Critical care : the official journal of the Critical Care Forum
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Severe sepsis continues to lead to critical illness. Few therapeutic options exist other than antibiotic therapy and general supportive care. ⋯ This commentary will discuss the therapeutic targets revealed by our new understanding of the Toll-like receptor. The potential clinical difficulties that may result from intervention at this pattern-recognition receptor will also be explored.
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The role of research ethics committees (RECs) is currently strained by increases in the number of protocols that are in need of review, the scientific and funding complexities of the protocols, and a lack of clear standards for ethics assessment. This commentary describes the significance of these strains and calls for clarification of reviewer accountability. To maintain or, in many cases, to restore public and professional trust in the ethics of human research and in REC review of protocols, it is imperative that steps be taken to clarify the accountability of RECs and their individual members.
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The Toll-like receptors (TLRs) are essential transmembrane signaling receptors of the innate immune system that alert the host to the presence of a microbial invader. The recent discovery of the TLRs has rapidly expanded our knowledge of molecular events that initiate host-pathogen interactions. ⋯ The fundamental significance of the TLRs in the generation of systemic inflammation and the pathogenesis of septic shock is reviewed. The potential clinical implications of therapeutic modulation of these recently characterized receptors of innate immunity are also discussed.
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Stress hyperglycaemia is a common event in acute critical illness. There is increasing evidence that maintaining normoglycaemia and treatment with insulin (or with glucose-insulin-potassium [GIK]), even in non-diabetic persons, is helpful in limiting organ damage after myocardial infarction, stroke, traumatic brain injury and other conditions, even though the conditions may be accompanied by insulin resistance. A landmark study now suggests that maintaining normoglycaemia with intensive insulin treatment in a heterogeneous population of critically ill patients decreases morbidity and mortality. The potential mechanisms that underlie such a beneficial effect are discussed.
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Infective endocarditis remains a disease associated with high mortality in certain groups of patients, with death resulting primarily from central nervous system complications and congestive heart failure. Combined medical and surgical therapy reduces both early and late mortality in complicated cases, especially in patients with valvular dysfunction related to heart failure. In these patients, heart failure is the strongest indication for valve replacement. ⋯ Limited data suggest that such surgery is feasible, even in complicated cases necessitating admission to the intensive care unit, and carries an acceptable risk for in-hospital mortality. It is important that critically ill patients with infective endocarditis are enrolled into multicenter studies, using adequate severity scoring systems to assess the impact of clinical and imaging variables on patients' outcome. Until such data are obtained, clinical judgement is still the best tool in decision-making regarding the individual patient.