Alterations in tissue oxygen saturation measured by near-infrared spectroscopy in trauma patients after initial resuscitation are associated with occult shock

Acord transformatiu CRUE-CSICPurpose: Persistent occult hypoperfusion after initial resuscitation is strongly associated with increased morbidity and mor- tality after severe trauma. The objective of this study was to analyze regional tissue oxygenation, along with other global markers, as potential detectors of occult shock in otherwise hemodynamically stable trauma patients. Methods: Trauma patients undergoing active resuscitation were evaluated 8 h after hospital admission with the measure- ment of several global and local hemodynamic/metabolic parameters. Apparently hemodynamically stable (AHD) patients, defined as having SBP ≥ 90 mmHg, HR < 100 bpm and no vasopressor support, were followed for 48 h, and finally classified according to the need for further treatment for persistent bleeding (defined as requiring additional red blood cell transfusion), initiation of vasopressors and/or bleeding control with surgery and/or angioembolization. Patients were labeled as "Occult shock" (OS) if they required any intervention or "Truly hemodynamically stable" (THD) if they did not. Regional tissue oxygenation (rSO2) was measured non-invasively by near-infrared spectroscopy (NIRS) on the forearm. A vascular occlu- sion test was performed, allowing a 3-min deoxygenation period and a reoxygenation period following occlusion release. Minimal rSO2 (rSO2min), Delta-down (rSO2-rSO2min), maximal rSO2 following cuff-release (rSO2max), and Delta-up (rSO2max-rSO2min) were computed. The NIRS response to the occlusion test was also measured in a control group of healthy volunteers. Results: Sixty-six consecutive trauma patients were included. After 8 h, 17 patients were classified as AHD, of whom five were finally considered to have OS and 12 THD. No hemodynamic, metabolic or coagulopathic differences were observed between the two groups, while NIRS-derived parameters showed statistically significant differences in Delta-down, rSO2min, and Delta-up. Conclusions: After 8 h of care, NIRS evaluation with an occlusion test is helpful for identifying occult shock in apparently hemodynamically stable patients

Nurses' perceptions of aids and obstacles to the provision of optimal end of life care in ICU

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Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population