Search

The aim of the study was to develop and validate a prediction model for hemorrhage in critically ill neonates which combines rotational thromboelastometry (ROTEM) parameters and clinical variables. This cohort study included 332 consecutive full-term and preterm critically ill neonates. We performed ROTEM and used the neonatal bleeding assessment tool (NeoBAT) to record bleeding events. We fitted double selection least absolute shrinkage and selection operator logit regression to build our prediction model. Bleeding within 24 hours of the ROTEM testing was the outcome variable, while patient characteristics, biochemical, hematological, and thromboelastometry parameters were the candidate predictors of bleeding. We used both cross-validation and bootstrap as internal validation techniques. Then, we built a prognostic index of bleeding by converting the coefficients from the final multivariable model of relevant prognostic variables into a risk score. A receiver operating characteristic analysis was used to calculate the area under curve (AUC) of our prediction index. EXTEM A10 and LI60, platelet counts, and creatinine levels were identified as the most robust predictors of bleeding and included them into a Neonatal Bleeding Risk (NeoBRis) index. The NeoBRis index demonstrated excellent model performance with an AUC of 0.908 (95% confidence interval [CI]: 0.870–0.946). Calibration plot displayed optimal calibration and discrimination of the index, while bootstrap resampling ensured internal validity by showing an AUC of 0.907 (95% CI: 0.868–0.947). We developed and internally validated an easy-to-apply prediction model of hemorrhage in critically ill neonates. After external validation, this model will enable clinicians to quantify the 24-hour bleeding risk.

Aim Limited data are available regarding the clinical relevance of platelet function measurements in stable patients with coronary artery disease (CAD). Our aim is to evaluate the agreement between multiple electrode aggregometry (MEA) and light transmittance aggregometry (LTA) in detecting clopidogrel low responders and their prognostic value in CAD patients with type 2 diabetes mellitus (T2DM) on dual platelet inhibition. Methods LTA and MEA were performed in 122 stable cardiovascular patients with T2DM. The upper quartile of patients according to maximum LTA (LTAmax) and MEA measurements were defined as clopidogrel low responders. Agreement between the two methods was evaluated by kappa statistics. We assessed the potential correlation between antiplatelet response and clinical outcome and the optimal cutoff value according to ROC analysis to predict the occurrence of major adverse cardiovascular events (MACE), during 1-year follow-up period. Results Cohen's kappa coefficients (0.214) indicated fair agreement (70.2%) between LTA and MEA. A total of 25 MACE occurred in 108 patients (23.1%). Patients with MACE had higher LTAmax than those without (57.1 ± 16.5 vs 49.3 ± 18.3, respectively, p = 0.023). MEA measurements were similar between patients with and without MACE (30.1 ± 15.4 vs 30.6 ± 20.8, respectively; p = 0.84). Multiple logistic regression showed LTAmax response as an independent predictor of death from cardiovascular causes (Odds Ratio, adjusted:0.2;0.05–0.81). ROC analysis indicated that LTAmax cutoff of 62.5% best predicted death (AUC = 0.67, sensitivity = 78%, specificity = 61.5%). Conclusions The assessment of platelet responsiveness remains highly test-specific. Our results support the prognostic role of LTA, but not MEA testing, for death risk evaluation in stable cardiovascular T2DM patients.

Objectives: Our aim was to assess blood utilization after implementation of a patient blood management (PBM) program in a Greek tertiary hospital. Methods: An electronic transfusion request form and a prospective audit of transfusion practice were implemented. After the one-year implementation period, a retrospective review was performed to assess transfusion practice in medical patients. Results: Pre-PBM, a total of 9478 RBC units were transfused (mean: 1.75 units per patient) compared with 9289 transfused units (mean: 1.57 units per patient) post-PBM. Regarding the post-PBM period, the mean hemoglobin (Hb) level of the 3099 medical patients without comorbidities transfused was 7.19 ± 0.79 gr/dL. Among them, 2065 (66.6%) had Hb levels &gt, 7.0 gr/dL, while 167 (5.3%) had Hb levels &gt, 8.0 gr/dL. In addition, 331 (25.3%) of the transfused patients with comorbidities had Hb &gt, 8.0 gr/dL. The Hb transfusion thresholds significantly differed across the clinics (p &lt, 0.001), while 21.8% of all medical non-bleeding patients received more than one RBC unit transfusion. Conclusion: A poor adherence with the restrictive transfusion threshold of 7.0 gr/dL was observed. The adoption of a less strict threshold might be a temporary step to allow physicians to become familiar with the program and be informed on the safety and advantages of the restrictive transfusion strategy.

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.

There is a complex and not fully elucidated association between pulmonary arterial hypertension (PAH) and coagulation disorders. The goal of this study was to evaluate platelet function, coagulation and fibrinolysis in PAH patients at diagnosis, before PAH-specific treatment initiation. We enrolled 20 healthy controls and 30 PAH patients (20 with connective tissue disease (CTD-PAH) and 10 idiopathic (iPAH)). None of the participants was on any antiplatelet or anticoagulation therapy. Blood samples from PAH patients were collected during the initial right heart catheterization. All subjects were assessed with platelet function analyzer-100 (PFA-100), epinephrine (Epi) and ADP-induced light transmission aggregometry (LTA), thromboelastometry (ROTEM) and endogenous thrombin potential (ETP). Our results showed that Epi and ADP-LTA values were significantly lower in newly diagnosed PAH patients compared to controls. Disaggregation was present in 73% of patients, a characteristic not seen in healthy individuals. In ROTEM assay, CT and CFT measurements were significantly higher and a angle lower compared to controls. ETP testing revealed significantly reduced outcomes in AUC, Cmax and Tmax. When CTD-PAH and iPAH patient groups were compared, iPAH ADP-LTA values were significantly decreased compared to CTD-PAH. In conclusion, newly diagnosed PAH patients presented with decreased platelet aggregation, clot propagation and thrombin generation, along with delayed initiation of the coagulation process. These hemostatic deficits could indicate an "exhaustion" of the coagulation process that could be caused by endothelial dysfunction and chronic activation of the procoagulant pathways. Further studies are warranted to confirm these laboratory findings and assess their potential clinical significance.

Pulmonary endothelium dysfunction is a key characteristic of ARDS. The aim of this study was to investigate endothelium-derived markers, such as angiopoietin-2 (Ang-2) and endothelial cell-specific molecule-1 (endocan), at the vascular and alveolar compartments as outcome predictors in ARDS. Fifty-three consecutive ARDS patients were studied. The primary outcome was 28-day mortality. Secondary endpoints were days of unassisted ventilation and days with organ failure other than ARDS, during the 28-day study period. Nonsurvivors presented higher lung injury scores and epithelial lining fluid (ELF) Ang-2 levels compared to survivors, with no significant differences in plasma Ang-2, endocan, and protein C concentrations between the two groups. In logistic regression analysis, ELF Ang-2 levels > 705 pg/ml were the only independent variable for 28-day mortality among the previous four. Plasma endocan values > 13 ng/pg were the only parameter predictive against days of unassisted ventilation during the 28-day study period. Finally, lung injury score > 2.25 and ELF Ang-2 levels > 705 pg/ml were associated with increased number of days with organ failure, other than ARDS. Our findings suggest that Ang-2 levels are increased in the alveolar compartment of ARDS patients, and this may be associated both with increased mortality and organ failure besides lung.

Reduced coronary velocity flow reserve (CFR) is associated with poor outcome in patients with cardiovascular disease. We investigated whether CFR is associated with tissue ischemia and acidosis, impaired myocardial deformation and adverse outcome in patients with septic shock.In 70 mechanically-ventilated patients with septic shock, we examined: a) S' and E' mitral annular velocities using tissue Doppler imaging (TDI), b) CFR of the left anterior descending artery after adenosine infusion using transesophageal Doppler echocardiography and c) lactate, pyruvate and glycerol in tissue by means of a microdialysis (MD) catheter inserted into the subcutaneous adipose tissue as markers of tissue ischemia and acidosis. SOFA and APACHE II prognostic scores and mortality in the intensive care unit (ICU) were recorded.Reduced CFR, S' and E' as well as increased E/E' correlated with increased SOFA, APACHE II and MD lactate to pyruvate ratio (p0.05 for all correlations). Impaired TDI markers also correlated with increased MD glycerol (p0.05). Reduced CFR correlated with decreased E' (p0.05). CFR was 1.8 ± 0.42 in non-survivors (n=34) versus 2.08 ± 0.44 in survivors (p=0.007). A CFR1.90 predicted mortality with sensitivity of 70% and specificity of 69% (area under the curve 77%; p=0.003). CFR had an additive value to APACHE (chi-square change: 4.358, p=0.03) and SOFA (chi-square change: 3.692, p=0.04) for the prediction of mortality.Tissue ischemia and acidosis is a common pathophysiological link between decreased CFR and impaired LV myocardial deformation in septic shock. CFR is an additive predictor of ICU mortality to traditional risk scores in septic shock.

Background Previous studies suggested a possible negative interference of proton pump inhibitors (PPIs) on clopidogrel’s antiplatelet effect because of the competitive inhibition of the CYP 2C19 isoenzyme. Moreover, carriers of the loss-of-function allele of CYP2C19 polymorphism (CYP2C19*2) display significantly lower responses to clopidogrel. In this study, we investigated the association between CYP2C19*2 genotype, PPI intake and clopidogrel resistance in patients with coronary artery disease (CAD) and their effect on clinical outcome. Methods We recruited 95 patients with CAD receiving chronic clopidogrel therapy in combination with aspirin. Platelet reactivity was simultaneously assessed by INNOVANCE PFA-100 P2Y, ADP-induced light transmission aggregometry (LTA), flow-cytometric vasodilator-stimulated phosphoprotein (VASP)-phosphorylation assay and multiple electrode aggregometry (Multiplate). Cardiovascular outcomes were recorded during 1-year follow-up period. Results Only platelet reactivity assessed by measuring platelet phosphorylated-VASP demonstrated a significant higher platelet reactivity in carriers of CYP2C19*2 (p = 0.023). The other methods displayed higher - but not statistically significant - platelet reactivity in patients carrying the CYP2C19*2 variant as compared with non-carriers. Patients on PPIs demonstrated almost similar suppression of platelet reactivity in comparison with those not treated with PPIs by all platelet function assays. In logistic regression analysis none of the platelet function assays measurements were related with clinical outcomes. Similarly neither CYP2C19*2 genetic variant nor PPI treatment were associated with adverse clinical events. Conclusions PPI co-administration did not influence clopidogrel’s antiplatelet effect on laboratory testing by all platelet function assays used. On the contrary, patients carrying CYP2C19*2 genotype had significantly higher residual platelet reactivity as estimated by VASP-phosphorylation assay.

Purpose Endothelial protein C receptor (EPCR) is expressed mainly in endothelial cells and is involved in regulation of the cytoprotective and anticoagulant pathways of protein C. We assessed whether haplotypes in the EPCR gene modify the risk of severe sepsis and/or septic shock (SS/SS) development in critically ill patients. Methods Three polymorphisms in the EPCR gene were genotyped in 389 Caucasian critically ill patients, hospitalized in the intensive care units of two major hospitals in Athens, Greece. Multivariate logistic regression analysis controlling for age, acute physiology and chronic health evaluation (APACHE) II and sequential organ failure assessment (SOFA) scores, sex, and diagnosis was performed to determine the effect of haplotypes H1 and H3 in the EPCR gene on the development of SS/SS. Results H2 carriers versus all other genotypes combined had a nonsignificant excess of SS/SS (p = 0.087). SS/SS occurred in 38.8 % of critically ill patients carrying minor alleles belonging to both H1 and H3 haplotypes, in 58.0 % of H1 carriers, 64.3 % of H3 carriers, and 65.2 % of patients carrying all common alleles (H2). Compared with H2 carriers, the odds ratios (OR) for developing SS/SS were 0.34 [95 % confidence interval (CI) 0.16–0.76, p = 0.008] for simultaneous H1 and H3 carriers, 0.65 (95 % CI 0.37–1.13, p = 0.123) for H1 carriers, and 0.82 (95 % CI 0.39–1.70, p = 0.590) for H3 carriers. Conclusions Our results indicate that simultaneous carriers of minor alleles belonging to both the H1 and H3 haplotypes may be at reduced risk of developing SS/SS in this cohort of critically ill patients.

Objectives Pulmonary nocardiosis is an uncommon opportunistic infection affecting mainly immunocompromised patients. We herein present a case of nocardiosis without profound underlying immunodeficiency. Background A female, 84-years' old patient with stage IV chronic obstructive pulmonary disease (COPD) is presented. No profound causes of immunodeficiency existed, such as HIV infection, diabetes mellitus, malignancy, alcoholism, chemotherapy or previous corticosteroid intake. The patient recovered after treatment with trimethoprim/sulfamethoxazole for 6 months. Results One year after infection resolution, stimulation of the patient's blood monocytes with Nocardia antigens revealed defective production of tumor necrosis factor-alpha, interleukin (IL)-6 and IL-17. Conclusion We provide preliminary evidence for a link between defective innate immune responses and predisposition for Nocardia infections. Further studies must be conducted in order to fully investigate this mechanism of infection acquisition.

The aim of this study was to measure subcutaneous tissue cortisol obtained by microdialysis (MD) in 35 mechanically ventilated septic patients.Upon intensive care unit admission, an MD catheter was inserted into the subcutaneous tissue of the thigh. Cortisol (CORT) was determined in a 5:00 to 9:00 am microdialysate sample collected within 72 hours. Concurrently, serum total (T-CORT) and free CORT (F-CORT) were measured. The Acute Physiology and Chronic Health Evaluation (APACHE II) and Sequential Organ Failure Assessment scores were calculated. Both T-CORT less than 10 μg/dL and F-CORT less than 0.8 μg/dL were considered as indicating critical illness-related corticosteroid insufficiency. Adrenal adequacy was defined as T-CORT greater than 20 μg/dL or F-CORT greater than 2.0 μg/dL.Total CORT correlated significantly with F-CORT (rs = +0.8, P.0001). Microdialysis CORT had a lower correlation with T-CORT (rs = +0.6, P.0001) and F-CORT (rs = +0.7, P.0001) and a weak correlation with APACHE II score (rs = +0.4, P.01). On the basis of MD-CORT, the patients were divided in quartiles. Although the median F-CORT and T-CORT levels were significantly different (P.001) among the MD-CORT quartiles, there was a considerable overlap between the subgroups. All patients with T-CORT less than 10 μg/dL and all but 3 patients with F-CORT less than 0.8 μg/dL had tissue CORT in the lower quartile. However, only 50% and 58% of patients with adequate T-CORT and F-CORT levels, respectively, had concordant MD-CORT in the highest quartile.Microdialysis CORT levels correlate moderately with circulating T-CORT and F-CORT. Of note, several patients presented with discrepant measurements between interstitial and circulating CORT concentrations. Thus, interstitial CORT measurements represent an additional tool to investigate the tissue CORT availability in critically ill patients.

The aim of this study was to explore the effect of red blood cell (RBC) transfusion on microdialysis-assessed interstitial fluid metabolic parameters in septic patients. We conducted a retrospective study of 37 patients with severe sepsis/septic shock requiring transfusion of one to two RBC units. Interstitial fluid metabolic alterations were monitored by a microdialysis catheter inserted in the subcutaneous adipose tissue. Samples were collected before (T0) and after transfusion at two time-points: T1a and T1b; median post-transfusion times of 120 [interquartile range (IQR); 45–180] and 360 (IQR; 285–320) min. Lactate, pyruvate, glycerol and glucose concentrations were measured with a bedside analyzer, and the lactate/pyruvate (LP) ratio was calculated automatically. RBC transfusions decreased the LP ratio from (T0) 18.80 [interquartile range (IQR); 14.85–27.45] to (T1a) 17.80 (IQR; 14.35–25.20; P

BACKGROUND Intensivists and nursing staff are often reluctant to admit patients with cancer to the intensive care unit even though these patients' survival rate has improved since the 1980s. OBJECTIVE To identify factors associated with mortality in cancer patients admitted to the intensive care unit and to assess and compare the effectiveness of 3 general prognostic models: the Acute Physiology and Chronic Health Evaluation (APACHE) II, the Simplified Acute Physiology Score (SAPS II), and the Sequential Organ Failure Assessment (SOFA). METHODS A prospective observational cohort study was performed in 2 general intensive care units. Discrimination was assessed by using area under the receiver operating characteristic curves, and calibration was evaluated by using Hosmer-Lemeshow goodness-of-fit tests. RESULTS A total of 126 patients were included during a 3-year period. The observed mortality was 46.8%. All 3 general models showed excellent discrimination (area under the curve >0.8) and good calibration (P = .17, .14, and .22 for APACHE II, SAPS II, and SOFA, respectively). However, discrimination was significantly better with APACHE II scores than with SOFA scores (P = .02). Multivariate analyses indicated that independent of the 3 severity-of-illness scores, unfavorable risk factors for mortality included a patient's preadmission performance status, source of admission (internal medicine vs surgery department), and the presence of septic shock, infection, or anemia. Combining SOFA and SAPS II scores with these variables created prognostic models with improved calibration and discrimination. CONCLUSIONS The general prognostic models seem fairly accurate in the prediction of mortality in critically ill cancer patients in the intensive care unit.

OBJECTIVE We hypothesized that pretreatment with atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, confers protection against lung injury caused by high-stretch mechanical ventilation. METHODS Twenty-four isolated sets of normal rabbit lungs were utilized. Treated animals received atorvastatin (20 mg/kg body weight/day by mouth) for 3 days before surgery. Lungs were perfused constantly (300 mL/min) and ventilated for 1 hr with pressure-control ventilation at either 23 (high pressure; resulting in tidal volume approximately 22 mL/kg) or 11 (low pressure; tidal volume approximately 10 mL/kg) cm H2O peak inspiratory pressure and positive end-expiratory pressure of 3 cm H2O. Four groups were examined: high pressure-no statin, high pressure-statin pretreatment, low pressure-no statin, and low pressure-statin pretreatment. RESULTS The high-pressure-no statin group sustained more damage than the low-pressure groups. In high-pressure groups, lungs of statin-pretreated vs. no statin-pretreated animals sustained a significantly lower increase in ultrafiltration coefficient (an accurate marker of alveolar capillary permeability; high-pressure-statin pretreatment vs. high-pressure-no statin, -0.013 +/- 0.017 g/min/mm Hg/100g vs. 1.723 +/- 0.495 g/min/mm Hg/100g; p < .001), lower weight gain (i.e., less edema formation; 4.62 +/- 1.50 grams vs. 17.75 +/- 4.71 grams; p = .005), improved hemodynamics (i.e., lower increase in mean pulmonary artery pressure; 0.56 +/- 0.51 mm Hg vs. 5.62 +/- 1.52 mm Hg; p = .04), lower protein concentration in bronchoalveolar lavage fluid (p < .001), and fewer histologic lesions (p = .013). Apoptosis of lung parenchyma cells was not different (p = .97). There was no difference between low-pressure-statin pretreatment and low-pressure-no statin groups regarding these outcomes. CONCLUSION In this model, atorvastatin improves alveolar capillary permeability and hemodynamics and, thus, attenuates lung injury caused by high-stretch mechanical ventilation.

The mechanisms of the N-terminal-pro-brain natriuretic peptide (NT-pro-BNP) release in intensive care unit (ICU) patients with preserved ejection fraction (EF) are unclear. We investigated whether left ventricular (LV) dysfunction, as assessed by tissue Doppler imaging (TDI), is related to NT-pro-BNP levels in ICU patients with preserved EF and has a complementary value to NT-pro-BNP in the determination of in-hospital mortality. We examined 58 mechanically ventilated patients with no history of heart failure (age, 60 +/- 18 years; EF, 63% +/- 7%). The systolic (S) and early diastolic (E') velocity of the mitral annulus by TDI and the E/E' as well as NT-pro-BNP, troponin, lactate acid, blood oxygen (P(O2)/Fi(O2)), sepsis, and ICU mortality were assessed. Systolic, E', and E/E' correlated with age, P(O2)/Fi(O2), lactate acid, NT-pro-BNP, troponin, history of arterial hypertension, and diabetes (P < 0.05). By multivariate analysis, the determinants of NT-pro-BNP were S (P = 0.024), E/E' (P = 0.017), and sepsis (P = 0.015). An NT-pro-BNP greater than 941 pg/mL was a reliable predictor of LV diastolic dysfunction defined as a composite of E' less than or equal to 8 cm/s and/or mean E/E greater than or equal to 13 (area under the curve, 75%; P = 0.03). Patients with combined NT-pro-BNP greater than 941 pg/mL and abnormal TDI markers had increased creatinine levels and a lower MAP, P(O2)/Fi(O2), and survival rate than those with abnormal TDI or NT-pro-BNP alone or patients with normal TDI markers and NT-pro-BNP (25%, 60%, 70%, and 84%, respectively; P < 0.05). The addition of abnormal TDI in a model including NT-pro-BNP and sepsis increased the model's value for in-hospital mortality (P for change = 0.01). In ICU patients with preserved EF, LV diastolic dysfunction and sepsis determine NT-pro-BNP levels. Tissue Doppler imaging markers and NT-pro-BNP have a complementary value for in-hospital mortality.

The present study aimed to determine whether amino-terminal pro-brain natriuretic peptide (NT-pro-BNP) predicts intensive care unit (ICU) mortality in a cohort of general, noncardiac, critically ill patients. To this end, a total of 233 consecutive mechanically ventilated patients (109 men) having a median age of 60 years and a wide range in admitting diagnoses, including medical (n = 118), surgical (n = 83), and multiple trauma (n = 32) cases were prospectively studied. Median Acute Physiology and Chronic Health Evaluation (APACHE) II and Sequential Organ Failure Assessment scores on ICU admission were 16 and 9, respectively. The study end point was ICU outcome. Blood samples were drawn on admission in the ICU and on postadmission days 1 and 2 to determine NT-pro-BNP levels. In a subgroup (n = 77), admission proinflammatory and anti-inflammatory cytokine levels, including TNF-alpha, IL-6, and IL-10, were also measured. Nonsurvivors (n = 98) had significantly higher NT-pro-BNP levels than survivors (n = 135) on admission in the ICU (2,074 vs. 283 pg/mL; P0.001), on day 1 (2,197 vs. 221 pg/mL; P0.001), and on day 2 (2,726 vs. 139 pg/mL; P0.001). Median values for TNF-alpha, IL-6, and IL-10 were 3.70, 131.57, and 111.88 pg/mL, respectively. Receiver operating characteristic analysis showed that the area under the receiver operating characteristic curve in predicting ICU mortality was 0.70 for APACHE II and 0.77 for admission NT-pro-BNP (P = 0.08). The cutoff in admission NT-pro-BNP that best predicted outcome was 941 pg/mL. Multiple logistic regression analysis revealed that APACHE II score (odds ratio, 1.06; P = 0.007) and the best cutoff point in admission NT-pro-BNP (odds ratio, 7.74; P0.001) independently predicted ICU mortality, even if cytokines were entered in the analysis. In conclusion, plasma NT-pro-BNP is frequently raised in noncardiac, mixed, critically ill patients, and nonsurvivors have consistently higher levels than survivors. Elevated admission NT-pro-BNP represents an independent predictor for poor ICU outcome in the presence of clinical severity scores.

There is increasing discussion of a potential role for statins in the management of sepsis. A search of PubMed, Embase, Scopus and the Cochrane Library databases was performed by combining the terms ‘statins’, ‘infection’, ‘sepsis’, ‘bacteraemia’, ‘pneumonia’, and ‘ICU infections’. A total of 22 studies were retrieved, which included 177 260 people and compared clinical outcomes between 51 193 statin users and 126 067 non-statin users. Nineteen were cohort studies (seven prospective and 12 retrospective), two were retrospective case–control studies, and one was a randomized controlled study. Nine studies examined the use of statins in sepsis, four in community-acquired pneumonia (CAP), three in bacteraemia, and three in post-operative patients. Mortality data were presented in 15 studies; in ten, mortality was lower among statin users (three of six sepsis studies, five of six CAP studies, and two of three bacteraemia studies). In four studies, there was no difference in mortality (two of six sepsis studies, one of six CAP studies, and one of three bacteraemia studies) and in one study there was increased mortality among septic intensive-care unit patients receiving statins. Five of the nine studies that examined the risk of developing sepsis/infection as a primary outcome (six of nine sepsis studies and all studies in the postoperative setting) found a decreased risk among statin users, whereas the remaining studies found no difference. Irrespective of their design (matched vs. non-matched), the majority of the studies suggested that statins have a beneficial effect on the outcome of infection; however, their observational design does not allow us to draw firm conclusions. The clinical benefit of statin therapy in sepsis remains to be determined by ongoing randomized controlled trials.

Intoduction Increased levels of plasminogen activator inhibitor-1 (PAI-1) have been associated with worse outcome in ALI/ARDS. A single guanosine insertion/deletion (4G/5G) polymorphism in the promoter region of the PAI-1 gene, may play an important role in the regulation of PAI-1 expression. The objective of the study was to evaluate the effect of this polymorphism on the outcome of critically ill patients with ALI/ARDS. Materials and Methods 52 consecutive ventilated patients with ALI/ARDS were studied. Bronchoalveolar lavage was performed within 48 hours from diagnosis. Measurement of plasma and BALF PAI-1 activity and D-dimers levels, and 4G/5G genotyping of PAI-1 were carried out. The primary outcome was 28-day mortality, and secondary outcomes included organ dysfunction and ventilator-free days. Results 17 patients were homozygotes for the 4G allele. Severity scores were not different between subgroups upon study enrollment. 28-day mortality was 70.6% and 42.9% for the 4G-4G and the non-4G-4G patients, respectively (p = 0.06). PAI-1 activity levels and D-dimer in plasma and BALF were not significantly different between the 4G-4G and the non-4G-4G subgroups. In the multivariate analysis, genotype 4G/4G was the only variable independently associated with 28-day mortality (Odds Ratio = 9.95, 95% CI: 1.79-55.28, p = 0.009). Furthermore, genotype 4G/4G and plasma PAI-1 activity levels were independently negatively associated with ventilator free days (p = 0.033 and p = 0.008, respectively). Conclusions ALI/ARDS patients, homozygous for the 4G allele of the PAI-1 gene, experienced higher 28-day mortality. This genotype was associated with a reduction in the number of days of unassisted ventilation and was inversely associated with the number of days without organ failure.

BACKGROUND: Mechanical ventilation and administration of a high oxygen concentration are simultaneously used in the management of respiratory failure. We conducted this study to evaluate the effect of a high inspired oxygen concentration on ventilator-induced lung injury. METHODS: Forty sets of isolated/perfused rabbit lungs were randomized for 60 min of pressure-control ventilation at a plateau inspiratory pressure of 25 or 15 cm H(2)O and positive end-expiratory pressure of 3 cm H(2)O while receiving 100% or 21% O(2). The temperature, pH, and partial pressure of CO(2) in the perfusate were maintained the same in all groups (n = 10 for each group). The outcome measures used to assess lung injury included: the change in weight gain and ultrafiltration coefficient, the frequency of vascular failure, the histological lesions and the concentration of tumor necrosis factor-alpha and malondialdehyde in the bronchoalveolar lavage fluid. RESULTS: The two groups ventilated at the higher inspiratory pressure/tidal volume experienced greater weight gain and increases in the ultrafiltration coefficient, more frequently suffered vascular failure, and presented higher composite scores of histological damage than the two groups ventilated at the lower inspiratory pressure/tidal volume. Hyperoxia was not found to further increase any of the monitored markers of lung injury. No difference was noticed among the four experimental groups in the alveolar lavage fluid levels of tumor necrosis factor-alpha or malondialdehyde. CONCLUSIONS: These findings suggest that short-term administration of a high oxygen concentration is not a major determinant of ventilator-induced lung injury in this experimental model.

Purpose Human DNA topoisomerases I and II (topo-I and -II) are essential for vital cellular processes such as DNA replication, transcription, translation, recombination, and repair. In the present study, we correlate topo-I and -II expression and outcome after chemotherapy in primary and relapsed colorectal cancer. Patients and methods Patients with colorectal cancer that had recurred, following surgery and adjuvant chemotherapy and underwent a second operation were included in the present study. All had undergone surgical resection of the primary tumor and received post-operatively 5-FU-based (5FU + Leucovorin, Mayo Clinic regimen) adjuvant chemotherapy. Tumor tissue was collected at the initial operation from the primary tumor and at the time of recurrence (during the second operation following chemotherapy). All tissue samples were analyzed for levels of expression of both topo-I and topo-IIa using standard three-step immunohistochemistry on paraffin sections. Results Forty patients were included. Levels of expression of topo-I and topo-II were higher in malignant cells from tumor recurrences compared to primary tumors (P = 0.0001 for both). There was a statistically significant positive relationship between patients age and levels of topo-I (P = 0.011) and topo-II (P = 0.011) expression. Conclusions The study results reported here underscore the role of topoisomerase expression in colorectal cancer and suggest a potential role in tumor recurrence.

Objective. This study was conducted to investigate the efficacy and safety of gabapentin monotherapy in the management of chemotherapy-induced neuropathic pain. Patients. Seventy-five cancer patients who had previously received chemotherapy, and had experienced at least one symptom of neuropathic pain were included in the intervention group. They received a fixed low-dose of gabapentin (800 mg/day). The control group consisted of 35 cancer patients with similar treatment history and symptomatology, who refused treatment with gabapentin and, therefore, received a fixed-dose combination of naproxen and codeine/paracetamol. Outcome Measures. Patients were grouped in three categories according to the severity of their neuropathic symptoms at baseline: mild, moderate, and severe. Analgesic efficacy of the study drug was assessed by means of a patient-answered questionnaire. Four stages of analgesic response were established: complete, partial, minor, and no response. Results. All patients completed the study and were evaluable. In the intervention arm, gabapentin led to a complete response in 25.3% of patients (19/75), partial response in 44% (33/75), minor response in 25.3% (19/75), and no response in 5.3% (4/75). The response to gabapentin correlated with the severity of the underlying neurotoxicity. Approximately 25% of patients receiving gabapentin experienced mild somnolence, but none discontinued it. In the control group, none experienced complete response (0/35), while partial, minor, and no response were observed in 5.7% (2/35), 45.7% (16/35), and 48.6% (17/35), respectively. Compared with the control group, gabapentin therapy led to a statistically significant better response in patients of each baseline neurotoxicity group. Conclusions. Gabapentin monotherapy seems to be well tolerated and useful for the management of chemotherapy-induced neuropathic pain.

Even though significant progress has been made, chemotherapy-induced emesis remains a challenging problem. Few studies focus on emesis in patients treated with carboplatin and the observation period is limited to the initial 24 h following chemotherapy. Thus, we investigated if tropisetron (T) monotherapy can adequately prevent acute and delayed emesis in non-small-cell lung cancer (NSCLC) patients receiving a moderately emetogenic chemotherapy (MEC) (carboplatin-containing) regimen. Furthermore, we explored the merits of adding dexamethasone (D) or alprazolam (A) to T, especially in the setting of a pre-existing high level of stress. We studied 60 patients with advanced NSCLC receiving carboplatin and taxanes in three consecutive cycles. During the first cycle, patients received 5 mg of T intravenously before chemotherapy and the same dose per os on each of the following 3 days. In the second cycle, T was co-administered with 8 mg of D once a day, while, during the third cycle, T was combined with per os A 0.25 mg every 12 h and continued over the following 3 days. Finally, we evaluated the impact of stress on the anti-emetic response achieved with the previously described regimens. The combination of T + A was superior to T monotherapy and the combination of T + D, regarding the prevention of acute and delayed emesis. Both T + A and T + D combinations led to appetite improvement, while patients receiving T + A experienced sedation more frequently. Interestingly, subgroup analysis revealed that patients without underlying stress obtained no further benefit by the addition of A or D, while both T + A and T + D combinations led to a better anti-emetic response in patients with stress. In conclusion, T monotherapy provides a satisfactory result in controlling nausea and emesis caused by a MEC regimen in patients without stress. However, the addition of D and, mainly, A improves its anti-emetic effect in patients with obvious stress.

Given the prevalence of leishmaniasis and cancer, the co-existence of these two diseases may be merely coincidental. However, a number of epidemiological, experimental and laboratory studies suggest that an association between these two entities does exist. The aim of this review is to summarise the occurrence of leishmaniasis as an opportunistic infection associated with malignant disorders and to present the available literature potentially linking this infection with the development of cancerous lesions. We searched electronic databases and evaluated 37 studies involving 44 patients. Four different types of association between leishmaniasis and cancer were established: leishmaniasis mimicking a malignant disorder, such as lymphoma; leishmaniasis arising as a difficult to diagnose and treat infection among patients receiving chemotherapy for various malignant disorders; simultaneous diagnosis of leishmaniasis and a neoplastic disorder in the same tissue samples of immunocompromised patients; and direct involvement of Leishmania spp. in the pathogenesis/occurrence of malignant lesions, especially of the skin and mucous membranes. The main conclusion of this review is that leishmaniasis can directly or indirectly affect the presentation, diagnosis and course of various malignant disorders and it should be considered in the differential diagnosis of malignancies in geographic areas where it is endemic and/or in patients with travel history to these areas.

Objective: Previous meta-analyses reported advantages of passive (i.e., heat and moisture exchangers, or HMEs) compared with active (i.e., heated humidifiers, or HHs) humidifiers in reducing the incidence of ventilator-associated pneumonia, but they did not examine the effect of these devices on mortality, length of intensive care unit stay, and duration of mechanical ventilation. In addition, relevant data were recently published. Design: Meta-analysis of randomized controlled trials comparing HMEs with HHs for the management of mechanically ventilated patients to determine the impact of these devices on clinical outcomes of such patients. Methods: We searched PubMed and the Cochrane Central Register of Controlled Trials as well as reference lists from publications, with no language restrictions. We estimated pooled odds ratios (ORs) and 95% confidence intervals (CIs), using a random effects model. Results: Thirteen randomized controlled trials, studying 2,580 patients, were included. There was no difference in incidence of ventilator-associated pneumonia among patients managed with HMEs and HHs (OR 0.85, 95% CI 0.62–1.16). There was no difference between the compared groups regarding mortality (OR 0.98, 95% CI 0.80–1.20), length of intensive care unit stay (weighted mean differences, -0.68 days, 95% CI -3.65 to 2.30), duration of mechanical ventilation (weighted mean differences, 0.11 days, 95% CI -0.90 to 1.12), or episodes of airway occlusion (OR 2.26, 95% CI 0.55–9.28). HMEs were cheaper than HHs in each of the randomized controlled trials. Conclusion: The available evidence does not support the preferential performance of either passive or active humidifiers in mechanical ventilation patients in terms of ventilator-associated pneumonia incidence, mortality, or morbidity.

Purpose of review The alarming epidemic of multidrug-resistant bacteria and the reluctance of the pharmaceutical industry to invest in the development of new antibiotics have forced clinicians to reintroduce forgotten antibiotics into their practice. This review highlights the effectiveness and safety of older antibiotics when used in the treatment of infections of critically ill patients. Recent findings Polymyxins emerged as useful antibiotics for the treatment of infections due to multidrug-resistant Gram-negative bacteria, in particular Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae. The nephrotoxicity and neurotoxicity associated with their use are less frequent and serious than previously reported. In addition, aerosolized polymyxins may be a useful weapon in the treatment of hospital-acquired pneumonia. Fosfomycin and chloramphenicol have a wide antimicrobial spectrum, are used extensively in Europe and Africa, respectively, and may have an expanded role in our antimicrobial arsenal. Fusidic acid remains active against various staphylococcal strains, while isepamicin (an aminoglycoside used in some European countries) is slightly more effective than amikacin against some Gram-negative bacteria. Summary The declining investment of the pharmaceutical industry in the development of new antibiotics and the increasing antimicrobial resistance create a fertile ground for the study and, probably, revival of older antibiotics for use, especially in critically ill patients.

Cardiotoxicity associated with 5-Fluorouracil (5FU) administration has been infrequently reported in literature, albeit various series of acute coronary syndromes have recorded a low but definite incidence of the above toxicity. In the present study, patients undergoing 5FU-based and oral capecitabine (Xeloda®)-based chemotherapy were tested for the potential development of cardiac-related symptoms during their administration. Six hundred and forty-four patients entered the study. Those experiencing any cardiac-related symptoms during 5FU infusion or oral capecitabine were subjected to ECG and serum cardiac enzymes determination. If cardiotoxicity was confirmed, 5FU infusion or oral capecitabine were interrupted, sublingual nitrates administered and cardiac monitoring initiated, while patients with >two-fold enzyme elevation were followed in a coronary care unit for at least 72 h. Cases with acute myocardial infarction were excluded from further 5FU or oral capecitabine treatment. Overall 26 patients (4.03%) developed symptoms and/or ECG abnormalities due to 5FU and capecitabine. Patients with continuous 5FU infusion presented a higher incidence of cardiotoxicity [14/209; 6.7%, 95% confidence interval (CI) = 3.3–10.1%] than the remaining (7/317; 2.3%, 95% CI = 0.8–3.3%) (P

Objectives: Infections due to multidrug-resistant (MDR) Gram-negative pathogens in the ICU have prompted the use of colistin, an antibiotic forgotten for decades. The aim of this retrospective observational study was to record and present the emergence of colistin-resistant Klebsiella pneumoniae (CRKB) in a Greek ICU. Methods: In a new university tertiary hospital, the first patients admitted in the ICU were already colonized or infected with MDR pathogens, and this led to frequent colistin use as part of empirical or microbiologically documented therapy. Colistin resistance was defined as MIC >4 mg/L by the Etest method. All CRKB isolated in surveillance cultures or clinical specimens in the ICU during the period 2004-5 were recorded along with patients' characteristics. Results: Eighteen CRKB were isolated from 13 patients over a 16 month period, representing either colonizing or infective isolates. Patients' mean age was 70 years, with a mean APACHE II score at admission of 22. They all had a long hospitalization (median 69 days) and a long administration of colistin (median 27 days). Colistin-resistant isolates were implicated as pathogens in two bacteraemias, a ventilator-associated pneumonia and two soft tissue infections. Repetitive extragenic palindromic PCR identified six distinct clones, and horizontal transmission was also documented. Conclusions: Selective pressure due to extensive or inadequate colistin use may lead to the emergence of colistin resistance among K. pneumoniae isolates, jeopardizing treatment options in the ICU, potentially increasing morbidity and mortality of critically ill patients and necessitating prudent use of colistin.

To establish whether cytokine release is implicated in thyroid hormone changes during surgical stress we studied 36 adult patients (20 men; mean age ± SD: 68.5 ± 10.5 years) undergoing elective major abdominal operations. We measured tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-8 and IL-10 and thyrotropin (TSH), free thyroxine (FT4) and triiodothyronine (T3) before scheduled non-emergency surgery, immediately postoperatively, on the 1st postoperative day (post-1) and on the 2nd postoperative day (post-2). TNF-α, IL-6 and IL-8 peaked on day post-1 whereas IL-10 peaked immediately postoperatively. Fourteen of 36 patients had low T3 levels after surgery, indicating non-thyroidal illness (NTI). Significant negative correlations were noted among TNF-α, IL-6 and IL-8 against T3 and FT4. Cytokines are responsible, at least in part, for NTI following major operations.

Background: The course of serum cytokine levels in patients with postoperative systemic inflammatory response syndrome (SIRS) after major abdominal surgery remains currently unclear. Methods: Blood was sampled pre- and post-operatively and on days 1 and 2 in 40 patients undergoing major abdominal surgery. Concentrations of tumour necrosis factor-alpha (TNFα), interleukin (IL) -6, IL-8, and IL-10 were measured by the LINCOplex assay; those of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay. Results: Compared to their pre-operative values, sTREM-1 was elevated on day 2; TNFα on day 1; IL-6 and IL-10 post-operatively and on days 1 and 2; and IL-8 post-operatively and on day 1. The duration of operation correlated with TNFα and IL-10 at all sampling times, and with IL-6 post-operatively. There were no differences in cytokine concentrations between patients who exhibited post-operative complications and those who did not. IL-10/TNFα below 30 was found in all patients with complications (100%) and in 20 patients without complications (64.5%, p: 0.043). Conclusions: SIRS following major surgery is characterised by complex alterations in cytokine concentrations. The balance between TNFα and IL-10 seems to determine the occurrence of post-operative complications.

MD is a bedside in vivo sampling technique that permits continuous analysis of a patient's interstitial fluid chemistry. As the interstitial fluid bathes the cells, its composition reflects the local metabolic activity of those cells thus reflecting intracellular metabolic changes and disorders. The primary substances that provide information about metabolism are lactate, pyruvate, glycerol and glucose. In addition, blood metabolic alterations have been well characterized in severely ill patients. In vivo MD is performed by implanting a commercially available catheter that mimics a blood capillary at the site of interest.

We sought to evaluate the potential enhanced fibrinolytic and antiplatelet activity of dabigatran etexilate (DE) due to decreased thrombin levels in patients with stroke or transient ischemic attack and non-valvular atrial fibrillation (NVAF).Consecutive patients with cerebrovascular diseases and NVAF that were treated with DE in a tertiary university hospital. Fibrinolysis and platelet function were assessed by thromboelastometry (ROTEM) and platelet function analyzer (PFA)-100, respectively, before and after treatment with DE. Conventional coagulation tests, endogenous thrombin potential (ETP) and hemoclot thrombin inhibitors (HTI), were also performed in order to detect any possible correlation between dabigatran plasma levels, its anticoagulant activity and the intensity of platelet dysfunction or fibrinolysis.A total of nineteen patients fulfilled our inclusion criteria (mean age 62.3±7.2years; 47% males; median CHADS2-score: 3; interquartile range: 2-4). DE treatment was associated with a significant reduction of the lysis index (LI60) at 60min (p=0.036), and prolongation of the PFA-100 CEPI closure time (p=0.024). After dabigatran treatment, abnormal PFA-100 results were obtained in two patients (11%, 95% CI: 2%-33%). DE levels (determined by HTI) were strongly inversely correlated (rho=-0.85; p0.001) with the area under the curve (AUC) values in ETP assay. Νo association was found between HTI and PFA-100 CEPI CT (p=0.64), or LI60 measurements (p=0.60).Our findings indicate that DE might affect platelet function and fibrinolysis and highlight the potential role of ETP as an alternative option in DE monitoring. The intensity and clinical relevance of DE antiplatelet and fibrinolytic effects require further investigation.

To investigate the pattern of pituitary-adrenal responses to human corticotropin-releasing hormone (hCRH) in critically ill patients and to examine the relation between responses and clinical outcome.Prospective study in consecutive critically ill patients in a general intensive care unit in a teaching hospital.The study included 37 critically ill, mechanically ventilated patients with diverse underlying diagnoses (28 men, 9 women; median age 56 years).A morning blood sample was obtained to measure baseline cortisol, corticotropin (ACTH), and cytokines. Patients were then injected with 100 microg hCRH, and plasma cortisol and ACTH were measured over a period of 2 h.In the overall patient population baseline and peak cortisol concentrations following hCRH were 16+/-5 and 21+/-5 microg/dl, respectively, and median baseline and peak ACTH levels 23 and 65 pg/ml, respectively. Higher ACTH levels and longer release of cortisol were noted in nonsurvivors (n=18) than in survivors (n=19). Furthermore, nonsurvivors had higher concentrations of interleukin 8 (115 vs. 38 pg/ml) and interleukin 6 (200 vs. 128 pg/ml) than survivors.Critically ill patients demonstrate altered pituitary-adrenal axis responses to hCRH. This is particularly evident in the sickest patients with the highest degree of inflammatory profile who ultimately do not survive.

An understanding of the epidemiology of multi-drug-resistant (MDR) Acinetobacter baumannii and Pseudomonas aeruginosa infections is necessary in order to develop strategies to curtail their spread. For this purpose, the evidence linking the isolation of MDR A. baumannii and P. aeruginosa with specific risk factors was evaluated. PubMed was searched for the 20-year period from September 1985 to September 2005, and eligible studies were considered to be those that: (1) linked the isolation of A. baumannii and P. aeruginosa with specific risk factors; (2) described the characteristics of the affected patients in detail; and (3) provided data on the antibiotic resistance profile of the isolated micro-organisms. Fifty-five studies were found referring to A. baumannii (28 with case-control methodology and 27 outbreak investigations without case-control methodology), and 42 studies were found referring to P. aeruginosa (25 with case-control methodology and 17 outbreak investigations without case-control methodology). Although heterogeneous study designs and investigated risk factors limited this analysis, it was concluded that acquisition and spread of these micro-organisms appear to be related to a large number of variables. Among the most important were deficiencies in the implementation of infection control guidelines and the use of broad-spectrum antibiotics. Use of carbapenems and third-generation cephalosporins appear to be related to the development of an MDR phenotype by A. baumannii, while carbapenems and fluoroquinolones are implicated in MDR P. aeruginosa. The diversity of risk factors associated with the development of MDR A. baumannii and P. aeruginosa suggests that a separate outbreak investigation should be performed in each hospital setting. The development of innovative control strategies is needed in order to limit the spread of these pathogens.

Spontaneous remission of acute myeloid leukemia (AML) in adults is a rare but well documented phenomenon. This study reports on a 64-year-old male patient with acute myelogenous leukemia (AML-M4, according to the French-American-British classification) that was developed on a background of chronic myelomonocytic leukemia (CMML) and then underwent remission after treatment with the gonadotropin-releasing hormone agonist (GnRH agonist) triptorelin for presumed prostate cancer. Remission persisted for at least 4 years before the patient was lost to follow-up. To the author' knowledge, this is the first report of remission in an AML-M4 case associated with hormone manipulation. Possible mechanisms of this phenomenon are discussed.

We report a case of severe ovarian hyperstimulation syndrome (OHSS) complicated by community-acquired methicillin-resistant Staphylococcus aureus-Panton-Valentine leukocidin positive (CAMRSA-PVL[+]) necrotizing pneumonia, sepsis and multiple organ failure (MOF) in a previously immunocompetent female. The patient required prolonged ventilatory support and intensive care unit (ICU) hospitalization. Multiple cavities and severely affected lung function persist 1 year after discharge.

The Osborn wave is a distinctive deflection occurring at the QRS-ST junction that appears characteristically in hypothermic patients after exposure to a cold environment.We present a critically ill hospitalized patient that developed Osborn waves in association with sepsis-induced hypothermia. A 56-year-old woman with metastatic breast cancer was admitted to our department with respiratory failure due to diaphragmatic paralysis. The arterial blood gas analysis on room air revealed hypercapnic and hypoxic respiratory acidosis with a pH of 7.30, PaO2 of 40.3 mm Hg, PaCO2 of 57.5mmHg, andHCO3 32.6mEq. The patient was transferred to the intensive care unit (ICU) and noninvasive positive pressure ventilation was started. Her hospital stay was complicated by superior vena cava syndrome and multiple nosocomial infections. During her hospitalization and while she was treated forCandida albicans peritonitis (diagnosed after ascitic fluid cultures), her rectal temperature decreased to 34.3 °C over the course of 3 h. She became hemodynamically unstable with blood pressure 92/ 35 mm Hg and heart rate 69 beats per minute. Prominent Osborn (J) waveswere noticed on themonitor's screen (Fig. 1). There was also a PR interval of borderline duration (200 ms) and a prolonged QT interval, (QTc 520 ms). Blood glucose level at that time was 90 mg/dl. White blood cell count was elevated (15,000/μl), while blood electrolyte levels were

We report the case of a 65-year-old male patient with acute myelogenous leukemia who developed severe respiratory failure after receiving cytarabine treatment. Chest radiograph showed bilateral alveolar infiltrates. He was intubated and underwent flexible bronchoscopy. An extensive diagnostic work-up revealed no evidence of infection. Steroids were added to empiric antibiotic treatment and the patient was successfully extubated in 5 days. Cytarabine-induced lung injury should be considered in the differential diagnosis of alveolar infiltrates in immunocompromised patients. If bronchoscopy fails to confirm an infectious cause, a short course of steroids must be tried, which probably leads to a favorable outcome.

Background A previous randomized study showed that clarithromycin decreases the risk of death due to ventilator-associated pneumonia and shortens the time until infection resolution. The efficacy of clarithromycin was tested in a larger population with sepsis. Methods Six hundred patients with systemic inflammatory response syndrome due to acute pyelonephritis, acute intra-abdominal infections or primary Gram-negative bacteraemia were enrolled in a double-blind, randomized, multicentre trial. Clarithromycin (1 g) was administered intravenously once daily for 4 days consecutively in 302 patients; another 298 patients were treated with placebo. Mortality was the primary outcome; resolution of infection and hospitalization costs were the secondary outcomes. Results The groups were well matched for demographics, disease severity, microbiology and appropriateness of the administered antimicrobials. Overall 28 day mortality was 17.1% (51 deaths) in the placebo arm and 18.5% (56 deaths) in the clarithromycin arm (P = 0.671). Nineteen out of 26 placebo-treated patients with septic shock and multiple organ dysfunctions died (73.1%) compared with 15 out of 28 clarithromycin-treated patients (53.6%, P = 0.020). The median time until resolution of infection was 5 days in both arms. In the subgroup with severe sepsis/shock, this was 10 days in the placebo arm and 6 days in the clarithromycin arm (P = 0.037). The cost of hospitalization was lower after treatment with clarithromycin (P = 0.044). Serious adverse events were observed in 1.3% and 0.7% of placebo- and clarithromycin-treated patients, respectively (P = 0.502). Conclusions Intravenous clarithromycin did not affect overall mortality; however, administration shortened the time to resolution of infection and decreased the hospitalization costs.

The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. We assessed simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of ARDS patients.

Despite a documented decrease in sepsis-associated mortality in the developed world over the past decade, sepsis remains a major public health problem that claims more than 200,000 deaths each year in the United States (US) alone (1,2). The ongoing challenge to understand the complex biological mechanisms underlying susceptibility to infection and organ dysfunction and its associated mortality is complemented by the persistent need for high-quality clinical epidemiology studies that provide investigators and health-policy makers with updated data about disease patterns.