IMPORTANCEIn patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. OBJECTIVE To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. INTERVENTIONS Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). MAIN OUTCOMES AND MEASURESThe primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. RESULTS Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, −7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, −2.1 [95% CI, −3.8 to −0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device.CONCLUSIONS AND RELEVANCE Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference.
In terms of the spawning migration of adult salmon, Salmo salar L., water flow is often considered the primary factor controlling river entry and fluctuations in flow controlling when the fish subsequently migrate upstream. However, water temperature has also been suggested to modify the spawning migration of salmon, particularly their movements within estuaries and the timing of freshwater entry. Freshwater temperature is more likely to impact salmonid biology than flow, particularly in relation to temperature dependant metabolic costs, time of spawning and fecundity. Therefore, temperature may be more of a factor regulating salmonid populations in fresh water than flow itself. This study focuses on two aspects of the impact of temperature on salmonids in fresh water: first, how salmon may modify their behaviour to adapt to changes in temperature and second the potential relationship between temperature, environmental conditions (e.g. water quality) and physiology (e.g. maturation and olfaction) in regulating adult migration.
The dermal layers of several elasmobranch species have been shown to be sexually dimorphic. Generally, when this occurs the females have thicker dermal layers compared to those of males. This sexual dimorphism has been suggested to occur as a response to male biting during mating. Although male biting as a copulatory behaviour in Scyliorhinus canicula has been widely speculated to occur, only relatively recently has this behaviour been observed. Male S. canicula use their mouths to bite the female’s pectoral and caudal fins as part of their pre-copulatory behaviour and to grasp females during copulation. Previous work has shown that female S. canicula have a thicker epidermis compared to that of males. The structure of the dermal denticles in females may also differ from that of males in order to protect against male biting or to provide a greater degree of friction in order to allow the male more purchase. This study reveals that the length, width and density of the dermal denticles of mature male and female S. canicula are sexually dimorphic across the integument in areas where males have been observed to bite and wrap themselves around females (pectoral fin, area posterior to the pectoral fin, caudal fin, and pelvic girdle). No significant differences in the dermal denticle dimensions were found in other body areas examined (head, dorsal skin and caudal peduncle). Sexually dimorphic dermal denticles in mature S. canicula could be a response to male biting/wrapping as part of the copulatory process.
Patients in ICUs represent a relatively small subgroup of hospitalised patients, but they account for approximately 25% of all hospital infections. Approximately 30% of ICU patients suffer from infection as a complication of critical illness, which increases the length of ICU stay, morbidity, mortality and cost. Gram-negative bacteria are the predominant cause of ICU-related infections and with the rise in multidrug-resistant strains we should focus our attention on nonantibiotic strategies in the prevention and treatment of nosocomial infections. Probiotics have been proposed as one option in this quest; however, mechanisms of action in the critically ill population require further investigation. Some of the beneficial effects appear to be associated with improvement in gastrointestinal barrier function, restoration of normal intestinal permeability and motility, modification of the balance of intestinal microbiota and immunomodulation. However, the information we have to date on the use of probiotics in the critical care setting is difficult to interpret due to small sample sizes, differences in ICU populations, the variety of probiotic combinations studied and differences in administration techniques. In this review we shall examine the use of probiotics in the critical care setting, look at some of the proposed mechanisms of action and discuss their potential benefits and drawbacks.
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