BACKGROUNDDe-escalation of empirical antimicrobial therapy, a key component of antibiotic stewardship, is considered difficult in ICUs with high rates of antimicrobial resistance.OBJECTIVESTo assess the feasibility and the impact of antimicrobial de-escalation in ICUs with high rates of antimicrobial resistance.METHODSMulticentre, prospective, observational study in septic patients with documented infections. Patients in whom de-escalation was applied were compared with patients without de-escalation by the use of a propensity score matching by SOFA score on the day of de-escalation initiation.RESULTSA total of 262 patients (mean age 62.2 ± 15.1 years) were included. Antibiotic-resistant pathogens comprised 62.9%, classified as MDR (12.5%), extensively drug-resistant (49%) and pandrug-resistant (1.2%). In 97 (37%) patients de-escalation was judged not feasible in view of the antibiotic susceptibility results. Of the remaining 165 patients, judged as patients with de-escalation possibility, de-escalation was applied in 60 (22.9%). These were matched to an equal number of patients without de-escalation. In this subset of 120 patients, de-escalation compared with no de-escalation was associated with lower all-cause 28 day mortality (13.3% versus 36.7%, OR 0.27, 95% CI 0.11-0.66, P = 0.006); ICU and hospital mortality were also lower. De-escalation was associated with a subsequent collateral decrease in the SOFA score. Cox multivariate regression analysis revealed de-escalation as a significant factor for 28 day survival (HR 0.31, 95% CI 0.14-0.70, P = 0.005).CONCLUSIONSIn ICUs with high levels of antimicrobial resistance, feasibility of antimicrobial de-escalation was limited because of the multi-resistant pathogens isolated. However, when de-escalation was feasible and applied, it was associated with lower mortality.

It is not unusual for systemic diseases to mimic sepsis and, in any case, the clinician should thoroughly investigate this possibility.

Background: Data regarding new onset atrial fibrillation (nAF) in general, non-cardiac, intensive care unit (ICU) patients are limited. However, it has been suggested that nAF is associated with worse clinical outcome in these patients. Objective: The purpose of the present work was to study the prognostic impact of nAF, in this setting. Methods: We prospectively studied all patients admitted to a single ICU for a period of 12 months. Patients admitted for brief post-operative monitoring, patients with chronic, intermittent atrial fibrillation and atrial fibrillation present upon admission, were excluded. Death during ICU stay (ICUD) was the pre-specified study end-point. Length of stay (LOS) for survivors was also reported. A number of factors related to the occurrence of nAF and the present disease were recorded for each patient. Results: The study population was comprised of 133 patients. Twenty (15%) of them manifested nAF. The end-point of ICUD was observed in 27.1% of the patients. The median LOS reported was 8 days. Patients with nAF seemed to have significantly worse prognosis, compared to those who did not manifest nAF (OR = 3.35, 95% CI: 1.26-8.92; P = 0.016). Additionally, nAF patients appear to require significantly extended LOS (P = 0.01). Nevertheless, when the effect of nAF on ICUD was adjusted for sepsis, there was no statistically significant difference between those that manifested nAF and the rest of the patients. Conclusion: Patients suffering nAF seem to have worse prognosis during ICU stay. However, a direct impact of nAF on mortality was not documented. (c) 2017 Australian College of Critical Care Nurses Ltd. Published by Elsevier Ltd. All rights reserved.

BACKGROUND: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.OBJECTIVES: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.METHODS: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.RESULTS: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%).CONCLUSION: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.

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 <0.001) for cardiac death. In conclusion, hsCRP levels at presentation represent an independent predictor for fatal and nonfatal events during long-term follow-up. HsCRP levels at 48 and 72 hours, which are close to peak hsCRP levels, independently predict only cardiac death.

Objectives 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. Design Single-centre prospective observational study. Setting Tertiary referral centre. Patients 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. Main outcome measures 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. Results 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 (pfor trend=0.011), 31-day (pfor trend=0.044) and 1-year (pfor 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 (p<0.001) mortality than those in the lowest quartile. Conclusions 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.

Objectives: The possible independent effect of mild-to-moderate anemia (hemoglobin value not <9 g/dl) on the short-term mortality of patients with decompensation of NYHA class III/IV chronic heart failure has not been investigated yet. 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.

Background 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). Methods 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. Results 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 (p<0.001). 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 (p<0.001). By multivariate Cox regression analysis, elevated serum levels of BNP (p=0.002), cTnI (p<0.001) and hs-CRP (p=0.02) were independent predictors of the study end point. Conclusions 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.

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.

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.

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-loo (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.

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.

Background 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.Methods 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-CT >193 seconds and nonresponders as those with a CEPI-CT <= 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.Results 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.Conclusion 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.

Background: 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.Methods: 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 of >= 0.10 mV compared with the reference ECG lasting for >= 1 minute.Results: The incidence of the composite of death, nonfatal myocardial infarction, and recurrent angina by the first year was 28.7%. Patients with >= 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 of >= 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).Conclusions: 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.

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 (p<0.001), SAA (p<0.001), 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 (p<0.001), 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.

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 > or = 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 > or = 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 > or = 60 min after thrombolysis initiation were at significantly higher risk compared with those who achieved this criterion in <60 min (P = 0.02). However, this association was true only for type 2 diabetic subjects (P = 0.01) and not for nondiabetic subjects (P = 0.9). 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.

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-alpha), 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-alpha 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.

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.