Study of prone positioning to reduce ventilator-associated pneumonia in hypoxaemic patients.

The aim of the present study was to examine whether prone positioning (PP) affects ventilator associated-pneumonia (VAP) and mortality in patients with acute lung injury/adult respiratory distress syndrome. 2,409 prospectively included patients were admitted over 9 yrs (2000-2008) to 12 French intensive care units (ICUs) (OUTCOMEREA). The patients required invasive mechanical ventilation (MV) and had arterial oxygen tension/inspiratory oxygen fraction ratios <300 during the first 48 h. Controls were matched to PP patients on the PP propensity score (+/-10%), MV duration longer than that in PP patients before the first turn prone, and centre. VAP incidence was similar in the PP and control groups (24 versus 13 episodes.1,000 patient-days MV(-1) respectively, p = 0.14). After adjustment, PP did not decrease VAP occurrence (HR 1.64 (95% CI 0.70-3.84); p = 0.25) but significantly delayed hospital mortality (HR 0.56 (95% CI 0.39-0.79); p = 0.001), without decreasing 28-day mortality (37% in both groups). Post hoc analyses indicated that PP did not protect against VAP but, when used for >1 day, might decrease mortality and benefit the sickest patients (Simplified Acute Physiology Score >50). In ICU patients with hypoxaemic acute respiratory failure, PP had no effect on the risk of VAP. PP delayed mortality without decreasing 28-day mortality. PP >1 day might decrease mortality, particularly in the sickest patients.

PRR2, a pseudo-response regulator, promotes salicylic acid and camalexin accumulation during plant immunity.

Calcium signalling mediated by Calmodulin (CaM) and calmodulin-like (CML) proteins is critical to plant immunity. CaM and CML regulate a wide range of target proteins and cellular responses. While many CaM-binding proteins have been identified, few have been characterized for their specific role in plant immunity. Here, we report new data on the biological function of a CML-interacting partner, PRR2 (PSEUDO-RESPONSE REGULATOR 2), a plant specific transcription factor. Until now, the physiological relevance of PRR2 remained largely unknown. Using a reverse genetic strategy in A. thaliana, we identified PRR2 as a positive regulator of plant immunity. We propose that PRR2 contributes to salicylic acid (SA)-dependent responses when challenged with the phytopathogenic bacterium Pseudomonas syringae. PRR2 is transcriptionally upregulated by SA and P. syringae, enhances SA biosynthesis and SA signalling responses; e.g. in response to P. syringae, PRR2 induces the production of SA and the accumulation of the defence-related protein PR1. Moreover, PRR2 overexpressing lines exhibit an enhanced production of camalexin, a phytoalexin that confers enhanced resistance against pathogens. Together, these data reveal the importance of PRR2 in plant immune responses against P. syringae and suggest a novel function for this particular plant specific transcription factor in plant physiology.

[Noninvasive ventilation. The 2015 guidelines from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF)]. / Ventilation non invasive. Les conseils 2015 du Groupe assistance ventilatoire (GAV) de la Société de pneumologie de langue française (SPLF).

A task force issued from the Groupe Assistance Ventilatoire (GAV) of the Société de Pneumologie de Langue Française (SPLF) was committed to develop a series of expert advice concerning various practical topics related to long-term non invasive ventilation by applying the Choosing Wisely® methodology. Three topics were selected: monitoring of noninvasive ventilation, the interpretation of data obtained from built-in devices coupled to home ventilators and the role of hybrid modes (target volume with variable pressure support. For each topic, the experts have developed practical tips based on a comprehensive analysis of recent insights and evidence from the literature and from clinical experience.

Usefulness of a strategy based on bronchoscopy with direct examination of bronchoalveolar lavage fluid in the initial antibiotic therapy of suspected ventilator-associated pneumonia.

OBJECTIVES: To evaluate (a) the routine accuracy of bronchoalveolar lavage by direct examination (BAL-D) in diagnosing ventilator-associated pneumonia (VAP), and (b) the impact of a diagnostic strategy including clinical judgment, bronchoscopy, and BAL-D on the initial diagnosis and appropriateness of treatment when VAP is suspected. DESIGN AND SETTING: Prospective cohort study in two academic ICUs in Paris, France. PATIENTS AND PARTICIPANTS: Mechanically ventilated patients with suspected VAP underwent bronchoscopy with BAL and protected specimen brush (PSB). BAL-D results were available within 2 h, BAL on culture and PSB results after 24 h, and antibiotic susceptibility after 48 h. At each step in the strategy the senior and the resident in charge of the patient were asked their diagnosis and their therapeutic plan on the basis of presently available data. Definite diagnosis of suspected VAP was based on histology, appearance of cavitation, positive pleural fluid culture, results of PSB and BAL culture, and follow-up. MEASUREMENT AND RESULTS: A total of 110 episodes of suspected VAP were studied; 94 definite diagnoses were made (47 VAP, 47 no VAP). Using a threshold 1% of infected cells, BAL-D discriminated well between patients with and those without VAP (sensitivity 93.6%, specificity 91.5%, area under the receiver-operating characteristic curve 0.953). The senior clinical judgment was correct in 71% cases. It was correct in 78% and 94% of cases after airway visualization and BAL-D findings, respectively. After BAL-D the positive and negative predictive values in diagnosing VAP were 90% and 98%, respectively. However, the therapeutic plan was correct in only 65% using clinical judgment (15 untreated patients, 3 ineffective treatment, 15 useless treatment), 66% using airway visualization (14 untreated VAP, 4 ineffective treatment, 14 useless treatment), and 88% using BAL-D results (1 untreated patients, 6 ineffective, 4 useless), according to definite diagnosis and final antibiotic susceptibility testings. CONCLUSIONS: A strategy based on bronchoscopy and BAL-D generally leads to a rapid and appropriate treatment of nosocomial pneumonia in ventilated patients.

Efficiency of inhaled nitric oxide as rescue therapy during severe ARDS: survival and factors associated with the first response.

PURPOSE: The purpose of this study was to determine if the response to inhaled nitric oxide (NO) as salvage therapy is an independent factor for survival in adult respiratory distress syndrome (ARDS) patients and to identify the factors that predict the response to inhaled NO during ARDS. MATERIALS AND METHODS: This was a multicenter, 2-year retrospective, clinical study in five university surgical or medical intensive care units, including all consecutive patients with ARDS in whom inhaled NO was tried. Clinical data (medical history, diagnoses), general severity scores (SAPS II, OSF), biological data, radiological and hemodynamic data at admission, at the beginning of the ARDS, and under treatment with inhaled NO were recorded. The NO response was defined as the variation of PaO2/Fio2 ratio before initiation and after 30 minutes of NO inhalation (VarPaO2/FiO2). RESULTS: Ninety-three patients aged 49 +/- 18 years were studied. Mean SAPS II was 45 +/- 16. Before the beginning of inhaled NO, PaO2/Fio2 ratio was 95 +/- 53 mm Hg and lung injury score 2.7 + 0.3. VarPao2/Fio2 when NO was started (11 +/- 4 ppm) was 26 +/- 44.5 mm Hg (median 17 mm Hg). Intensive care unit mortality was 74%. None of the parameters studied were predictors of response to inhaled NO, although there was a tendency for the youngest patients with the more severe hypoxemia to have a better response. Response to first inhaled NO test (VarPaO2/FiO2) was univariately associated with survival (Survivors: 45 +/- 44 mm Hg vs. Nonsurvivors: 20 +/- 43 mm Hg, P = .01), but this difference disappeared after adjusting for other prognostic factors (P = .16) selected by multivariate analysis. Finally, inhaled NO was continued for more than 1 day for 75 patients, and definitively stopped for 18 patients. Intensive care unit mortality (73% vs. 78%) was not different between these groups (P = .25, Log-rank test). CONCLUSIONS: We conclude that (1) efficacy of inhaled NO in improving oxygenation was moderate and difficult to predict, (2) response to first NO inhalation was not associated with prognosis, and (3) treatment of the most severe ARDS patients with inhaled NO did not influenced their intensive care unit survival.

Relationship between blood lactate and early hepatic dysfunction in acute circulatory failure.

PURPOSE: The purpose of this study was to assess the influence of early hepatic dysfunction on lactate level in patients with acute circulatory failure in a retrospective study. MATERIALS AND METHODS: Blood lactate was compared between patients in acute circulatory failure (systolic blood pressure < or = 80 mm Hg despite fluid challenge) with or without early hepatic dysfunction (bilirubin > 60 micromol/L or SGOT > 100 IU/L during the first 48 hours). Univariate and multivariate analysis were performed to assess the effects of early hepatic dysfunction and other clinical and biological data on serum lactate levels in patients with acute circulatory failure. RESULTS: The study included 92 patients, mean age 64+/-15 years, mean simplified acute physiology score (SAPS) 18.4+/-4.1. Early hepatic dysfunction was identified in 29 patients (32%). Mean initial blood lactate was 5.54+/-4.78 mmol/L. Overall intensive care unit mortality was 67.3%. Although patients with and without hepatic dysfunction showed no significant difference in terms of mean SAPS, mean lowest systolic blood pressure, and mortality, serum lactate was higher in the group with hepatic dysfunction than in the group without hepatic dysfunction (8.24+/-6.49 mmol/L v4.29+/-3.09 mmol/L, P < .001). Factors independently associated with serum lactate were the existence of early hepatic dysfunction (P < .01), a nondistributive type of shock (P < .05), and the mean initial amount of epinephrine (P < .05). CONCLUSIONS: This study suggests that early hepatic dysfunction plays an important role in serum lactate elevation in acute circulatory failure.

[Principal clinical manifestations during the course of disease caused by the human immunodeficiency virus (HIV) in Pointe-Noire (Republic of Congo). (307 cases hospitalized during 2 years at the medical service of the Regional Hospital of the Army)]. / Principales manifestations cliniques au cours de la maladie due au virus de l'immunodéficience humaine (VIH) à Pointe-Noire (République du Congo). (A propos de 307 observations de malades hospitalisés en 2 ans dans le Service de Médecine de l'Hôpital Régional des Armées).

At the sight of the hospitalization of 307 patients, attacked by AIDS, inside the department of Medicine of the Military Hospital in Pointe-Noire (Congo) between 1990-1992, the authors try to point out the principal epidemiological characteristics of their patients; give a semeiological and clinical descriptions of the key symptoms encountered; try to draw a scale depending on the apparition and frequency of the opportunistic infections. The great number of some diseases (tuberculosis, cryptococcal meningitidis, herpes zoster, diarrhea, neurologic complications ...) the more or less absence of others (pneumocystis carinii pneumonia) grant to Central Africa AIDS an undeniable originality compared to those of Europe and America. This analysis shows that a certain number of clinic signs in tropical area must attract the attention of the physician (facial palsy, herpes zoster, dementia, focal brain disorders), and so, to include the detection of AIDS, in the etiology of these affections.

Short-term effect of inhaled nitric oxide and prone positioning on gas exchange in patients with severe acute respiratory distress syndrome.

OBJECTIVE: To compare the short-term effects of inhaled nitric oxide (NO) and prone positioning in improving oxygenation in acute respiratory distress syndrome (ARDS). METHODS: Charts of consecutive ARDS patients (lung injury score >2) during a 2-yr period, tested for both inhaled NO and prone positioning efficacy were retrospectively reviewed. Variations in the Pao2/Fio2 ratio induced by inhaled NO and prone positioning were evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-seven patients (age, 42+/-17 yrs) were included. Simplified Acute Physiology Score II was 45+/-14. Mortality rate in the intensive care unit was 63%. The causes of ARDS were pneumonia (n = 14), extra-lung infection (n = 5), and noninfectious systemic inflammatory response syndrome (n = 8). Lung injury score was 2.7+/-0.3. At baseline, before the initiation of inhaled NO, the Pao2/Fio2 ratio was 97+/-46 torr and before prone positioning, 92+/-26 torr. Variations in the Pao2/Fio2 ratio were lower at start of NO therapy (11+/-4 ppm) than that observed at prone positioning initiation (23+/-31 vs. 62+/-78 torr, p<.05). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with prone positioning in 16 patients (59%) and with NO inhalation in 13 patients (48%) (not significant). An increase in variations in the Pao2/Fio2 ratio of >15 torr was associated with both techniques in only six patients (22%). There was no correlation between the response to prone positioning and the response to inhaled NO (r2 = .005; p = .73). CONCLUSIONS: Prone positioning improves hypoxemia significantly better than does inhaled NO. The response to one technique is not predictive of the response to the other technique.

Presence of high levels of leukocyte-associated interleukin-8 upon cell activation and in patients with sepsis syndrome.

In inflammatory and infectious diseases, the presence of circulating cytokines in plasma strongly suggests, following their exacerbated production, that saturation of specific binding sites has occurred or that an equilibrium between receptor-bound and free cytokines has been reached. In this report, we demonstrate that in addition to circulating interleukin-8 (IL-8), high levels of cell-associated IL-8 were detected in blood samples from patients with sepsis syndrome. The following analysis will reveal that in addition to erythrocytes, which have been dubbed a "sink" for IL-8, peripheral blood mononuclear cells (PBMC) and polymorphonuclear cells (PMN) contributed to the detection of cell-associated IL-8. On a per cell basis, 2,000 to 7,000 times the amount of IL-8 was found associated with PMN than with erythrocytes. In addition, circulating cells may well be the source of the leukocyte-associated form of IL-8. Similarly, in vitro experiments, such as whole-blood stimulation assays or the addition of exogenous IL-8 in blood samples, demonstrated that a large proportion of the IL-8 was associated with leukocytes. This suggests that the trapping of free cytokines onto the cell surface and the internalization of the IL-8 bound to its receptor, occurring both in vitro and in vivo, allows the detection of this cell-associated form. This analysis of cell-associated cytokines was extended to IL-1ra, another component of the inflammatory response, which, in contrast to IL-8, has been demonstrated to exist as an intracellular form. Indeed, cell-associated IL-1ra was also detected in septic patients. The measurement of cell-associated proinflammatory and anti-inflammatory cytokines in patients is clearly a more reliable reflection of their production than is the simple measurement in plasma and may provide useful indication to further understand the inflammatory process.

Use of tunneled femoral catheters to prevent catheter-related infection. A randomized, controlled trial.

BACKGROUND: The risk for catheter-related infection seems higher with femoral catheters than with catheters inserted at other sites. OBJECTIVE: To evaluate the effect of catheter tunneling on femoral catheter-related infection in critically ill patients. DESIGN: Randomized, controlled trial. SETTING: Three intensive care units at academic hospitals in Paris, France. PATIENTS: 345 adult patients requiring a femoral venous catheter for more than 48 hours. INTERVENTION: Tunneled or nontunneled femoral catheters. MEASUREMENTS: Time to occurrence of systemic catheter-related sepsis, catheter-related bloodstream infection, and quantitative catheter tip culture with a cutoff of 10(3) colony-forming units/mL. RESULTS: Of 345 randomly assigned patients, 336 were evaluable. Probable systemic catheter-related sepsis occurred in 15 of 168 patients who received a nontunneled femoral catheter (controls) and in 5 of 168 patients who received a tunneled femoral catheter (estimated absolute risk reduction, 6% [95% CI, 0.9% to 11%]). Time to occurrence of catheter-related bloodstream infection was not significantly modified (relative risk, 0.28 [CI, 0.03 to 1.92]; P = 0.18); 3 events occurred in the control group and 1 event occurred in the tunneled-catheter group. After stratification by treatment center and adjustment for variables that were prognostic (use of broad-spectrum antimicrobial agents at catheter insertion) or imbalanced between both groups (mechanical ventilation at insertion), tunnelized catheterization reduced the proportion of patients who developed systemic catheter-related sepsis (relative risk, 0.25 [CI, 0.09 to 0.72]; P = 0.005) and positive quantitative culture of the catheter tip (relative risk, 0.48 [CI, 0.23 to 0.99]; P = 0.045). CONCLUSION: The incidence of femoral catheter-related infections in critically ill patients can be reduced by using subcutaneous tunneling.

Procalcitonin (PCT) is useful in predicting the bacterial origin of an acute circulatory failure in critically ill patients.

OBJECTIVE: To evaluate the accuracy of procalcitonin (PCT) in predicting bacterial infection in ICU medical and surgical patients. SETTING: A 10-bed medical surgical unit. DESIGN: PCT, C-reactive protein (CRP), interleukin 6 (IL-6) dosages were sampled in four groups of patients: septic shock patients (SS group), shock without infection (NSS group), patients with systemic inflammatory response syndrome related to a proven bacterial infection (infect. group) and ICU patients without shock and without bacterial infection (control group). RESULTS: Sixty patients were studied (SS group:n=16, NSS group,n=18, infect. group,n=16, control group,n=10). The PCT level was higher in patients with proven bacterial infection (72+/-153 ng/ml vs 2.9+/-10 ng/ml,p=0.0003). In patients with shock, PCT was higher when bacterial infection was diagnosed (89 ng/ml+/-154 vs 4.6 ng/ml+/-12,p=0.0004). Moreover, PCT was correlated with severity (SAPS:p=0.00005, appearance of shock:p=0.0006) and outcome (dead: 71.3 g/ml, alive: 24.0 g/ml,p=0.006). CRP was correlated with bacterial infection (p<10(-5)) but neither with SAPS nor with day 28 mortality. IL-6 was correlated with neither infection nor day 28 mortality but was correlated with SAPS. Temperature and white blood cell count were unable to distinguish shocked patients with or without infection. Finally, when CRP and PCT levels were introduced simultaneously in a stepwise logistic regression model, PCT remained the unique marker of infection in patients with shock (PCT> or =5 ng/ml, OR: 6.2, 95% CI: 1.1-37,p=0.04). CONCLUSION: The increase of PCT is related to the appearance and severity of bacterial infection in ICU patients. Thus, PCT might be an interesting parameter for the diagnosis of bacterial infections in ICU patients.

Association of TNF2, a TNF-alpha promoter polymorphism, with septic shock susceptibility and mortality: a multicenter study.

CONTEXT: Tumor necrosis factor alpha (TNF-alpha) is believed to be a cytokine central to pathogenesis of septic shock. TNF2, a polymorphism within the TNF-alpha gene promoter, has been associated with enhanced TNF-alpha production and negative outcome in some severe infections. OBJECTIVES: To investigate the frequency of the TNF2 allele in patients with septic shock and to determine whether the allele is associated with the occurrence and outcome of septic shock. DESIGN: Multicenter case-control study conducted from March 1996 to June 1997. SETTING: Seven medical intensive care units in university hospitals. SUBJECTS: Eighty-nine patients with septic shock and 87 healthy unrelated blood donors. MAIN OUTCOME MEASURES: Frequency of the TNF2 allele among patients with septic shock and among those who died and the level of corresponding TNF-alpha concentrations. RESULTS: Mortality among patients with septic shock was 54%, consistent with the predicted mortality from the Simplified Acute Physiologic Score (SAPS II) value. The polymorphism frequencies of the controls and the patients with septic shock differed only at the TNF2 allele (39% vs 18% in the septic shock and control groups, respectively, P =.002). Among the septic shock patients, TNF2 polymorphism frequency was significantly greater among those who had died (52% vs 24% in the survival group, P =.008). Concentrations of TNF-alpha were higher in 68% and 52% with the TNF2 and TNF1 polymorphisms, respectively, but their median values (48 pg/mL vs 29 pg/mL) were not statistically different (P = .31). After controlling for age and the probability of death, derived by the SAPS II score, multiple logistic regression analysis showed that, for the same rank of SAPS II value, patients with the TNF2 allele had a 3.7-fold risk of death (95% confidence interval, 1.37-10.24). CONCLUSION: The TNF2 allele is strongly associated with susceptibility to septic shock and death due to septic shock.