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Purpose Studies on the impact of tapered-cuff tracheal tubes on rates of microaspiration and ventilator-associated pneumonia (VAP) in intubated patients have reported conflicting results. The aim of this study was to determine the influence of this shape of tracheal cuff on abundant microaspiration of gastric contents in critically ill patients. Methods All patients intubated in the intensive care unit (ICU) and requiring mechanical ventilation for at least 48 h were eligible for this multicenter cluster-randomized controlled cross-over open-label study. The primary outcome was abundant microaspiration of gastric contents, defined by the presence of pepsin at significant level in >30% of tracheal aspirates. Quantitative measurement of pepsin and salivary amylase was performed in all tracheal aspirates during the 48 h following enrollment. Results A total of 326 patients were enrolled in the ten participating ICUs (162 in the PVC tapered-cuff group and 164 in the standard-cuff group). Patient characteristics were similar in the two study groups. The proportion of patients with abundant microaspiration of gastric contents was 53.5% in the tapered-cuff and 51.0% in the standard-cuff group (odds ratio 1.14, 95% CI 0.72–1.82). While abundant microaspiration of oropharyngeal secretions was not significantly different (77.4 vs 68.6%, p  = 0.095), the proportion of patients with tracheobronchial colonization was significantly lower (29.6 vs 43.3%, p  = 0.01) in the tapered-cuff than in the standard-cuff group. No significant difference between the two groups was found for other secondary outcomes, including ventilator-associated events and VAP. Conclusions This trial showed no significant impact of tapered-cuff tracheal tubes on abundant microaspiration of gastric contents. Trial registration ClinicalTrials.gov, number NCT01948635.

Background Ventilator-associated pneumonia (VAP) is the most common infection in intubated critically ill patients. Microaspiration of the contaminated gastric and oropharyngeal secretions is the main mechanism involved in the pathophysiology of VAP. Tracheal cuff plays an important role in stopping the progression of contaminated secretions into the lower respiratory tract. Previous in vitro studies suggested that conical cuff shape might be helpful in improving tracheal sealing. However, clinical studies found conflicting results. The aim of this study is to determine the impact of conical tracheal cuff shape on the microaspiration of gastric contents in critically ill patients. Methods/Design This prospective cluster randomized controlled crossover open-label trial is currently being conducted in ten French intensive care units (ICUs). Patients are allocated to intubation with a polyvinyl chloride (PVC) standard (barrel)-shaped or a PVC conical-shaped tracheal tube. The primary objective is to determine the impact of the conical shaped tracheal cuff on abundant microaspiration of gastric contents. Secondary outcomes include the incidence of microaspiration of oropharyngeal secretions, tracheobronchial colonization, VAP and ventilator-associated events. Abundant microaspiration is defined as the presence of pepsin at significant level (>200 ng/ml) in at least 30 % of the tracheal aspirates. Pepsin and amylase are quantitatively measured in all tracheal aspirates during the 48 h following inclusion. Quantitative tracheal aspirate culture is performed at inclusion and twice weekly. We plan to recruit 312 patients in the participating ICUs. Discussion BEST Cuff is the first randomized controlled study evaluating the impact of PVC tracheal-cuff shape on gastric microaspirations in patients receiving invasive mechanical ventilation. Enrollment began in June 2014 and is expected to end in October 2015. Trial registration ClinicalTrials.gov Identifier: NCT01948635 (registered 31 August 2013).

Signalosomes are high-order protein machineries involved in complex mechanisms controlling regulated immune defense and cell death execution. The immune response is initiated by the recognition of exogeneous or endogenous signals, triggering the signalosome assembly process. The final step of signalosome fate often involves membrane-targeting and activation of pore-forming execution domains, leading to membrane disruption and ultimately cell death. Such cell death-inducing domains have been thoroughly characterized in plants, mammals and fungi, notably for the fungal cell death execution protein domain HeLo. However, little is known on the mechanisms of signalosome-based immune response in bacteria, and the conformation of cell death executors in bacterial signalosomes is still poorly characterized. We recently uncovered the existence of NLR signalosomes in various multicellular bacteria and used genome mining approaches to identify putative cell death executors in Streptomyces olivochromogenes . These proteins contain a C-terminal amyloid domain involved in signal transmission and a N-terminal domain, termed BELL for Bacteria analogous to fungal HeLL (HeLo-like), presumably responsible for membrane-targeting, pore-forming and cell death execution. In the present study, we report the high yield expression of S. olivochromogenes BELL2 and its characterization by solution NMR spectroscopy. BELL is folded in solution and we report backbone and sidechain assignments. We identified five α-helical secondary structure elements and a folded core much smaller than its fungal homolog HeLo. This study constitutes the first step toward the NMR investigation of the full-length protein assembly and its membrane targeting.