High flow nasal oxygen therapy to avoid invasive mechanical ventilation in SARS-CoV-2 pneumonia: a retrospective study.

BACKGROUND: The efficacy of high flow nasal canula oxygen therapy (HFNO) to prevent invasive mechanical ventilation (IMV) is not well established in severe coronavirus disease 2019 (COVID-19). The aim of this study was to compare the risk of IMV between two strategies of oxygenation (conventional oxygenation and HFNO) in critically ill COVID 19 patients. METHODS: This was a bicenter retrospective study which took place in two intensive care units (ICU) of tertiary hospitals in the Paris region from March 11, to May 3, 2020. We enrolled consecutive patients hospitalized for COVID-19 and acute respiratory failure (ARF) who did not receive IMV at ICU admission. The primary outcome was the rate of IMV after ICU admission. Secondary outcomes were death at day 28 and day 60, length of ICU stay and ventilator-free days at day 28. Data from the HFNO group were compared with those from the standard oxygen therapy (SOT) group using weighted propensity score. RESULTS: Among 138 patients who met the inclusion criteria, 62 (45%) were treated with SOT alone, and 76 (55%) with HFNO. In HFNO group, 39/76 (51%) patients received IMV and 46/62 (74%) in SOT group (OR 0.37 [95% CI, 0.18-0.76] p = 0.007). After weighted propensity score, HFNO was still associated with a lower rate of IMV (OR 0.31 [95% CI, 0.14-0.66] p = 0.002). Length of ICU stay and mortality at day 28 and day 60 did not significantly differ between HFNO and SOT groups after weighted propensity score. Ventilator-free days at days 28 was higher in HNFO group (21 days vs 10 days, p = 0.005). In the HFNO group, predictive factors associated with IMV were SAPS2 score (OR 1.13 [95%CI, 1.06-1.20] p = 0.0002) and ROX index > 4.88 (OR 0.23 [95%CI, 0.008-0.64] p = 0.006). CONCLUSIONS: High flow nasal canula oxygen for ARF due to COVID-19 is associated with a lower rate of invasive mechanical ventilation.

Long-term evolution of the natural isolate of Escherichia coli 536 in the mouse gut colonized after maternal transmission reveals convergence in the constitutive expression of the lactose operon.

In vitro experimental evolution has taught us many lessons on the molecular bases of adaptation. To move towards more natural settings, evolution in the mice gut has been successfully performed. Yet, these experiments suffered from the use of laboratory strains as well as the use of axenic or streptomycin-treated mice to maintain the inoculated strains. To circumvent these limitations, we conducted a one-year experimental evolution in vivo using a natural isolate of E. coli, strain 536, in conditions mimicking as much as possible natural environment with mother-to-offspring microbiota transmission. Mice were then distributed in 24 independent cages and separated into two different diets: a regular one (chow diet, CD) and high-fat and high-sugar one (Western Diet, WD). Genome sequences revealed an early and rapid selection during the breastfeeding period that selected the constitutive expression of the well-characterized lactose operon. E. coli was lost significantly more in CD than WD; however, we could not detect any genomic signature of selection, nor any diet specificities during the later part of the experiments. The apparently neutral evolution presumably due to low population size maintained nevertheless at high frequency the early selected mutations affecting lactose regulation. The rapid loss of lactose operon regulation challenges the idea that plastic gene expression is both optimal and stable in the wild.

Evolution of a Dominant Natural Isolate of Escherichia coli in the Human Gut over the Course of a Year Suggests a Neutral Evolution with Reduced Effective Population Size.

In vitro and in vivo evolution experiments on Escherichia coli revealed several principles of bacterial adaptation. However, few data are available in the literature describing the behavior of E. coli in its natural environment. We attempted here to study the evolution in the human gut of a commensal dominant E. coli clone, ED1a belonging to the B2 phylogroup, through a longitudinal genomic study. We sequenced 24 isolates sampled at three different time points within a healthy individual over almost a year. We computed a mutation rate of 6.90 × 10-7 mutations per base per year of the chromosome for E. coli ED1a in healthy human gut. We observed very limited genomic diversity and could not detect any evidence of selection, in contrast to what is observed in experimental evolution over a similar length of time. We therefore suggest that ED1a, being well adapted to the healthy human gut, evolves mostly neutrally with a low effective population size (Ne of ≈500 to 1,700).IMPORTANCE In this study, we follow the genomic fate of a dominant clone of Escherichia coli in the human gut of a healthy individual over about a year. We could compute a low annual mutation rate that supports low diversity, and we could not retrieve any clear signature of selection. These observations support a neutral evolution of E. coli in the human gut, compatible with a very limited effective population size that deviates drastically with the observations made previously in experimental evolution.

Using long-term experimental evolution to uncover the patterns and determinants of molecular evolution of an Escherichia coli natural isolate in the streptomycin-treated mouse gut.

Although microbial ecology of the gut is now a major focus of interest, little is known about the molecular determinants of microbial adaptation in the gut. Experimental evolution coupled with whole-genome sequencing can provide insights of the adaptive process. In vitro experiments have revealed some conserved patterns: intermediate convergence, and epistatic interactions between beneficial mutations and mutations in global regulators. To test the relevance of these patterns and to identify the selective pressures acting in vivo, we have performed a long-term adaptation of an E. coli natural isolate, the streptomycin-resistant strain 536, in the digestive tract of streptomycin-treated mice. After a year of evolution, a clone from 15 replicates was sequenced. Consistently with in vitro observations, the identified mutations revealed a strong pattern of convergence at the mutation, gene, operon and functional levels. Yet, the rate of molecular evolution was lower than in in vitro, and no mutations in global regulators were recovered. More specific targets were observed: the dgo operon, involved in the galactonate pathway that improved growth on D-galactonate, and rluD and gidB, implicated in the maturation of the ribosomes, which mutations improved growth only in the presence of streptomycin. As in vitro, the nonrandom associations of mutations within the same pathways suggested a role of epistasis in shaping the adaptive landscape. Overall, we show that 'evolve and sequence' approach coupled with an analysis of convergence, when applied to a natural isolate, can be used to study adaptation in vivo and uncover the specific selective pressures of that environment.

Esmolol Corrects Severe Hypoxemia in Patients with Femoro-Femoral Venoarterial Extracorporeal Life Support for Lung Transplantation.

Competitive flows syndrome result in severe regional hypoxemia when the deoxygenated flow from the native left ventricle (LV) competes with oxygenated flow from extracorporeal life support (ECLS) pump with potentially severe consequences for the cerebral and coronary circulations. Fast correction of hypoxemia could be obtained by decreasing native LV flow by infusion of a short-acting beta-blocker (esmolol). Our purpose was to retrospectively review the efficacy of esmolol in this situation and hypothesize on the potential mechanisms of action and the associated risks. This is a retrospective analysis of five clinical cases, who underwent lung transplantation and a femoro-femoral venoarterial (VA) ECLS. The patients presented severe hypoxemia (SpO2 < 85%) measured through photoplethysmography on a right hand finger. From the patients' medical records and anesthesia flowcharts, hemodynamic, right heart catheterization, echocardiography variables, and arterial blood gas results were noted before and after injection of esmolol. Mechanical ventilation and VA ECLS function variables were optimized and unchanged before and after esmolol injection. All patients had terminal respiratory failure with pulmonary hypertension and conserved LV systolic function. Immediately following esmolol injection (1.3 ± .7 mg/kg; mean ± 1 SD), SpO2 increased from 73% ± 12 to 95% ± 6; blood to arterial partial pressure in CO2 (PaCO2) decreased from 52 ± 18 to 35 ± 7 mmHg systolic pulmonary artery pressure decreased from 61 ± 8 to 50 ± 12 mmHg; the pulmonary artery oxygen saturation (SvO2); increased from 51% ± 24 to 77% ± 12; systemic arterial pressure or catecholamine requirements were unchanged. In conclusion, these results suggest that injection of esmolol allowed rapid correction of regional hypoxemia occurring during lung transplantation despite femoro-femoral VA ECLS. The mechanism is probably a decreased cardiac output of the native LV due to esmolol-induced negative inotropic and chronotropic effects without significant adverse effects on systemic tissue perfusion.

Assessment of pain during labor with pupillometry: a prospective observational study.

BACKGROUND: Pain intensity is usually self-rated by patients with a numeric rating scale (NRS) but this scale cannot be used for noncommunicating patients. In anesthetized patients, experimental noxious stimulus increases pupillary diameter (PD) and pupillary light reflex amplitude (PLRA), the difference between PD before and after light stimulation. Labor pain is an intense acute nonexperimental stimulus, effectively relieved by epidural analgesia. In this prospective observational study, we therefore describe the effects of labor pain and pain relief with epidural analgesia on PD and PLRA, determine their association with pain intensity and determine the ability of a single measurement of PD or PLRA to assess pain. METHODS: In the first stage, pain (11-point NRS), PD, and PLRA were measured in 4 conditions in 26 laboring women: before and after epidural analgesia and in the presence and absence of a uterine contraction. Pupillometry values among the 4 conditions were compared, and the strength of the association between absolute values of pain and PD or PLRA and between pain and changes in PD or PLRA brought about by uterine contraction was assessed with r(2). In the second stage, 1 measurement was performed in 104 laboring women. The strength of the association between pain and PD or PLRA was assessed with r(2). The ability of PD or PLRA to discriminate pain (NRS > 4) was also assessed. RESULTS: In the first stage, a statistically significant increase in pain, PD, and PLRA was observed during a contraction, and this change was abolished after epidural analgesia. The r(2) for the association between pain and changes in PD (r(2) = 0.25 [95% confidence interval, 0.07-0.46] or PLRA (r(2) = 0.34 [0.14-0.56]) brought about by a uterine contraction was higher than the r(2) for the association between pain and absolute values of PD (r(2) = 0.14 [0.04-0.28]) or PLRA (r(2) = 0.22 [0.10-0.37]) suggesting a stronger association for changes than for absolute values. In the second stage, r(2) was 0.23 [0.10-0.38] for PD and 0.26 [0.11-0.40] for PLRA and the area under the receiver operating characteristics curve was 0.82 [0.73-0.91] and 0.80 [0.71-0.89], respectively. CONCLUSIONS: Changes in PD and PLRA brought about by a uterine contraction may be used as a tool to assess analgesia in noncommunicating patients.