Modelling thirty-day mortality in the acute respiratory distress syndrome (ARDS) in an adult ICU

Publisher's copy made available with the permission of the publisher © Australian Society of AnaesthetistsVariables predicting thirty-day outcome from Acute Respiratory Distress Syndrome (ARDS) were analysed using Cox regression structured for time-varying covariates. Over a three-year period, 1996-1998, consecutive patients with ARDS (bilateral chest X-ray opacities, PaO₂/FiO₂ ratio of <200 and an acute precipitating event) were identified using a prospective computerized data base in a university teaching hospital ICU. The cohort, 106 mechanically ventilated patients, was of mean (SD) age 63.5 (15.5) years and 37% were female. Primary lung injury occurred in 45% and 24% were postoperative. ICU-admission day APACHE II score was 25 (8); ARDS onset time from ICU admission was 1 day (median: range 0-16) and 30 day mortality was 41% (95% CI: 33%-51%). At ARDS onset, PaO₂/FiO₂ ratio was 92 (31), 81% had four-quadrant chest X-ray opacification and lung injury score was 2.75 (0.45). Average mechanical ventilator tidal volume was 10.3 ml/ predicted kg weight. Cox model mortality predictors (hazard ratio, 95% CI) were: APACHE II score, 1.15 (1.09-1.21); ARDS lag time (days), 0.72 (0.58-0.89); direct versus indirect injury, 2.89 (1.45-5.76); PaO₂/FiO₂ ratio, 0.98 (0.97-0.99); operative versus non-operative category, 0.24 (0.09-0.63). Time-varying effects were evident for PaO₂/FiO₂ ratio, operative versus non-operative category and ventilator tidal volume assessed as a categorical predictor with a cut-point of 8 ml/kg predicted weight (mean tidal volumes, 7.1 (1.9) vs 10.7 (1.6) ml/kg predicted weight). Thirty-day survival was improved for patients ventilated with lower tidal volumes. Survival predictors in ARDS were multifactorial and related to patient-injury-time interaction and level of mechanical ventilator tidal volume.J. L. Moran, P. J. Solomon, V. Fox, M. Salagaras, P. J. Williams, K. Quinlan, A. D. Berstenhttp://www.aaic.net.au/Article.asp?D=200332

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

A biological acoustic survey in the marginal ice-edge zone of the Bellingshausen Sea

An acoustic survey at 38 kHz was carried out from R.R.S. Discovery in the Bellingshausen Sea from 23 November to 7 December 1992 as part of the U.K. Joint Global Ocean Flux Study (JGOFS) Southern Ocean investigations [Turner D. and N. J. P. Owens (1995) Deep-Sea Research II, 42, 907–932]. A total of 285 targets were identified and described from the chart record of the echo sounder. Mean volume backscattering strength data were collected using an echo integration system. These data are used to describe the spatial and temporal variability of krill (Euphausia superba) distribution and biomass in the marginal ice-edge zone. Krill biomass density varied from a mean of 42 g m−2 during the first survey phase to 20 g m−2 on the second survey phase. The number of small swarms detected during the second phase was greater than during the first phase. On this first survey a large swarm (2.8 km in extent) had a potential biomass of 3.7 × 104 tonnes. Some calculations are presented to show the potential impact of krill on the flux of carbon in the area of the survey

The shelf break front to the east of the sub-Antarctic island of South Georgia

The sub-Antarctic island of South Georgia lies in polar waters to the south of the Polar Front and is influenced by the Weddell Scotia Confluence whose waters reach the island’s south east coast. In January 1996 a detailed hydrographic survey to the east of the island showed that on-shelf waters were both warmer and fresher than those off-shelf. These differences were not confined to surface waters. The inherent density differences resulted in a shelf break front, the position of which was defined as the point where the 26.96 kg m-3 isopycnal crossed 30 dbar as it rose towards the surface. The slope of the shelf break front between the on- and off-shelf waters was found to be approximately geostrophic. Although the position of the shelf break front was not linked to any particular bottom depth, its position was strongly influenced by the bottom topography in the region. Evidence is presented for upwelling in one specific region along the front. Differences between the on- and off-shelf waters are also observed in nutrient and chlorophyll a data: These data implied greater productivity on-shelf. Both physical and chemical data suggest that on- and off-shelf waters communicate at depth. This study also shows that shelf water can cross the shelf break front and remain in the vicinity of the island