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1.  Brain not processing: is finding a role for BNP in sepsis like fitting a square peg into a round hole? 
Critical Care  2014;18(4):161.
Since its introduction to the intensive care setting a decade ago, B-type natriuretic peptide has been the focus of studies in different areas (in particular, sepsis). With this biomarker, as with many newly identified biomarkers, its diagnostic performance was pursued initially and then its ability to predict outcomes. Despite all the efforts, results have not been consistent and the applications of B-type natriuretic peptide in the intensive care setting remain by and large academic. Will such studies one day become clinical practice? Or are we too obsessed with finding a place for every biomarker?
PMCID: PMC4095610  PMID: 25042534
2.  Appreciating the Strengths and Weaknesses of Transthoracic Echocardiography in Hemodynamic Assessments 
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.
PMCID: PMC3290825  PMID: 22454777
3.  Is early ventricular dysfunction or dilatation associated with lower mortality rate in adult severe sepsis and septic shock? A meta-analysis 
Critical Care  2013;17(3):R96.
Reversible myocardial depression occurs early in severe sepsis and septic shock. The question of whether or not early ventricular depression or dilatation is associated with lower mortality in these patients remains controversial. Most studies on this topic were small in size and hence lacked statistical power to answer the question. This meta-analysis attempted to answer the question by increasing the sample size via pooling relevant studies together.
PubMed, Embase (and Medline) databases and conference abstracts were searched to July 2012 for primary studies using well-defined criteria. Two authors independently screened and selected studies. Eligible studies were appraised using defined criteria. Additional information was sought the corresponding authors if necessary. Study results were pooled using random effects models. Standardized mean differences (SMD) between survivor and non-survivor groups were used as the main effect measures.
A total of 62 citations were found. Fourteen studies were included in the analysis. The most apparent differences between the studies were sample sizes and exclusion criteria. All studies, except four pre-1992 studies, adopted the Consensus definition of sepsis. Altogether, there were >700 patients available for analysis of the left ventricle and >400 for the right ventricle. There were no significant differences in left ventricular ejection fractions, right ventricular ejection fractions, and right ventricular dimensions between the survivor and non-survivor groups. When indexed against body surface area or body height, the survivors and non-survivors had similar left ventricular dimensions. However, the survivors had larger non-indexed left ventricular dimensions.
This meta-analysis failed to find any evidence to support the view that the survivors from severe sepsis or septic shock had lower ejection fractions. However, non-indexed left ventricular dimensions were mildly increased in the survivor group but the indexed dimensions were similar between the groups. Both survivors and non-survivors had similar right ventricular dimensions.
PMCID: PMC4056117  PMID: 23706109
4.  A distinct influenza infection signature in the blood transcriptome of patients with severe community-acquired pneumonia 
Critical Care  2012;16(4):R157.
Diagnosis of severe influenza pneumonia remains challenging because of a lack of correlation between the presence of influenza virus and clinical status. We conducted gene-expression profiling in the whole blood of critically ill patients to identify a gene signature that would allow clinicians to distinguish influenza infection from other causes of severe respiratory failure, such as bacterial pneumonia, and noninfective systemic inflammatory response syndrome.
Whole-blood samples were collected from critically ill individuals and assayed on Illumina HT-12 gene-expression beadarrays. Differentially expressed genes were determined by linear mixed-model analysis and overrepresented biological pathways determined by using GeneGo MetaCore.
The gene-expression profile of H1N1 influenza A pneumonia was distinctly different from those of bacterial pneumonia and systemic inflammatory response syndrome. The influenza gene-expression profile is characterized by upregulation of genes from cell-cycle regulation, apoptosis, and DNA-damage-response pathways. In contrast, no distinctive gene-expression signature was found in patients with bacterial pneumonia or systemic inflammatory response syndrome. The gene-expression profile of influenza infection persisted through 5 days of follow-up. Furthermore, in patients with primary H1N1 influenza A infection in whom bacterial co-infection subsequently developed, the influenza gene-expression signature remained unaltered, despite the presence of a superimposed bacterial infection.
The whole-blood expression-profiling data indicate that the host response to influenza pneumonia is distinctly different from that caused by bacterial pathogens. This information may speed the identification of the cause of infection in patients presenting with severe respiratory failure, allowing appropriate patient care to be undertaken more rapidly.
PMCID: PMC3580747  PMID: 22898401
5.  Cardiac biomarkers in the intensive care unit 
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.
PMCID: PMC3313856  PMID: 22397488
6.  Do we need a critical care ultrasound certification program? Implications from an Australian medical-legal perspective 
Critical Care  2010;14(3):313.
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.
PMCID: PMC2911686  PMID: 20550724
7.  Genome-wide transcription profiling of human sepsis: a systematic review 
Critical Care  2010;14(6):R237.
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.
Electronic searches were performed in Medline and Embase (1987 to October 2010), supplemented by additional searches in multiple microarray data repositories. We included studies that (1) used microarray, (2) were performed in humans and (3) investigated the host response mediated by circulating leukocytes.
We identified 12 cohorts consisting of 784 individuals providing genome-wide expression data in early and late sepsis. Sepsis elicited an immediate activation of pathogen recognition receptors, accompanied by an increase in the activities of signal transduction cascades. These changes were consistent across most cohorts. However, changes in inflammation related genes were highly variable. Established inflammatory markers, such as tumour necrosis factor-α (TNF-α), interleukin (IL)-1 or interleukin-10, did not show any consistent pattern in their gene-expression across cohorts. The finding remains the same even after the cohorts were stratified by timing (early vs. late sepsis), patient groups (paediatric vs. adult patients) or settings (clinical sepsis vs. endotoxemia model). Neither a distinctive pro/anti-inflammatory phase nor a clear transition from a pro-inflammatory to anti-inflammatory phase could be observed during sepsis.
Sepsis related inflammatory changes are highly variable on a transcriptional level. We did not find strong genomic evidence that supports the classic two phase model of sepsis.
PMCID: PMC3219990  PMID: 21190579
8.  Bench-to-bedside review: The value of cardiac biomarkers in the intensive care patient 
Critical Care  2008;12(3):215.
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.
PMCID: PMC2481437  PMID: 18557993

Results 1-8 (8)