Wingless-related integration site (WNT) signaling is activated during the inflammatory response upon cardiac surgery: A translational study

ObjectiveCardiac surgery and the use of cardiopulmonary bypass initiate a systemic inflammatory response. Wingless-related integration site (WNT) signaling is part of the innate immunity and has been attributed a major role in the regulation of inflammation. In preclinical research, WNT-5a may sustain an inflammatory response and cause endothelial dysfunction. Our aim was to investigate WNT signaling after cardiac surgery and its association with postoperative inflammation (Clinicaltrials.gov, NCT04058496).MethodsIn this prospective, single-center, observational study, 64 consecutive patients for coronary artery bypass grafting (CABG) ± valve surgery were assigned into three groups: off-pump CABG (n = 28), on-pump CABG (n = 16) and combined valve-CABG surgery (n = 20). Blood samples were acquired before surgery, at intensive care unit (ICU) admission and 4, 8, and 48 h thereafter. Plasma concentrations of WNT-5a and its antagonists Secreted frizzled-related protein 1 (sFRP-1), Secreted frizzled-related protein 5 (sFRP-5), and WNT inhibitory factor 1 (WIF-1) were determined by enzyme-linked immunosorbent assay. In addition, plasma concentrations of six inflammatory cytokines were measured by multiplex immunoassay. Parameters were analyzed for evolution of plasma concentration over time, interactions, intergroup differences, and association with clinical outcome parameters.ResultsAt baseline, WNT-5a, sFRP-1, and WIF-1 were present in a minimal concentration, while sFRP-5 was elevated. A higher baseline value of WNT-5a, sFRP-5, and WIF-1 resulted in higher subsequent values of the respective parameter. At ICU admission, WNT-5a and sFRP-5 reached their maximum and minimum value, respectively. WIF-1 decreased over time and was lowest 8 h after surgery. sFRP-1 changed minimally over time. While WNT-5a returned to the baseline within 48 h, sFRP-5 and WIF-1 did not reach their baseline value at 48 h. Of the investigated WNT system components, only WIF-1 partially reflected the severity of surgery. WNT-5a and WIF-1 had an impact on postoperative fluid balance and noradrenaline requirement.ConclusionWNT-5a, sFRP-5, and WIF-1 are part of the systemic inflammatory response after cardiac surgery. WNT-5a peaks immediately after cardiac surgery and returns to baseline within 48 h, presumably modulated by its antagonist sFRP-5. Based on this translational study, WNT-5a antagonism may be further investigated to assess potentially beneficial effects in patients with a dysregulated inflammation after cardiac surgery

Chains of Viscoelastic Spheres

Given a chain of viscoelastic spheres with fixed masses of the first and last particles. We raise the question: How to chose the masses of the other particles of the chain to assure maximal energy transfer? The results are compared with a chain of particles for which a constant coefficient of restitution is assumed. Our simple example shows that the assumption of viscoelastic particle properties has not only important consequences for very large systems (see [1]) but leads also to qualitative changes in small systems as compared with particles interacting via a constant restitution coefficient.Comment: 11 pages, 6 figure

Patient blood management in Europe

Preoperative anaemia is common in patients undergoing orthopaedic and other major surgery. Anaemia is associated with increased risks of postoperative mortality and morbidity, infectious complications, prolonged hospitalization, and a greater likelihood of allogeneic red blood cell (RBC) transfusion. Evidence of the clinical and economic disadvantages of RBC transfusion in treating perioperative anaemia has prompted recommendations for its restriction and a growing interest in approaches that rely on patients' own (rather than donor) blood. These approaches are collectively termed ‘patient blood management' (PBM). PBM involves the use of multidisciplinary, multimodal, individualized strategies to minimize RBC transfusion with the ultimate goal of improving patient outcomes. PBM relies on approaches (pillars) that detect and treat perioperative anaemia and reduce surgical blood loss and perioperative coagulopathy to harness and optimize physiological tolerance of anaemia. After the recent resolution 63.12 of the World Health Assembly, the implementation of PBM is encouraged in all WHO member states. This new standard of care is now established in some centres in the USA and Austria, in Western Australia, and nationally in the Netherlands. However, there is a pressing need for European healthcare providers to integrate PBM strategies into routine care for patients undergoing orthopaedic and other types of surgery in order to reduce the use of unnecessary transfusions and improve the quality of care. After reviewing current PBM practices in Europe, this article offers recommendations supporting its wider implementation, focusing on anaemia management, the first of the three pillars of PB

Influence of airway‐occluding instruments on airway pressure during jet ventilation for rigid bronchoscopy

We measured changes in airway pressure (Paw) caused by microsurgical instruments introduced into a rigid bronchoscope during high frequency jet ventilation (HFJV). With approval of the institutional Ethics Committee, 10 adults undergoing elective tracheobronchial endoscopy and endosonography during general anaesthesia were investigated. Inflation of an endosonography probe balloon in the left main stem bronchus caused airway obstruction. Pressure measurements proximal and distal to the obstruction were compared after three degrees of obstruction (0%, 50% and 90%) and with two different driving pressure settings. Airway obstruction increased the mean (sd) peak inspiratory pressure (PIP) from 7.5 (2.6) to 9.5 (3.5) mm Hg for 2 atm (P=0.0008) and from 9.7 (3.7) to 13.0 (5.1) mm Hg for 3 atm (P=0.0001). Airway obstruction did not alter peripheral PIP (7.2 (4.1) to 7.1 (3.7) mm Hg for 2 atm and 8.8 (4.3) to 9.4 (5.2) mm for 3 atm), but resulted in an end‐expiratory pressure (EEP) beyond the narrowing being significantly greater than in the unobstructed airway (2.5 (3.4) to 5.5 (3.7) mm Hg for 2 atm; P=0.0005) and 3.2 (3.6) to 8.0 (4.3) mm for 3 atm; P<0.0001). Severe airway narrowing increases inspiratory pressure proximal and expiratory pressure distal to the obstruction in relation to the applied driving pressure. Since the distal EEP never exceeded PIP, even near‐total airway obstruction should not cause severe lung distension or barotrauma in subjects with normal lungs. Br J Anaesth 2000; 85: 463-

Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative coronary stenting†

In this report we present the case of a 77-yr-old man who underwent resection of the upper lobe of the left lung for a carcinoma, six weeks after percutaneous transluminal coronary angioplasty (PTCA) with stenting of the left anterior descending (LAD) and circumflex coronary arteries. Antiplatelet therapy with clopidogrel was interrupted two weeks before surgery to allow for epidural catheter placement and to minimize haemorrhage. The surgical procedure was uneventful. In the immediate postoperative period, however, the patient suffered severe myocardial ischaemia. Emergency coronary angiography showed complete thrombotic occlusion of the LAD stent. In spite of successful recanalization, reinfarction occurred and the patient died in cardiogenic shock. Prophylactic preoperative coronary stenting may put the patient at risk of stent thrombosis if surgery cannot be postponed for three months. In such cases, other strategies such as perioperative β-blockade for preoperative cardiac management should be considered. Br J Anaesth 2004; 92: 743-

The population of propellers in Saturn's A Ring

We present an extensive data set of ~150 localized features from Cassini images of Saturn's Ring A, a third of which are demonstrated to be persistent by their appearance in multiple images, and half of which are resolved well enough to reveal a characteristic "propeller" shape. We interpret these features as the signatures of small moonlets embedded within the ring, with diameters between 40 and 500 meters. The lack of significant brightening at high phase angle indicates that they are likely composed primarily of macroscopic particles, rather than dust. With the exception of two features found exterior to the Encke Gap, these objects are concentrated entirely within three narrow (~1000 km) bands in the mid-A Ring that happen to be free from local disturbances from strong density waves. However, other nearby regions are similarly free of major disturbances but contain no propellers. It is unclear whether these bands are due to specific events in which a parent body or bodies broke up into the current moonlets, or whether a larger initial moonlet population has been sculpted into bands by other ring processes.Comment: 31 pages, 10 figures; Accepted at A

A model for collisions in granular gases

We propose a model for collisions between particles of a granular material and calculate the restitution coefficients for the normal and tangential motion as functions of the impact velocity from considerations of dissipative viscoelastic collisions. Existing models of impact with dissipation as well as the classical Hertz impact theory are included in the present model as special cases. We find that the type of collision (smooth, reflecting or sticky) is determined by the impact velocity and by the surface properties of the colliding grains. We observe a rather nontrivial dependence of the tangential restitution coefficient on the impact velocity.Comment: 11 pages, 2 figure