The efficacy of venovenous extracorporeal membrane oxygenation (ECMO) in patients with severe acute respiratory distress syndrome (ARDS) remains controversial.
In an international clinical trial, we ...randomly assigned patients with very severe ARDS, as indicated by one of three criteria - a ratio of partial pressure of arterial oxygen (Pao
) to the fraction of inspired oxygen (Fio
) of less than 50 mm Hg for more than 3 hours; a Pao
:Fio
of less than 80 mm Hg for more than 6 hours; or an arterial blood pH of less than 7.25 with a partial pressure of arterial carbon dioxide of at least 60 mm Hg for more than 6 hours - to receive immediate venovenous ECMO (ECMO group) or continued conventional treatment (control group). Crossover to ECMO was possible for patients in the control group who had refractory hypoxemia. The primary end point was mortality at 60 days.
At 60 days, 44 of 124 patients (35%) in the ECMO group and 57 of 125 (46%) in the control group had died (relative risk, 0.76; 95% confidence interval CI, 0.55 to 1.04; P=0.09). Crossover to ECMO occurred a mean (±SD) of 6.5±9.7 days after randomization in 35 patients (28%) in the control group, with 20 of these patients (57%) dying. The frequency of complications did not differ significantly between groups, except that there were more bleeding events leading to transfusion in the ECMO group than in the control group (in 46% vs. 28% of patients; absolute risk difference, 18 percentage points; 95% CI, 6 to 30) as well as more cases of severe thrombocytopenia (in 27% vs. 16%; absolute risk difference, 11 percentage points; 95% CI, 0 to 21) and fewer cases of ischemic stroke (in no patients vs. 5%; absolute risk difference, -5 percentage points; 95% CI, -10 to -2).
Among patients with very severe ARDS, 60-day mortality was not significantly lower with ECMO than with a strategy of conventional mechanical ventilation that included ECMO as rescue therapy. (Funded by the Direction de la Recherche Clinique et du Développement and the French Ministry of Health; EOLIA ClinicalTrials.gov number, NCT01470703 .).
The COVID-19 pandemic has seen a surge of patients with acute respiratory distress syndrome (ARDS) in intensive care units across the globe. As experience of managing patients with ...COVID-19-associated ARDS has grown, so too have efforts to classify patients according to respiratory system mechanics, with a view to optimising ventilatory management. Personalised lung-protective mechanical ventilation reduces mortality and has become the mainstay of treatment in ARDS. In this Viewpoint, we address ventilatory strategies in the context of recent discussions on phenotypic heterogeneity in patients with COVID-19-associated ARDS. Although early reports suggested that COVID-19-associated ARDS has distinctive features that set it apart from historical ARDS, emerging evidence indicates that the respiratory system mechanics of patients with ARDS, with or without COVID-19, are broadly similar. In the absence of evidence to support a shift away from the current paradigm of ventilatory management, we strongly recommend adherence to evidence-based management, informed by bedside physiology, as resources permit.
Objective
To investigate whether people with subjective memory complaints (SMC) but no objective deficits are at increased risk of developing mild cognitive impairment (MCI) and dementia.
Method
...Major electronic databases were searched till 03/2014, and a meta‐analysis was conducted using inception cohort studies.
Results
Across 28 studies, there were 29 723 unique individuals (14 714 with SMC and 15 009 without SMC) (mean 71.6 years) followed on average for 4.8 years through to dementia. The annual conversion rate (ACR) of SMC to dementia was 2.33% (95% CI = 1.93%–2.78%) a relative risk (RR) of 2.07 (95% CI = 1.76–2.44) compared with those without SMC (n = 15 009). From 11 studies the ACR of developing MCI was 6.67% (95% CI = 4.70–8.95%). In long‐term studies over 4 years, 14.1% (9.67–19.1%) of people with SMC developed dementia and 26.6% (95% CI = 5.3–39.7) went on to develop MCI. The ACR from SMC to dementia and MCI were comparable in community and non‐community settings.
Conclusion
Older people with SMC but no objective complaints are twice as likely to develop dementia as individuals without SMC. Approximately 2.3% and 6.6% of older people with SMC will progress to dementia and MCI per year.
Cardiometabolic comorbidities present a considerable burden for patients with rheumatoid arthritis (RA) or psoriatic arthritis (PsA). Both RA and PsA are associated with an increased risk of ...cardiovascular disease (CVD). PsA more often exhibits an increased risk of metabolically linked comorbidities such as obesity, insulin resistance, type 2 diabetes mellitus and non-alcoholic fatty liver disease. Although both RA and PsA are characterized by a state of chronic inflammation, the mechanisms that contribute to CVD risk in these conditions might not be identical. In RA, systemic inflammation is thought to directly contribute to CVD risk, whereas in PsA, adiposity is thought to contribute to a notable metabolic phenotype that, in turn, contributes to CVD risk. Hence, appropriate management strategies that consider the increased risk of cardiometabolic comorbidities in patients with inflammatory arthropathy are important. In RA, such strategies should focus on the prediction of CVD risk and its management through targeting chronic inflammation and traditional CVD risk factors. In PsA, management strategies should additionally focus on targeting metabolic components, including weight management, which might not only help improve disease activity in the joints, entheses and skin, but also reduce the risk of metabolic comorbidities and improve the quality of life of patients.
Stress is the inevitable consequence of the process of transferring animals from farm to slaughter. The effects of chronic stress on muscle glycogen depletion and the consequent dark cutting ...condition have been well documented. However, there has been little examination of the consequences of acute stress immediately pre-slaughter on ruminant meat quality. New evidence is emerging to show that non pH-mediated effects on meat quality can occur through pre-slaughter stress in cattle and sheep. This paper reviews the general aspects of pre-slaughter stress in the pre-slaughter context. It then examines the impacts of pre-slaughter stressors on ruminant carcass and meat quality and considers remedial strategies for remediating and preventing pre-slaughter stress. Further quantification of the biological costs of pre-slaughter stress and the consequences to meat quality is required.
Response to positive end-expiratory pressure (PEEP) in acute respiratory distress syndrome depends on recruitability. We propose a bedside approach to estimate recruitability accounting for the ...presence of complete airway closure.
To validate a single-breath method for measuring recruited volume and test whether it differentiates patients with different responses to PEEP.
Patients with acute respiratory distress syndrome were ventilated at 15 and 5 cm H
O of PEEP. Multiple pressure-volume curves were compared with a single-breath technique. Abruptly releasing PEEP (from 15 to 5 cm H
O) increases expired volume: the difference between this volume and the volume predicted by compliance at low PEEP (or above airway opening pressure) estimated the recruited volume by PEEP. This recruited volume divided by the effective pressure change gave the compliance of the recruited lung; the ratio of this compliance to the compliance at low PEEP gave the recruitment-to-inflation ratio. Response to PEEP was compared between high and low recruiters based on this ratio.
Forty-five patients were enrolled. Four patients had airway closure higher than high PEEP, and thus recruitment could not be assessed. In others, recruited volume measured by the experimental and the reference methods were strongly correlated (
= 0.798;
< 0.0001) with small bias (-21 ml). The recruitment-to-inflation ratio (median, 0.5; range, 0-2.0) correlated with both oxygenation at low PEEP and the oxygenation response; at PEEP 15, high recruiters had better oxygenation (
= 0.004), whereas low recruiters experienced lower systolic arterial pressure (
= 0.008).
A single-breath method quantifies recruited volume. The recruitment-to-inflation ratio might help to characterize lung recruitability at the bedside.Clinical trial registered with www.clinicaltrials.gov (NCT02457741).
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•Placental perfusion yields large amounts of STBEV.•Differential centrifugation isolates enriched preparations of STBMV and STBEX.•fl-NTA can be optimised using an EV ...‘standard’.•fl-NTA reliably detects STBMV using the specific marker PLAP.
The human placenta releases multiple types and sizes of syncytiotrophoblast (STB) extracellular vesicles (EV) into the maternal circulation that exhibit diverse biological activities. The placental perfusion technique enables isolation of these STBEV, but conventional flow cytometry can only be used to phenotype EV down to ∼300nm in size. Fluorescence Nanoparticle Tracking Analysis (fl-NTA) has the potential to phenotype EV down to ∼50nm, thereby improving current characterisation techniques. The aims of this study were to prepare microvesicle and exosome enriched fractions from human placental perfusate (n=8) and improve fl-NTA STBEV detection. Differential centrifugation and filtration effectively removed contaminating red blood cells from fresh placental perfusates and pelleted a STB microvesicle (STBMV) fraction (10,000×g pellet – 10KP; NTA modal size 395±12nm), enriched for the STB marker placental alkaline phosphatase (PLAP) and a STB exosome (STBEX) fraction (150,000×g pellet – 150KP; NTA modal size 147±6nm), enriched for PLAP and exosome markers Alix and CD63. The PLAP positivity of ‘standard’ 10KP and 150KP pools (four samples/pool), determined by immunobead depletion, was used to optimise fl-NTA camera settings. Individual 10KP and 150KP samples (n=8) were 54.5±5.7% (range 17.8–66.9%) and 30.6±5.6% (range 3.3–51.7%) PLAP positive, respectively. We have developed a reliable method for enriching STBMV and STBEX from placental perfusate. We also standardised fl-NTA settings and improved measurement of PLAP positive EV in STBMV. However, fl-NTA is not as sensitive as anti-PLAP Dynabead capture for STBEX detection, possibly due to STBEX having lower surface expression of PLAP. These important developments will facilitate more detailed studies of the role of STBMV and STBEX in normal and pathological pregnancies.
Timely elimination of damaged mitochondria is essential to protect cells from the potential harm of disordered mitochondrial metabolism and release of proapoptotic proteins. In mammalian red blood ...cells, the expulsion of the nucleus followed by the removal of other organelles, such as mitochondria, are necessary differentiation steps. Mitochondrial sequestration by autophagosomes, followed by delivery to the lysosomal compartment for degradation (mitophagy), is a major mechanism of mitochondrial turnover. Here we show that mice lacking the essential autophagy gene Atg7 in the hematopoietic system develop severe anemia. Atg7⁻/⁻ erythrocytes accumulate damaged mitochondria with altered membrane potential leading to cell death. We find that mitochondrial loss is initiated in the bone marrow at the Ter119⁺/CD71High stage. Proteomic analysis of erythrocyte ghosts suggests that in the absence of autophagy other cellular degradation mechanisms are induced. Importantly, neither the removal of endoplasmic reticulum nor ribosomes is affected by the lack of Atg7. Atg7 deficiency also led to severe lymphopenia as a result of mitochondrial damage followed by apoptosis in mature T lymphocytes. Ex vivo short-lived hematopoietic cells such as monocytes and dendritic cells were not affected by the loss of Atg7. In summary, we show that the selective removal of mitochondria by autophagy, but not other organelles, during erythropoeisis is essential and that this is a necessary developmental step in erythroid cells.
Spin-triplet superfluids can support exotic objects, such as half-quantum vortices characterized by the nontrivial winding of the spin structure. We present cantilever magnetometry measurements ...performed on mesoscopic samples of Sr(2)RuO(4), a spin-triplet superconductor. With micrometer-sized annular-shaped samples, we observed transitions between integer fluxoid states as well as a regime characterized by "half-integer transitions"--steps in the magnetization with half the height of the ones we observed between integer fluxoid states. These half-height steps are consistent with the existence of half-quantum vortices in superconducting Sr(2)RuO(4).
In order for livestock industries to consistently produce high quality meat, there must be an understanding of the factors that cause quality to vary, as well as the contribution of genetics. A brief ...overview of meat tenderness is presented to understand how genotype and environment may interact to influence this trait. Essentially, meat tenderness is determined from the contribution of connective tissue, sarcomere length determined pre-rigor and rate of proteolysis during ageing, as well as contributions from intramuscular fat and post-mortem energy metabolism. The influence of mutations in myostatin, the
callipyge gene, the
Carwell or
rib eye muscle gene as well as the calpain system on meat tenderness is presented. Specific examples of interactions between the production or processing environment and genetics are presented for both sheep and cattle. The day-to-day variation in tenderness is evident across experiments and this variation needs to be controlled in order to consistently produce tender meat.
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