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Pardo-Oviedo, Juan Mauricio/0000-0003-0084-3449; Lopez-Delgado, Juan Carlos/0000-0003-3324-1129; Corradi, Francesco/0000-0002-5588-2608; De Backer, Daniel/0000-0001-9841-5762; POTA, VINCENZO/0000-0001-9999-3388; Tomescu, Dana/0000-0001-9673-5754; Sabetian, Golnar/0000-0001-8764-2150; Girardis, Massimo/0000-0002-2453-0829; Brazzi, Luca/0000-0001-7059-0622; Leone, Marc/0000-0002-3097-758X; Zabolotskikh, Igor Borisovich/0000-0002-3623-2546; De Lange, Dylan/0000-0002-0191-7270; ALMEKHLAFI, GHALEB A./0000-0002-0323-7025; Elke, Gunnar/0000-0002-4948-1605; Grigoras, Ioana/0000-0001-9412-9574; Czuczwar, Miroslaw/0000-0002-9025-6717; Nora, David/0000-0002-1133-7368; Masjedi, Mansoor/0000-0001-6175-9289; Gunst, Jan/0000-0003-2470-6393; Vidal-Cortes, Pablo/0000-0003-0225-9975; Szakmany, Tamas/0000-0003-3632-8844; Dimopoulos, George/0000-0002-3784-3103; Rello, Jordi/0000-0003-0676-6210; U nal, Necmettin/0000-0002-9440-7893; Tiberio, Iolanda FLC/0000-0002-5662-7895; Cortegiani, Andrea/0000-0003-1416-9993; Morton, Ben/0000-0002-6164-2854; Labeau, Sonia/0000-0003-3863-612X; Velickovic, Dejan/0000-0002-7312-2880; Paul, John/0000-0002-9307-3465; Pereira, Rui/0000-0002-3010-8384; Silversides, Jon/0000-0002-9562-5462; Paiva, Jose-Artur/0000-0003-4323-0220; Smuszkiewicz, Piotr/0000-0003-3067-8229; Paul, Cherish/0000-0001-6133-0036; Santos, Lurdes/0000-0002-0622-6823; PANTAZOPOULOS, IOANNIS/0000-0002-8846-519X; Ostermann, Marlies/0000-0001-9500-9080; Blot, Stijn/0000-0003-2145-0345; Naylor, Amanda/0000-0002-6431-0230; Shyamsundar, Murali/0000-0003-3797-8080; Aldecoa, Cesar/0000-0001-8789-5959; Summers, Charlotte/0000-0002-7269-2873; biskup, ewelina/0000-0002-9871-927X; Cornet, Alexander/0000-0002-9917-5251; Trenado Alvarez, Jose/0000-0002-2930-0766; Volta, Carlo/0000-0003-3533-6121; Gritsan, Alexey/0000-0002-0500-2887; Urkmez, Seval/0000-0002-3412-4226 WOS:000493268200001 PubMed ID: 31664501 PurposeTo describe the epidemiology of intra-abdominal infection in an international cohort of ICU patients according to a new system that classifies cases according to setting of infection acquisition (community-acquired, early onset hospital-acquired, and late-onset hospital-acquired), anatomical disruption (absent or present with localized or diffuse peritonitis), and severity of disease expression (infection, sepsis, and septic shock).MethodsWe performed a multicenter (n=309), observational, epidemiological study including adult ICU patients diagnosed with intra-abdominal infection. Risk factors for mortality were assessed by logistic regression analysis.ResultsThe cohort included 2621 patients. Setting of infection acquisition was community-acquired in 31.6%, early onset hospital-acquired in 25%, and late-onset hospital-acquired in 43.4% of patients. Overall prevalence of antimicrobial resistance was 26.3% and difficult-to-treat resistant Gram-negative bacteria 4.3%, with great variation according to geographic region. No difference in prevalence of antimicrobial resistance was observed according to setting of infection acquisition. Overall mortality was 29.1%. Independent risk factors for mortality included late-onset hospital-acquired infection, diffuse peritonitis, sepsis, septic shock, older age, malnutrition, liver failure, congestive heart failure, antimicrobial resistance (either methicillin-resistant Staphylococcus aureus, vancomycin-resistant enterococci, extended-spectrum beta-lactamase-producing Gram-negative bacteria, or carbapenem-resistant Gram-negative bacteria) and source control failure evidenced by either the need for surgical revision or persistent inflammation.ConclusionThis multinational, heterogeneous cohort of ICU patients with intra-abdominal infection revealed that setting of infection acquisition, anatomical disruption, and severity of disease expression are disease-specific phenotypic characteristics associated with outcome, irrespective of the type of infection. Antimicrobial resistance is equally common in community-acquired as in hospital-acquired infection. Pfizer investigator-initiated research grant AbSeS is a Trials Group Study of the European Society of Intensive Care Medicine. The study was supported by a Pfizer investigator-initiated research grant.

How circulating inflammatory mediators change upon sepsis progression has not been studied. We studied the follow-up changes of circulating vasoactive peptides and cytokines until the improvement or the worsening of a patient and progression into specific organ dysfunctions. In a prospective study, concentrations of tumor necrosis factor-alpha (TNFα), interleukin (IL)-6, IL-8, IL-10, interferon-gamma (IFNγ), endocan and angiopoietin-2 (Ang-2) were measured in serum by an enzyme immunoassay in 175 patients at baseline; this was repeated within 24 h upon progression into new organ dysfunction (n = 141) or improvement (n = 34). Endocan and Ang-2 were the only parameters that were significantly increased among patients who worsened. Any increase of endocan was associated with worsening with odds ratio 16.65 (p

Invasive fungal infections are common in intensive care units (ICUs) but there is a great variability in factors affecting costs of different antifungal treatment strategies in clinical practice. To determine factors affecting treatment cost in adult ICU patients with or without documented invasive fungal infection receiving systemic antifungal therapy (SAT) we have performed a prospective, multicentre, observational study enrolling patients receiving SAT in participating ICUs in Greece. During the study period, 155 patients received SAT at 14 participating ICUs: 37 (23.9%) for proven fungal infection before treatment began, 10 (6.5%) prophylactically, 77 (49.7%) empirically and 31 (20.0%) pre-emptively; 66 patients receiving early SAT (55.9%) were subsequently confirmed to have proven infection with Candida spp. (eight while on treatment). The most frequently used antifungal drugs were echinocandins (89/155; 57.4%), fluconazole (31/155; 20%) and itraconazole (20/155; 12.9%). Mean total cost per patient by SAT strategy was €20 458 (proven), €15 054 (prophylaxis), €23 594 (empiric) and €22 184 (pre-emptive). Factors associated with significantly increased cost were initial treatment failure, length of stay (LOS) in ICU before starting SAT (i.e. from admission until treatment start), fever and proven candidaemia (all P≤.05). Conclusion Early administration of antifungal drugs was not a substantial component of total hospital costs. However, there was a significant adverse impact on costs with increasing LOS in febrile patients in ICU for whom diagnosis of fungaemia was delayed before starting SAT, and with initial treatment failure. Awareness of potential candidaemia and initiation of pre-emptive or empirical strategy as early appropriate treatment may improve ICU patient outcomes while reducing direct medical costs.

Background Guillain-Barré syndrome is an autoimmune disorder in which autoantibodies mainly affect the peripheral nervous system. Autonomic dysfunction is a common and severe complication of Guillain-Barré syndrome. Cardiomyopathy, though, is a rare complication in Guillain-Barré syndrome, with only a few cases reported in the literature. Case Presentation We present a case of a 65-year-old Greek woman with Guillain-Barré syndrome who developed cardiomyopathy shortly after admission to the intensive care unit due to respiratory deterioration. Her estimated left ventricular ejection fraction upon admission was 20%. The result of coronary angiography was negative for coronary artery disease, and cardiac magnetic resonance imaging excluded myocarditis. Her clinical condition improved with supportive therapy, and her estimated left ventricular ejection fraction at discharge was normal. Conclusions Clinicians should be aware of this potentially lethal complication of Guillain-Barré syndrome and the therapeutic options, because early diagnosis can improve prognosis. Routine electrocardiographic and echocardiographic assessments should be performed in patients with Guillain-Barré syndrome presenting with hemodynamic instability.

Background It is not unusual for systemic diseases to mimic sepsis and, in any case, the clinician should thoroughly investigate this possibility. Case presentation We present the case of a 21-year-old Greek woman who presented to the Intensive Care Unit of our hospital with severe septic shock – multiple organ failure as a result of a suspected gynecological infection of the ovaries. An immediate improvement of her clinical condition in combination with strong clinical suspicion and negative cultures led to the differential diagnosis of diseases other than sepsis. Based on the results of the biopsies that were obtained by research laparotomy, our patient suffered from primary Burkitt ovarian lymphoma. Her clinical condition improved with supportive treatment and chemotherapy. Chemotherapy is the dominant treatment for Burkitt’s lymphoma, while surgery or radiotherapy has no place. Conclusions All intensivists should be aware of clinical conditions that mimic sepsis as early diagnosis can lead to appropriate therapy and avoid unnecessary diagnostic tests and antibiotic abuse.

Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting.Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality.In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p0.0001) and 14.9% and 3.7%, respectively, in the ICU (p0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004).Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

To investigate the prognostic value of circulating levels of asymmetric dimethylarginine (ADMA) in patients with acute decompensation of (New York Heart Association (NYHA) class III/IV) chronic heart failure and reduced left ventricular ejection fraction.Single-centre prospective observational study.Tertiary referral centre.A total of 651 consecutive and eligible hospitalised patients were studied. Patients were divided into four groups according to the quartiles of circulating levels of ADMA upon presentation.Incidence of in-hospital (or 7-day in the case of prolonged hospitalisation), 31-day and 1-year cardiac mortality were the pre-specified study end points.Cumulative rates of in-hospital, 31-day and 1-year cardiac mortality were 10.6%, 18.7% and 36.4%, respectively. There was a gradual increased risk of in-hospital (p(for trend)=0.011), 31-day (p(for trend)=0.044) and 1-year (p(for trend)0.001) mortality with increasing ADMA quartiles. After adjustment for possible confounders, patients at the highest ADMA quartile were at significantly higher risk for in-hospital (p=0.042), 31-day (p=0.032) and 1-year (p0.001) mortality than those in the lowest quartile.According to the present results, an elevated circulating level of ADMA is a strong independent predictor of short-term and long-term mortality in patients with acute decompensation of NYHA class III/IV chronic heart failure and reduced left ventricular ejection fraction. ADMA levels upon presentation may confer enhanced risk stratification in this setting.

Bloodstream infections (BSIs) caused by Klebsiella pneumoniae carbapenemases (KPC)-producing K. pneumoniae (KPC-KP) are associated with high mortality rates. We investigated outcomes, risk factors for mortality and impact of appropriate antimicrobial treatment in patients with BSIs caused by molecularly confirmed KPC-KP. All consecutive patients with KPC-KP BSIs between May 2008 and May 2010 were included in the study and followed-up until their discharge or death. Potential risk factors for infection mortality were examined by a case-control study. Case-patients were those who died from the BSI and control-patients those who survived. Appropriate antimicrobial therapy was defined as treatment with in vitro active antimicrobials for at least 48 h. A total of 53 patients were identified. Overall mortality was 52.8% and infection mortality was 34%. Appropriate antimicrobial therapy was administered to 35 patients; mortality due to infection occurred in 20%. All 20 patients that received combination schemes had favourable infection outcome; in contrast, seven of 15 patients given appropriate monotherapy died (p 0.001). In univariate analysis, risk factors for mortality were age (p

Objectives: The possible independent effect of mild-to-moderate anemia (hemoglobin value not Methods: A total of 725 consecutive hospitalized patients were studied. All-cause mortalities during hospitalization and by day 31 were the prespecified study end points. Results: A total of 76 (10.5%) and 133 (18.3%) patients died during hospital stay and by day 31 of follow-up, respectively. Patients in the first hemoglobin tertile were at a significantly higher risk of death than those in the second (p = 0.003 and p < 0.001 for unadjusted in-hospital and 31-day mortality, respectively) or third terile (p < 0.001 and p < 0.001, for unadjusted in-hospital and 31-day mortality, respectively). However, after adjustment for concomitant baseline comorbidities and biochemical parameters, there was no significant difference in the risk of death among hemoglobin tertiles. Conclusions: Mild-to-moderate anemia seems not to contribute independently to short-term mortality in patients with decompensation of NYHA class III/IV chronic heart failure. An adverse concomitant baseline risk profile may have a key role in the induction of mild-to-moderate anemia and in the increased risk of death in these patients.

A matched 1:3 case-control study investigated factors predicting colistin-resistant versus colistin-susceptible KPC-producing Klebsiella pneumoniae acquisition and its impact on patient outcomes. Case patients were more often admitted from other institutions ( P = 0.019) and had longer therapy with β-lactam/β-lactamase inhibitors ( P = 0.002) and higher overall mortality ( P = 0.05). All 52 study isolates were clonally related, suggesting horizontal dissemination. None of these parameters independently predicted colistin resistance, which probably occurred in a susceptible KPC-KP strain that was subsequently disseminated horizontally.

To investigate the combined prognostic value of admission serum levels of B-type natriuretic peptide (BNP), cardiac troponin I (cTnI) and high sensitivity C-reactive protein (hs-CRP), in patients hospitalized because of acutely decompensated severe (New York Heart Association class III/IV) low-output chronic heart failure (CHF).A total of 577 consecutive patients recruited in the 5 participating centers, were studied. Cardiac mortality by 31 days was the prespecified primary study end point.A total of 102 (17.7%) patients died by 31 days. When the study patients were divided according to the number of elevated study biomarkers, there was a significant gradual increased risk of 31-day cardiac death with increasing in the number of elevated biomarkers (p0.001). The value of the discriminant C statistic for the Cox regression analysis, increased significantly when each of the study biomarkers was incorporated with the other risk predictors into a Cox regression model, with the highest C statistic value for the Cox regression model that included all the study biomarkers (p0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p0.001) and hs-CRP (p=0.02) were independent predictors of the study end point.In conclusion, in patients hospitalized for acute decompensation of severe (NYHA III/IV) low-output CHF, BNP, cTnI and hs-CRP upon admission offers enhanced early risk stratification. With increasing number of elevated biomarkers, the risk of 31-day cardiac death increases gradually that implies treatment intensification, and closer follow-up.

Decreased responsiveness to oral antiplatelet drug therapy has been associated with an adverse outcome after coronary stenting (CS), but more studies are needed. The purpose of the present study was to prospectively evaluate this issue.A total of 612 consecutive patients with stable or unstable coronary artery disease who underwent CS after at least 12 hours of aspirin and clopidogrel loading were studied. The study population was divided into responders and nonresponders to oral antiplatelet therapy, according to the values of preprocedural Platelet Function Analyzer-100 (Dade Behring, Marburg, Germany) collagen epinephrine closure time (CEPI-CT). In particular, responders were considered as patients with a CEPI-CT193 seconds and nonresponders as those with a CEPI-CTor = 193 seconds. The 1-year incidence of the composite of cardiac death and rehospitalization for nonfatal myocardial infarction was the prespecified primary study end point.At 1 year, 9.1% of patients reached the primary end point. Nonresponders to oral antiplatelet therapy were at significantly higher risk for the primary end point (18.7% vs 7.6%) than responders. Nonresponsiveness to oral antiplatelet therapy was a predictor of the primary end point by both univariate (hazard ratio 2.7, 95% CI 1.6-4.5, P.001) and multivariate (hazard ratio 2.5, 95% CI 1.6-3.8, P.001) Cox regression analysis.Based on the present data, preprocedural responsiveness to oral antiplatelet therapy, assessed by Platelet Function Analyzer-100 CEPI-CT, is an independent predictor of long-term outcome after CS.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26–0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p

The possible long-term prognostic value of transient ST ischemic episodes detected by continuous multilead electrocardiographic (ECG) monitoring after successful coronary stenting (CS) has not been thoroughly investigated.A total of 739 consecutive patients, who underwent a 24-hour, continuous 12-lead electrocardiographic (ECG) ST monitoring in the first day after successful CS, were studied. An ST ischemic episode was defined as a transient ST shift (depression or elevation) in any lead ofor = 0.10 mV compared with the reference ECG lasting foror = 1 minute.The incidence of the composite of death, nonfatal myocardial infarction, and recurrent angina by the first year was 28.7%. Patients withor = 3 (defined by receiver operating characteristics analysis) ST ischemic episodes, detected by continuous 12-lead ECG ST monitoring, were at significantly higher risk for the 1-year composite primary end point than those with either 1 and 2 (52.7% vs 25.7%, hazard ratio [HR] 2.1, 95% CI 1.4-3.7, P.001) or no (52.7% vs 25%, HR 2.2, 95% CI 1.2-2.9, P.001) ST ischemic episodes. By multivariate Cox regression analysis, the occurrence ofor = 3 ST ischemic episodes in the first postprocedural day was independently associated with a significant increased risk of the 1-year composite primary end point (HR 1.9, 95% CI 1.4-3.9, P = .002).The present study suggests that continuous 12-lead ECG ST monitoring in the first day after successful CS may serve as an affordable tool for the identification of patients with an increased risk of fatal or nonfatal ischemic complication during the first year after the procedure.

Background: Continuous 12-lead electrocardiographic (ECG) ST monitoring and the Thrombolysis In Myocardial Infarction Risk Score (TIMI-RS), both have been shown to be useful for early risk stratification in patients with non-ST elevation acute coronary syndromes (NSTACS). Hypothesis: Transient ST ischemic events, detected by continuous 12-lead ECG ST monitoring, early in the course of NSTACS, may add prognostic information to the TIMI-RS. Methods: In all, 567 consecutive patients with a NSTACS underwent 24-h continuous 12-lead ECG ST monitoring. An ST ischemic event was defined as a transient ST shift in any lead of ≥ 0.10 mV compared with the reference ECG, lasting for ≥l min. Results: The incidence of the composite of death, nonfatal myocardial infarction (or reinfarction) and recurrent ischemia by Day 14 was 22.2%. By Day 30, the incidence of the composite of death and nonfatal myocardial infarction (or reinfarction) was 14.7%. There was a significantly increased risk of 14-day (p value for trend < 0.001) or 30-day (p value for trend

Increased creatine kinase-MB isoenzymes after coronary stenting are common, and many studies have suggested an association of this increase with an adverse long-term prognosis. How such postprocedural creatine kinase-MB release affects long-term prognosis remains unclear. Whether any actual causal relation exists remains unanswered.

OBJECTIVE—There are conflicting results regarding the impact of type 2 diabetes on intravenous thrombolysis effectiveness during ST elevation myocardial infarction (STEMI). The present study, using a continuous 12-lead electrocardiogram, examined the possible association of type 2 diabetes with both acute intravenous thrombolysis effectiveness and long-term prognosis in this setting. RESEARCH DESIGN AND METHODS—The study included 726 consecutive subjects (214 type 2 diabetic subjects) with STEMI who received intravenous thrombolysis in the first 6 h from index pain and were followed up for 3.5 years. RESULTS—Type 2 diabetic subjects had significantly lower incidence of sustained ≥50% ST recovery than nondiabetic subjects (P = 0.03). Additionally, the former required a significantly greater time interval through the achievement of this criterion than the latter (P < 0.001). In both type 2 diabetic (P < 0.001) and nondiabetic subjects (P < 0.001), those who had not attained ≥50% ST recovery were at significantly higher risk of cardiac death than subjects who had reached this criterion. The subjects who attained the above electrocardiographic criterion in ≥60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in CONCLUSIONS—The present study suggests that type 2 diabetes is a strong predictor of acute intravenous thrombolysis failure during STEMI. This finding may significantly contribute to the worse prognosis for type 2 diabetic subjects compared with nondiabetic ones in this setting.

Contains fulltext : 152177.pdf (Publisher’s version ) (Closed access) INTRODUCTION: Adenosine exerts anti-inflammatory and tissue-protective effects during systemic inflammation. While the tissue-protective effects might limit organ damage, its anti-inflammatory properties may induce immunoparalysis and impede bacterial clearance. The common 34C>T loss-of-function variant of AMPD1 (rs17602729) is associated with increased adenosine formation, but effects on immune function and outcome in sepsis patients are unknown. METHODS: The effects of the presence of the 34C>T variant on sepsis susceptibility, immune function, multi-organ dysfunction, and mortality in septic patients were studied. Patients suffering from community acquired pneumonia (CAP, initial cohort n = 285; replication cohort n = 212) and ventilator-associated pneumonia (VAP, n = 117; n = 33) and control patients without infection (n = 101) were enrolled. Genetic distributions of the AMPD1 SNP were CC 76%, CT 22%, and TT 2% in the initial cohort and CC 80%, CT 18%, and TT 2% in the replication cohort. RESULTS: The occurrence of septic CAP, but not septic VAP, was increased for the CT versus CC genotype (OR (95% CI) 2.0 (1.1-3.7); P = 0.02) in the initial cohort. The increased risk for the CT versus CC genotype was also observed in the replication cohort but did not reach statistical significance there (P = 0.38), resulting in an OR of the total group of 1.7 (95% CI 1.0-3.1), P = 0.07. In septic patients carrying the CT genotype, the ex vivo production of TNF-alpha by LPS-stimulated monocytes was attenuated (P = 0.005), indicative of a more pronounced immunoparalytic state in these patients. CONCLUSIONS: Presence of the AMPD1 34C>T variant is associated with higher infection susceptibility to CAP, but not to VAP. More pronounced immunoparalysis in these patients mediated by the anti-inflammatory effects of adenosine may account for this observation.

Ventilator-associated pneumonia (VAP) is one of the most common causes of morbidity and mortality in intensive care unit patients. However, the diagnosis is quite difficult. Gram stain (GS) of bronchoalveolar lavage (BAL) sample is a time-saving diagnostic method for VAP. However, its clinical significance has not been adequately investigated. The aim of this study was to determine its sensitivity and specificity for VAP diagnosis. We prospectively performed GS and quantitative bacterial cultures (QBC) of BAL samples, obtained through fiberoptic bronchoscope, in 75 consecutive postoperative and/or multiple trauma patients with suspected VAP. We considered BAL-GS as positive for VAP diagnosis when (i) polymorphonuclear neutrophils were > 25 per optic field at a magnification x 100 (p.o.f x 100); (ii) squamous epithelial cells were < 1% p.o.f x 100; and (iii) one or more microorganisms were seen p.o.f. at a magnification x 1,000 (p.o.f. x 1,000). VAP was diagnosed with criteria similar to those used in previous studies. Pneumonia was the final diagnosis in 22/75 (29%) patients. The BAL-GS was positive in 17/22 patients with VAP and in 7/53 patients without VAP. Accordingly, the sensitivity of BAL-GS for VAP diagnosis was 77%, the specificity 87%, the positive predictive value 71% and the negative predictive value 90%. Our data suggest that BAL-GS has good sensitivity and high specificity for VAP diagnosis. It could therefore constitute a useful complementary tool in the task of early diagnosis and treatment of VAP.

OBJECTIVE: To evaluate the effect of tracheal gas insufflation (TGI) in spontaneously breathing, intubated patients with chronic obstructive pulmonary disease (COPD) undergoing weaning from the mechanical ventilation. DESIGN: A prospective study in humans. SETTING: Polyvalent intensive care unit (14-bed ICU) in a 700-bed general university hospital. PATIENTS: Twelve patients with chronic obstructive pulmonary disease (COPD) who required intubation and mechanical ventilation were studied. All patients met standard criteria for weaning from mechanical ventilation. Seven patients (group 1) had been transorally intubated during episodes of acute respiratory failure. Five patients, all men (group 2), had previously undergone tracheostomy and had a transtracheal tube in place. INTERVENTIONS: Intratracheal, humidified, O2-mixture insufflation (TGI) was given via a catheter placed in distal or proximal position. Gas delivered through the intratracheal catheter was blended to match the fractional of inspired gas through the endotracheal tube. Continuous flows of 3 and 6 l/min in randomized order were used in each catheter position. Prior to data collection at each stage, an equilibration period of at least 30 min was observed, and thereafter blood gases were analyzed every 5 min. A new steady state was assumed to have been established when values of both PaCO2 and V CO2 changed by less than 5% between adjacent measurements. The last values of blood gases were taken as representative. The new steady state was confirmed within 35-50 min. Baseline measurements with zero Vcath were made at the beginning and end of the experiment. RESULTS: This study shows that VT, MV, PaCO2, and VD/VT are reduced in a flow-dependent manner when gas is delivered through an oral-tracheal tube (group 1). The distal catheter position was more effective than the proximal one. In contrast, when gas was delivered through tracheostomy (group 2), TGI was ineffective in the proximal position and less effective than in group 1 in distal position. CONCLUSION: Under the experimental conditions, tracheal gas insufflation decreased dead space, increased alveolar ventilation and possibly reduced work of breathing. From the preliminary data reported here, we believe that TGI may help patients experiencing difficulty during weaning. Intensive Care Med

It has been reported that increased levels of C-reactive protein are related to adverse long-term prognosis in the setting of ST-segment elevation acute myocardial infarction (MI). In previous studies, the timing of C-reactive protein determination has varied widely. In the present study, serial high-sensitivity C-reactive protein (hsCRP) measurements were performed to investigate if any of the measurements is superior regarding long-term prognosis. A total of 861 consecutive patients admitted for ST-segment elevation MI and treated with intravenous thrombolysis within the first 6 hours from the index pain were included. HsCRP levels were determined at presentation and at 24, 48, and 72 hours. The median follow-up time was 3.5 years. New nonfatal MI and cardiac death were the study end points. By the end of follow-up, cardiac death was observed in 22.4% and nonfatal MI in 16.1% of the patients. HsCRP levels were found to be increasing during the first 72 hours. Multivariate Cox regression analysis demonstrated that hsCRP levels at presentation were an independent predictor of the 2 end points (relative risk [RR] 2.8, p = 0.002, and RR 2.1, p = 0.03, for MI and cardiac death, respectively), while hsCRP levels at 24 hours did not yield statistically significant results (RR 1.4, p = 0.40, and RR 1.1, p = 0.80, for MI and cardiac death, respectively). The corresponding RRs at 48 hours were 1.2 (p = 0.5) for MI and 3.2 (p = 0.007) for cardiac death and at 72 hours were 1.6 (p = 0.30) for MI and 3.9 (p

Introduction Intensive care may prolong the dying process in patients who have been unresponsive to the treatment already provided. Limitation of life-sustaining therapy, by either withholding or withdrawing support, is an ethically acceptable and common worldwide practice. The purpose of the present study was to examine the frequency, types, and rationale of limiting life support in Greek intensive care units (ICUs), the clinical and demographic parameters associated with it, and the participation of relatives in decision making. Methods This was a prospective observational study conducted in eight Greek multidisciplinary ICUs. We studied all consecutive ICU patients who died, excluding those who stayed in the ICU less than 48 hours or were brain dead. Results Three hundred six patients composed the study population, with a mean age of 64 years and a mean APACHE II score on admission of 21. Of study patients, 41% received full support, including unsuccessful cardiopulmonary resuscitation (CPR); 48% died after withholding of CPR; 8%, after withholding of other treatment modalities besides CPR; and 3%, after withdrawal of treatment. Patients in whom therapy was limited had a longer ICU (P < 0.01) and hospital (P = 0.01) length of stay, a lower Glasgow Coma Scale score (GCS) on admission (P < 0.01), a higher APACHE II score 24 hours before death (P < 0.01), and were more likely to be admitted with a neurologic diagnosis (P < 0.01). Patients who received full support were more likely to be admitted with either a cardiovascular (P = 0.02) or trauma diagnosis (P = 0.05) and to be surgical rather than medical (P = 0.05). The main factors that influenced the physician's decision were, when providing full support, reversibility of illness and prognostic uncertainty, whereas, when limiting therapy, unresponsiveness to treatment already offered, prognosis of underlying chronic disease, and prognosis of acute disorder. Relatives' participation in decision making occurred in 20% of cases and was more frequent when a decision to provide full support was made (P < 0.01). Advance directives were rare (1%). Conclusions Limitation of life-sustaining treatment is a common phenomenon in the Greek ICUs studied. However, in a large majority of cases, it is equivalent to the withholding of CPR alone. Withholding of other therapies besides CPR and withdrawal of support are infrequent. Medical paternalism predominates in decision making.

Objectives: To investigate the long-term impact of right ventricular myocardial involvement (RVI) after acute inferior ST-segment elevation myocardial infarction (STEMI). Methods: A total of 1208 consecutive patients, who survived to discharge after hospitalization for acute inferior STEMI, were studied. Patients were divided into those with (n = 459) or without (n = 749) of RVI involvement, defined as ST-segment elevation ≥1 mm in V4R. Cardiac death by 3 years was the primary study end point. Results: By the end of follow-up, 207 (17.1%) patients had died. Patients with RVI were at similar risk for death at 3 years than those without (17.6% vs 16.8%, hazard ratio 1.1, 95% confidence interval 0.8-1.4, P = .79). By multivariate Cox analysis, several variables, but not RVI, were associated with the incidence of 3 years cardiac death. Conclusions: Right ventricular myocardial involvement does not portend any increased risk for long-term mortality, in patients who survived to discharge after hospitalization for acute inferior STEMI.

Background Aspirin resistance has been associated with an adverse long-term outcome in patients with atherosclerotic coronary artery disease, but more studies are needed. Hypothesis The aim of this study was to investigate the impact of aspirin resistance, assessed by the Platelet Function Analyzer-100 (PFA-100) (Dade Behring Inc., Deerfield, Ill., USA) on the long-term prognosis in patients with non-ST segment elevation acute coronary syndromes (NSTE-ACS). Methods A total of 496 consecutive patients were studied. The 1-y incidence of cardiovascular death was the prespecified study endpoint. The patients were divided, according to the values of PFA-100 collagen epinephrine closure time (CEPI-CT) upon presentation, into aspirin sensitives (those with a PFA-100 CEPI-CT > 193 sec) and aspirin resistants (those with a PFA-100 CEPI-CT ≤ 193 sec). Results Aspirin resistants were younger (p-value = 0.04), and less frequently hypertensives (p-value = 0.05) or diabetics (p-value = 0.04) than aspirin sensitives. By 1 y, the incidence of cardiovascular deaths in the entire cohort was 12.9% (64/496), and aspirin resistants were at significantly higher risk of cardiovascular death (23.1% versus 9.6%; hazard ratio [HR] = 2.6; 95% confidence interval [CI] = 1.6–4.3; p-value < 0.001), than aspirin sensitives. By multivariate Cox regression analysis, aspirin resistance (a PFA-100 CEPI-CT ≤ 193 sec) was among the most potent predictors of the 1-y incidence of cardiovascular death (HR = 2.8; 95% CI = 1.7–4.6; p-value < 0.001). Conclusion According to the present data, aspirin resistance, assessed by the PFA-100, is an independent predictor of long-term cardiovascular mortality in patients with NSTE-ACS. Copyright © 2009 Wiley Periodicals, Inc.

We report the first two cases of community-acquired necrotizing pneumonia and bacteremia complicated by acute respiratory distress syndrome (ARDS) due to Panton-Valantine leukocidin-producing methicillin-resistant Staphylococcus aureus (MRSA-PVL) in Greece, together with a short literature review. Diagnosis was made by culture and broad spectrum PCR of respiratory secretions and blood. One patient received appropriate therapy and recovered fully. The other one died rapidly due to septic shock and life-threatening hemoptysis. Clinicians should be suspicious of community-acquired pneumonia due to MRSA-PVL strain, because rigorous microbiological diagnosis, early and appropriate therapy is essential for favorable outcome.

Background Apoptosis represents a physiological clearance mechanism in human tissues. The role of apoptosis has not been examined in normal lung cell populations, such as alveolar macrophages and polymorphonuclear cells. What is the percentage, as well as the role, of apoptosis in the alveolar microenvironment of the healthy human lung? Patients and methods Bronchoalveolar lavage was obtained from 21 volunteers without lung disease. The specimens were analyzed using: Annexin V binding, DNA laddering, light microscopy and immunohistochemistry for bcl-2 expression. Results Apoptosis of the total bronchoalveolar lavage cell population was 51.2%. Both alveolar macrophages and polymorphonuclear cells had a high apoptotic rate (62.1% and 48.3%, respectively) as determined by Annexin V binding. These findings were further confirmed using morphological criteria for apoptosis and gel electrophoresis for DNA fragmentation. In the majority of the individuals examined, (8 out of 21), the bcl-2 gene was expressed in the lymphocyte population mainly. Conclusions The percentage of apoptosis in lung cells of healthy humans is high. Apoptosis plays a key role in normal lung cell death. It appears to be the mechanism that opposes cell proliferation by eliminating, aged or damaged cells thus facilitating the process of lung remodeling.

The aim of the present study was to evaluate whether an elevated plasma C-reactive protein (CRP) level provides any additional prognostic information to the validated Thrombolysis In Myocardial Infarction (TIMI) risk score in patients with acute coronary syndromes. For this purpose, 1,846 consecutive patients with either acute ST-segment elevation myocardial infarction (STEMI; 861 patients) or non-ST-segment elevation acute coronary syndrome (NSTEACS; 985 patients) were included. The incidence of 30-day death and 14-day composite of death, myocardial infarction (or repeat myocardial infarction) and recurrent ischemia was the prespecified primary end point in the STEMI and NSTEACS cohorts, respectively. The incidence of the primary end point was 9.8% and 23.6% in the STEMI and NSTEACS cohorts, respectively. A significantly increased risk of the primary end point was present with an increase in the STEMI and NSTEACS TIMI risk score (p(trend)0.001 for the 2 groups). A plasma CRP value ofor = 5 andor = 3 mg/L (defined by receiver-operating characteristic analysis) was associated with a significantly increased risk of the primary end point in the STEMI and NSTEACS cohorts, respectively (p0.001 for the 2 cohorts), and it was true throughout the subgroups of STEMI and NSTEACS TIMI risk scores. In conclusion, an elevated plasma CRP level appears to be a marker that adds prognostic information to the validated STEMI and NSTEACS TIMI risk score. The plasma CRP and TIMI risk score may be used together for enhanced risk stratification in the setting of acute coronary syndromes.

We evaluated the possible association of the serum levels of C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, and cardiac troponin I (cTnI) with the presence of complex angiographic characteristics throughout the coronary artery tree in 519 consecutive patients with non-ST-elevation acute myocardial infarction (NSTEMI). Blood samples were obtained in the first 12h of NSTEMI invasion and all patients underwent in-hospital coronary angiography. Coronary lesions were classified as complex lesion (CL) or non-CL according to Ambrose criteria. Serum levels of CRP (p0.001), SAA (p0.001), or fibrinogen (p=0.001), but not of cTnI (p=0.9), were significantly related to the presence of multiple (or =2) CLs. On the contrary, serum levels of cTnI (p0.001), but not of CRP (p=0.5), SAA (p=0.9), or fibrinogen (p=0.9), were significantly associated with the severity of coronary artery disease. The results of the present study suggest that elevated levels of inflammatory biomarkers are associated with a generalized activation of coronary artery tree while elevated cTnI levels are associated with the severity of coronary artery disease in the setting of NSTEMI. It seems that inflammatory biomarkers and cTnI reflect different aspect of the process involved in unstable coronary artery disease.

Churg-Strauss syndrome (CSS) is a rare pulmonary and systemic vasculitis associated with asthma, with peripheral blood and/or tissue eosinophilia. We report the case of a 53-year-old woman who was admitted to the hospital with pneumonia and coma secondary to right hemisphere intracerebral hemorrhage. Although she recovered from the pneumonia, she remained comatose and had sinusitis and persisting blood eosinophilia. A muscle biopsy revealed eosinophilic vasculitis. The diagnosis of CSS was made and the patient recovered after being treated with prednisone and cyclophosphamide. This case reports the very rare appearance of CSS 30 years after the first appearance of ulcerative colitis and 27 years after the onset of asthma.

Atrial fibrillation (AF) is thought to be a relatively common arrhythmia in the setting of noncardiac intensive care unit (ICU). However, data concerning AF deriving from such populations are scarce. In addition, it is unclear which of the wide spectrum of AF predictors are relevant to the ICU setting.The aim of our study was to evaluate the incidence of new-onset AF and investigate the factors that contribute to its occurrence in ICU patients.We prospectively studied all patients admitted to our ICU during a 1-year period. Patients admitted for brief postoperative monitoring and patients with chronic or intermittent AF and AF present upon admission were excluded. A number of conditions incriminated as AF risk factors or "triggers" from demographics, medical history, present disease, and cardiac echocardiography as well as circumstances of AF onset were recorded.The study population consisted of 133 patients (90 males). Atrial fibrillation was observed in 15% of them. Age older than 65 years (P=.001), arterial hypertension (P=.03), systemic inflammatory response syndrome (P.001), sepsis (P=.001), left atrial dilatation (P=.01), and diastolic dysfunction (P=.04) were significantly associated with the occurrence of AF. By multivariate analysis, it was demonstrated that only older than 65 years (odds ratio, 7.0; 95% confidence interval, 2.0-24.6; P=.003) and sepsis (odds ratio, 6.5; 95% confidence interval, 2.0-21.1; P=.002) independently predict new-onset AF. Patients manifesting AF were frequently hypovolemic (30%) and had electrolyte disorders (40%) as well as elevated and rising serum C-reactive protein (70%).A significant fraction of ICU patients manifest AF. The predictors of interest for the ICU patients might be considerably different than those of the general population and other subgroups with systemic inflammation possibly having a pivotal role.

In an attempt to improve our ability to diagnose the cause of ventilator-associated pneumonia (VAP), we explore the usefulness of the conditional evaluation of bronchoalveolar lavage (BAL) samples from the involved and non-involved areas in patients with suspected unilateral lobar VAP (UL-VAP).Prospective study.University teaching hospital intensive care unit.We studied 19 consecutive patients with suspected UL-VAP.Nine of the 12 patients (47%) developed UL-VAP. There was a significant difference between the involved and non-involved areas in UL-VAP patients (P0.001) in respect of the quantitative bacterial cultures (QBCs) of BAL samples for each micro-organism, whereas there was no difference in patients without UL-VAP. When we applied the criterion of usual BAL (one micro-organism in concentrations10(5) colony-forming units per millilitre) for UL-VAP diagnosis, the sensitivity was 100%, the specificity 70%, the positive predictive value 75%, and the negative predictive value 100%. When we used the conditional evaluation of the BAL results for UL-VAP diagnosis, in the involved and non-involved areas, the sensitivity was 78%, the specificity 90%, the positive predictive value 87.5% and the negative predictive value 82%. A statistically significant difference was found when we compared the difference in QBCs between the BAL samples for each micro-organism, between the involved and non-involved areas in patients with and without VAP (P0.001).These data suggest that utilisation of the conditional evaluation of the QBCs of BAL samples improves significantly our ability to diagnose the cause of UL-VAP.

Pneumocystis carinii pneumonia (PCP) usually occurs in immunocompromised patients, and it is a life-threatening infection. We report the case of a human immunodeficiency virus (HIV)-seronegative patient with untreated rheumatoid arthritis (RA), who developed fatal PCP related to uncommon CD4+ T-lymphocytopenia. Although extremely rare and of uncertain aetiology, suppression of cellular immunity and subsequent opportunistic infections should be suspected in such patients.

PURPOSE: The objective of this study is to define if early changes of procalcitonin (PCT) may inform about prognosis and appropriateness of administered therapy in sepsis. METHODS: A prospective multicenter observational study was conducted in 289 patients. Blood samples were drawn on day 1, that is, within less than 24 hours from advent of signs of sepsis, and on days 3, 7, and 10. Procalcitonin was estimated in serum by the ultrasensitive Kryptor assay (BRAHMS GmbH, Hennigsdorf, Germany). Patients were divided into the following 2 groups according to the type of change of PCT: group 1, where PCT on day 3 was decreased by more than 30% or was below 0.25 ng/mL, and group 2, where PCT on day 3 was either increased above 0.25 ng/mL or decreased less than 30%. RESULTS: Death occurred in 12.3% of patients of group 1 and in 29.9% of those of group 2 (P < .0001). Odds ratio for death of patients of group 1 was 0.328. Odds ratio for the administration of inappropriate antimicrobials of patients of group 2 was 2.519 (P = .003). CONCLUSIONS: Changes of serum PCT within the first 48 hours reflect the benefit or not of the administered antimicrobial therapy. Serial PCT measurements should be used in clinical practice to guide administration of appropriate antimicrobials. J Crit Care

Background The predictive role of many cytokines and adhesion molecules has not been studied systematically in acute respiratory distress syndrome (ARDS). Methods We measured prospectively tumour necrosis factor alpha (TNF-α), interleukin (IL)-1, soluble vascular adhesion molecule-1 (VCAM-1) and soluble intercellular adhesion molecule-1 (ICAM-1) in serum and bronchoalveolar lavage fluid (BALF) within 2 hours following admission, in 65 patients. The patients were divided into: those fulfilling the criteria for ARDS (n = 23, group A), those who were pre-ARDS and who developed ARDS within 24 hours (n = 14, group B), and those on pre-ARDS but who never developed ARDS (n = 28, group C). Results All the measured molecules were only found at higher levels in the serum of patients that died either with or without ARDS (P < 0.05 – P < 0.0001). Patients at risk exhibited a good negative predictive value (NPV) of the measured molecules for ARDS development both in their serum (89 to 95%) and BALF (86 to 92%) levels. In contrast to BALF, serum levels of IL-1 and adhesion molecules exhibited a good NPV (68 to 96%), sensitivity (60 to 88%) and survival specificity (74 to 96%) in all groups. All molecules in serum and BALF IL-1 were correlated with the APACHE II (P < 0.05 – P < 0.0001). Serum and BALF IL-1 as well as BALF TNF-α were negatively correlated to PaO2/FiO2 (all P < 0.05). Conclusions The studied molecules have good NPV for ARDS development both in serum and BALF. Serum rather than BALF levels seem to be related to outcome.

Introduction Early risk assessment is the mainstay of management of patients with sepsis. APACHE II is the gold standard prognostic stratification system. A prediction rule that aimed to improve prognostication by APACHE II with the application of serum suPAR (soluble urokinase plasminogen activator receptor) is developed. Methods A prospective study cohort enrolled 1914 patients with sepsis including 62.2% with sepsis and 37.8% with severe sepsis/septic shock. Serum suPAR was measured in samples drawn after diagnosis by an enzyme-immunoabsorbent assay; in 367 patients sequential measurements were performed. After ROC analysis and multivariate logistic regression analysis a prediction rule for risk was developed. The rule was validated in a double-blind fashion by an independent confirmation cohort of 196 sepsis patients, predominantly severe sepsis/septic shock patients, from Sweden. Results Serum suPAR remained stable within survivors and non-survivors for 10 days. Regression analysis showed that APACHE II ≥17 and suPAR ≥12 ng/ml were independently associated with unfavorable outcome. Four strata of risk were identified: i) APACHE II