Iron deficiency without anemia is responsible for decreased left ventricular function and reduced mitochondrial complex I activity in a mouse model

BACKGROUND: Iron deficiency (ID), with or without anemia, is frequent in heart failure patients, and iron supplementation improves patient condition. However, the link between ID (independently of anemia) and cardiac function is poorly understood, but could be explained by an impaired mitochondrial metabolism. Our aim was to explore this hypothesis in a mouse model. METHODS AND RESULTS: We developed a mouse model of ID without anemia, using a blood withdrawal followed by 3-weeks low iron diet. ID was confirmed by low spleen, liver and heart iron contents and the repression of HAMP gene coding for hepcidin. ID was corrected by a single ferric carboxymaltose (FCM) injection (ID + FCM mice). Hemoglobin levels were similar in ID, ID + FCM and control mice. ID mice had impaired physical performances and left ventricular function (echocardiography). Mitochondrial complex I activity of cardiomyocytes was significantly decreased in ID mice, but not complexes II, III and IV activities. ID + FCM mice had improved physical performance, cardiac function and complex I activity compared to ID mice. Using BN-PAGE, we did not observe complex I disassembly, but a reduced quantity of the whole enzyme complex I in ID mice, that was restored in ID + FCM mice. CONCLUSIONS: ID, independently of anemia, is responsible for a decreased left ventricular function, through a reduction in mitochondrial complex I activity, probably secondary to a decrease in complex I quantity. These abnormalities are reversed after iron treatment, and may explain, at least in part, the benefit of iron supplementation in heart failure patients with ID

Early lung ultrasonography predicts the occurrence of acute respiratory distress syndrome in blunt trauma patients

PURPOSE: Extent of lung contusion on initial computed tomography (CT) scan predicts the occurrence of acute respiratory distress syndrome (ARDS) in blunt chest trauma patients. We hypothesized that lung ultrasonography (LUS) on admission could also predict subsequent ARDS. METHODS: Forty-five blunt trauma patients were prospectively studied. Clinical examination, chest radiography, and LUS were performed on arrival at the emergency room. Lung contusion extent was quantified using a LUS score and compared to CT scan measurements. The ability of the LUS score to predict ARDS was tested using the area under the receiver operating characteristic curve (AUC-ROC). The diagnostic accuracy of LUS was compared to that of combined clinical examination and chest radiography for pneumothorax, lung contusion, and hemothorax, with thoracic CT scan as reference. RESULTS: Lung contusion extent assessed by LUS on admission was predictive of the occurrence of ARDS within 72 h (AUC-ROC = 0.78 [95 % CI 0.64-0.92]). The extent of lung contusion on LUS correlated well with CT scan measurements (Spearman\u27s coefficient = 0.82). A LUS score of 6 out of 16 was the best threshold to predict ARDS, with a 58 % [95 % CI 36-77] sensitivity and a 96 % [95 % CI 76-100] specificity. The diagnostic accuracy of LUS was higher than that of combined clinical examination and chest radiography: (AUC-ROC) 0.81 [95 % CI 0.50-1.00] vs. 0.74 [0.48-1.00] (p = 0.24) for pneumothorax, 0.88 [0.76-1.00] vs. 0.69 [0.47-0.92] (p < 0.05) for lung contusion, and 0.84 [0.59-1.00] vs. 0.73 [0.51-0.94] (p < 0.05) for hemothorax. CONCLUSIONS: LUS on admission identifies patients at risk of developing ARDS after blunt trauma. In addition, LUS allows rapid and accurate diagnosis of common traumatic thoracic injuries

The STOP-BANG questionnaire and the risk of perioperative respiratory complications in urgent surgery patients: A prospective, observational study

Introduction The STOP-BANG (SB) questionnaire, a tool originally proposed for identifying patients at risk of obstructive sleep apnoea, may also identify patients at increased risk of perioperative complications (when > 3). Perioperative complications, including respiratory ones, are more frequent in emergency surgery. This study aimed at evaluating whether the SB is predictive of perioperative respiratory complications in urgent surgery. Methods Consecutive adult patients admitted for an urgent surgery under general anaesthesia were included. The STOP-BANG questionnaire was completed before anaesthesia. Perioperative respiratory complications were prospectively recorded during surgery and in the postoperative care unit (PACU). Results One hundred and eighty-nine patients were included (women 46%, median age 60 [43–78] years old) of which 104 (55%) were SB+. Diabetes mellitus and arrhythmia were more frequent in the SB+ patients than in SB-. The ASA class was higher in SB+ patients compared with SB-, but type and duration of surgery were statistically similar. The incidence of respiratory complications was higher in SB+ patients both during surgery (21% versus 6%, P < 0.002) and in the PACU (57% versus 34%, P = 0.0015). Furthermore, SB+ patients had a prolonged length of hospital stay (6 [3–12] versus 4 [2–7] days, P = 0.0002). In a multivariate analysis, the STOP-BANG score was independently associated with respiratory complications (OR [CI 95%] = 1.44 [1.03–2.03], P = 0.03). Conclusions An elevated STOP-BANG score (≥  3) is associated with an increased risk of perioperative respiratory complications and with prolonged length of stay in urgent surgery patients

Efficient and accurate simulations of deformable particles immersed in a fluid using a combined immersed boundary lattice Boltzmann finite element method

The deformation of an initially spherical capsule, freely suspended in simple shear flow, can be computed analytically in the limit of small deformations [D. Barthes-Biesel, J. M. Rallison, The Time-Dependent Deformation of a Capsule Freely Suspended in a Linear Shear Flow, J. Fluid Mech. 113 (1981) 251-267]. Those analytic approximations are used to study the influence of the mesh tessellation method, the spatial resolution, and the discrete delta function of the immersed boundary method on the numerical results obtained by a coupled immersed boundary lattice Boltzmann finite element method. For the description of the capsule membrane, a finite element method and the Skalak constitutive model [R. Skalak et al., Strain Energy Function of Red Blood Cell Membranes, Biophys. J. 13 (1973) 245-264] have been employed. Our primary goal is the investigation of the presented model for small resolutions to provide a sound basis for efficient but accurate simulations of multiple deformable particles immersed in a fluid. We come to the conclusion that details of the membrane mesh, as tessellation method and resolution, play only a minor role. The hydrodynamic resolution, i.e., the width of the discrete delta function, can significantly influence the accuracy of the simulations. The discretization of the delta function introduces an artificial length scale, which effectively changes the radius and the deformability of the capsule. We discuss possibilities of reducing the computing time of simulations of deformable objects immersed in a fluid while maintaining high accuracy.Comment: 23 pages, 14 figures, 3 table

Does IV Iron Induce Plasma Oxidative Stress in Critically Ill Patients? A Comparison With Healthy Volunteers*

Objective: To compare the oxidative stress induced by IV iron infusion in critically ill patients and in healthy volunteers. Design: Multicenter, interventional study. Setting: Two ICUs and one clinical research center. Subjects: Anemic critically ill patients treated with IV iron and healthy volunteers. Interventions: IV infusion of 100 mg of iron sucrose. Measurements and Main Results: Thirty-eight anemic patients (hemoglobin, median [interquartile range] = 8.4 g/dL [7.7–9.2]) (men, 25 [66%]; aged 68 yr [48–77]; Simplified Acute Physiology Score II, 48.5 [39–59]) and 39 healthy volunteers (men, 18 [46%]; aged 42.1 yr [29–50]) were included. Blood samples were drawn before (H0) and 2, 6, and 24 hours (H2, H6, and H24) after a 60-minute iron infusion for the determination of nontransferrin bound iron, markers of lipid peroxidation—8α-isoprostanes, protein oxidation—advanced oxidized protein product, and glutathione reduced/oxidized. Iron infusion had no effect on hemodynamic parameter in patients and volunteers. At baseline, patients had much higher interleukin-6, C-reactive protein, and hepcidin levels. 8α-isoprostanes was also higher in patients at baseline (8.5 pmol/L [6.5–12.9] vs 4.6 pmol/L [3.5–5.5]), but the area under the curve above baseline from H0 to H6 was not different (p = 0.38). Neither was it for advanced oxidized protein product and nontransferrin bound iron. The area under the curve above baseline from H0 to H6 (glutathione reduced/oxidized) was lower in volunteers (p = 0.009). Eight patients had a second set of dosages (after the fourth iron infusion), showing higher increase in 8α-isoprostanes. Conclusions: In our observation, IV iron infusion does not induce more nontransferrin bound iron, lipid, or protein oxidation in patients compared with volunteers, despite higher inflammation, oxidative stress, and hepcidin levels and lower antioxidant at baseline. In contrary, iron induces a greater decrease in antioxidant, compatible with higher oxidative stress in volunteers than in critically ill patients

SmartPilot® view-guided anaesthesia improves postoperative outcomes in hip fracture surgery: a randomized blinded controlled study

Background Both under-dosage and over-dosage of general anaesthetics can harm frail patients. We hypothesised that computer-assisted anaesthesia using pharmacokinetic/pharmacodynamic models guided by SmartPilot® View (SPV) software could optimise depth of anaesthesia and improve outcomes in patients undergoing hip fracture surgery. Methods This prospective, randomized, single-centre, blinded trial included patients undergoing hip fracture surgery under general anaesthesia. In the intervention group, anaesthesia was guided using SPV with predefined targets. In the control group, anaesthesia was delivered by usual practice using the same agents (propofol, sufentanil and desflurane). The primary endpoint was the time spent in the “appropriate anaesthesia zone” defined as bispectral index (BIS) (blinded to the anaesthetist during surgery) of 45–60 and systolic arterial pressure of 80–140 mm Hg. Postoperative complications were recorded for one month in a blinded manner. Results Of 100 subjects randomised, 97 were analysed (n=47 in SPV and 50 in control group). Anaesthetic drug consumption was reduced in the SPV group (for propofol and desflurane). Intraoperative duration of low BIS (<45) was similar, but cumulative time of low systolic arterial pressure (<80 mm Hg) was significantly shorter in the SPV group (median (Q1-Q3); 3 (0–40) vs 5 (0–116) min, P=0.013). SPV subjects experienced fewer moderate or major postoperative complications at 30-days (8 (17)% vs 18 (36)%, P=0.035) and shorter length of hospitalisation (8 (2–20) vs 8 (2–60) days, P=0.017). Conclusions SmartPilot® View-guided anaesthesia reduces intraoperative hypotension duration, occurrence of postoperative complications and length of stay in hip fracture surgery patients

EPIdemiology of Surgery-Associated Acute Kidney Injury (EPIS-AKI) : Study protocol for a multicentre, observational trial

More than 300 million surgical procedures are performed each year. Acute kidney injury (AKI) is a common complication after major surgery and is associated with adverse short-term and long-term outcomes. However, there is a large variation in the incidence of reported AKI rates. The establishment of an accurate epidemiology of surgery-associated AKI is important for healthcare policy, quality initiatives, clinical trials, as well as for improving guidelines. The objective of the Epidemiology of Surgery-associated Acute Kidney Injury (EPIS-AKI) trial is to prospectively evaluate the epidemiology of AKI after major surgery using the latest Kidney Disease: Improving Global Outcomes (KDIGO) consensus definition of AKI. EPIS-AKI is an international prospective, observational, multicentre cohort study including 10 000 patients undergoing major surgery who are subsequently admitted to the ICU or a similar high dependency unit. The primary endpoint is the incidence of AKI within 72 hours after surgery according to the KDIGO criteria. Secondary endpoints include use of renal replacement therapy (RRT), mortality during ICU and hospital stay, length of ICU and hospital stay and major adverse kidney events (combined endpoint consisting of persistent renal dysfunction, RRT and mortality) at day 90. Further, we will evaluate preoperative and intraoperative risk factors affecting the incidence of postoperative AKI. In an add-on analysis, we will assess urinary biomarkers for early detection of AKI. EPIS-AKI has been approved by the leading Ethics Committee of the Medical Council North Rhine-Westphalia, of the Westphalian Wilhelms-University Münster and the corresponding Ethics Committee at each participating site. Results will be disseminated widely and published in peer-reviewed journals, presented at conferences and used to design further AKI-related trials. Trial registration number NCT04165369

Mineral Type and Solution Chemistry Affect the Structure and Composition of Actively Growing Bacterial Communities as Revealed by Bromodeoxyuridine Immunocapture and 16S rRNA Pyrosequencing

© 2016, Springer Science+Business Media New York. Understanding how minerals affect bacterial communities and their in situ activities in relation to environmental conditions are central issues in soil microbial ecology, as minerals represent essential reservoirs of inorganic nutrients for the biosphere. To determine the impact of mineral type and solution chemistry on soil bacterial communities, we compared the diversity, composition, and functional abilities of a soil bacterial community incubated in presence/absence of different mineral types (apatite, biotite, obsidian). Microcosms were prepared containing different liquid culture media devoid of particular essential nutrients, the nutrients provided only in the introduced minerals and therefore only available to the microbial community through mineral dissolution by biotic and/or abiotic processes. By combining functional screening of bacterial isolates and community analysis by bromodeoxyuridine DNA immunocapture and 16S rRNA gene pyrosequencing, we demonstrated that bacterial communities were mainly impacted by the solution chemistry at the taxonomic level and by the mineral type at the functional level. Metabolically active bacterial communities varied with solution chemistry and mineral type. Burkholderia were significantly enriched in the obsidian treatment compared to the biotite treatment and were the most effective isolates at solubilizing phosphorous or mobilizing iron, in all the treatments. A detailed analysis revealed that the 16S rRNA gene sequences of the OTUs or isolated strains assigned as Burkholderia in our study showed high homology with effective mineral-weathering bacteria previously recovered from the same experimental site