Stelios Kokkoris

Serum S100B protein is increased and correlates with interleukin 6, hypoperfusion indices, and outcome in patients admitted for surgical control of hemorrhage.

ABSTRACT S100B protein, an acknowledged biomarker of brain injury, has been reported to be increased in hemorrhagic shock. Also, acute hemorrhage is associated with inflammatory response. The aim of this study was to investigate the concentrations of serum S100B and the potential relationships with interleukin 6 (IL-6), severity of tissue hypoperfusion, and prognosis in patients admitted for surgical control of severe hemorrhage. Patients undergoing elective abdominal aortic aneurysm surgery participated as control subjects. Serum samples were drawn before, at the end of surgery, and after 6 and 24 h. Sixty-four patients with severe hemorrhage (23 trauma and 41 nontrauma) and 17 control subjects were included. Increased preoperative concentrations of S100B protein (1.70 ± 2.13 and 0.81 ± 1.23 &mgr;g/L) and IL-6 (241 ± 291 and 226 ± 238 pg/mL) were found in patients with traumatic and nontraumatic reason, respectively, and remained elevated throughout 24 h. Compared with nontrauma, trauma patients exhibited higher preoperative S100B levels (P < 0.05). Overall mortality was 47%. In control subjects, preoperative S100B and IL-6 levels were within normal limits and increased at the end of surgery (P < 0.001 and P < 0.01, respectively). Preoperative S100B correlated with IL-6 (r = 0.78, P < 0.01), arterial lactate (r = 0.50, P < 0.01), pH (r = −0.45, P < 0.01), and bicarbonate (r = −0.40, P < 0.01). Multiple analysis revealed that preoperative S100B in trauma and lactate in nontrauma patients were independently associated with outcome. In predicting death, preoperative S100B yielded receiver operator characteristics curve areas of 0.75 for all patients and 0.86 for those with trauma. These results indicate that severe hemorrhage in patients without brain injury is associated with increased serum levels of S100B, which correlates with IL-6 and tissue hypoperfusion. Moreover, the predictive ability of S100B for mortality, suggests that it could be a marker of potential clinical value in identifying, among patients with severe hemorrhage, those at greater risk for adverse outcome.

Combination of Renal Biomarkers Predicts Acute Kidney Injury in Critically Ill Adults

Objective: Most studies so far have focused on the performance of individual biomarkers to detect early acute kidney injury (AKI) in the adult intensive care unit (ICU) patients; however, they have not determined the predictive ability of their combinations. The aim of this study was to compare the predictive abilities of plasma neutrophil gelatinase-associated lipocalin (pNGAL), urine neutrophil gelatinase-associated lipocalin (uNGAL), plasma cystatin C (pCysC), serum creatinine (sCr), and their combinations in detecting AKI in an adult general ICU population. Methods: A total of 100 consecutive ICU patients were included in the analysis. AKI was defined according to RIFLE criteria. Biomarker predictive abilities were evaluated by area under the curve (AUC), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Results: AKI occurred in 36% of patients 7 days post-admission. All three novel biomarkers as well as sCr had moderate predictive abilities for AKI occurrence. The most efficient combinations (pNGAL + sCr and pNGAL + uNGAL + sCr) were selected to participate in the subsequent analyses. Both combinations, when added to a reference clinical model, increased its AUC significantly (0.858, p = 0.04). Their NRI (0.78, p = 0.0002) was equal to that of pNGAL, but higher than that of the other three biomarkers, whereas their IDI was higher than that of any individual biomarker (0.23, p = 0.0001). Both combinations had better specificities, positive likelihood ratios, and positive predictive values than those of any individual biomarker. Conclusion: The biomarker combinations had better predictive characteristics compared with those of each biomarker alone.

High-dose tigecycline-associated alterations in coagulation parameters in critically ill patients with severe infections

We read with great interest in a recent issue of the International ournal of Antimicrobial Agents the report by Molina-Manso et al. n the in vitro susceptibility to nine antibiotics of staphylococci solates recovered from orthopaedic infections [1]. All antibiotics ested are commonly used in the treatment of prosthetic joint infecions (PJIs). The authors revealed that none of the antibiotics proved to be otally effective against biofilms with regard to minimum biofilm radication concentration (MBEC) data, even with concentrations ighly above the minimum inhibitory concentration (MIC) of the solates. These results were obtained with the static Calgary Biofilm evice (CBD) method, which allows determination of the MBEC, hich is the concentration of antibiotic killing nearly 100% of bacteia in a biofilm. Unfortunately, this method does not detect the ctual number of bacteria in the biofilm used as an inoculum in BEC tests. As inoculum size and (extended) incubation time (24 h) nfluence the results of susceptibility test challenge, MBEC values ould be mistaken [2]. Despite these drawbacks, and although this method needs wellrained technicians, these data are interesting especially because he authors reported and confirmed the best activity of rifampicin even if the results were poor with this system), the pivotal antibitic used to eradicate staphylococci PJIs. None of the antibiotics as effective in eradicating the biofilm but, at 24 h, with this ystem rifampicin remains a key antibiotic against Gram-positive athogens [3]. In this study, Molina-Manso et al. could not identify ny difference in antibiofilm activity. We agree with the authors hat all of the strains tested were able to form biofilms on the CBD egs but in their conditions. According to our experience, whatever the system used to detect iofilm or adherence abilities with the BioFilm Ring Test, Staphyococcus aureus clinical isolates involved in hip and knee PJIs can roduce biofilm. Nevertheless, the comparison remains delicate ecause this last method investigates the first step of adhesion in he biofilm cycle life [4]. In contrast, the CBD method as well as he Christensen or resazurin methods are considered as endpoint ethods. Thus, we need to keep in mind that technical conditions, specially the medium used, pH, oxygenation, ionic concentrations nd glucose concentration, could lead to huge variations in biofilm etermination that do not mimic real life. Therefore, these MBEC esults should be interpreted with caution according to the limits nd performance of the method used [4]. Second, we were surprised to find a slight activity of tigecyline, a bacteriostatic antibiotic. According to personal data and the iterature, with time–kill curve and biofilm studies, tigecycline conrmed its bacteriostatic activity. Moreover, with an in vitro MBEC etermination method using microcalorimetry [5], we systematially did not observe any efficacy against an early or mature biofilm ut only a delay in the time of growth. It would have been interestng to compare the MIC and minimum bactericidal concentration n logarithmic and stationary phase with the MBEC determination btained with this system. Antimicrobial Agents 45 (2015) 84–95

Novel Biomarkers of Acute Kidney Injury in the General Adult ICU: A Review

Acute kidney injury is one of the most frequent problems occurring in the critically ill patients of the intensive care units and it is well established that it increases both morbidity and mortality in these patients. Moreover, despite technological and pharmaceutical advances during the last decades, the incidence as well as the mortality associated with acute kidney injury in these patients remains unchanged. Creatinine, the most common renal dysfunction biomarker in use, has many disadvantages, such as time delay in its increase and the influence by other factors on its serum concentration, such as age, gender, muscle mass, etc. Hence, the need for better renal biomarkers in order to timely intervene for acute kidney injury prevention is imperative. The lack of an early biomarker is an obstacle for the development of new acute kidney injury prevention strategies. With the incidence of acute kidney injury reaching epidemic dimensions, the need for novel markers is urgent. During the last years, the research for finding such biomarkers has been intense. The purpose of the present article is to review the studies which have tested the predictive ability of those markers (in urine and/or plasma) for early detection of acute kidney injury in the mixed adult intensive care unit population and underline the potential limitations encountered in the various studies.

Microcirculatory alterations during continuous renal replacement therapy in ICU: A novel view on the 'dialysis trauma' concept.

OBJECTIVE The purpose of this study was to evaluate microcirculation over 24 h renal replacement therapy (CRRT) in critically ill patients. METHODS We conducted a single-center, prospective, observational study, measuring microcirculation parameters, monitored by near infrared spectroscopy (NIRS) before hemodiafiltration onset (H0), and at six (H6) and 24 h (H24) during CRRT in critically ill patients. Serum Cystatin C (sCysC) and soluble (s)E-selectin levels were measured at the same time points. Twenty-eight patients [19 men (68%)] were included in the study. RESULTS Tissue oxygen saturation (StO2, %) [76.5 ± 12.5 (H0) vs 75 ± 11 (H6) vs 70 ± 16 (H24), p = 0.04], reperfusion rate, indicating endothelial function (EF, %/sec) [2.25 ± 1.44 (H0) vs 2.1 ± 1.8 (H6) vs 1.6 ± 1.4 (H24), p = 0.02] and sCysC (mg/L) [2.7 ± 0.8 (H0) vs 2.2 ± 0.6 (H6) vs 1.8 ± 0.8 (H24), p < 0.0001] significantly decreased within the 24 h CRRT. Change of EF positively correlated with changes of sCysC within 24 h CRRT (r = 0.464, p = 0.013) while in patients with diabetes the change of StO2 correlated with dose (r = − 0.8, p = 0.01). No correlation existed between hemoglobin and temperature changes with the deteriorated microcirculation indices. sE-Selectin levels in serum were elevated; no difference was established over the 24 h CRRT period. A strong correlation existed between the sE-Selectin concentration change at H6 and H24 and the mean arterial pressure change in the same period (r = 0.77, p < 0.001). CONCLUSIONS During the first 24 h of CRRT implementation in critically ill patients, deterioration of microcirculation parameters was noted. Microcirculatory alterations correlated with sCysC changes and with dose in patients with diabetes.