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The Lancet 02/2013; 381(9866):534-5. · 38.28 Impact Factor
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Nature Reviews Gastroenterology & Hepatology 09/2012; 9(10):563-4. · 8.10 Impact Factor
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ABSTRACT: The complex metabolic relationships between the host and its microbiota change throughout life and vary extensively between individuals, affecting disease risk factors and therapeutic responses through drug metabolism. Elucidating the biochemical mechanisms underlying this human supraorganism symbiosis is yielding new therapeutic insights to improve human health, treat disease, and potentially modify human disease risk factors. Therapeutic options include targeting drugs to microbial genes or co-regulated host pathways and modifying the gut microbiota through diet, probiotic and prebiotic interventions, bariatric surgery, fecal transplants, or ecological engineering. The age-associated co-development of the host and its microbiota provides a series of windows for therapeutic intervention from early life through old age.
Science translational medicine 06/2012; 4(137):137rv6. · 7.80 Impact Factor
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ABSTRACT: The composition and activity of the gut microbiota codevelop with the host from birth and is subject to a complex interplay that depends on the host genome, nutrition, and life-style. The gut microbiota is involved in the regulation of multiple host metabolic pathways, giving rise to interactive host-microbiota metabolic, signaling, and immune-inflammatory axes that physiologically connect the gut, liver, muscle, and brain. A deeper understanding of these axes is a prerequisite for optimizing therapeutic strategies to manipulate the gut microbiota to combat disease and improve health.
Science 06/2012; 336(6086):1262-7. · 31.20 Impact Factor
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ABSTRACT: Medical infusion devices are an integral component within the delivery of healthcare management. The aim of this study was to develop a training simulation in the virtual world of Second Life for the management of adverse events associated with infusion devices. Forty nurses were subsequently recruited to participate within the simulation and assess its feasibility.
Studies in health technology and informatics 01/2012; 173:338-43.
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Jia V Li,
Hutan Ashrafian,
Marco Bueter, James Kinross,
Caroline Sands,
Carel W le Roux,
Stephen R Bloom,
Ara Darzi,
Thanos Athanasiou,
Julian R Marchesi,
Jeremy K Nicholson,
Elaine Holmes
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ABSTRACT: Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is required to enhance patient benefits and operative outcomes.
The authors applied a parallel and statistically integrated bacterial profiling and metabonomic approach to characterise Roux-en-Y gastric bypass (RYGB) effects in a non-obese rat model.
Substantial shifts of the main gut phyla towards higher concentrations of Proteobacteria (52-fold), specifically Enterobacter hormaechei, are shown. Low concentrations of Firmicutes (4.5-fold) and Bacteroidetes (twofold) in comparison with sham-operated rats were also found. Faecal extraction studies revealed a decrease in faecal bile acids and a shift from protein degradation to putrefaction through decreased faecal tyrosine with concomitant increases in faecal putrescine and diaminoethane. Decreased urinary amines and cresols were found and indices of modulated energy metabolism were demonstrated after RYGB, including decreased urinary succinate, 2-oxoglutarate, citrate and fumarate. These changes could also indicate renal tubular acidosis, which is associated with increased flux of mitochondrial tricarboxylic acid cycle intermediates. A surgically induced effect on the gut-brain-liver metabolic axis is inferred from modulated faecal γ-aminobutyric acid and glutamate.
This profound co-dependence of mammalian and microbial metabolism, which is systematically altered after RYGB surgery, suggests that RYGB exerts local and global metabolic effects. The effect of RYGB surgery on the host metabolic-microbial cross-talk augments our understanding of the metabolic phenotype of bariatric procedures and can facilitate enhanced treatments for obesity-related diseases.
Gut 05/2011; 60(9):1214-23. · 10.11 Impact Factor
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ABSTRACT: The `gut origin of sepsis' concept describes the role of the intestine in the development of sepsis and the postoperative Multi Organ Dysfunction Syndrome (MODS). Translocation of the microbiota from the gut into the systemic milieu is thought to be integral to this process. However, advances in molecular biology have demonstrated numerous mechanisms of interkingdom signalling within the gut and evidence suggests that the gut microbiota may directly influence the mammalian phenotype. The gut ecosystem fluctuates significantly in response to exogenous and surgical trauma yet until recently it has not been possible to study this non invasively and thus it is not known how current perioperative infection control strategies influence the microbiome and the consequences of this intervention for the host. However, novel analytical techniques such as metabonomics and metagenomics are permitting the in vivo analysis of the gut microbiome and are creating new avenues of research that have significant surgical applications. Furthermore, the protective mechanisms of commensal biota are increasingly being recognised, suggesting that perioperative modulation of the gut microbiome with pre, pro and synbiotics may beneficially influence surgical outcome. This paper reviews the role of the gut microbiome in determining surgical outcome, and highlights research into the mammalian microbial symbiotic axis which is leading to novel therapeutic interventions in surgery.
Current Pharmaceutical Design 04/2009; 15(13):1537-1545. · 3.87 Impact Factor
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Annals of surgery 04/2009; 249(3):546-7; author reply 547-8. · 7.90 Impact Factor
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ABSTRACT: Intestinal ischemia/reperfusion (I/R) injury initiates a systemic inflammatory response syndrome with a high associated mortality rate. Early diagnosis is essential for reducing surgical mortality, yet current clinical biomarkers are insufficient. Metabonomics is a novel strategy for studying intestinal I/R, which may be used as part of a systems approach for quantitatively analyzing the intestinal microbiome during gut injury. By deconvolving the mammalian-microbial symbiotic relationship systems biology thus has the potential for personalized risk stratification in patients exposed to intestinal I/R. This review describes the mechanism of intestinal I/R and explores the essential role of the intestinal microbiota in the initiation of systemic inflammatory response syndrome. Furthermore, it analyzes current and future approaches for elucidating the mechanism of this condition.
Biomarkers in Medicine 04/2009; 3(2):175-92. · 0.86 Impact Factor
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ABSTRACT: The 'gut origin of sepsis' concept describes the role of the intestine in the development of sepsis and the post-operative Multi Organ Dysfunction Syndrome (MODS). Translocation of the microbiota from the gut into the systemic milieu is thought to be integral to this process. However, advances in molecular biology have demonstrated numerous mechanisms of interkingdom signalling within the gut and evidence suggests that the gut microbiota may directly influence the mammalian phenotype. The gut ecosystem fluctuates significantly in response to exogenous and surgical trauma yet until recently it has not been possible to study this non invasively and thus it is not known how current perioperative infection control strategies influence the microbiome and the consequences of this intervention for the host. However, novel analytical techniques such as metabonomics and metagenomics are permitting the in vivo analysis of the gut microbiome and are creating new avenues of research that have significant surgical applications. Furthermore, the protective mechanisms of commensal biota are increasingly being recognised, suggesting that perioperative modulation of the gut microbiome with pre, pro and synbiotics may beneficially influence surgical outcome. This paper reviews the role of the gut microbiome in determining surgical outcome, and highlights research into the mammalian microbial symbiotic axis which is leading to novel therapeutic interventions in surgery.
Current pharmaceutical design 02/2009; 15(13):1537-45. · 4.41 Impact Factor
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BMJ (Clinical research ed.). 02/2008; 337:a683.
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Annals of Surgery 07/2007; 245(6):1000. · 7.49 Impact Factor
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ABSTRACT: Heparinization of the blood contact surface in cardiopulmonary bypass circuits has been promoted as an important step in the development of open heart surgery. As it decreases the inflammatory response resulting from the extracorporeal circulation, it may have a positive effect on clinical outcomes. This meta-analysis was carried out to examine if heparin-bonded circuits (HBCs) reduce the need for blood products and improve overall clinical outcome. A systematic literature search was performed to identify randomized controlled trials reporting outcomes of HBCs compared with non-HBCs. Primary outcomes assessed were postoperative blood/blood-product transfusion and blood loss. Secondary outcomes included all-cause mortality, acute postoperative myocardial infarction, stroke, re-sternotomy for postoperative bleeding, wound infection, atrial fibrillation, duration of ventilation, intensive care unit (ICU) and hospital-length of stay (LOS). Random effects meta-analytical techniques were applied to identify differences in outcomes between the two groups. Quality of the included studies and heterogeneity were assessed. From an initial review of 762-published studies, 41-randomized trials fulfilled the inclusion criteria, leaving 3434-patients' data for analysis. HBCs significantly decreased the incidence of blood transfusion required (OR=0.8; 95% CI=0.6:0.9, P=0.004). It also significantly decreased re-sternotomy (OR=0.6; 95% CI=0.4:0.8, P=0.002), duration of ventilation (WMD= -1.3h; 95% CI= -1.9:-0.6, P<0.001), ICU-LOS (WMD= -9.3h; 95% CI=-14.7:-3.9, P<0.001) and hospital-LOS (WMD= -0.5 day; 95% CI= -0.9:-0.1, P=0.02). HBCs had no effect on other adverse events evaluated. Although HBCs showed a positive effect on some of the clinical outcomes, we identified only marginal differences for other outcomes. Further evaluation of the cost-effectiveness of this technology is required.
European Journal of Cardio-Thoracic Surgery 06/2007; 31(6):1058-69. · 2.55 Impact Factor
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ABSTRACT: It is known that cardiopulmonary bypass causes an inflammatory reaction with an associated morbidity and mortality. Several anti-inflammatory strategies have been implemented to reduce this response, including leukocyte removal from the circulation using specialised filters. The aim of this study is to systematically review the available evidence on leukocyte filtration in cardiac surgery, focusing on its effect on systemic inflammation and whether this has influenced clinical outcomes. Five electronic databases were systematically searched for studies reporting the effect of leukocyte filtration at any point within the cardiopulmonary bypass circuit in humans. Reference lists of all identified studies were checked for any missing publications. Two authors independently extracted the data from the included studies. Whilst systemic leukodepleting filters do not appear to consistently lower leukocyte counts, they may preferentially remove activated leukocytes. Small improvements in early post-operative lung function in patients receiving systemic leukodepletion have been reported, but this does not lead to reduced hospital stay or decreased mortality. There is substantial evidence that cardioplegic leukocyte filtration attenuates the reperfusion injury at a cellular level, but this has not been translated into clinical improvements. Finally, whilst various strategies involving multiple leukocyte filters, or the incorporation of pharmacological agents into leukocyte-depleting protocols have been evaluated, the current available results are not conclusive. Our study suggests that there is not enough high quality or consistent evidence to draw guidelines regarding the use of leukocyte-depleting filters within routine cardiac surgical practice.
European Journal of Cardio-Thoracic Surgery 05/2007; 31(4):665-76. · 2.55 Impact Factor
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Annals of emergency medicine 01/2007; 48(6):761-2. · 4.23 Impact Factor
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ABSTRACT: This study was designed to evaluate the diagnostic accuracy of serum procalcitonin (PCT) for the diagnosis of severity in acute pancreatitis (AP), compared with routine clinical, biochemical, radiological, and combination severity scoring systems.
Quantitative meta-analysis was performed on prospective studies, comparing serum PCT, against validated scoring systems for diagnosing severe AP. The sensitivity, specificity, and diagnostic odds ratio were calculated for each study. Summary receiver operating characteristic (SROC) curves and subgroup analysis were undertaken. Study quality and heterogeneity were evaluated. Meta-regression meta-analysis was used to evaluate the effect of using serum PCT in the diagnostic accuracy severity scoring in AP.
Summary receiver operating characteristic analysis of nine studies showed an overall sensitivity and specificity of 74% (range: 66%-81%) and 83% (range: 79%-87%), respectively. Overall unweighted area under the curve (AUC) was 0.91 (DOR = 16.26 95% CI: 5.68-46.60), demonstrating significant heterogeneity (Q-value = 25.32; P = 0.001). When high-quality studies alone were evaluated, there was an increase in the overall sensitivity (89%); however, specificity was similar (82%), with an overall unweighted AUC of 0.94 (DOR 41.46, 95% CI: 17.95-95.80), with no significant heterogeneity. Meta-regression analysis confirmed the significant effect of study quality on the diagnostic accuracy of severity scoring using serum PCT (P = 0.025).
The use of PCT for severity scoring in AP has a moderate sensitivity but higher specificity. However, the overall accuracy for predicting severity in AP is high. The prognosis of severity, especially early on (<48 hours from onset of symptoms), and the evaluation of potential infectious complications of AP may be the most useful factors to assess in subsequent clinical trials to identify its exact application in clinical practice in the management of AP.
World Journal of Surgery 09/2006; 30(9):1713-21. · 2.36 Impact Factor
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ABSTRACT: Emergency laparoscopic surgery allows both the evaluation of acute abdominal pain and the treatment of many common acute abdominal disorders. This review critically evaluates the current evidence base for the use of laparoscopy, both diagnostic and interventional, in the emergency abdomen, and provides guidance for surgeons as to current best practise. Laparoscopic surgery is firmly established as the best intervention in acute appendicitis, acute cholecystitis and most gynaecological emergencies but requires further randomised controlled trials to definitively establish its role in other conditions.
World Journal of Emergency Surgery 02/2006; 1:24.
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ABSTRACT: The effect of minimally invasive great saphenous vein harvest on patient morbidity (wound infection and other healing disturbances) has been extensively investigated, yet its impact on the quality of the venous conduit is less well known. This study aims to review the literature with regard to macroscopic quality, postoperative myocardial infarction rates, and angiographic patency of the minimally invasive versus conventionally harvested vein using meta-analytic techniques where appropriate. Results suggest that conduits are comparable in macroscopic quality with minimally invasively harvested veins requiring more repairs prior to grafting. Postoperative myocardial infarction rates were not significantly different between groups, which is supported by the limited evidence on angiographic patency.
The Annals of thoracic surgery 01/2006; 80(6):2407-14. · 3.74 Impact Factor
