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Background: Leukocyte-mediated pulmonary inflammation is a key pathophysiological mechanism involved in acute respiratory distress syndrome (ARDS). Massive sequestration of leukocytes in the pulmonary microvasculature is a major triggering event of the syndrome. We therefore investigated the potential role of leukocyte stiffness and adhesiveness in the sequestration of leukocytes in microvessels., Methods: This study was based on in vitro microfluidic assays using patient sera. Cell stiffness was assessed by measuring the entry time (ET) of a single cell into a microchannel with a 6 × 9-μm cross-section under a constant pressure drop (ΔP = 160 Pa). Primary neutrophils and monocytes, as well as the monocytic THP-1 cell line, were used. Cellular adhesiveness to human umbilical vein endothelial cells was examined using the laminar flow chamber method. We compared the properties of cells incubated with the sera of healthy volunteers (n = 5), patients presenting with acute cardiogenic pulmonary edema (ACPE; n = 6), and patients with ARDS (n = 22), of whom 13 were classified as having moderate to severe disease and the remaining 9 as having mild disease., Results: Rapid and strong stiffening of primary neutrophils and monocytes was induced within 30 minutes (mean ET >50 seconds) by sera from the ARDS group compared with both the healthy subjects and the ACPE groups (mean ET <1 second) (p < 0.05). Systematic measurements with the THP-1 cell line allowed for the establishment of a strong correlation between stiffening and the severity of respiratory status (mean ET 0.82 ± 0.08 seconds for healthy subjects, 1.6 ± 1.0 seconds for ACPE groups, 10.5 ± 6.1 seconds for mild ARDS, and 20.0 ± 8.1 seconds for moderate to severe ARDS; p < 0.05). Stiffening correlated with the cytokines interleukin IL-1β, IL-8, tumor necrosis factor TNF-α, and IL-10 but not with interferon-γ, transforming growth factor-β, IL-6, or IL-17. Strong stiffening was induced by IL-1β, IL-8, and TNF-α but not by IL-10, and incubations with sera and blocking antibodies against IL-1β, IL-8, or TNF-α significantly diminished the stiffening effect of serum. In contrast, the measurements of integrin expression (CD11b, CD11a, CD18, CD49d) and leukocyte-endothelium adhesion showed a weak and slow response after incubation with the sera of patients with ARDS (several hours), suggesting a lesser role of leukocyte adhesiveness compared with leukocyte stiffness in early ARDS., Conclusions: The leukocyte stiffening induced by cytokines in the sera of patients might play a role in the sequestration of leukocytes in the lung capillary beds during early ARDS. The inhibition of leukocyte stiffening with blocking antibodies might inspire future therapeutic strategies.

Purpose: Patients with severe acute respiratory distress syndrome (ARDS) are candidates for extracorporeal membrane oxygenation (ECMO) therapy. The evaluation of organ severity is difficult in patients considered for cannulation in a distant hospital. This study was designed to identify early factors associated with hospital mortality in ARDS patients treated with ECMO and retrieved from referring hospitals., Methods: Data from 85 consecutive ARDS patients equipped with ECMO by our mobile team and consequently admitted to our ICU were prospectively collected and analyzed., Results: The main ARDS etiologies were community-acquired bacterial pneumonia (35%), influenza pneumonia (23%) (with 12 patients having been treated during the first half of the study period), and nosocomial pneumonia (14%). The median (interquartile range) time between contact from the referring hospital and patient cannulation was 3 (1-4) h. ECMO was venovenous in 77 (91%) patients. No complications occurred during transport by our mobile unit. Forty-eight patients died at the hospital (56%). Based on a multivariate logistic regression, a score including age, SOFA score, and a diagnosis of influenza pneumonia was constructed. The probability of hospital mortality following ECMO initiation was 40% in the 0-2 score class (n = 58) and 93% in the 3-4 score class (n = 27). Patients with an influenza pneumonia diagnosis and a SOFA score before ECMO of less than 12 had a mortality rate of 22%., Conclusions: Age, SOFA score, and a diagnosis of influenza may be used to accurately evaluate the risk of death in ARDS patients considered for retrieval under ECMO from distant hospitals.

Introduction: It has been suggested that delayed intensive care unit (ICU) transfer is associated with increased mortality for patients with community-acquired pneumonia (CAP). However, ICU admission policies and patient epidemiology vary widely across the world depending on local hospital practices and organizational constraints. We hypothesized that the time from the onset of CAP symptoms to invasive mechanical ventilation could be a relevant prognostic factor., Methods: One hundred patients with a CAP and necessitating invasive mechanical ventilation were included. Prospectively collected data were retrospectively analysed. Two study groups were identified based on the time of the initiation of invasive mechanical ventilation (rapid respiratory failure requiring mechanical ventilation within 72 h of the onset of CAP and progressive respiratory failure requiring invasive mechanical ventilation 4 or more days after the onset of CAP)., Results: Excepting more COPD patients in the rapid respiratory failure group and more patients with diabetes in the progressive respiratory failure group, these patients had similar characteristics. The overall in-hospital mortality rate was 28% in the rapid respiratory failure group and 51% in the progressive respiratory failure group (P = 0.03). The ICU and the day 30 mortality rates were higher in the progressive respiratory failure group (47% vs. 23%, P = 0.02; and 37.7% vs. 21.3%, P = 0.03; respectively). After adjusting for the propensity score and other potential confounding factors, progressive respiratory failure remained associated with hospital mortality only after 12 days of invasive mechanical ventilation., Conclusions: This study suggested that the duration or delay in the time to intubation from the onset of CAP symptoms was associated with the outcomes in those patients who ultimately required invasive mechanical ventilation.

Background: Patients admitted to intensive care units are frequently exposed to pathogenic microorganisms present in their environment. Exposure to these microbes may lead to the development of hospital-acquired infections that complicate the illness and may be fatal. Amoeba-associated microorganisms (AAMs) are frequently isolated from hospital water networks and are reported to be associated to cases of community and hospital-acquired pneumonia., Methodology/principal Findings: We used a multiplexed immunofluorescence assay to test for the presence of antibodies against AAMs in sera of intensive care unit (ICU) pneumonia patients and compared to patients at the admission to the ICU (controls). Our results show that some AAMs may be more frequently detected in patients who had hospital-acquired pneumonia than in controls, whereas other AAMs are ubiquitously detected. However, ICU patients seem to exhibit increasing immune response to AAMs when the ICU stay is prolonged. Moreover, concomitant antibodies responses against seven different microorganisms (5 Rhizobiales, Balneatrix alpica, and Mimivirus) were observed in the serum of patients that had a prolonged ICU stay., Conclusions/significance: Our work partially confirms the results of previous studies, which show that ICU patients would be exposed to water amoeba-associated microorganisms, and provides information about the magnitude of AAM infection in ICU patients, especially patients that have a prolonged ICU stay. However, the incidence of this exposure on the development of pneumonia remains to assess.

Despite the considerable number of studies reported to date, the causative agents of pneumonia are not completely identified. We comprehensively applied modern and traditional laboratory diagnostic techniques to identify microbiota in patients who were admitted to or developed pneumonia in intensive care units (ICUs). During a three-year period, we tested the bronchoalveolar lavage (BAL) of patients with ventilator-associated pneumonia, community-acquired pneumonia, non-ventilator ICU pneumonia and aspiration pneumonia, and compared the results with those from patients without pneumonia (controls). Samples were tested by amplification of 16S rDNA, 18S rDNA genes followed by cloning and sequencing and by PCR to target specific pathogens. We also included culture, amoeba co-culture, detection of antibodies to selected agents and urinary antigen tests. Based on molecular testing, we identified a wide repertoire of 160 bacterial species of which 73 have not been previously reported in pneumonia. Moreover, we found 37 putative new bacterial phylotypes with a 16S rDNA gene divergence ≥ 98% from known phylotypes. We also identified 24 fungal species of which 6 have not been previously reported in pneumonia and 7 viruses. Patients can present up to 16 different microorganisms in a single BAL (mean ± SD; 3.77 ± 2.93). Some pathogens considered to be typical for ICU pneumonia such as Pseudomonas aeruginosa and Streptococcus species can be detected as commonly in controls as in pneumonia patients which strikingly highlights the existence of a core pulmonary microbiota. Differences in the microbiota of different forms of pneumonia were documented.

Objective: Cytomegalovirus (CMV) and herpes simplex virus (HSV) are common viruses that can affect critically ill patients who are not immunocompromised. The aim of this study was to determine whether the identification of CMV and/or HSV in mechanically ventilated critically ill patients suspected of having pneumonia was associated with an increased mortality. Design: Prospective epidemiological study. Setting: Medical intensive care unit of a tertiary medical center. Patients: Ninety-three patients with suspected pneumonia. Interventions: Patients with suspected pneumonia had bronchoalveolar lavage and blood samples taken to confirm the diagnosis. Antigenemia was used to detect CMV in the blood. Bronchoalveolar lavage samples were submitted to testing using quantitative real-time Polymerase Chain Reaction. Measurements and Main Results: We identified 22 patients with a CMV infection, 26 patients with an HSV infection and 45 patients without CMV or HSV infection (control group). Mortality at day 60 was higher in patients with a CMV infection than in patients from the control group (55% vs. 20%, P<0.01). Mortality at day 60 was not significantly increased in the group with HSV infection. Duration of ICU stay and ICU mortality were significantly higher in patients with CMV infections when compared to patients from the control group, whereas ventilator free days were significantly lower in patients with CMV infections when compared to patients from the control group. Conclusions: In critically ill patients, a CMV infection is associated with an increased mortality. Further interventional studies are needed to evaluate whether treatment could improve the prognosis. [ABSTRACT FROM AUTHOR]

Introduction: Ventilator-associated pneumonia (VAP) may contribute to the mortality associated with acute respiratory distress syndrome (ARDS). We aimed to determine the incidence, outcome, and risk factors of bacterial VAP complicating severe ARDS in patients ventilated by using a strictly standardized lung-protective strategy.Methods: This prospective epidemiologic study was done in all the 339 patients with severe ARDS included in a multicenter randomized, placebo-controlled double-blind trial of cisatracurium besylate in severe ARDS patients. Patients with suspected VAP underwent bronchoalveolar lavage to confirm the diagnosis.Results: Ninety-eight (28.9%) patients had at least one episode of microbiologically documented bacterial VAP, including 41 (41.8%) who died in the ICU, compared with 74 (30.7%) of the 241 patients without VAP (P = 0.05). After adjustment, age and severity at baseline, but not VAP, were associated with ICU death. Cisatracurium besylate therapy within 2 days of ARDS onset decreased the risk of ICU death. Factors independently associated with an increased risk to develop a VAP were male sex and worse admission Glasgow Coma Scale score. Tracheostomy, enteral nutrition, and the use of a subglottic secretion-drainage device were protective.Conclusions: In patients with severe ARDS receiving lung-protective ventilation, VAP was associated with an increased crude ICU mortality which did not remain significant after adjustment. [ABSTRACT FROM AUTHOR]

The article presents a study which assess the incidence, risk factors and outcome of active cytomegalovirus (CMV) infection to nonimmunosuppressed patients in intensive care unit (ICU). Result shows that patients with active CMV infection had longer mechanical ventilation and longer stay in ICU are at risk to develop bacterial nosocomial infections. Risk factors include enteral feeding and costicosteriod use prior to ICU admission were associated with the occurrence of active CMV infection.

The article determines whether a positive serology for mimivirus was associated with increased morbidity and mortality in patients with a suspicion of ventilator-associated pneumonia (VAP). According to the authors, the effectiveness of matching was 94.8%. They add that patients with a positive serology for mimivirus had longer duration of mechanical ventilation and intensive care unit stay with median excesses of seven days and 10 days, respectively.

Objectives: This study in critically ill patients with shock assessed the prognostic value of body weight variations occurring each day from day 3 to day 7 on the 30-day outcome in terms of mortality, occurrence of ventilator-associated pneumonia and of bedsore, and occurrence of length of stay.Design: Retrospective analysis of data. Multivariate subdistribution survival models were used at each day, from day 3 to day 7. The impact of body weight variations on length of stay was estimated through a multivariate negative binomial regression model.Setting: Prospective multicenter cohort study.Patients: Critically ill patients admitted in ICU with shock and requiring mechanical ventilation within 48 hours.Intervention: None.Measurements and Main Results: Two-thousand three-hundred seventy-four patients were included. Their median body weight variations increased from 0.4 kg (interquartile range, 0-4.8 kg) on day 3 to 3 kg (interquartile range, -0.4 to 8.2 kg) on day 7. Categories of body weight variations were defined depending on body weight variations interquartiles: weight loss, no weight gain, moderate and severe weight gain. A severe weight gain tended to be associated with death at days 5 and 6 (day 5: subdistribution hazard ratio, 1.27; 95% CI, 0.99-1.63; p = 0.06 and day 6: subdistribution hazard ratio, 1.43; 95% CI, 1.08-1.89; p = 0.01), a weight loss tended to be associated with bedsore, and a severe gain between at days 5 and 6 was associated with ventilator-associated pneumonia. Any body weight variations were associated with an increased length of stay.Conclusions: In survivors at day 3, body weight variations during the first days of ICU stay might be a clinically relevant tool to prevent weight gain but also for prognostication of 30-day mortality, occurrence of ventilator-associated pneumonia, and occurrence of prolonged ICU stay. [ABSTRACT FROM AUTHOR]