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Glutamine-dependent amidotransferases have been known for more than 30 years. The mechanism by which these enzymes generate ammonia from the glutamine amide nitrogen and transfer it to seven different chemical classes of acceptors has been the subject of intense scrutiny for the last 5 years. The increasing number of biochemical and structural studies dealing with amidotransferases and with mechanistically related enzymes has disclosed the dichotomy of the mechanisms within these enzymes for achieving the glutamine amide bond cleavage. Some of them use a catalytic Cys/His/Glu triad similar to serine protease, whereas the aminoterminal cysteine of the others is believed to play the same function. The transfer of ammonia from the glutamine site to the acceptor site which must operate in a concerted manner has been demonstrated in two cases to involve channelling but is still matter of investigation.

Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation. In this trial, the investigators found a benefit with respect to all-cause mortality with this change in body position in patients with severe ARDS. Prone positioning has been used for many years to improve oxygenation in patients who require mechanical ventilatory support for management of the acute respiratory distress syndrome (ARDS). Randomized, controlled trials have confirmed that oxygenation is significantly better when patients are in the prone position than when they are in the supine position. 1 , 2 Furthermore, several lines of evidence have shown that prone positioning could prevent ventilator-induced lung injury. 3 – 6 In several previous trials, these physiological benefits did not translate into better patient outcomes, since no significant improvement was observed in patient survival with prone positioning. 7 – 10 However, meta-analyses 2 , 11 have . . .

Objective To assess quality of life (QOL), mortality rate and renal function 6 months after onset of renal replacement therapy (RRT) for acute kidney injury (AKI) in the ICU. Participants and setting This prospective observational study was conducted in seven ICUs in France over 9 months. Inclusion criteria were: age ≥18 years, RRT delivered for AKI and informed consent signed. AKI was defined from the RIFLE score. Recipients of kidney grafts or patients undergoing chronic RRT were not included. Measurements and results QOL was assessed using the Short Form Health Survey (SF-36) questionnaire together with the Index of Activities of Daily Living (ADL) (0: full assistance to 6: no assistance). SF-36 was compared to a reference age- and sex-matched French population. Patient status, place of residence, and persistence of RRT, ADL and SF-36 were assessed at 28 days, 3 months and 6 months from inclusion. In the study period, 205 patients were included and 1 withdrew. At 6 months, 77/204 were alive (mortality 62%). SF-36 and ADL significantly increased from day 28 to 6 months. In the survivors at 6 months, SF-36 items were significantly lower than in the reference population, with the physical items more severely affected than the mental items; 64% were fully autonomous (ADL score = 6); 69% were living in their homes, and 12% were still undergoing RRT; 94% would agree to undergo the same management again. Conclusions ICU survivors from RRT for AKI have an impaired QOL at 6 months, but sustained autonomy in their daily lives.

To investigate the effects of prone position (PP) on alveolar recruitment and oxygenation in acute respiratory failure. Prospective physiologic study. Medical ICU two in a university hospital. Twelve adult patients intubated and mechanically ventilated with medical primary acute lung injury/adult respiratory distress syndrome (ALI/ARDS) in whom PP was indicated. We constructed the static inflation volume-pressure curves (V-P) of the respiratory system in the 12 patients and differentiated between lung and chest wall in ten of them. We determined the difference between end-expiratory lung volume on positive end-expiratory pressure (PEEP) and relaxation volume of the respiratory system on zero PEEP (delta FRC). The recruited alveolar volume was computed as the delta FRC times the ratio of static elastance of the respiratory system to the lung. These measurements together with arterial blood gases determination were made in supine position (SP1), after 1 h of PP and after 1 h of supine repositioning (SP2) at the same level of PEEP. The PaO2/FIO2 ratio improved from SP1 to PP (136 +/- 17 vs 204 +/- 24 mm Hg; p < 0.01). An PP-induced alveolar recruitment was found in five patients. The change in oxygenation correlated to the recruited volume. The static elastance of the chest wall decreased from 4.62 +/- 0.99 cmH2O/l in SP1 to 6.26 +/- 0.54 cmH2O/l in PP (p < 0.05) without any correlation to the change in oxygenation. Alveolar recruitment may be a mechanism of oxygenation improvement in some patients with acute hypoxemic respiratory failure. No correlation was found between change in oxygenation and chest wall elastic properties.

Background: Human Papillomavirus (HPV) infection is recognised as aetiological factor of carcinogenesis in oropharyngeal squamous cell carcinomas (OPC). HPV-related OPC respond better to treatments and have a significantly favourable outcome. Epithelial to mesenchymal transition (EMT) implicated in tumour invasion, is a hallmark of a poor prognosis in carcinomas. Methods: We have studied the relationship of EMT markers (E-cadherin, β -catenin and vimentin) with HPV infection (DNA and E6/E7 mRNA detection), p16 INK4a expression and survival outcomes in a cohort of 296 patients with OPC. Results: Among the 296 OPSSC, 26% were HPV positive, 20.3% had overt EMT (>25% of vimentin positive tumour cells). Lower E-cadherin expression was associated with a higher risk of distant metastasis in univariate ( P =0.0110) and multivariate analyses (hazard ratios (HR)=6.86 (1.98; 23.84)). Vimentin expression tends towards worse metastasis-free survival (MFS; HR=2.53 (1.00; 6.41)) and was an independent prognostic factor of progression-free survival (HR=1.55 (1.03; 2.34)). Conclusions: There was a non significant association of EMT with HPV status. This may be explained by a mixed subpopulation of patients HPV positive with associated risk factors (HPV, tobacco and alcohol). Thus, the detection of EMT in OPC represents another reliable approach in the prognosis and the management of OPC whatever their HPV status.

Several studies have pointed out ethical shortcomings in the decision-making process for withholding or withdrawing life-supporting treatments. We conducted a study to evaluate the perceptions of all caregivers involved in this process in the intensive care unit. A closed-ended questionnaire was completed by 3,156 nursing staff members and 521 physicians from 133 French intensive care units (participation rate, 42%). Decision-making processes were perceived as satisfactory by 73% of physicians and by only 33% of the nursing staff. More than 90% of caregivers believed that decision-making should be collaborative, but 50% of physicians and only 27% of nursing staff members believed that the nursing staff was actually involved (p < 0.001). Fear of litigation was a reason given by physicians for modifying information given to competent patients, families, and nursing staff. Perceptions by nursing staff may be a reliable indicator of the quality of medical decision-making processes and may serve as a simple and effective tool for evaluating everyday practice. Recommendations and legislation may help to build consensus and avoid conflicts among caregivers at each step of the decision-making process.

Two air entrainment mechanisms driven by vortex instability are reported in the unstable relaxation of a horizontal shear layer below a free surface. This flow is experimentally investigated by means of planar laser-induced fluorescence (PLIF) and particle image velocimetry (PIV) coupled with surface profilometry. PLIF identifies counter-rotating vortex pairs (CRVP) emanating from the surface following the growth of high steepness two-dimensional millimetre-size waves for Reynolds and Weber numbers based on the momentum thickness of 177 to 222 and 7.59 to 13.9, respectively. High spatio-temporal resolution PIV reveals the role of surface-generated vorticity and flow separation in the highly curved trough of the waves on the injection of a CRVP. Air bubbles are entrapped in the wake of these CRVPs at Reynolds number above 190. PIV data and spanwise PLIF images show two initiation mechanisms: primary vortex instability modulating the spanwise location where the flow separates, resulting in the pinch off of an air ligament, and secondary vortex instability turning a CRVP into $\\unicode[STIX]{x1D6FA}$ -shaped loops pulling the surface down. Instability wavelengths agree with linear stability analysis, and models for these new air entrainment mechanisms are proposed.

(1) To determine the incidence of expiratory flow limitation (FL) at ICU admission, at the time of extubation, and at ICU discharge in intubated patients with COPD receiving mechanical ventilation for acute respiratory failure (ARF); and (2) to assess the feasibility of inspiratory capacity (IC) as an indication of pulmonary dynamic hyperinflation in this setting. Prospective, observational pilot study with physiologic measurements performed at ICU admission and during the weaning process driven by the clinician. A 60-min T-tube trial was initiated once criteria for weaning were present. The decision to extubate or reventilate patients was made by the clinician at the end of this session. Assessment of failure or success of T-tube trials was performed independently. A 25-bed ICU of a tertiary teaching university hospital. Over a 13-month period, 25 intubated patients with COPD receiving mechanical ventilation for ARF were included. None. At ICU admission, FL assessed by the negative expiratory pressure test was measured under passive ventilatory conditions at the baseline ventilatory settings, on zero end-expiratory pressure, and in a semirecumbent position. During weaning, FL, respiratory pattern, and IC were measured during T-tube trials, before extubation, 1 h after extubation, and at ICU discharge. At ICU admission, 24 of 25 patients presented FL with, on average, 73 ± 22% of the tidal volume. Ten patients were unavailable for follow-up due to death (n = 6) unplanned extubation (n = 3), or refusal (n = 1), so that only 15 patients completed the whole protocol (all 15 patients were extubated). For these 15 patients, the incidence of FL was 93% at ICU admission, 47% before extubation, and 40% at ICU discharge. IC was significantly greater at ICU discharge than before extubation (36 ± 11% predicted vs 44 ± 12% predicted, p < 0.01) and in successful T-tube trials compared with unsuccessful T-tube trials (38 ± 13% predicted vs 24 ± 8% predicted, p < 0.01). The incidence of expiratory FL is high in patients with COPD receiving mechanical ventilation, and is reduced during aggressive therapy when the patient is placed on mechanical ventilatory support and the time that weaning begins during the ICU stay. IC was lower in patients in whom weaning was unsuccessful. Further large-scale studies are required to confirm these preliminary results.