High Frequency of Specific Polysaccharide Antibody Deficiency in Adults With Unexplained, Recurrent and/or Severe Infections With Encapsulated Bacteria.

BACKGROUND: Primary immunodeficiencies (PIDs) in adults are mainly revealed by recurrent and/or severe bacterial infections. The objective of this study was to evaluate a systematic research strategy of PIDs in adults with unexplained bacterial infections, with a special focus on specific polysaccharide antibody deficiency (SPAD). METHODS: In this prospective multicenter study, inclusion criteria were recurrent benign upper and lower respiratory tract infections (RTIs) for at least two years (group 1), at least one upper or lower RTI requiring hospitalization (group 2), and/or at least one invasive infection documented with encapsulated bacteria (group 3). Main exclusion criteria were all local and general conditions that could explain infections. If no PID diagnosis was made, response to polysaccharide antigens was assessed using a pneumococcal polysaccharide vaccine. RESULTS: From March 2015 to March 2020, 118 patients were included (37 males, median age of 41 years): 73, 17, and 28 in groups 1, 2, and 3, respectively. Forty-seven PIDs were diagnosed, giving an estimated frequency of 39.8% (95% confidence interval [CI] [30.4, 48.8]). SPAD was the most frequent diagnosis by far (n = 37/47, 78.7%), and was made in 23, 5, and 9 patients from groups 1 to 3, respectively. All SPAD patients received conjugate vaccines and, according to their infectious history, were on surveillance or treated with preventive antibiotics (n = 6) and/or with immunoglobulins replacement therapy (n = 10), the latter being dramatically efficient in all cases. CONCLUSIONS: Considering its high prevalence among adults with unexplained recurrent and/or severe bacterial infections, SPAD should be screened in those patients. CLINICAL TRIALS REGISTRATION: NCT02972281.

Electron-Phonon beyond Fröhlich: Dynamical Quadrupoles in Polar and Covalent Solids.

We include the treatment of quadrupolar fields beyond the Fröhlich interaction in the first-principles electron-phonon vertex in semiconductors. Such quadrupolar fields induce long-range interactions that have to be taken into account for accurate physical results. We apply our formalism to Si (nonpolar), GaAs, and GaP (polar) and demonstrate that electron mobilities show large errors if dynamical quadrupoles are not properly treated.

ABINIT: Overview and focus on selected capabilities.

abinit is probably the first electronic-structure package to have been released under an open-source license about 20 years ago. It implements density functional theory, density-functional perturbation theory (DFPT), many-body perturbation theory (GW approximation and Bethe-Salpeter equation), and more specific or advanced formalisms, such as dynamical mean-field theory (DMFT) and the "temperature-dependent effective potential" approach for anharmonic effects. Relying on planewaves for the representation of wavefunctions, density, and other space-dependent quantities, with pseudopotentials or projector-augmented waves (PAWs), it is well suited for the study of periodic materials, although nanostructures and molecules can be treated with the supercell technique. The present article starts with a brief description of the project, a summary of the theories upon which abinit relies, and a list of the associated capabilities. It then focuses on selected capabilities that might not be present in the majority of electronic structure packages either among planewave codes or, in general, treatment of strongly correlated materials using DMFT; materials under finite electric fields; properties at nuclei (electric field gradient, Mössbauer shifts, and orbital magnetization); positron annihilation; Raman intensities and electro-optic effect; and DFPT calculations of response to strain perturbation (elastic constants and piezoelectricity), spatial dispersion (flexoelectricity), electronic mobility, temperature dependence of the gap, and spin-magnetic-field perturbation. The abinit DFPT implementation is very general, including systems with van der Waals interaction or with noncollinear magnetism. Community projects are also described: generation of pseudopotential and PAW datasets, high-throughput calculations (databases of phonon band structure, second-harmonic generation, and GW computations of bandgaps), and the library libpaw. abinit has strong links with many other software projects that are briefly mentioned.

Strong electron-phonon coupling driven pseudogap modulation and density-wave fluctuations in a correlated polar metal.

There is tremendous interest in employing collective excitations of the lattice, spin, charge, and orbitals to tune strongly correlated electronic phenomena. We report such an effect in a ruthenate, Ca3Ru2O7, where two phonons with strong electron-phonon coupling modulate the electronic pseudogap as well as mediate charge and spin density wave fluctuations. Combining temperature-dependent Raman spectroscopy with density functional theory reveals two phonons, B2P and B2M, that are strongly coupled to electrons and whose scattering intensities respectively dominate in the pseudogap versus the metallic phases. The B2P squeezes the octahedra along the out of plane c-axis, while the B2M elongates it, thus modulating the Ru 4d orbital splitting and the bandwidth of the in-plane electron hopping; Thus, B2P opens the pseudogap, while B2M closes it. Moreover, the B2 phonons mediate incoherent charge and spin density wave fluctuations, as evidenced by changes in the background electronic Raman scattering that exhibit unique symmetry signatures. The polar order breaks inversion symmetry, enabling infrared activity of these phonons, paving the way for coherent light-driven control of electronic transport.

Is COPD associated with increased risk for microaspiration in intubated critically ill patients?

BACKGROUND: Although COPD patients are at higher risk for aspiration when breathing spontaneously, no information is available on the risk for microaspiration in invasively ventilated COPD patients. The aim of our study was to determine the relationship between COPD and abundant microaspiration in intubated critically ill patients. METHODS: This was a retrospective analysis of prospectively collected data, provided by 3 randomized controlled trials on microaspiration in critically ill patients receiving invasive mechanical ventilation for more than 48 h. Abundant microaspiration was defined as the presence of pepsin and or alpha-amylase at significant levels in tracheal aspirates. In all study patients, pepsin and alpha-amylase were quantitatively measured in all tracheal aspirates collected during a 48-h period. COPD was defined using spirometry criteria. RESULTS: Among the 515 included patients, 70 (14%) had proven COPD. Pepsin and alpha-amylase were quantitatively measured in 3873 and 3764 tracheal aspirates, respectively. No significant difference was found in abundant microaspiration rate between COPD and non-COPD patients (62 of 70 patients (89%) vs 366 of 445 (82%) patients, p = 0.25). Similarly, no significant difference was found in abundant microaspiration of gastric contents (53% vs 45%, p = 0.28), oropharyngeal secretions (71% vs 71%, p = 0.99), or VAP (19% vs 22%, p = 0.65) rates between the two groups. No significant difference was found between COPD and non-COPD patients in duration of mechanical ventilation, ICU length of stay, or ICU mortality. CONCLUSIONS: Our results suggest that COPD is not associated with increased risk for abundant microaspiration in intubated critically ill patients.

Antimicrobial treatment for ventilator-associated tracheobronchitis: a randomized, controlled, multicenter study.

INTRODUCTION: Ventilator-associated tracheobronchitis (VAT) is associated with increased duration of mechanical ventilation. We hypothesized that, in patients with VAT, antibiotic treatment would be associated with reduced duration of mechanical ventilation. METHODS: We conducted a prospective, randomized, controlled, unblinded, multicenter study. Patients were randomly assigned (1:1) to receive or not receive intravenous antibiotics for 8 days. Patients with ventilator-associated pneumonia (VAP) prior to VAT and those with severe immunosuppression were not eligible. The trial was stopped early because a planned interim analysis found a significant difference in intensive care unit (ICU) mortality. RESULTS: Fifty-eight patients were randomly assigned. Patient characteristics were similar in the antibiotic (n = 22) and no antibiotic (n = 36) groups. Pseudomonas aeruginosa was identified in 32% of VAT episodes. Although no difference was found in mechanical ventilation duration and length of ICU stay, mechanical ventilation-free days were significantly higher (median [interquartile range], 12 [8 to 24] versus 2 [0 to 6] days, P < 0.001) in the antibiotic group than in the no antibiotic group. In addition, subsequent VAP (13% versus 47%, P = 0.011, odds ratio [OR] 0.17, 95% confidence interval [CI] 0.04 to 0.70) and ICU mortality (18% versus 47%, P = 0.047, OR 0.24, 95% CI 0.07 to 0.88) rates were significantly lower in the antibiotic group than in the no antibiotic group. Similar results were found after exclusion of patients with do-not-resuscitate orders and those randomly assigned to the no antibiotic group but who received antibiotics for infections other than VAT or subsequent VAP. CONCLUSION: In patients with VAT, antimicrobial treatment is associated with a greater number of days free of mechanical ventilation and lower rates of VAP and ICU mortality. However, antibiotic treatment has no significant impact on total duration of mechanical ventilation. TRIAL REGISTRATION: ClinicalTrials.gov, number NCT00122057.

Impact of tapered-cuff tracheal tube on microaspiration of gastric contents in intubated critically ill patients: a multicenter cluster-randomized cross-over controlled trial.

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.

Impact of tracheal cuff shape on microaspiration of gastric contents in intubated critically ill patients: study protocol for a randomized controlled trial.

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).