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Heidelberg, Australia

Garcia-Alvarez M.,Hospital de Sant Pau | Marik P.,Eastern Virginia Medical School | Bellomo R.,Austin Hospital | Bellomo R.,Australian and New Zealand Intensive Care Research Center
Critical Care

There is overwhelming evidence that sepsis and septic shock are associated with hyperlactatemia (sepsis-associated hyperlactatemia (SAHL)). SAHL is a strong independent predictor of mortality and its presence and progression are widely appreciated by clinicians to define a very high-risk population. Until recently, the dominant paradigm has been that SAHL is a marker of tissue hypoxia. Accordingly, SAHL has been interpreted to indicate the presence of an 'oxygen debt' or 'hypoperfusion', which leads to increased lactate generation via anaerobic glycolysis. In light of such interpretation of the meaning of SAHL, maneuvers to increase oxygen delivery have been proposed as its treatment. Moreover, lactate levels have been proposed as a method to evaluate the adequacy of resuscitation and the nature of the response to the initial treatment for sepsis. However, a large body of evidence has accumulated that strongly challenges such notions. Much evidence now supports the view that SAHL is not due only to tissue hypoxia or anaerobic glycolysis. Experimental and human studies all consistently support the view that SAHL is more logically explained by increased aerobic glycolysis secondary to activation of the stress response (adrenergic stimulation). More importantly, new evidence suggests that SAHL may actually serve to facilitate bioenergetic efficiency through an increase in lactate oxidation. In this sense, the characteristics of lactate production best fit the notion of an adaptive survival response that grows in intensity as disease severity increases. Clinicians need to be aware of these developments in our understanding of SAHL in order to approach patient management according to biological principles and to interpret lactate concentrations during sepsis resuscitation according to current best knowledge. © 2014 Garcia-Alvarez et al. licensee BioMed Central Ltd. Source

Bagshaw S.M.,University of Alberta | Bellomo R.,Austin Hospital
Current Opinion in Critical Care

Purpose of Review: This review will summarize and discuss the role of cystatin C in the diagnosis of acute kidney injury. Recent Findings: Cystatin C is easily measured and has the characteristics of an ideal marker of kidney function. Data suggest that cystatin C is modified by age, sex, muscle mass, obesity, smoking status, thyroid function, inflammation, and malignancy. These factors suggest the need for age-specific and sex-specific reference standards. Cystatin C-based glomerular filtration rate estimates may perform better than creatinine in selected patient populations (elderly, children, transplantation, cirrhosis, malnourished). Cystatin C has been evaluated for the early diagnosis of acute kidney injury (AKI) in several populations. Serum cystatin C has value for the diagnosis of acute kidney injury; however, it has often performed similarly to creatinine. Urinary cystatin C has potential as an early marker. Summary: Cystatin C is an accurate biomarker for the early detection of AKI, and may, in selected populations, be superior to creatinine; however, data have been inconsistent. It also has reasonable discrimination for important outcomes such as death and renal replacement therapy (RRT). Additional studies are needed that focus on the cost-effectiveness of earlier detection of AKI with cystatin C compared with creatinine, and whether these biomarkers have complementary value. © 2010 Wolters Kluwer Health | Lippincott Williams &Wilkins. Source

Egi M.,Okayama University | Finfer S.,University of Sydney | Bellomo R.,Austin Hospital

Hyperglycemia is common in critically ill patients, with approximately 90% of patients treated in an ICU developing blood glucose concentrations > 110 mg/dL (6.1 mmol/L). Landmark trials in Leuven, Belgium, suggested that targeting normoglycemia(a blood glucose concentration of 80-110 mg/dL [4.4-6.1 mmol/L]) reduced mortality and morbidity, but other investigators have not been able to replicate these findings. Recently, the international multicenter Normoglycemia in Intensive Care Evaluation-Survival Using Glucose Algorithm Regulation (NICE-SUGAR) study reported increased mortality with this approach, and recent meta-analyses do not support intensive glucose control for critically ill patients. Although the initial trials in Leuven produced enthusiasm and recommendations for intensive blood glucose control, the results of the NICE-SUGAR study have resulted in the more moderate recommendation to target a blood glucose concentration between 144 mg/dL and 180 mg/dL (8-10 mmol/L). As critical care practitioners pay greater attention to glycemic control, it has become clear that currently used point-of-care measuring systems are not accurate enough to target tight glucose control. Unresolved issues include whether increased blood glucose variability is inherently harmful and whether even moderate hypoglycemia can be tolerated in the quest for tighter blood glucose control. Future research must first address whether intensive glucose control can be delivered safely, and whether computerized decision support systems and newer technologies that allow accurate and continuous or near-continuous measurement of blood glucose can make this possible. Until such time, clinicians would be well advised to abide by the age-old adage to "first, do no harm." © 2011 American College of Chest Physicians. Source

Steinfort D.P.,Royal Melbourne Hospital | Johnson D.F.,Austin Hospital | Irving L.B.,Royal Melbourne Hospital
European Respiratory Journal

Few data exist concerning possible infectious complications associated with endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA). The present prospective evaluation was undertaken in order to determine the incidence of bacteraemia and infectious complications associated with EBUS-TBNA. Consecutive patients undergoing EBUS-TBNA for evaluation of mediastinal or hilar lymph node lesions were studied. Venesection was performed within 60 s of TBNA for aerobic and anaerobic blood culture. Sterile saline washing of TBNA needles was also performed. Patients with positive blood cultures were reviewed immediately, and all patients underwent clinical review within 1 week of EBUS-TBNA. A total of 43 patients underwent EBUS-TBNA, with bacteraemia demonstrated in three (7%). All bacterial isolates were typical oropharyngeal commensal organisms. The TBNA needle washing culture was positive in 15 (35%) patients. None of the three bacteraemic patients had clinical features suggestive of infection, and no complications were seen among the cohort. The incidence of bacteraemia following EBUS-TBNA is comparable to that following routine flexible bronchoscopy. Performance of TBNA does not appear to measurably increase the risk of bacteraemia over that associated with insertion of the bronchoscope into the airway. Contamination of the TBNA needle with oropharyngeal commensal bacteria is common; however, clinically significant infection following EBUS-TBNA appears rare. Copyright©ERS 2010. Source

• This is the first of a two part series reviewing the nature and clinical significance of in situ cellular proliferations in the prostate gland. • This first part examines prostatic intraepithelial neoplasia (PIN), while the second part in the next supplement discusses intraductal carcinoma and ductal adenocarcinoma of the prostate. • PIN is a precursor lesion in the development of some forms of adenocarcinoma of the prostate. In the 1990s, high-grade PIN (HGPIN) on biopsy was a significant predictor of carcinoma, but this was due to incomplete sampling with sextant biopsies. With more extensive sampling in the last decade, the likelihood of identifying cancer after a diagnosis of HGPIN is not significantly different from a benign diagnosis. • In several recent studies, it is now recognised that multifocal HGPIN is a better predictor of cancer than unifocal HGPIN. Most cases of cancer will be detected in the vicinity of the HGPIN, but up to 40% of cancers will occur in different sextants. • In assessing potential markers for carcinoma in men with HGPIN on biopsy, α-methylacyl coenzyme-A racemase (AMACR) has emerged as a promising diagnostic tool. • HGPIN with strong staining for AMACR is associated with a higher rate of cancer detection in subsequent biopsies compared with AMACR-negative HGPIN. Also, AMACR positivity in HGPIN is more commonly seen adjacent to carcinoma, and this may provide guidance as to the site of future biopsies. © 2012 The Authors © 2012 BJU International. Source

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