Clinical solutions: not always what they seem?

Brenner and colleagues, in their article published in Critical Care, showed elevated levels of the reactive carbonyl species (RCS) methylglyoxal (MG) in the circulation of patients with septic shock. We commend the authors’ bravery in launching this molecule into a field well-populated with biomarkers and where clinical diagnosis persists as the ‘gold standard’

Repetitive vascular occlusion stimulus (RVOS) versus standard care to prevent muscle wasting in critically ill patients (ROSProx):a study protocol for a pilot randomised controlled trial

Background Forty per cent of critically ill patients are affected by intensive care unit-acquired weakness (ICU-AW), to which skeletal muscle wasting makes a substantial contribution. This can impair outcomes in hospital, and can cause long-term physical disability after hospital discharge. No effective mitigating strategies have yet been identified. Application of a repetitive vascular occlusion stimulus (RVOS) a limb pressure cuff inducing brief repeated cycles of ischaemia and reperfusion, can limit disuse muscle atrophy in both healthy controls and bed-bound patients recovering from knee surgery. We wish to determine whether RVOS might be effective in mitigating against muscle wasting in the ICU. Given that RVOS can also improve vascular function in healthy controls, we also wish to assess such effects in the critically ill. We here describe a pilot study to assess whether RVOS application is safe, tolerable, feasible and acceptable for ICU patients. Methods This is a randomised interventional feasibility trial. Thirty-two ventilated adult ICU patients with multiorgan failure will be recruited within 48 h of admission and randomised to either the intervention arm or the control arm. Intervention participants will receive RVOS twice daily (except only once on day 1) for up to 10 days or until ICU discharge. Serious adverse events and tolerability (pain score) will be recorded; feasibility of trial procedures will be assessed against pre-specified criteria and acceptability by semi-structured interview. Together with vascular function, muscle mass and quality will be assessed using ultrasound and measures of physical function at baseline, on days 6 and 11 of study enrolment, and at ICU and hospital discharge. Blood and urine biomarkers of muscle metabolism, vascular function, inflammation and DNA damage/repair mechanism will also be analysed. The Health questionnaire will be completed 3 months after hospital discharge. Discussion If this study demonstrates feasibility, the derived data will be used to inform the design (and sample size) of an appropriately-powered prospective trial to clarify whether RVOS can help preserve muscle mass/improve vascular function in critically ill patients.</p

The Gene Expression Analysis of Blood Reveals S100A11 and AQP9 as Potential Biomarkers of Infective Endocarditis

BACKGROUND: The diagnostic and prognostic assessments of infective endocarditis (IE) are challenging. To investigate the host response during IE and to identify potential biomarkers, we determined the circulating gene expression profile using whole genome microarray analysis. METHODS AND RESULTS: A transcriptomic case-control study was performed on blood samples from patients with native valve IE (n = 39), excluded IE after an initial suspicion (n = 10) at patient's admission, and age-matched healthy controls (n = 10). Whole genome microarray analysis showed that patients with IE exhibited a specific transcriptional program with a predominance of gene categories associated with cell activation as well as innate immune and inflammatory responses. Quantitative real-time RT-PCR performed on a selection of highly modulated genes showed that the expression of the gene encoding S100 calcium binding protein A11 (S100A11) was significantly increased in patients with IE in comparison with controls (P<0.001) and patients with excluded IE (P<0.05). Interestingly, the upregulated expression of the S100A11 gene was more pronounced in staphylococcal IE than in streptococcal IE (P<0.01). These results were confirmed by serum concentrations of the S100A11 protein. Finally, we showed that in patients with IE, the upregulation of the aquaporin-9 gene (AQP9) was significantly associated with the occurrence of acute heart failure (P = 0.02). CONCLUSIONS: Using transcriptional signatures of blood samples, we identified S100A11 as a potential diagnostic marker of IE, and AQP9 as a potential prognostic factor

Epidemiology and risk factors for Staphylococcus aureus colonization in children in the post-PCV7 era

<p>Abstract</p> <p>Background</p> <p>The incidence of community-associated methicillin-resistant <it>Staphylococcus aureus </it>(MRSA) has risen dramatically in the U.S., particularly among children. Although <it>Streptococcus pneumoniae </it>colonization has been inversely associated with <it>S. aureus </it>colonization in unvaccinated children, this and other risk factors for <it>S. aureus </it>carriage have not been assessed following widespread use of the heptavalent pneumococcal conjugate vaccine (PCV7). Our objectives were to (1) determine the prevalence of <it>S. aureus </it>and MRSA colonization in young children in the context of widespread use of PCV7; and (2) examine risk factors for <it>S. aureus </it>colonization in the post-PCV7 era, including the absence of vaccine-type <it>S. pneumoniae </it>colonization.</p> <p>Methods</p> <p>Swabs of the anterior nares (<it>S. aureus</it>) were obtained from children enrolled in an ongoing study of nasopharyngeal pneumococcal colonization of healthy children in 8 Massachusetts communities. Children 3 months to <7 years of age seen for well child or sick visits in primary care offices from 11/03–4/04 and 10/06–4/07 were enrolled. <it>S. aureus </it>was identified and antibiotic susceptibility testing was performed. Epidemiologic risk factors for <it>S. aureus </it>colonization were collected from parent surveys and chart reviews, along with data on pneumococcal colonization. Multivariate mixed model analyses were performed to identify factors associated with <it>S. aureus </it>colonization.</p> <p>Results</p> <p>Among 1,968 children, the mean age (SD) was 2.7 (1.8) years, 32% received an antibiotic in the past 2 months, 2% were colonized with PCV7 strains and 24% were colonized with non-PCV7 strains. The prevalence of <it>S. aureus </it>colonization remained stable between 2003–04 and 2006–07 (14.6% vs. 14.1%), while MRSA colonization remained low (0.2% vs. 0.9%, p = 0.09). Although absence of pneumococcal colonization was not significantly associated with <it>S. aureus </it>colonization, age (6–11 mo vs. ≥5 yrs, OR 0.39 [95% CI 0.24–0.64]; 1–1.99 yrs vs. ≥5 yrs, OR 0.35 [0.23–0.54]; 2–2.99 yrs vs. ≥5 yrs, OR 0.45 [0.28–0.73]; 3–3.99 yrs vs. ≥5 yrs, OR 0.53 [0.33–0.86]) and recent antibiotic use were significant predictors in multivariate models.</p> <p>Conclusion</p> <p>In Massachusetts, <it>S. aureus </it>and MRSA colonization remained stable from 2003–04 to 2006–07 among children <7 years despite widespread use of pneumococcal conjugate vaccine. <it>S. aureus </it>nasal colonization varies by age and is inversely correlated with recent antibiotic use.</p

Year in review in Intensive Care Medicine 2010: I. Acute renal failure, outcome, risk assessment and ICU performance, sepsis, neuro intensive care and experimentals

SCOPUS: re.jinfo:eu-repo/semantics/publishe

Association between preoperative plasma sRAGE levels and recovery from cardiac surgery

Background. The receptor for advanced glycation end products (RAGE) is an inflammation-perpetuating receptor, and soluble RAGE (sRAGE) is a marker of cellular RAGE expression. This study investigated whether raised plasma levels prior to surgery of sRAGE or S100A8/A9 (a RAGE ligand) were associated with longer duration of hospital care in patients undergoing cardiac surgery necessitating cardiopulmonary bypass. Methods. Patients ( = 130) undergoing elective cardiac surgery were enrolled prospectively. Plasma sRAGE and S100A8/A9 concentrations were measured before and 2 h after surgery. Results. Preoperative plasma sRAGE increased significantly ( < 0.0001) from 1.06 ng/mL (IQR, 0.72–1.76) to 1.93 ng/mL (IQR, 1.14–2.63) 2 h postoperatively. Plasma S100A8/9 was also significantly ( < 0.0001) higher 2 h postoperatively (2.37 g/mL, IQR, 1.81–3.05) compared to pre-operative levels (0.41 g/mL, IQR, 0.2–0.65). Preoperative sRAGE, but not S100A8/A9, was positively and significantly correlated with duration of critical illness ( = 0.3, = 0.0007) and length of hospital stay (LOS; = 0.31, < 0.0005). Multivariate binary logistic regression showed preoperative sRAGE to be, statistically, an independent predictor of greater than median duration of critical illness (odds ratio 16.6, = 0.014) and to be, statistically, the strongest independent predictor of hospital LOS. Conclusion. Higher preoperative plasma sRAGE levels were associated with prolonged duration of care in adults undergoing cardiac surgery requiring cardiopulmonary bypass

Plasma S100A8/A9 heterodimer is an early prognostic marker of acute kidney injury associated with cardiac surgery

We investigated whether plasma levels of the inflammation marker S100A8/A9, could predict acute kidney injury (AKI) onset in patients undergoing cardiac surgery necessitating cardiopulmonary bypass (CPB). Patients & methods: Plasma levels of S100A8/A9 and other neutrophil cytosolic proteins were measured in 39 patients pre- and immediately post-CPB. Results: All markers increased significantly post-CPB with S100A8/A9, S100A12 and myeloperoxidase levels significantly higher in patients who developed AKI within 7 days. S100A8/A9 had good prognostic utility for AKI, with an area under the receiver operating characteristic curve of 0.81 (95% CI: 0.676–0.949) and a cut-off value of 10.6 μg/ml (85.7% sensitivity and 75% specificity) irrespective of age. Conclusion: Plasma S100A8/A9 levels immediately after cardiac surgery, can predict onset of AKI, irrespective of age

Safety and Feasibility Assessment of Repetitive Vascular Occlusion Stimulus (RVOS) Application to Multi-Organ Failure Critically Ill Patients: A Pilot Randomised Controlled Trial.

Muscle wasting is implicated in the pathogenesis of intensive care unit acquired weakness (ICU-AW), affecting 40% of patients and causing long-term physical disability. A repetitive vascular occlusion stimulus (RVOS) limits muscle atrophy in healthy and orthopaedic subjects, thus, we explored its application to ICU patients. Adult multi-organ failure patients received standard care +/- twice daily RVOS {4 cycles of 5 min tourniquet inflation to 50 mmHg supra-systolic blood pressure, and 5 min complete deflation} for 10 days. Serious adverse events (SAEs), tolerability, feasibility, acceptability, and exploratory outcomes of the rectus femoris cross-sectional area (RFCSA), echogenicity, clinical outcomes, and blood biomarkers were assessed. Only 12 of the intended 32 participants were recruited. RVOS sessions (76.1%) were delivered to five participants and two could not tolerate it. No SAEs occurred; 75% of participants and 82% of clinical staff strongly agreed or agreed that RVOS is an acceptable treatment. RFCSA fell significantly and echogenicity increased in controls (n = 5) and intervention subjects (n = 4). The intervention group was associated with less frequent acute kidney injury (AKI), a greater decrease in the total sequential organ failure assessment score (SOFA) score, and increased insulin-like growth factor-1 (IGF-1), and reduced syndecan-1, interleukin-4 (IL-4) and Tumor necrosis factor receptor type II (TNF-RII) levels. RVOS application appears safe and acceptable, but protocol modifications are required to improve tolerability and recruitment. There were signals of possible clinical benefit relating to RVOS application