Randomised open-label trial comparing intravenous iron and an erythropoiesis-stimulating agent versus oral iron to treat preoperative anaemia in cardiac surgery (INITIATE trial).

BACKGROUND: Preoperative anaemia is a risk factor for adverse postoperative outcomes after cardiac surgery. Iron deficiency is a frequent cause of low preoperative haemoglobin. An effective treatment for preoperative anaemia associated with iron deficiency has not been determined. METHODS: We conducted a single-centre, open-label, pragmatic randomised trial, enrolling 156 elective cardiac surgery patients who had low preoperative haemoglobin (100-130 g L-1) with iron deficiency (serum ferritin <100 µg L-1 or transferrin saturation <30%) to compare intravenous ferric derisomaltose 1000 mg and darbepoetin 200 µg subcutaneously (intervention group) with oral ferrous sulphate 600 mg daily (control group). The primary outcome was transfusion of at least one unit of allogeneic red cells during surgery and within the following 5 days. Secondary outcomes included the change in haemoglobin concentration between randomisation and surgery, red cell transfusion volume, postoperative blood loss, pre-specified postoperative complications, length of hospital stay, and in-hospital death. RESULTS: The odds of red cell transfusion were lower in the intervention group compared with the control group (adjusted odds ratio=0.33; 95% confidence interval [CI], 0.15-0.75; P=0.008). Of the secondary outcomes, the only significant difference was the increase in haemoglobin between randomisation and surgery, intervention vs control 9.5 g L-1 (95% CI, 6.8-12.2; P<0.001). CONCLUSIONS: In patients with a low preoperative haemoglobin and iron deficiency, preoperative treatment with a single dose of ferric derisomaltose and darbepoetin decreased the proportion of participants who received a perioperative blood transfusion as a consequence of a greater increase in haemoglobin compared with treatment with oral ferrous sulphate. CLINICAL TRIAL REGISTRATION: ISRCTN Number: 41421863; EUDRACT number: 2011-003695-36.

Our Italian experience using lung ultrasound for identification, grading and serial follow-up of severity of lung involvement for management of patients with COVID-19.

Lung ultrasound (LU) has rapidly become a tool for assessment of patients stricken by the novel coronavirus 2019 (COVID-19). Over the past two and a half months (January, February, and first half of March 2020) we have used this modality for identification of lung involvement along with pulmonary severity in patients with suspected or documented COVID-19 infection. Use of LU has helped us in clinical decision making and reduced the use of both chest x-rays and computed tomography (CT).

RIPC Remains a Promising Technique for Protection of the Myocardium during Open Cardiac Surgery: A Meta-Analysis and Systematic Review.

BACKGROUND: Remote ischemic preconditioning (RIPC) is the process of inducing brief ischemia in a tissue to prevent ischemic damage in another. This preconditioning can be induced simply by inflating a blood pressure cuff on a limb. Previous randomized controlled trials (RCT) have suggested that RIPC may infer myocardial protection during open cardiac surgery. One method of assessing the degree of myocardial damage incurred in these studies is to assay troponin concentration. Troponin is a cardiac enzyme released by damaged myocardiocytes. With the recent publication of several large RCTs in this area, a meta-analysis of the evidence was undertaken. METHODS: A systematic search of PubMed, EMBASE, and clinicaltrials.gov.uk was conducted using MeSH terms "ischaemic preconditioning" and "cardiac surgery." RCTs that examined post-surgery troponin concentrations were included in this review. The primary outcome investigated was troponin levels at six hours post-cardiac surgery. Secondary outcomes included six to eight hour and twenty-four hour troponin release. RESULTS: Thirteen RCTs, comprising 1398 participants, were identified for inclusion in this meta-analysis. Twelve hour postoperative troponin was significantly reduced by RIPC, standardized mean difference 1.29 (95% CI 0.34-2.24). Six to eight and twenty-four hour troponin were also significantly reduced, standardized mean differences 1.23 (95% CI 0.62-1.84) and 1.25 (95% CI 0.31-2.19) respectively. CONCLUSIONS: The reduction in troponin concentration suggests that RIPC reduces myocardial damage during open cardiac surgery, however, the degree of bias in the studies assessed may have had a significant impact on this result.

Hyper- and hypocoagulability in COVID-19 as assessed by thromboelastometry -two case reports.

BACKGROUND: Coronavirus disease (COVID-19)-associated coagulopathy is most often characterized by elevated D-dimer, interleukin-6, and plasma fibrinogen concentrations as well as hypercoagulability in thromboelastometry with increased clot firmness in the EXTEM, INTEM, and FIBTEM assays. Clinically, it manifests with a very high incidence of thrombosis, particularly in the pulmonary system, whereas bleeding complications are infrequent. CASE: Here, we describe two critically ill patients with COVID-19 admitted to our intensive care unit demonstrating different thromboelastometry and biomarker patterns. One patient presented with hypercoagulability and the other patient with hypocoagulability and fibrinolysis shutdown in thromboelastometry. The pathophysiology and the potential impact on treatment options are discussed. CONCLUSIONS: A combination of biomarkers and thromboelastometry results can be helpful in the future to decide which therapeutic strategy might be most appropriate for critically ill patients with COVID-19. This would be an important step to establish precision medicine in this high-risk patient population.

Link between Gas Phase Reaction Chemistry and the Electronic Conductivity of Atomic Layer Deposited Titanium Oxide Thin Films.

In situ monitoring of gas phase composition reveals the link between the changing gas phase chemistry during atomic layer deposition (ALD) half-cycle reactions and the electronic conductivity of ALD-TiO2 thin films. Dimethylamine ((CH3)2NH, DMA) is probed as the main product of both the TDMAT and water vapor half-reactions during the TDMAT/H2O ALD process. In-plane electronic transport characterization of the ALD grown films demonstrates that the presence of DMA, a reducing agent, in the ALD chamber throughout each half-cycle is correlated with both an increase in the films' electronic conductivity, and observation of titanium in the 3+ oxidation state by ex situ X-ray photoelectron spectroscopy analysis of the films. DMA annealing of as-grown TiO2 films in the ALD chamber produces a similar effect on their electronic characteristics, indicating the importance of DMA-induced oxygen deficiency of ALD-TiO2 in dictating the electronic conductivity of as-grown films.

The Role of Catalyst Adhesion in ALD-TiO2 Protection of Water Splitting Silicon Anodes.

Atomic layer deposited titanium dioxide (ALD-TiO2) has emerged as an effective protection layer for highly efficient semiconductor anodes which are normally unstable under the potential and pH conditions used to oxidize water in a photoelectrochemical cell. The failure modes of silicon anodes coated with an Ir/IrO x oxygen evolution catalyst layer are investigated, and poor catalyst/substrate adhesion is found to be a key factor in failed anodes. Quantitative measurements of interfacial adhesion energy show that the addition of TiO2 significantly improves reliability of anodes, yielding an adhesion energy of 6.02 ± 0.5 J/m2, more than double the adhesion energy measured in the absence of an ALD-TiO2 protection layer. These results indicate the importance of catalyst adhesion to an interposed protection layer in promoting operational stability of high efficiency semiconducting anodes during solar-driven water splitting.

Paradoxical air embolism and neurological insult during removal of a pulmonary artery catheter introducer.

A 54-year-old man was admitted to the intensive care unit following cardiac surgery. On day 6 postoperatively, approximately 2-3 min following the removal of the pulmonary artery (PA) catheter introducer sited in the right internal jugular vein, the patient became agitated, confused and then unresponsive. He was urgently moved onto the bed, laid supine, sedated with a propofol infusion, intubated and mechanically ventilated. A bedside transthoracic echocardiogram revealed extensive multiple air emboli in all cardiac chambers and review of the patient's intraoperative imaging confirmed the presence of patent foramen ovale (PFO). The following morning, sedation was discontinued and the trachea extubated. The patient was later transferred to the ward and then discharged home with no evidence of neurological deficit. This case reminds us of the importance of strict adherence to safety protocols when manipulating centrally positioned catheters and the high prevalence of undiagnosed PFO.

Powerful, multifunctional torsional micromuscles activated by phase transition.

Micro bimorph coils driven by a metalinsulator phase transition in VO2 function as powerful torsional muscles. Reversible torsional motion over one million cycles without degradation is demonstrated, with a superior rotational speed up to ca. 200,000 rpm, an amplitude of 500° per mm length, and a power density up to ca. 39 kW kg⁻¹.

Temporal and spatial variations of cell-free layer width in arterioles.

Separation of red blood cells and plasma in microcirculatory vessels produces a cell-free layer at the wall. This layer may be an important determinant of blood viscosity and wall shear stress in arterioles, where most of the hydraulic pressure loss in the circulatory system occurs and flow regulatory mechanisms are prominent. With the use of a newly developed method, the width of the cell-free layer was rapidly and repeatedly determined in arterioles (10- to 50-microm inner diameter) in the rat cremaster muscle at normal arterial pressure. The temporal variation of the cell-free layer width was non-Gaussian, but calculated mean and median values differed by <0.2 microm. The correlation length of the temporal variations downstream (an indication of mixing) was approximately 30 microm and was independent of pseudoshear rate (ratio of mean velocity to vessel diameter) and of vessel diameter. The cell-free layer width was significantly different on opposite sides of the vessel and inversely related. Increasing red blood cell aggregability reduced this inverse relation but had no effect on correlation length. In the diameter range studied, the mean width of the cell-free layer increased from 0.8 to 3.1 microm and temporal variations increased from 30% to 70% of the mean width. Increased aggregability did not alter either relationship. In summary, the cell-free layer width in arterioles is diameter dependent and shows substantial non-Gaussian temporal variations. The temporal variations increase as diameter increases and are inversely related on opposite sides of the vessel.

A computer-based method for determination of the cell-free layer width in microcirculation.

OBJECTIVES: The cell-free layer between the erythrocyte column and the vessel wall is an important determinant of hydrodynamic resistance in microcirculatory vessels. The authors report a method for continuous measurement of the width of this layer. METHODS: The light intensity of a linear array of pixels perpendicular to the vessel axis is continuously determined from a video image of a microcirculatory vessel. A threshold level based on Otsu's method is used to establish the interface between the cell-free layer and the erythrocyte column. To test the method, video images at 750-4500 frames/s were obtained from venules and arterioles in rat spinotrapezius muscle at normal and reduced arterial pressures before and after induction of erythrocyte aggregation with Dextran 500. The current measurements were compared to manual measurements of the same images. RESULTS: Values obtained by the manual and the new methods were in agreement within the 95% confidence limit by the Bland-Altman analysis and within 90-95% range by the correlation coefficient (R2). The more frequent measurements reveal substantial, rapid variations in cell-free layer width and changes in mean values with alteration of arterial pressure and red cell aggregability. CONCLUSIONS: A new, computer-based technique has been developed that provides measurements of rapid, time-dependent variations in the width of the cell-free layer in the microcirculation.

Clinical trial of the neuroprotectant clomethiazole in coronary artery bypass graft surgery: a randomized controlled trial.

BACKGROUND: The neuroprotective property of clomethiazole has been demonstrated in several animal models of global and focal brain ischemia. In this study the authors investigated the effect of clomethiazole on cerebral outcome in patients undergoing coronary artery bypass surgery. METHODS: Two hundred forty-five patients scheduled for coronary artery bypass surgery were recruited at two centers and prospectively randomized to clomethiazole edisilate (0.8%), 225 ml (1.8 mg) loading dose followed by a maintenance dose of 100 ml/h (0.8 mg/h) during surgery, or 0.9% NaCl (placebo) in a double-blind trial. Coronary artery grafting was completed during moderate hypothermic (28-32 degrees C) cardiopulmonary bypass. Plasma clomethiazole was measured at several intervals during and up to 24 h after the end of infusion. A battery of eight neuropsychological tests was administered preoperatively and repeated 4-7 weeks after surgery. Analysis of the change in neuropsychological test scores from baseline was used to determine the effect of treatment. RESULTS: Neuropsychological assessments were completed in 219 patients (110 clomethiazole; 109 placebo). The mean plasma concentration of clomethiazole during surgery was 66.2 microm. There was no difference between the clomethiazole and placebo group in the postoperative change in neuropsychological test scores. CONCLUSION: Clomethiazole did not improve cerebral outcome following coronary artery bypass surgery.