86 Haemodynamic effects of the enteral administration of tranexamic acid in an experimental model of haemorrhagic shock

Aim Systemic proteolysis has been proposed as part of the complex pathologic events occurring during haemorrhagic shock (HS). Hypoperfusion may increase permeability of the gut mucosa, promoting intestinal proteases translocation into the circulation and multiorgan failure ('autodigestion hypothesis'). 1 The interruption of this cascade of events may improve systemic perfusion and organ functions. Method The present study investigated the effects of the enteral administration of a protease inhibitor, i.e. tranexamic acid (TXA), on hemodynamics in a porcine model of controlled severe acute bleeding, fluid resuscitation and blood transfusion. Six animals underwent HS without any treatment while five animals were treated with enteral TXA. Results Baseline measurements were similar in both HS and TXA groups. Both groups showed a significant reduction in mean arterial pressure (MAP) after bleeding compared to baseline values, however at the end of the fluid resuscitation MAP was significantly higher in the TXA group (62.67±13.17 vs 92.20±22.35 mmHg, p Conclusion In this experimental model of HS the enteral administration of TXA was associated with a global improvement in hemodynamics; however, only small benefits were observed on mixed venous saturation and lactate levels. Reference . Schmid-Schonbein GW. 2008landis award lecture. Inflammation and the autodigestion hypothesis. Microcirculation 2009;16(4):289–306. Conflict of interest None Funding Non

LUCAS Versus Manual Chest Compression During Ambulance Transport : A Hemodynamic Study in a Porcine Model of Cardiac Arrest

Background-Mechanical chest compression (CC) is currently suggested to deliver sustained high-quality CC in a moving ambulance. This study compared the hemodynamic support provided by a mechanical piston device or manual CC during ambulance transport in a porcine model of cardiopulmonary resuscitation. Methods and Results-In a simulated urban ambulance transport, 16 pigs in cardiac arrest were randomized to 18 minutes of mechanical CC with the LUCAS (n=8) or manual CC (n=8). ECG, arterial and right atrial pressure, together with end-tidal CO2 and transthoracic impedance curve were continuously recorded. Arterial lactate was assessed during cardiopulmonary resuscitation and after resuscitation. During the initial 3 minutes of cardiopulmonary resuscitation, the ambulance was stationary, while then proceeded along a predefined itinerary. When the ambulance was stationary, CC-generated hemodynamics were equivalent in the 2 groups. However, during ambulance transport, arterial and coronary perfusion pressure, and end-tidal CO(2 )were significantly higher with mechanical CC compared with manual CC (coronary perfusion pressure: 43 +/- 4 versus 18 +/- 4 mmHg; end-tidal CO2: 31 +/- 2 versus 19 +/- 2 mmHg, P Conclusions-This model adds evidence in favor of the use of mechanical devices to provide ongoing high-quality CC and tissue perfusion during ambulance transport.Peer reviewe

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

A pilot intent estimator for haptic support systems in helicopter maneuvering tasks

Haptic support systems are commonly designed as feedback systems that track a known trajectory. However, when a pilot performs a maneuver in a free airspace, the desired trajectory is not known a priori. Thus, an estimation of the pilot intended trajectory is needed. This paper investigates the estimation of the pilot desired trajectory for designing a haptic support system that helps pilots perform helicopter maneuvers in a free airspace. A probabilistic algorithm is implemented to estimate the pilot intended trajectory according to the actions made on the control devices. The haptic aid is developed as a feedback controller able to follow the estimated intended trajectory. Two simulations were conducted to test the effectiveness of the proposed algorithm. First, filtered step-wise pilot control inputs were considered. Then, real pilot inputs were employed, which were recorded in a lateral reposition maneuver performed on a motion simulator. The developed algorithm was able to recognize the intended path according to the given pilot inputs in both scenarios

Design of a Haptic Helicopter Trainer for inexperienced pilots

This paper investigates the effectiveness of a novel method of training for helicopter pilots, with flight simulators. A software trainer based on haptic force-feedback was implemented, namely the Haptic Helicopter Trainer (HHT). The HHT is an extension of an existing automated trainer based on a Optimal Control pilot Model. With the addition of a force-feedback, the HHT is able to mimic the action of an instructor pilot on dual controls. To test the effectiveness of the HHT with respect to other types of training, an experiment was performed in a fixed-based helicopter simulator with three groups of participants: one group trained with the HHT, one group trained with the automated trainer and a control group. The training was carried out as a realistic flight lesson, divided in phases to bring the student pilots to satisfying skill levels. Results showed that the designed training phases are effective for learning how to stabilize the helicopter model. Moreover, the group trained with the HHT achieved better performances than the other groups, proving the effectiveness of the haptic force-feedback in the training of inexperienced helicopter pilots

Micro-CT evaluation of the hind limb muscle mass and definition of the index of muscle mass (IMM).

<p>(A) Mice were placed prone on the micro-CT bed leaving the hind limbs in a natural position (foot and tibia angle mean ± SD: 41° ± 6, n = 30). (B) Scanned raw images were reconstructed in 3D and analyzed using Micro View analysis software. Scale bar, 2 mm. (C) For the evaluation of the muscle mass, the following parameters from 3D reconstructed images were measured: the distance from the upper extremity of the tibia (ut) to the medial malleolus (m), defined as the length of the tibia (L), and the perpendicular distance from the half-length of the tibia to the external margin of the hind limb muscle, referred to as the thickness of the muscle (T). These measurements were assessed on the plane in which the patella (p) and the upper extremity of tibia (ut) were clearly visualized. Scale bar, 2 mm.</p

Apelin Resistance Contributes to Muscle Loss during Cancer Cachexia in Mice

Cancer cachexia consists of dramatic body weight loss with rapid muscle depletion due to imbalanced protein homeostasis. We found that the mRNA levels of apelin decrease in muscles from cachectic hepatoma-bearing rats and three mouse models of cachexia. Furthermore, apelin expression inversely correlates with MuRF1 in muscle biopsies from cancer patients. To shed light on the possible role of apelin in cachexia in vivo, we generated apelin 13 carrying all the last 13 amino acids of apelin in D isomers, ultimately extending plasma stability. Notably, apelin D-peptides alter cAMP-based signaling in vitro as the L-peptides, supporting receptor binding. In vitro apelin 13 protects myotube diameter from dexamethasone-induced atrophy, restrains rates of degradation of long-lived proteins and MuRF1 expression, but fails to protect mice from atrophy. D-apelin 13 given intraperitoneally for 13 days in colon adenocarcinoma C26-bearing mice does not reduce catabolic pathways in muscles, as it does in vitro. Puzzlingly, the levels of circulating apelin seemingly deriving from cachexia-inducing tumors, increase in murine plasma during cachexia. Muscle electroporation of a plasmid expressing its receptor APJ, unlike apelin, preserves myofiber area from C26-induced atrophy, supporting apelin resistance in vivo. Altogether, we believe that during cachexia apelin resistance occurs, contributing to muscle wasting and nullifying any possible peptide-based treatment

RANKL Expression Is Increased in Circulating Mononuclear Cells of Patients with Calcific Aortic Stenosis

We aimed to investigate whether the expression of the OPG/RANK/RANKL triad in peripheral blood mononuclear cells (PBMC) and circulating levels of markers of ectopic mineralization (OPG, FGF-23, PPi) are modified in patients with calcific aortic valve disease (CAVD). We found that patients affected by CAVD (n\u2009=\u200950) had significantly higher circulating levels of OPG as compared to control individuals (p\u2009=\u20090.003). No differences between the two groups were found in FGF-23 and PPi levels. RANKL expression was higher in the PBMC from CAVD patients (p\u2009=\u20090.018) and was directly correlated with the amount of valve calcification (p\u2009=\u20090.032). In vitro studies showed that treatment of valve interstitial cells (VIC) with RANKL plus phosphate was followed by increase in matrix mineralization (p\u2009=\u20090.001). In conclusion, RANKL expression is increased in PBMC of patients with CAVD, is directly correlated with the degree of valve calcification, and promotes pro-calcific differentiation of VIC