aviation. Being both an ATP/CFII and a professor at a flight-oriented university, but teaching in a non-flight department, provided a unique, close up, but outsider\u27s view of collegiate flight education. Three criteria come to mind for evaluating the efficacy of collegiate flight program philosophies: training, education, and experience. Training means training for flight, both on the ground and in the air; education refers to both traditional academia and also to flight education, the latter a possibly new concept; and experience means marketable flight experience as opposed to just hours logged. This paper looks at flight education and these three standards, based both on lifelong participation in general aviation at multiple levels and also time spent observing a big name flight university

Malnutrition in the acutely ill patient: is it more than just protein and energy?

Malnutrition has traditionally been thought to involve deficiencies in protein and energy (macronutrients); however, we know that specific key nutrients, when deficient. can also lead to significant morbidity and mortality. Large studies performed with replacement of single nutrients, such as zinc, in malnourished populations in Africa and other developing countries has led to reductions in respiratory infections and diarrhoeal diseases. In this regard, It is being increasingly that acutely ill hospitalized patients may not only be malnourished from a macronutrient standpoint, but that such patients may also be deficient in a number of key functional pharmaconutrients. This new knowledge creates a new era in nutritional support, where nutritional therapy is presenting the surgical and critical care community with a “unique opportunity” to improve patient outcomes with a safe, relatively inexpensive and effective intervention. Our vision for the future of nutritional pharmacology in surgery and critical care is one where there will be initiation of early (< 24-48 hours post-surgery or ICU admission) nutrient delivery, preferentially via the enteral route. This should be supplemented by parenteral nutrition in “at risk” patients, when adequate energy cannot be provided enterally. Pharmaconutrients to target therapy to specific disease states in such should be administered as separate components, in a manner similar to that of administering an antibiotic or drug.Keywords: arginine, glutamine, omega-3 fatty acids, npo, bowel sounds, nutritio

Editorial: Glutamine, heat shock protein, and inflammation — opportunity from the midst of difficulty

No Abstract Available South African Journal of Clinical Nutrition Vol.17(3) 2004: 84-8