Gastric intramucosal pH predicts outcome after surgery for ruptured abdominal aortic aneurysm

Objective:The mortality associated with repair of ruptured abdominal aortic aneurysms (RAAA) remains obstinately high and many deaths result from multiple organ failure which is likely to be related to splanchnic ischaemia. The aim of this study is to investigate the importance of splanchnic ischaemia in determining outcome from RAAA by comparing gastric intramucosal pH with other methods of assessing the adequacy of splanchnic oxygenation.Design and setting:Prospective cohort of patients following surgery for RAAA admitted to the Intensive Care Unit of Guy's Hospital, London.Outcome measures:Gastric intramucosal pH (pHim) and global haemodynamic, oxygen transport and metabolic variables were measured on admission, at 12 h and at 24 h after admission. Results were compared between survivors and non-survivors and Receiver Operating Characteristic (ROC) curves were constructed to assess the ability of each measurement to predict outcome.Results:The median 24 h APACHE II was 18 and the ICU mortality 45.5%. Gastric pHim was significantly higher in survivors than non-survivors at 24 h (7.42 vs. 7.24, p < 0.01). In survivors who had a low intramucosal pH (pHim) on admission there was a significant improvement over the first 24 h (7.26 to 7.40, p < 0.05), whereas in patients who subsequently died, and had a normal pHim on admission, there was a significant fall in pHim (7.35 to 7.16, p < 0.05). ROC curves showed that gastric pHim was the most sensitive measurement for predicting outcome in these patients.Conclusions:Gastric intramucosal pH is the most reliable indicator of adequacy of tissue oxygenation in patients with RAAA, suggesting that splanchnic ischaemia may have played an important role in determining survival

GW190814: gravitational waves from the coalescence of a 23 solar mass black hole with a 2.6 solar mass compact object

We report the observation of a compact binary coalescence involving a 22.2–24.3 Me black hole and a compact object with a mass of 2.50–2.67 Me (all measurements quoted at the 90% credible level). The gravitational-wave signal, GW190814, was observed during LIGO’s and Virgo’s third observing run on 2019 August 14 at 21:10:39 UTC and has a signal-to-noise ratio of 25 in the three-detector network. The source was localized to 18.5 deg2 at a distance of - + 241 45 41 Mpc; no electromagnetic counterpart has been confirmed to date. The source has the most unequal mass ratio yet measured with gravitational waves, - + 0.112 0.009 0.008, and its secondary component is either the lightest black hole or the heaviest neutron star ever discovered in a double compact-object system. The dimensionless spin of the primary black hole is tightly constrained to �0.07. Tests of general relativity reveal no measurable deviations from the theory, and its prediction of higher-multipole emission is confirmed at high confidence. We estimate a merger rate density of 1–23 Gpc−3 yr−1 for the new class of binary coalescence sources that GW190814 represents. Astrophysical models predict that binaries with mass ratios similar to this event can form through several channels, but are unlikely to have formed in globular clusters. However, the combination of mass ratio, component masses, and the inferred merger rate for this event challenges all current models of the formation and mass distribution of compact-object binaries

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