Christina Sotiropoulou

Angiopoietin-2 is increased in severe sepsis: correlation with inflammatory mediators.

Objective: Angiopoietin (Ang)‐2 is an endothelium‐specific growth factor, regulated by proinflammatory stimuli, that destabilizes vascular endothelium and increases vascular leakage; consequently, Ang‐2 may contribute to sepsis pathophysiology. We have studied 1) serum Ang‐2 levels in critically‐ill patients and investigated potential relationships with inflammatory mediators and indices of disease severity and 2) the effect of sepsis‐related inflammatory mediators on Ang‐2 production by lung endothelium in vitro. Design: Prospective clinical study followed by cell culture studies. Setting: General intensive care unit and research laboratory of a university hospital. Subjects: Human and bovine lung microvascular endothelial cells and 61 patients (32 men). Patients were grouped according to their septic stage as having: no systemic inflammatory response syndrome (n = 6), systemic inflammatory response syndrome (n = 8), sepsis (n = 16), severe sepsis (n = 18), and septic shock (n = 13). Interventions: Cells were exposed to lipopolysaccharide, tumor necrosis factor‐&agr;, and interleukin‐6. Measurements and Main Results: Patients’ serum Ang‐2 levels were significantly increased in severe sepsis as compared with patients with no systemic inflammatory response syndrome or sepsis (p < .05 by analysis of variance). Positive linear relationships were observed with: serum tumor necrosis factor‐&agr; (rs = 0.654, p < .001), serum interleukin‐6 (rs = 0.464, p < .001), Acute Physiology and Chronic Health Evaluation II score (rs = 0.387, p < .001), and Sequential Organ Failure Assessment score (rs = 0.428, p < .001). Multiple regression analysis revealed that serum Ang‐2 is mostly related to serum tumor necrosis factor‐&agr; and severe sepsis. Treatment of human lung microvascular endothelial cells with all mediators resulted in a concentration‐dependent Ang‐2 reduction. Treatment of bovine lung microvascular endothelial cells with lipopolysaccharide and tumor necrosis factor‐&agr; increased Ang‐2 release, and interleukin‐6 reduced basal Ang‐2 levels. Conclusions: First, patients’ serum Ang‐2 levels are increased during severe sepsis and associated with disease severity. The strong relationship of serum Ang‐2 with serum tumor necrosis factor‐&agr; suggests that the latter may participate in the regulation of Ang‐2 production in sepsis. Second, inflammatory mediators reduce Ang‐2 release from human lung microvascular endothelial cells, implying that this vascular bed may not be the source of increased Ang‐2 in human sepsis.

Longitudinal study of PTSD, depression, and quality of life among adolescents after the Parnitha earthquake

OBJECTIVE To investigate the course of PTSD, depression, and current quality of life among adolescents 32-months after the 1999 Parnitha earthquake in Greece. METHODS The follow-up was conducted among 511 adolescents originally evaluated at 3-months post-earthquake using the UCLA PTSD Reaction Index (PTSD-RI), Depression Self-Rating Scale (DSRS), and Quality of Life Questionnaire (QOLQ). RESULTS Mean PTSD scores for the whole sample had subsided to mild levels; however, 8.8% were still experiencing moderate to severe levels of symptoms, and 13.6% met criteria for clinical depression. Frequency of experiencing reminders of the earthquake in the past month best explained the variance (15%) in PTSD severity, followed by depression at 3-months (8%). The QOLQ domain scores were negatively correlated with PTSD and depression. Depression at 3-months was the best predictor of QOLQ at 32-months, explaining 16% of the variance. LIMITATIONS Self-report instruments were used; hence the responses may have been over- or under-estimated; also, the findings may not be generalizable to other ethnic groups. CONCLUSION Ongoing screening is recommended after disaster to identify adolescents who continue to experience moderate to severe levels of PTSD and depressive symptoms. Specific interventions to reduce reactivity to earthquake-related reminders should be a component of post-disaster recovery programs. A quality of life measure can provide important information in addition to traditional scales for monitoring the course of recovery among adolescents after disasters.

Expiratory flow limitation in morbidly obese postoperative mechanically ventilated patients

Although obesity promotes tidal expiratory flow limitation (EFL), with concurrent dynamic hyperinflation (DH), intrinsic PEEP (PEEPi) and risk of low lung volume injury, the prevalence and magnitude of EFL, DH and PEEPi have not yet been studied in mechanically ventilated morbidly obese subjects.

MRC chronic Dyspnea Scale: Relationships with cardiopulmonary exercise testing and 6-minute walk test in idiopathic pulmonary fibrosis patients: a prospective study.

BackgroundExertional dyspnea is the most prominent and disabling feature in idiopathic pulmonary fibrosis (IPF). The Medical Research Chronic (MRC) chronic dyspnea score as well as physiological measurements obtained during cardiopulmonary exercise testing (CPET) and the 6-minute walk test (6MWT) are shown to provide information on the severity and survival of disease.MethodsWe prospectively recruited IPF patients and examined the relationship between the MRC score and either CPET or 6MWT parameters known to reflect physiologic derangements limiting exercise capacity in IPF patientsResultsTwenty-five patients with IPF were included in the study. Significant correlations were found between the MRC score and the distance (r = -.781, p < 0.001), the SPO2 at the initiation and the end (r = -.542, p = 0.005 and r = -.713, p < 0.001 respectively) and the desaturation index (r = .634, p = 0.001) for the 6MWT; the MRC score and VO2 peak/kg (r = -.731, p < 0.001), SPO2 at peak exercise (r = -. 682, p < 0.001), VE/VCO2 slope (r = .731, p < 0.001), VE/VCO2 at AT (r = .630, p = 0.002) and the Borg scale at peak exercise (r = .50, p = 0.01) for the CPET. In multiple logistic regression analysis, the only variable independently related to the MRC is the distance walked at the 6MWT.ConclusionIn this population of IPF patients a good correlation was found between the MRC chronic dyspnoea score and physiological parameters obtained during maximal and submaximal exercise testing known to reflect ventilatory impairment and exercise limitation as well as disease severity and survival. This finding is described for the first time in the literature in this group of patients as far as we know and could explain why a simple chronic dyspnea score provides reliable prognostic information on IPF.

Plasma pro- and anti-inflammatory cytokine levels and outcome prediction in unselected critically ill patients

PURPOSE To determine the inter-relationships between cytokine levels and physiological scores in predicting outcome in unselected, critically ill patients. METHODS To this end, 127 patients (96 men), having a mean+/-SD age of 45+/-20 years, with a wide range in admission diagnoses (medical, surgical, and multiple trauma patients) were prospectively investigated. Severity of critical illness and organ dysfunction were graded by acute physiology and chronic health evaluation (APACHE II) and sequential organ failure assessment (SOFA) scores, respectively. Blood samples were drawn on admission in the ICU to determine pro- and anti-inflammatory cytokines, including tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, IL-8, and IL-10. The main outcome measure was 28-day mortality. RESULTS Overall, 88 patients survived and 39 patients died. Univariate logistic regression analysis showed that SOFA, APACHE II, IL-8, IL-6, and IL-10 on admission in the ICU were related to mortality. Multiple logistic regression analysis in the entire cohort of critically ill patients revealed that SOFA (OR=1.341, p<0.001) and IL-6 (OR=1.075, p=0.01) constituted independent outcome predictors. receiver operator characteristics curve analysis showed that SOFA, APACHE II, and IL-6 had the highest area under the curve values. IL-6 correlated with APACHE II (r(s)=0.44, p<0.0001) and SOFA (r(s)=0.40, p<0.0001) scores. CONCLUSIONS In mixed ICU patients cytokine concentrations on admission in the ICU represent independent outcome predictors in the presence of disease severity scores.

Application of the sequential organ failure assessment (SOFA) score to bacteremic ICU patients

Background:Patients admitted to intensive care units (ICUs) are at a high risk of acquiring blood stream infections. We examined whether SOFA score on ICU admission and on the day of bacteremia can predict the occurrence of bacteremia and the outcome of bacteremic ICU patients.Patients and Methods:All patients admitted to a multidisciplinary ICU for more than 48 h from January 1, 2002 to December 31, 2004, were prospectively studied. Demographic, clinical and laboratory data were recorded on admission for all patients and additionally, on the day of the first bacteremic episode for those patients who developed bacteremia. Accordingly, APACHE II and SOFA scores were calculated on the same day.Results:A total of 185 patients developed one or more episodes of bacteremia, giving an incidence of 9.6 per 1,000 ICU days. The ICU mortality rate was 43.9% for bacteremic and 25.8% for the remaining patients (p < 0.001). Admission SOFA score was independently associated with the occurrence of bacteremia (OR = 1.20, 95% CI: 1.11–1.26, p < 0.001). Among bacteremic patients, SOFA score on the day of bacteremia was the only independent prognostic factor for outcome (OR = 1.44, 95% CI: 1.21–1.71, p < 0.001). When all patients were included in the multivariate analysis, admission SOFA (OR = 1.3, CI: 1.16–1.38, p < 0.001), APACHE II (OR = 1.1, CI: 1.02–1.11, p = 0.003) score and the presence of bacteremia (OR = 1.8, CI: 1.1–2.9, p = 0.023) were independently associated with the outcome.Conclusion:Admission SOFA score is independently associated with the occurrence of ICU-acquired bacteremia, whereas it is not sufficient to predict the outcome of patients who subsequently will develop this complication. However, SOFA score on the first day of bacteremia is an independent prognostic factor for outcome in these patients.

CD8+ T lymphocytes in bronchoalveolar lavage in idiopathic pulmonary fibrosis

BackgroundRecently it was shown that in Idiopathic Pulmonary Fibrosis (IPF) tissue infiltrating CD8+ T lymphocytes (TLs) are associated with breathlessness and physiological indices of disease severity, as well as that CD8+ TLs recovered by bronchoalveolar lavage (BAL) relate to those infiltrating lung tissue. Since BAL is a far less invasive technique than tissue biopsy to study mechanisms in IPF we further investigated the usefulness offered by this means by studying the relationship between BAL macrophages, neutrophils, eosinophils, CD3+, CD4+, CD8+, CD8+/38+ TLs and CD4+/CD8+ ratio with breathlessness and physiological indices.Patients and methods27 IPF patients, 63 ± 9 years of age were examined. Cell counts were expressed as percentages of total cells and TLs were evaluated by flow cytometry. FEV1, FVC, TLC, RV, D LCO, PaO2, and PaCO2 were measured in all. Breathlessness was assessed by the Medical Research Council (MRC) chronic dyspnoea scale.ResultsCD8+ TLs correlated positively (rs = 0.46, p = 0.02), while CD4+/CD8+ ratio negatively (rs = -0.54, p = 0.006) with the MRC grade. CD8+ TLs correlated negatively with RV (rs = -0.50, p = 0.017). CD8+/38+ TLs were negatively related to the FEV1 and FVC (rs = -0.53, p = 0.03 and rs = -0.59, p = 0.02, respectively). Neutrophils correlated positively with the MRC grade (rs = 0.42, p = 0.03), and negatively with the D LCO (rs = -0.54, p = 0.005), PaO2 (rs = -0.44, p = 0.03), and PaCO2 (rs = -0.52, p = 0.01).ConclusionBAL CD8+ TLs associations with physiological and clinical indices seem to indicate their implication in IPF pathogenesis, confirming our previous tissue study.

Exhaled Breath Condensate in Mechanically Ventilated Brain-injured Patients with No Lung Injury or Sepsis

BACKGROUND The inflammatory influence of prolonged mechanical ventilation in uninjured lungs remains a matter of controversy and largely unexplored in humans. The authors investigated pulmonary inflammation by using exhaled breath condensate (EBC) in mechanically ventilated, brain-injured patients in the absence of acute lung injury or sepsis and explored the potential influence of positive end-expiratory pressure (PEEP). METHODS Inflammatory EBC markers were assessed in 27 mechanically ventilated, brain-injured patients with neither acute lung injury nor sepsis and in 12 healthy and 8 brain-injured control subjects. Patients were ventilated with 8 ml/kg during zero end-expiratory pressure (ZEEP group, n = 12) or 8 cm H(2)O PEEP (PEEP group, n = 15). EBC was collected on days 1, 3, and 5 of mechanical ventilation to measure pH; interleukins (IL)-10, 1β, 6, 8, and 12p70; and tumor necrosis factor-α. RESULTS EBC pH was lower, whereas IL-1β and tumor necrosis factor-α were greater in both patient groups compared with either control group; IL-6 was higher, whereas IL-10 and IL-12p70 were sporadically higher than in healthy control subjects; no differences were noted between the two patient groups, except for IL-10, which decreased by day 5 during PEEP. Leukocytes, soluble IL-6, and soluble triggering receptor expressed on myeloid cells-1 in blood were constantly higher during zero end-expiratory pressure; EBC cytokines appeared mostly related to soluble IL-8 and inversely related to soluble triggering receptor expressed on myeloid cells-1. CONCLUSIONS In brain-injured, mechanically ventilated patients with neither acute lung injury nor sepsis, EBC markers appear to indicate the presence of subtle pulmonary inflammation that is mostly unaffected by PEEP. There is evidence for a systemic inflammatory response, especially in patients during zero end-expiratory pressure.

Risk factors for and influence of bloodstream infections on mortality: a 1-year prospective study in a Greek intensive-care unit.

To determine the incidence, risk factors for, and the influence of bloodstream infections (BSIs) on mortality of patients in intensive-care units (ICUs), prospectively collected data from all patients with a stay in an ICU >48 h, during a 1-year period, were analysed. Of 572 patients, 148 developed a total of 232 BSI episodes (incidence 16.3 episodes/1000 patient-days). Gram-negative organisms with high level of resistance to antibiotics were the most frequently isolated pathogens (157 strains, 67.8%). The severity of illness on admission, as estimated by APACHE II score (OR 1.07, 95% CI 1.04-1.1, P<0.001), the presence of acute respiratory distress syndrome (OR 3.57, 95% CI 1.92-6.64, P<0.001), and a history of diabetes mellitus (OR 2.37, 95% CI 1.36-4.11, P=0.002) were risk factors for the occurrence of BSI whereas the development of an ICU-acquired BSI was an independent risk factor for death (OR 1.76, 95% CI 1.11-2.78, P=0.015). Finally, the severity of organ dysfunction on the day of the first BSI episode, as estimated by SOFA score, and the level of serum albumin, independently affected the outcome (OR 1.44, 95% CI 1.22-1.7, P<0.001 and OR 0.47, 95% CI 0.23-0.97, P=0.04 respectively).

Predictors of positive sputum cultures in exacerbations of chronic obstructive pulmonary disease.

Background and objective:  Although sputum culture in patients with an acute exacerbation of COPD is of uncertain value, it is routinely done. The ability to clinically identify patients likely or unlikely to yield bacterial sputum isolates would potentially reduce unnecessary tests. The objective of this study was to identify the clinical predictors of positive sputum cultures in this patient population.