%0 Journal Article %~ PubMed %A Parnell, Grant P %A McLean, Anthony S %A Booth, David R %A Armstrong, Nicola J %A Nalos, Marek %A Huang, Stephen J %A Manak, Jan %A Tang, Wilson %A Tam, Oi-Yan %A Chan, Stanley %A Tang, Benjamin M %T A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia. %B Critical Care %D 2012 %C United Kingdom %I BioMed Central Ltd. %V 16 %N 4 %P R157 %@ 1466-609X %X %Z FOR Codes: 60405 110309 %0 Journal Article %~ PubMed %A Huang, Stephen J %A McLean, Anthony S %T Appreciating the strengths and weaknesses of transthoracic echocardiography in hemodynamic assessments. %B Cardiology Research and Practice %D 2012 %C United States %I Hindawi Publishing Corporation %V 2012 %N %P 894308 %@ 2090-0597 %X Transthoracic echocardiography (TTE) is becoming the choice of hemodynamic assessment tool in many intensive care units. With an ever increasing number of training programs available worldwide, learning the skills to perform TTE is no longer a limiting factor. Instead, the future emphasis will be shifted to teach the users how to recognize measurement errors and artefacts (internal validity), to realize the limitations of TTE in various applications, and finally how to apply the information to the patient in question (external validity). This paper aims to achieve these objectives in a common area of TTE application-hemodynamic assessments. We explore the strengths and weaknesses of TTE in such assessments in this paper. Various methods of hemodynamic assessments, such as cardiac output measurements, estimation of preload, and assessment of fluid responsiveness, will be discussed. %Z FOR Codes: 110201 110310 %0 Journal Article %~ PubMed %A McLean, Anthony S %A Huang, Stephen J %T Cardiac biomarkers in the intensive care unit. %B Annals of Intensive Care %D 2012 %C Germany %I SpringerOpen %V 2 %N %P 8 %@ 2110-5820 %X ABSTRACT: Cardiac biomarkers (CB) were first developed for assisting the diagnosis of cardiac events, especially acute myocardial infarction. The discoveries of other CB, the better understanding of cardiac disease process and the advancement in detection technology has pushed the applications of CB beyond the ''diagnosis'' boundary. Not only the measurements of CB are more sensitive, the applications have now covered staging of cardiac disease, timing of cardiac events and prognostication. Further, CB have made their way to the intensive care setting where their uses are not just confined to cardiac related areas. With the better understanding of the CB properties, CB can now help detecting various acute processes such as pulmonary embolism, sepsis-related myocardial depression, acute heart failure, renal failure and acute lung injury. This article discusses the properties and the uses of common CB, with special reference to the intensive care setting. The potential utility of "multimarkers" approach and microRNA as the future CB are also briefly discussed. %Z FOR Codes: 110310 110201 %0 Journal Article %~ PubMed %A McLean, Anthony S %T Down but not out: myocardial depression in sepsis. %B Critical Care %D 2012 %C United Kingdom %I BioMed Central Ltd. %V 16 %N 3 %P 132 %@ 1466-609X %X ABSTRACT: Myocardial depression in septic patients is well recognized yet still poorly understood. The prognostic significance in terms of overall mortality when it is identified, remains in dispute. Parameters of left ventricular function measured by tissue Doppler imaging may assist in resolving whether dysfunction identified early in the course of sepsis is a good prognostic sign. %Z FOR Codes: 110305 %0 Journal Article %~ PubMed %A Nalos, Marek %A Santner-Nanan, Brigitte %A Parnell, Grant %A Tang, Benjamin %A McLean, Anthony S %A Nanan, Ralph %T Immune effects of interferon gamma in persistent staphylococcal sepsis. %B American journal of respiratory and critical care medicine %D 2012 %C United States %I American Thoracic Society %V 185 %N 1 %P 110-112 %@ 1073-449X %X %Z FOR Codes: 110203 110703 %0 Journal Article %~ PubMed %A Parnell, Grant %A McLean, Anthony %A Booth, David %A Huang, Stephen %A Nalos, Marek %A Tang, Benjamin %T Aberrant cell cycle and apoptotic changes characterise severe influenza A infection--a meta-analysis of genomic signatures in circulating leukocytes. %B PloS one %D 2011 %C United States %I Public Library of Science %V 6 %N 3 %P e17186 %@ 1932-6203 %X Influenza A infection is a global disease that has been responsible for four pandemics over the last one hundred years. However, it remains poorly understood as to why some infected individuals succumb to life threatening complications whilst others recover and are relatively unaffected. Using gene-expression analysis of circulating leukocytes, here we show that the progression towards severe influenza A infection is characterised by an abnormal transcriptional reprogramming of cell cycle and apoptosis pathways. In severely infected humans, leukocyte gene-expression profiles display opposing cell cycle activities; an increased aberrant DNA replication in the G(1)/S phase yet delayed progression in the G(2)/M phase. In mild infection, cell cycle perturbations are fewer and are integrated with an efficient apoptotic program. Importantly, the loss of integration between cell cycle perturbations and apoptosis marks the transition from a mild viral illness to a severe, life threatening infection. Our findings suggest that circulating immune cells may play a significant role in the evolution of the host response. Further study may reveal alternative host response factors previously unrecognized in the current disease model of influenza. %Z FOR Codes: 30405 %0 Journal Article %~ PubMed %A McLean, A S %A Kot, M B %T Cardiac collapse associated with the ingestion of khat. %B Internal Medicine Journal %D 2011 %C Australia, United Kingdom, Netherlands, United States %I Wiley-Blackwell Publishing Asia %V 41 %N 7 %P 579-581 %@ 1445-5994 %X %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Follath, F %A Yilmaz, M B %A Delgado, J F %A Parissis, J T %A Porcher, R %A Gayat, E %A Burrows, Nigel %A McLean, A %A Vilas-Boas, F %A Mebazaa, A %T Clinical presentation, management and outcomes in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). %B Intensive Care Medicine %D 2011 %C Germany %I Springer %V 37 %N 4 %P 619-626 %@ 1432-1238 %X We performed a survey on acute heart failure (AHF) in nine countries in four continents. We aimed to describe characteristics and management of AHF among various countries, to compare patients with de novo AHF versus patients with a pre-existing episode of AHF, and to describe subpopulations hospitalized in intensive care unit (ICU) versus cardiac care unit (CCU) versus ward. %Z FOR Codes: 110201 110310 %0 Journal Article %~ PubMed %A McLean, A S %A Huang, S J %A Kot, M %A Rajamani, A %A Hoyling, L %T Comparison of cardiac output measurements in critically ill patients: FloTrac/Vigileo vs transthoracic Doppler echocardiography. %B Anaesthesia and Intensive Care %D 2011 %C Australia, New Zealand %I Australian Society of Anaesthetists Ltd. %V 39 %N 4 %P 590-598 %@ 0310-057X %X Measurement of cardiac output is an integral part of patient management in the intensive care unit. FloTrac/Vigileo is a continuous cardiac output monitoring device that does not need re-calibration. However its reliability has been questioned in some studies, especially involving surgical patients. In this study, we evaluated the comparability of FloTrac/Vigileo and transthoracic Doppler echocardiography in 53 critically ill patients requiring continuous cardiac output monitoring. Most of these patients had septic or cardiogenic shock. Cardiac output was measured by both FloTrac/Vigileo and transthoracic Doppler echocardiography. The bias and precision (mean and SD) between the two devices was 0.35 +/- 1.35 l/minute. The limits of agreement were -2.3 to 3.0 l/minute (%error = 49.3%). When patients with irregular heart rhythms and aortic stenosis were excluded, the bias and precision was 0.02 +/- 0.80 l/minute (n = 42). The limits of agreement were -1.55 to 1.59 l/minute (%error = 29.5%). Patient demographics (body surface area, gender and age) did not affect the bias, but there was a mild tendency for FloTrac/ Vigileo to register a higher cardiac output at high heart rates. Changes in cardiac output for two consecutive days correlated well between the two methods (r = 0.86; P < 0.001). In summary, with the exceptions of patients with irregular heart rhythms and significant aortic stenosis, FloTrac/Vigileo is clinically comparable to transthoracic Doppler echocardiography in cardiac output measurements in critically ill patients. %Z FOR Codes: 110299 60699 110310 %0 Journal Article %~ PubMed %A Sutherland, Allison %A Thomas, Mervyn %A Brandon, Roslyn A %A Brandon, Richard B %A Lipman, Jeffrey %A Tang, Benjamin %A McLean, Anthony %A Pascoe, Ranald %A Price, Gareth %A Nguyen, Thu %A Stone, Glenn %A Venter, Deon %T Development and validation of a novel molecular biomarker diagnostic test for the early detection of sepsis. %B Critical Care %D 2011 %C United Kingdom %I BioMed Central Ltd. %V 15 %N 3 %P R149 %@ 1466-609X %X Sepsis is a complex immunological response to infection characterized by early hyper-inflammation followed by severe and protracted immunosuppression, suggesting that a multi-marker approach has the greatest clinical utility for early detection, within a clinical environment focused on Systemic Inflammatory Response Syndrome (SIRS) differentiation. Pre-clinical research using an equine sepsis model identified a panel of gene expression biomarkers that define the early aberrant immune activation. Thus, the primary objective was to apply these gene expression biomarkers to distinguish patients with sepsis from those who had undergone major open surgery and had clinical outcomes consistent with systemic inflammation due to physical trauma and wound healing. %Z FOR Codes: 110202 60502 %0 Journal Article %~ PubMed %A McLean, Anthony S %T International recommendations on competency in critical care ultrasound: pertinence to Australia and New Zealand. %B Critical Care and Resuscitation %D 2011 %C Australia %I Australasian Academy of Critical Care Medicine %V 13 %N 1 %P 56-58 %@ 1441-2772 %X The use of echocardiography and other applications of ultrasound in the management of critically ill patients is becoming mainstream. With increased accessibility to equipment, the main challenges are in providing training and drawing up an outline of what levels of competency should be achieved. An international body of experienced critical care physician sonographers has reached consensus on guidelines in training and on two levels of competency - basic and advanced. Formal structures to aid the physician have been developed in Australia and New Zealand. %Z FOR Codes: 110320 110310 %0 Journal Article %~ PubMed %A McLean, Anthony S %T Mind over matter! %B Critical Care Medicine %D 2011 %C United States %I Lippincott Williams & Wilkins %V 39 %N 6 %P 1593-1594 %@ 0090-3493 %X %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A Chew, M S %A Hawthorne, W J %A Bendall, J %A Whereat, S %A Huang, S %A Ting, I %A Simond, D %A McLean, A %T No beneficial effects of levosimendan in acute porcine endotoxaemia. %B Acta anaesthesiologica Scandinavica %D 2011 %C Denmark %I Wiley-Blackwell Publishing, Inc. %V 55 %N 7 %P 851-61 %@ 1399-6576 %X Levosimendan has been proposed as an attractive alternative to adrenergic agents for the treatment of sepsis-induced heart failure and haemodynamic derangements. Its use in this setting is, however, still not well investigated. The aim of this study was to test the hypothesis that levosimendan is able to attenuate endotoxin-induced pulmonary hypertension and improve myocardial function in a porcine model. The secondary aims were to investigate its effect on renal and liver function, and the plasma cytokine response. %Z FOR Codes: 110305 111699 %0 Journal Article %~ PubMed %A Whereat, Sarah E %A McLean, Anhony S %T Survey of the current status of intensive care teaching in Australia and New Zealand medical schools. %B Critical care medicine %D 2011 %C United States %I Lippincott Williams & Wilkins %V 40 %N 2 %P 430-4 %@ 0090-3493 %X The place of Intensive Care Medicine education within Medical Schools in Australia and New Zealand was investigated by survey in 2009. %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A Parissis, John T %A Nikolaou, Maria %A Mebazaa, Alexandre %A Ikonomidis, Ignatios %A Delgado, Juan %A Vilas-Boas, Fabio %A Paraskevaidis, Ioannis %A Mc Lean, Antony %A Kremastinos, Dimitrios %A Follath, Ferenc %T Acute pulmonary oedema: clinical characteristics, prognostic factors, and in-hospital management. %B European Journal of Heart Failure %D 2010 %C Netherlands %I Oxford University Press %V 12 %N 11 %P 1193-1202 %@ 1879-0844 %X Acute pulmonary oedema (APE) is the second, after acutely decompensated chronic heart failure (ADHF), most frequent form of acute heart failure (AHF). This subanalysis examines the clinical profile, prognostic factors, and management of APE patients (n = 1820, 36.7%) included in the Acute Heart Failure Global Survey of Standard Treatment (ALARM-HF). %Z FOR Codes: 110201 %0 Journal Article %~ PubMed %A Huang, Stephen J %A McLean, Anthony S %T Do we need a critical care ultrasound certification program? Implications from an Australian medical-legal perspective. %B Critical Care %D 2010 %C United Kingdom, Unit %I BioMed Central Ltd. %V 14 %N 3 %P 313 %@ 1466-609X %X Medical practitioners have a duty to maintain a certain standard of care in providing their services. With critical care ultrasound gaining popularity in the ICU, it is envisaged that more intensivists will use the tool in managing their patients. Ultrasound, especially echocardiography, can be an ''easy to learn, difficult to manage'' skill, and the competency in performing the procedure varies greatly. In view of this, several recommendations for competency statements have been published in recent years to advocate the need for a unified approach to training and certification. In this paper, we take a slightly different perspective, from an Australian medical-legal viewpoint, to argue for the need to implement a critical care ultrasound certification program. We examine various issues that can potentially lead to a breach of the standard of care, hence exposing the practitioners and/or the healthcare institutions to lawsuits in professional negligence or breach of contract. These issues, among others, include the failure to use ultrasound in appropriate situations, the failure of hospitals to ensure practitioners are properly trained in the skills, the failure of practitioners to perform an ultrasound study that is of a reasonable standard, and the failure of practitioners to keep themselves abreast of the latest developments in treatment and management. The implications of these issues and the importance of having a certification process are discussed. %Z FOR Codes: 220106 %0 Journal Article %~ PubMed %A Tang, Benjamin M %A Huang, Stephen J %A McLean, Anthony S %T Genome-wide transcription profiling of human sepsis: a systematic review. %B Critical care (London, England) %D 2010 %C United Kingdom %I BioMed Central Ltd. %V 14 %N 6 %P R237 %@ 1466-609X %X Sepsis is thought to be an abnormal inflammatory response to infection. However, most clinical trials of drugs that modulate the inflammatory response of sepsis have been unsuccessful. Emerging genomic evidence shows that the host response in sepsis does not conform to a simple hyper-inflammatory/hypo-inflammatory model. We, therefore, synthesized current genomic studies that examined the host response of circulating leukocytes to human sepsis. %Z FOR Codes: 30405 60406 110706 %0 Journal Article %~ PubMed %A Eslick, Guy D %A Thampan, Binu V %A Nalos, Marek %A McLean, Anthony S %A Sluyter, Ronald %T Circulating interleukin-18 concentrations and a loss-of-function P2X7 polymorphism in heart failure. %B International journal of cardiology %D 2009 %C Ireland %I Elsevier Ireland Ltd %V 137 %N 0 %P 81-3 %@ 0167-5273 %X We examined if a loss-of-function polymorphism in the P2X(7) receptor (1513C) corresponded with circulating interleukin(IL)-18 concentrations in heart failure (HF) patients. IL-18 values were significantly elevated in HF subjects compared to healthy control subjects. No association was seen between the polymorphism and IL-18 concentrations in HF patients. In HF patients, IL-18 values had an inverse relationship with ejection fraction, mean arterial pressure and body mass index, while high IL-18 concentrations were associated with increased mortality. %Z FOR Codes: 110704 110101 %0 Journal Article %~ PubMed %A Tang, Benjamin M P %A McLean, Anthony S %A Dawes, Ian W %A Huang, Stephen J %A Lin, Ruby C Y %T Gene-expression profiling of peripheral blood mononuclear cells in sepsis. %B Critical Care Medicine %D 2009 %C United States %I Lippincott Williams & Wilkins %V 37 %N 3 %P 882-888 %@ 0090-3493 %X OBJECTIVES: It has been shown that gene-expression profiling of circulating neutrophils could identify signature genes of sepsis. However, whether similar transcriptional changes occurred in peripheral blood mononuclear cells (PBMC) was not known. Using microarray technology, we performed gene-expression profiling of PBMC to identify signature genes that distinguish sepsis from noninfectious causes of systemic inflammatory response syndrome (SIRS), between Gram-positive and Gram-negative sepsis. DESIGN: A cross-sectional, observational study. SETTING: A 20-bed general intensive care unit of a tertiary referral hospital. PATIENTS: Seventy critically ill patients (46 sepsis and 24 SIRS). INTERVENTIONS: Intravenous blood was collected for leukocyte separation and RNA extraction. Gene-expression profiling was performed on PBMC using Affymetrix GeneChip microarrays with 54,675 transcripts. Data were divided into a training set (n = 35) and a validation set (n = 35). A molecular signature was developed in the training set using support vector machine and was then validated in the validation set. MEASUREMENTS AND MAIN RESULTS: We identified a molecular signature of 138 genes that could differentiate between sepsis and SIRS patients with 91% and 80% accuracy in the training and validation sets, respectively. There were no signature genes that could differentiate between Gram-positive and Gram-negative sepsis. The expression of genes involved in inflammatory response and immune function was significantly reduced in septic patients when compared with those with SIRS. Genes involved in apoptosis, on the other hand, were more highly expressed in septic patients. CONCLUSION: There was evidence of sepsis-related immunosuppression and reduced inflammatory response in mononuclear cells on a transcriptome level. These characteristic transcriptional changes can be used to aid the diagnosis of sepsis. %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A McLean, Anthony %T Procalcitonin: seeking a niche. %B Critical Care %D 2009 %C United Kingdom %I BioMed Central Ltd. %V 13 %N 3 %P 149 %@ 1466-609X %X For over a decade there has been intense interest given to the role of procalcitonin in the diagnosis and management of sepsis in critically ill patients. Early opinions strongly supported the diagnostic role but data accumulating from numerous subsequent studies are less supportive, even when used in very selective settings. Although there remains sufficient reason to support the use of procalcitonin in guiding antibiotic therapy or perhaps providing prognostic information, it may be time to focus our efforts on the early diagnosis of sepsis in the critically care setting on alternative, more promising methods. %Z FOR Codes: 111709 %0 Journal Article %~ PubMed %A Tang, Benjamin M P %A Craig, Jonathan C %A Eslick, Guy D %A Seppelt, Ian %A McLean, Anthony S %T Use of corticosteroids in acute lung injury and acute respiratory distress syndrome: a systematic review and meta-analysis. %B Critical Care Medicine %D 2009 %C 530 Walnut St, Philadelphia, Pa, 19106-3621 %I Lippincott Williams & Wilkins %V 37 %N 5 %P 1594-1603 %@ 0090-3493 %X OBJECTIVE: Controversy remains as to whether low-dose corticosteroids can reduce the mortality and morbidity of acute lung injury (ALI) or the acute respiratory distress syndrome (ARDS) without increasing the risk of adverse reactions. We aimed to evaluate all studies investigating prolonged corticosteroids in low-to-moderate dose in ALI or ARDS. DATA SOURCES: MEDLINE, EMBASE, Current Content, and Cochrane Central Register of Controlled Trials, and bibliographies of retrieved articles. STUDY SELECTION: Randomized controlled trials (RCTs) and observational studies reported in any language that used 0.5-2.5 mg.kg.d of methylprednisolone or equivalent to treat ALI/ARDS. DATA EXTRACTION: Data were extracted independently by two reviewers and included study design, patient characteristics, interventions, and mortality and morbidity outcomes. DATA SYNTHESIS: Both cohort studies (five studies, n = 307) and RCTs (four trials, n = 341) showed a similar trend toward mortality reduction (RCTs relative risk 0.51, 95% CI 0.24-1.09; p = 0.08; cohort studies relative risk 0.66, 95% CI 0.43-1.02; p = 0.06). The overall relative risk was 0.62 (95% CI 0.43-0.91; p = 0.01). There was also improvement in length of ventilation-free days, length of intensive care unit stay, Multiple Organ Dysfunction Syndrome Score, Lung Injury Scores, and improvement in Pao2/Fio2. There was no increase in infection, neuromyopathy, or any major complications. There was significant heterogeneity in the pooled studies. Subgroup and meta-regression analyses showed that heterogeneity had minimal effect on treatment efficacy; however, these findings were limited by the small number of studies used in the analyses. CONCLUSION: The use of low-dose corticosteroids was associated with improved mortality and morbidity outcomes without increased adverse reactions. The consistency of results in both study designs and all outcomes suggests that they are an effective treatment for ALI or ARDS. The mortality benefits in early ARDS should be confirmed by an adequately powered randomized trial. %Z FOR Codes: 110310 110399 %0 Journal Article %~ PubMed %A Kloth, N %A Weisbrodt, L %A McLean, A %A Nalos, M %T [Impact of pandemic H1N1 2009 influenza virus on critical care in Australia: a single centre case series] %B Vnitrni Lekarstvi %D 2009 %C Czech Republic %I Medica Healthworld a.s. %V 55 %N 12 %P 1141-1144 %@ 0042-773X %X INTRODUCTION: In late May 2009, an outbreak of the novel swine - influenza A virus (H1N1) was identified in the Southern hemisphere. We describe the clinical and epidemiologic characteristics ofpatients infected with H1N1 requiring intensive care (ICU) admission at a Sydney University Hospital. METHODS: We retrospectively reviewed medical charts and laboratory results ofall patients who tested positively for H1N1 by viral polymerase chain reaction (PCR) on nasopharyngeal smear or endobronchial secretions. RESULTS: From June 1st until August 31st, 2009 a total of 17 patients required admission to the Intensive Care Unit at Nepean Hospital, a tertiary teaching hospital. There were 9 males and 8 females with a mean age of 42 years. The majority of patients were admitted to the ICU within 48 hours of hospital presentation. All patients had flu like symptoms and most presented with respiratory distress and tachycardia. More than half of patients had patchy alveolar infiltrates on chest X ray. Patients who developed acute lung injury and acute respiratory distress syndrome (ALI/ARDS) typically presented with normal leukocyte count, lymphopenia, raised C-reactive protein, creatinkinase, transaminases but normal urea and creatinine. Fourteen patients required intubation while two received non-invasive ventilation. Several patients tested negative for H1N1 on nasopharyngeal smear PCR but tested positive on endobronchial secretions and the rapid flu antigen test proved unreliable. Two patients died during hospital admission but neither from respiratory failure or its consequences. The median duration of intensive care stay was 12 days while hospital stay was 18 days. DISCUSSION: The Nepean Hospital''s patient profile and outcomes are similar to the data for all H1N1 associated ICU admission in Australia and New Zealand. H1N1 is capable of causing severe respiratory infection especially in the young to middle aged and the impact on intensive care units is disproportionate to seasonal flu. To reliably test for H1N1 in intubated patients we recommend performing viral PCR on endobronchial secretions. %Z FOR Codes: 110309 111706 %0 Journal Article %~ PubMed %A Nalos, Marek %A Huang, Stephen %A Sluyter, Ronald %A Khan, Alamgir %A Santner-Nanan, Brigitte %A Nanan, Ralph %A McLean, Anthony %T "Host tissue damage" signal ATP impairs IL-12 and IFNgamma secretion in LPS stimulated whole human blood. %B Intensive care medicine %D 2008 %C Germany %I Springer %V 34 %N 10 %P 1891-7 %@ 0342-4642 %X Critical illness is associated with tissue damage, inflammation and the development of immune dysfunction. Leukocyte reprogramming occurs leading to insufficient production of pro-inflammatory cytokines upon subsequent stimulation. Cellular nucleotides released during tissue damage act via purinergic receptors to modulate immune function. We hypothesized that extracellular nucleotides in concentrations similar to those found near injured and ischemic tissues will modulate cytokine secretion. %Z FOR Codes: 110310 110309 %0 Journal Article %~ PubMed %A McLean, Anthony %A Huang, Stephen %A Salter, Mark %T Bench-to-bedside review: The value of cardiac biomarkers in the intensive care patient. %B Critical care (London, England) %D 2008 %C United Kingdom %I BioMed Central Ltd. %V 12 %N 3 %P 215 %@ 1466-609X %X The use of cardiac biomarkers in the intensive care setting is gaining increasing popularity. There are several reasons for this increase: there is now the facility for point-of-care biomarker measurement providing a rapid diagnosis; biomarkers can be used as prognostic tools; biomarkers can be used to guide therapy; and, compared with other methods such as echocardiography, the assays are easier and much more affordable. Two important characteristics of the ideal biomarker are disease specificity and a linear relationship between the serum concentration and disease severity. These characteristics are not present, however, in the majority of biomarkers for cardiac dysfunction currently available. Those clinically useful cardiac biomarkers, which naturally received the most attention, such as troponins and B-type natriuretic peptide, are not as specific as was originally thought. In the intensive care setting, it is important for the user to understand the degree of specificity of these biomarkers and that the interpretation of the results should always be guided by other clinical information. The present review summarizes the available biomarkers for different cardiac conditions. Potential biomarkers under evaluation are also briefly discussed. %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A Tang, Benjamin M P %A McLean, Anthony S %A Dawes, Ian W %A Huang, Stephen J %A Cowley, Mark J %A Lin, Ruby C Y %T Gene-expression profiling of gram-positive and gram-negative sepsis in critically ill patients. %B Critical care medicine %D 2008 %C United States %I Lippincott Williams & Wilkins %V 36 %N 4 %P 1125-1128 %@ 0090-3493 %X OBJECTIVE: It is unclear whether the host response of gram-positive sepsis differs from gram-negative sepsis at a transcriptome level. Using microarray technology, we compared the gene-expression profiles of gram-positive sepsis and gram-negative sepsis in critically ill patients. DESIGN: A prospective cross-sectional study. SETTING: A 20-bed general intensive care unit of a tertiary referral hospital. PATIENTS: Seventy-two patients admitted to the intensive care unit. INTERVENTIONS: Intravenous blood was collected for leukocyte separation and RNA extraction. Microarray experiments were then performed examining the expression level of 18,664 genes in each sample. MEASUREMENTS AND MAIN RESULTS: There was no difference in the expression profile between gram-positive and gram-negative sepsis. The finding remained unchanged even when genes with lower expression level were included or after statistical stringency was lowered. There were, however, 94 genes differentially expressed between sepsis and control patients. These genes included those involved in immune regulation, inflammation, and mitochondrial function. Hierarchical cluster analysis confirmed that the difference in gene expression profile existed between sepsis and control patients but not between gram-positive and gram-negative patients. CONCLUSIONS: Gram-positive sepsis and gram-negative sepsis share a common host response at a transcriptome level. These findings support the hypothesis that the septic response is nonspecific and is designed to provide a more general response that can be elicited by a wide range of different microorganisms. %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A Tang, Benjamin M P %A Eslick, Guy D %A Craig, Jonathan C %A McLean, Anthony S %T Accuracy of procalcitonin for sepsis diagnosis in critically ill patients: systematic review and meta-analysis. %B The Lancet infectious diseases %D 2007 %C United Kingdom %I The Lancet Publishing Group %V 7 %N 3 %P 210-217 %@ 1473-3099 %X Procalcitonin is widely reported as a useful biochemical marker to differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome. In this systematic review, we estimated the diagnostic accuracy of procalcitonin in sepsis diagnosis in critically ill patients. 18 studies were included in the review. Overall, the diagnostic performance of procalcitonin was low, with mean values of both sensitivity and specificity being 71% (95% CI 67-76) and an area under the summary receiver operator characteristic curve of 0.78 (95% CI 0.73-0.83). Studies were grouped into phase 2 studies (n=14) and phase 3 studies (n=4) by use of Sackett and Haynes'' classification. Phase 2 studies had a low pooled diagnostic odds ratio of 7.79 (95% CI 5.86-10.35). Phase 3 studies showed significant heterogeneity because of variability in sample size (meta-regression coefficient -0.592, p=0.017), with diagnostic performance upwardly biased in smaller studies, but moving towards a null effect in larger studies. Procalcitonin cannot reliably differentiate sepsis from other non-infectious causes of systemic inflammatory response syndrome in critically ill adult patients. The findings from this study do not lend support to the widespread use of the procalcitonin test in critical care settings. %Z FOR Codes: %0 Journal Article %~ PubMed %A McLean, Anthony %A Yastrebov, Konstantin %T Echocardiography training for the intensivist. %B Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine %D 2007 %C Australia %I Australasian Academy of Critical Care Medicine %V 9 %N 4 %P 319-322 %@ 1441-2772 %X The value of echocardiography in the critically ill patient is well established, yet applying the modality to patients who could benefit presents considerable logistical challenges. Central is a lack of readily available, trained operators. Although many intensive care specialists and trainees are keen to fill this gap, there are numerous hurdles to obtaining the necessary training. To address this problem, the Australian and New Zealand Intensive Care Society has set up a Committee on Echocardiography Training and Certification for Intensivists. The Committee proposes a formal training and assessment program. This would not only provide guidance to intensivists wishing to learn echocardiography, but also clearly set out acceptable levels of expertise. It is important that, after training, intensivists can be readily credentialed in their home institutions. The intensive care community needs to determine the vehicle for training and credentialling in echocardiography. This could be achieved solely by bodies representing intensive care or in collaboration with the Australasian Society for Ultrasound in Medicine. %Z FOR Codes: %0 Journal Article %~ PubMed %A Tang, Benjamin Mp %A Eslick, Guy D %A Craig, Jonathan C %A McLean, Anthony S %T Meta-analysis of procalcitonin for sepsis detection - Authors' reply. %B The Lancet infectious diseases %D 2007 %C United Kingdom %I The Lancet Publishing Group %V 7 %N 8 %P 502-503 %@ 1473-3099 %X %Z FOR Codes: %0 Journal Article %~ PubMed %A Tang, Benjamin %A Huang, Stephen %A Seppelt, Ian %A McLean, Anthony %T Predictive value of N-terminal pro-brain natriuretic peptide in sepsis. %B Critical care medicine %D 2007 %C US %I Lippincott Williams & Wilkins %V 35 %N 10 %P 2464 %@ 0090-3493 %X %Z FOR Codes: 110310 %0 Journal Article %~ PubMed %A McLean, Anthony S %A Huang, Stephen J %A Hyams, Stephanie %A Poh, Genie %A Nalos, Marek %A Pandit, Rahul %A Balik, Martin %A Tang, Ben %A Seppelt, Ian %T Prognostic values of B-type natriuretic peptide in severe sepsis and septic shock. %B Critical care medicine %D 2007 %C US %I Lippincott Williams & Wilkins %V 35 %N 4 %P 1019-10126 %@ 0090-3493 %X OBJECTIVE: To investigate the changes in B-type natriuretic peptide concentrations in patients with severe sepsis and septic shock and to investigate the value of B-type natriuretic peptide in predicting intensive care unit outcomes. DESIGN: Prospective observational study. SETTING: General intensive care unit. PATIENTS: Forty patients with severe sepsis or septic shock. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: B-type natriuretic peptide measurements and echocardiography were carried out daily for 10 consecutive days. In-hospital mortality and length of stay were recorded. The admission B-type natriuretic peptide concentrations were generally increased (747 +/- 860 pg/mL). B-type natriuretic peptide levels were elevated in patients with normal left ventricular systolic function (568 +/- 811 pg/mL), with sepsis-related reversible cardiac dysfunction (630 +/- 726 pg/mL), and with chronic cardiac dysfunction (1311 +/- 1097 pg/mL). There were no significance changes in B-type natriuretic peptide levels over the 10-day period. The daily B-type natriuretic peptide concentrations for the first 3 days neither predicted in-hospital mortality nor correlated with length of intensive care unit or hospital stay. CONCLUSION: B-type natriuretic peptide concentrations were increased in patients with severe sepsis or septic shock regardless of the presence or absence of cardiac dysfunction. Neither the B-type natriuretic peptide levels for the first 3 days nor the daily changes in B-type natriuretic peptide provided prognostic value for in-hospital mortality and length of stay in this mixed group of patients, which included patients with chronic cardiac dysfunction. %Z FOR Codes: %0 Journal Article %~ PubMed %A Tang, Benjamin Mp %A McLean, Anthony S %A Dawes, Ian W %A Huang, Stephen J %A Lin, Ruby Cy %T The Use of Gene-Expression Profiling to Identify Candidate Genes in Human Sepsis. %B American journal of respiratory and critical care medicine %D 2007 %C United States %I American Thoracic Society %V 176 %N 7 %P 676-84 %@ 1535-4970 %X Our understanding of the pathophysiology of sepsis remains incomplete. Genomewide study offers an unbiased, system biology approach to examine the expression patterns of circulating leukocytes and may reveal novel insights into the host response to sepsis. %Z FOR Codes: %0 Journal Article %~ PubMed %A Naylor, Justine M %A McLean, Anthony %A Chow, Chin-Moi %A Heard, Robert %A Ting, Iris %A Avolio, Albert %T A modified postural drainage position produces less cardiovascular stress than a head-down position in patients with severe heart disease: A quasi-experimental study. %B The Australian journal of physiotherapy %D 2006 %C Australia %I Australian Physiotherapy Association %V 52 %N 3 %P 201-9 %@ 0004-9514 %X Question: Does a modified postural drainage position (horizontal) produce less cardiovascular and respiratory stress than a head-down postural drainage position (30 degrees) in people with severe heart disease? Design: A quasi-experimental study. Participants: Thirty-one patients (mean age 69 years, SD 13) with severe left ventricular systolic dysfunction (mean ejection fraction 23%, SD 7) who were stable, receiving regular medication and free of acute respiratory illness. Intervention: Two manoeuvres were performed - one from long sitting to a modified (horizontal) postural drainage position, and one from long sitting to a head-down (30 degrees) postural drainage position. Outcome measures: Cardiovascular responses examined were blood pressure, sphygmocardiographic indices, and cardiac rhythm. Respiratory responses examined were respiratory rate, transcutaneous arterial oxyyhaemoglobin saturation, and dyspnoea. Results: Three participants were intolerant to the postural drainage positions - two during head-down and one during modified positioning. The remaining 28 participants maintained their resting cardiac rhythm and did not complain of chest pain or dyspnoea. The changes in cardiovascular responses during the sitting to head-down postural drainage manoeuvre in the tolerant participants were significantly greater (p < 0.05) than the changes during the sitting to the modified postural drainage manoeuvre for most of the sphygmocardiographic indices. In contrast, there were no significant respiratory responses to either postural drainage manoeuvre. Conclusion: Modified positioning is associated with less cardiovascular stress than head-down positioning, yet for most patients with severe heart disease, both positions are generally well tolerated. For a subset of these patients, either position may be inappropriate. This suggests that modified positioning should be attempted first but that a head-down position may be attempted if the modified position proves ineffective. %Z FOR Codes: %0 Journal Article %~ PubMed %A Nalos, M %A Huang, S J %A Pandit, R %A McLean, A S %T Endotoxin stimulated interleukin-10 production is enhanced by adenosine. Possible key to septic shock associated immune deficiency? %B Anaesthesia and intensive care %D 2006 %C Australia %I Australian Society of Anaesthetists %V 34 %N 6 %P 719-23 %@ 0310-057X %X The aim of this bench study was to investigate whether adenosine influences secretion of interleukin-10 (IL-O) in human whole blood culture stimulated with lipopolysaccharide. Whole blood from healthy human volunteers was mixed ex vivo in 1:1 ratio with RPMI 1640 culture medium and subsequently cultured at 37 degrees C with or without adenosine (total of 120 microM added in four aliquots over two hours) in the presence or absence of 100 ng/ml lipopolysaccharide for four and eight hours, respectively. There was only a minimal IL-10 production after four hours of culture regardless of the experimental conditions. However, lipopolysaccharide stimulated whole blood cultures with added adenosine released large amounts of IL-lO after eight hours. The response was similar whether adenosine was added before (5.99 pg/ml/10(6) leucocytes) or after (10.35 microg/ml/10(6) leucocytes) stimulation with lipopolysaccharide and interindividual variation was present. In conclusion adenosine enhances lipopolysaccharide stimulated IL-10 production in whole human blood and may contribute to the IL-10 mediated immune dysfunction in sepsis. %Z FOR Codes: %0 Journal Article %~ PubMed %A McLean, Anthony S %A Eslick, Guy D %A Coats, Andrew J S %T The epidemiology of heart failure in Australia. %B International journal of cardiology %D 2006 %C Ireland %I Elsevier Ireland Ltd %V 118 %N %P 370-4 %@ 0167-5273 %X The epidemiology of heart failure is poorly understood. Australia has one of the highest rates of cardiovascular disease in the world with heart failure representing a large proportion of this group, yet there is minimal data on the incidence or prevalence. %Z FOR Codes: %0 Journal Article %~ PubMed %A McLean, Anthony S %A Ting, Iris %A Huang, Stephen J %A Wesley, Sarah %T The use of the right ventricular diameter and tricuspid annular tissue Doppler velocity parameter to predict the presence of pulmonary hypertension. %B European journal of echocardiography : the journal of the Working Group on Echocardiography of the European Society of Cardiology %D 2006 %C UK %I WB Saunders Co. Ltd. %V 8 %N 0 %P 128-36 %@ 1525-2167 %X Detecting the presence of pulmonary hypertension (PH) is important especially with unexplained dyspnoea and suspected thromboembolism. Although PH can be detected invasively by right ventricular (RV) catheterisation, accurate non-invasive assessment by echocardiography has many advantages. This however relies on the presence of tricuspid regurgitation (TR). We examined if the presence of PH can be predicted echocardiographically without relying on TR. %Z FOR Codes: 110201 110201 111699