Hepatocyte-derived biomarkers predict liver-related events at 2 years in Child-Pugh class A alcohol-related cirrhosis.

BACKGROUND & AIMS: In patients with compensated alcohol-related cirrhosis, reliable prognostic biomarkers are lacking. Keratin-18 and hepatocyte-derived large extracellular vesicle (lEV) concentrations reflect disease activity, but their ability to predict liver-related events is unknown. METHODS: We measured plasma keratin-18 and hepatocyte lEV concentrations in 500 patients with Child-Pugh class A alcohol-related cirrhosis. The ability of these hepatocyte-derived biomarkers, alone or combined with model for end-stage liver disease (MELD) and FibroTest scores, to predict liver-related events at 2 years was analyzed, taking into account the alcohol consumption at inclusion and during follow-up. RESULTS: Keratin-18 and hepatocyte lEV concentrations increased with alcohol consumption. In patients without active alcohol consumption at enrollment (n = 419), keratin-18 concentration predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both keratin-18 concentrations >285 U/L and FibroTest >0.74 had a 24% cumulative incidence of liver-related events at 2 years, vs. 5% to 14% in other groups of patients. Similar results were obtained when combining keratin-18 concentrations >285 U/L with MELD >10. In patients with active alcohol consumption at enrollment (n = 81), hepatocyte lEVs predicted liver-related events at 2 years, independently of FibroTest and MELD. Patients with both hepatocyte lEV concentrations >50 U/L and FibroTest >0.74 had a 62% cumulative incidence of liver-related events at 2 years, vs. 8% to 13% in other groups of patients. Combining hepatocyte lEV concentrations >50 U/L with MELD >10 had a lower discriminative ability. Similar results were obtained when using decompensation of cirrhosis, defined according to Baveno VII criteria, as an endpoint. CONCLUSION: In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers with FibroTest or MELD scores identifies patients at high risk of liver-related events, and could be used for risk stratification and patient selection in clinical trials. IMPACT AND IMPLICATIONS: In patients with compensated alcohol-related cirrhosis, reliable predictors of outcome are lacking. In patients with Child-Pugh class A alcohol-related cirrhosis, combining hepatocyte-derived biomarkers (keratin-18 and hepatocyte-large extracellular vesicles) with FibroTest or MELD scores identifies those at high risk of liver-related events at 2 years. The identified patients at high risk of liver-related events are the target-of-choice population for intensive surveillance (e.g., referral to tertiary care centers; intensive control of risk factors) and inclusion in clinical trials.

Cell-specific targeting of extracellular vesicles through engineering the glycocalyx.

Extracellular vesicles (EVs) are promising carriers for the delivery of a variety of chemical and biological drugs. However, their efficacy is limited by the lack of cellular specificity. Available methods to improve the tissue specificity of EVs predominantly rely on surface display of proteins and peptides, largely overlooking the dense glycocalyx that constitutes the outermost layer of EVs. In the present study, we report a reconfigurable glycoengineering strategy that can endogenously display glycans of interest on EV surface. Briefly, EV producer cells are genetically engineered to co-express a glycosylation domain (GD) inserted into the large extracellular loop of CD63 (a well-studied EV scaffold protein) and fucosyltransferase VII (FUT7) or IX (FUT9), so that the engineered EVs display the glycan of interest. Through this strategy, we showcase surface display of two types of glycan ligands, sialyl Lewis X (sLeX) and Lewis X, on EVs and achieve high specificity towards activated endothelial cells and dendritic cells, respectively. Moreover, the endothelial cell-targeting properties of sLeX-EVs were combined with the intrinsic therapeutic effects of mesenchymal stem cells (MSCs), leading to enhanced attenuation of endothelial damage. In summary, this study presents a reconfigurable glycoengineering strategy to produce EVs with strong cellular specificity and highlights the glycocalyx as an exploitable trait for engineering EVs.

The impact of "To Err Is Human" on patient safety in anesthesiology. A bibliometric analysis of 20 years of research.

Background: Patient safety gained public notoriety following the 1999 report of the Institute of Medicine: To Err is Human - Building a Safer Health System which summarized a culminated decades' worth of research that had so far been largely ignored. The aim of this study was to analyze the report's impact on patient safety research in anesthesiology. Methods: A bibliometric analysis was performed on all anesthesiologic publications from 2000 to 2019 that referenced To Err Is Human. In bibliometric literature, references are understood to represent an author's conscious decision to express a relationship between his own manuscript and the cited document. Results: The anesthesiologic data base contained 1.036 publications. The journal with the most references to the IOM report is Anesthesia & Analgesia. By analyzing author keywords and patterns of collaboration, changes in the patient safety debate and its core themes in anesthesiology over time could be visualized. The generic notion of "error," while initially a central topic in the scientific discourse, was subsequently replaced by terms representing a more granular, team-oriented, and educational approach. Patient safety research in anesthesia, while profiting from a certain intellectual and conceptual head start, showed a discursive shift toward more managerial, quality-management related topics as observed in the health care system as a whole. Conclusions: Over the last 20 years, the research context expanded from the initial focus set forth by the IOM report, which ultimately led to an underrepresentation of research on critical incident reporting and systemic approaches to safety. Important collaborations with safety researchers from outside of health care dating back to the 1990's were gradually reduced, while previous research within anesthesiology was aligned with a broader, more managerial patient safety agenda.

Correlation between safety attitudes and early adoption of cognitive aids in the German culture sphere: a multicenter survey study.

BACKGROUND: Cognitive Aids (checklists) are a common tool to improve patient safety. But the factors for their successful implementation and continuous use are not yet fully understood. Recent publications suggest safety culture to play a key role in this context. However, the effects on the outcome of implementation measures remain unclear. Hospitals and clinics that are involved in cognitive aid development and research might have significantly different safety cultures than their counterparts, resulting in skewed assessments of proper implementation. Therefore, the objective of this study was to assess the correlation between cognitive aid implementation and safety attitudes of staff members in early adopting and later adopting clinics. METHODS: An online survey of the Safety Attitudes Questionnaire (SAQ) was carried out in German anaesthesiology departments during the initial implementation of a new checklist for emergencies during anesthesia ("eGENA" app). Subsequently an analysis between subgroups ("eGENA" app usage and occupation), with Kruskal-Wallis- and Mann-Whitney-U-Tests was carried out for the general SAQ, as well as it six subscales. RESULTS: Departments that introduced "eGENA" app (Median 3,74, IQR 0,90) reported a significantly higher median SAQ (U (NeGENA = 6, Nnon eGENA = 14) = 70,0, z = 2,31, p = 0,02, r = 0,516) than their counterparts (Median 2,82, IQR 0,77) with significant differences in the dimensions teamwork climate, work satisfaction, perception of management and working conditions. CONCLUSION: Early adopters of cognitive aids are likely to show a significantly higher perception of safety culture in the SAQ. Consequently, successful implementation steps from these settings might not be sufficient in different clinics. Therefore, further investigation of the effects of safety culture on cognitive aid implementation should be conducted.

Role of extracellular vesicles in atherosclerosis: An update.

Extracellular vesicles (EVs) are membrane particles released by most cell types in response to different stimuli. They are composed of a lipid bilayer that encloses a wide range of bioactive material, including proteins and nucleic acids. EVs have garnered increasing attention over recent years, as their role in intercellular communication has been brought to light. As such, they have been found to regulate pathophysiologic pathways like inflammation, angiogenesis, or senescence, and are therefore implicated in key aspects atherosclerosis initiation and progression. Interestingly, EVs appear to have a multifaceted role; depending on their cargo, they can either facilitate or hamper the development of atherosclerotic lesions. In this review, we examine how EVs of varying origins may be implicated in the different phases of atherosclerotic lesion development. We also discuss the need to standardize isolation and analysis procedures to fully fulfil their potential as biomarkers and therapeutics for cardiovascular diseases.

[Extracellular vesicles and cardiovascular diseases]. / Vésicules extracellulaires et maladies cardiovasculaires.

Cardiovascular diseases remain the leading cause of death globally. There is therefore a need to develop new approaches for the treatment and early detection of these ailments. In the past decades, extracellular vesicles (EVs) have attracted significant attention as their role in intercellular communication has been brought to light. They have been shown to regulate pathways such as cellular inflammation or angiogenesis, and are therefore involved in key aspects of cardiovascular pathophysiology. Interestingly, EVs appear to have a multifaceted role which depends on their origin and cargo. Though at times deleterious, they have also been proposed as promising diagnostic tools and potential therapeutics. This review highlights recent advances in the role of extracellular vesicles in cardiovascular pathologies.

TITLE: Vésicules extracellulaires et maladies cardiovasculaires. ABSTRACT: Les maladies cardiovasculaires constituent la principale cause de décès dans le monde. Il est donc urgent de développer de nouvelles approches pour le traitement et la détection de ces maladies. Les vésicules extracellulaires (VE) ont attiré une attention considérable au vu de leur rôle dans la communication intercellulaire. Elles régulent en effet des processus clés comme l'inflammation ou l'angiogenèse, et sont donc impliquées dans de nombreux aspects de la physiopathologie cardiovasculaire. Les VE semblent avoir une action complexe qui dépend de leur origine et de leur contenu. Bien que leur présence soit parfois délétère, elles sont également considérées comme des outils diagnostiques et thérapeutiques potentiels. Cette revue résume les avancées récentes dans la compréhension du rôle des VE dans les maladies cardiovasculaires.

Intended and Unintended Consequences of a Community-Based Fresh Fruit and Vegetable Dietary Intervention on the Flathead Reservation of the Confederated Salish and Kootenai Tribes.

Tribal communities in the United States face disparities to accessing healthy foods including high-quality produce. A six-week fresh fruit and vegetable (FV) dietary intervention, Eat Fresh, was co-designed with a Community Advisory Board of local food and nutrition stakeholders on the Flathead Reservation of the Confederated Salish and Kootenai Tribes in Montana. Eat Fresh was implemented as a pilot study with low-income participants (n = 19) enrolled in the Food Distribution Program on Indian Reservations toward improving dietary quality and perceptions of well-being. We evaluated Eat Fresh at pre- and post-intervention on the basis on food procurement practices, dietary quality using the Healthy Eating Index (HEI), Body Mass Index (BMI), blood pressure, and participant perceptions of health. Participants reported consuming a greater number of types of FVs daily during the intervention (p < 0.005 for fruits and p > 0.19 for vegetables). Overall, participants found Eat Fresh moderately challenging to adhere to with the main barriers being access to ingredients in recipes (39.51% of responses), time constraints to cook (35.80%), and lack of financial resources (33.33%). Dietary quality improved during the intervention from a mean HEI score of 48.82 (± 11.88) out of 100-56.92 (± 11.88; (p > 0.12). HEI scores for fruit consumption significantly increased (p < 0.05) from 1.69 (out of 5 points) during the pre-intervention to 2.96 during the post-intervention. BMI and blood pressure increased for several participants, highlighting an unintended consequence. Most participants responded that FV consumption made them feel either very good (51.16%) or good about their health (43.02%) with the majority (83%) perceiving an improvement in energy. Findings of this pilot study highlight both intended and unintended consequences of a dietary intervention that provide lessons in co-designing community-based programs.

How novice and expert anaesthetists understand expertise in anaesthesia: a qualitative study.

BACKGROUND: The development of expertise in anaesthesia requires personal contact between a mentor and a learner. Because mentors often are experienced clinicians, they may find it difficult to understand the challenges novices face during their first months of clinical practice. As a result, novices' perspectives may be an important source of pedagogical information for the expert. The aim of this study was to explore novice and expert anaesthetists understanding of expertise in anaesthesia using qualitative methods. METHODS: Semi-structured interviews were conducted with 9 novice and 9 expert anaesthetists from a German University Hospital. Novices were included if they had between 3 and 6 months of clinical experience and experts were determined by peer assessment. Interviews were intended to answer the following research questions: What do novices think expertise entails and what do they think they will need to become an expert? What do experts think made them the expert person and how did that happen? How do both groups value evidence-based standards and how do they negotiate following written guidance with following one's experience? RESULTS: The clinical experience in both groups differed significantly (novices: 4.3 mean months vs. experts: 26.7 mean years; p < 0.001). Novices struggled with translating theoretical knowledge into action and found it difficult to talk about expertise. Experts no longer seem to remember being challenged as novice by the complexity of routine tasks. Both groups shared the understanding that the development of expertise was a socially embedded process. Novices assumed that written procedures were specific enough to address every clinical contingency whereas experts stated that rules and standards were essentially underspecified. For novices the challenge was less to familiarise oneself with written standards than to learn the unwritten, quasi-normative rules of their supervising consultant(s). Novices conceptualized decision making as a rational, linear process whereas experts added to this understanding of tacit knowledge and intuitive decision making. CONCLUSIONS: Major qualitative differences between a novice and an expert anaesthetist's understanding of expertise can create challenges during the first months of clinical training. Experts should be aware of the problems novices may have with negotiating evidence-based standards and quasi-normative rules.

Data Model Requirements for a Digital Cognitive Aid for Anesthesia to Support Intraoperative Crisis Management.

OBJECTIVE: The aim of this study is to define data model requirements supporting the development of a digital cognitive aid (CA) for intraoperative crisis management in anesthesia, including medical emergency text modules (text elements) and branches or loops within emergency instructions (control structures) as well as their properties, data types, and value ranges. METHODS: The analysis process comprised three steps: reviewing the structure of paper-based CAs to identify common text elements and control structures, identifying requirements derived from content, design, and purpose of a digital CA, and validating requirements by loading exemplary emergency checklist data into the resulting prototype data model. RESULTS: The analysis of paper-based CAs identified 19 general text elements and two control structures. Aggregating these elements and analyzing the content, design and purpose of a digital CA revealed 20 relevant data model requirements. These included checklist tags to enable different search options, structured checklist action steps (items) in groups and subgroups, and additional information on each item. Checklist and Item were identified as two main classes of the prototype data model. A data object built according to this model was successfully integrated into a digital CA prototype. CONCLUSION: To enable consistent design and interactivity with the content, presentation of critical medical information in a digital CA for crisis management requires a uniform structure. So far it has not been investigated which requirements need to be met by a data model for this purpose. The results of this study define the requirements and structure that enable the presentation of critical medical information. Further research is needed to develop a comprehensive data model for a digital CA for crisis management in anesthesia, including supplementation of requirements resulting from simulation studies and feasibility analyses regarding existing data models. This model may also be a useful template for developing data models for CAs in other medical domains.

A Digital Cognitive Aid for Anesthesia to Support Intraoperative Crisis Management: Results of the User-Centered Design Process.

BACKGROUND: Stressful situations during intraoperative emergencies have negative impact on human cognitive functions. Consequently, task performance may decrease and patient safety may be compromised. Cognitive aids can counteract these effects and support anesthesiologists in their crisis management. The Professional Association of German Anesthesiologists set up a project to develop a comprehensive set of digital cognitive aids for intraoperative emergencies. A parallel development for several software platforms and stationary and mobile devices will accommodate the inhomogeneity of the information technology infrastructure within German anesthesia departments. OBJECTIVE: This paper aimed to provide a detailed overview of how the task of developing a digital cognitive aid for intraoperative crisis management in anesthesia was addressed that meets user requirements and is highly user-friendly. METHODS: A user-centered design (UCD) process was conducted to identify, specify, and supplement the requirements for a digital cognitive aid. The study covered 4 aspects: analysis of the context of use, specification of user requirements, development of design solutions, and evaluation of design solutions. Three prototypes were developed and evaluated by end users of the application. Following each evaluation, the new requirements were prioritized and used for redesign. For the first and third prototype, the System Usability Scale (SUS) score was determined. The second prototype was evaluated with an extensive Web-based questionnaire. The evaluation of the third prototype included a think-aloud protocol. RESULTS: The chosen methods enabled a comprehensive collection of requirements and helped to improve the design of the application. The first prototype achieved an average SUS score of 74 (SD 12), indicating good usability. The second prototype included the following main revisions: 2-column layout, initial selection of patient type (infant, adult, or parturient), 4 offered search options, and the option to check off completed action steps. Its evaluation identified the following major revision points: add quick selection for resuscitation checklists, design the top bar and tabs slightly larger, and add more pictograms to the text. The third prototype achieved an average SUS score of 77 (SD 15). The evaluation of the think-aloud protocol revealed a good intuitiveness of the application and identified a missing home button as the main issue. CONCLUSIONS: Anesthesiology-as an acute medical field-is particularly characterized by its high demands on decision making and action in dynamic, or time-critical situations. The integration of usability aspects is essential for everyday and emergency suitability. The UCD process allowed us to develop a prototypical digital cognitive aid, exhibiting high usability and user satisfaction in the demanding environment of anesthesiological emergencies. Both aspects are essential to increase the acceptance of the application in later stages. The study approach, combining different methods for determining user requirements, may be useful for other implementation projects in a highly demanding environment.

The influence of different patient positions during rapid induction with severe regurgitation on the volume of aspirate and time to intubation: a prospective randomised manikin simulation study.

BACKGROUND: Aspiration is a main contributor to morbidity and mortality in anaesthesia. The ideal patient positioning for rapid sequence induction remains controversial. A head-down tilt and full cervical spine extension (Sellick) might prevent aspiration but at the same time compromise airway management. We aimed to determine the influence of three different positions during induction of general anaesthesia on the volume of aspirate and on participants' airway management. METHODS: Eighty-four anaesthetic trainees and consultants participated in a prospective randomised simulation study. Anaesthesia was induced in reverse Trendelenburg position (+ 15°) in a manikin capable of dynamic fluid regurgitation. Participants were randomised to change to Trendelenburg position (- 15°) a) as soon as regurgitation was noticed, b) as soon as 'patient' had been anaesthetised, and c) as soon as 'patient' had been anaesthetised and with full cervical spine extension (Sellick). Primary endpoints were the aspirated volume and the time to intubation. Secondary endpoints were ratings of the laryngoscopic view and the intubation situation (0-100 mm). RESULTS: Combining head-down tilt with Sellick position significantly reduced aspiration (p < 0.005). Median time to intubate was longer in Sellick position (15 s [8-30]) as compared with the head in sniffing position (10 s [8-12.5]; p < 0.05). Participants found laryngoscopy more difficult in Sellick position (39.3 ± 27.9 mm) as compared with the sniffing position (23.1 ± 22.1 mm; p < 0.05). Both head-down tilt intubation situations were considered equally difficult: 34.8 ± 24.6 mm (Sniffing) vs. 44.2 ± 23.1 mm (Sellick; p = n.s). CONCLUSIONS: In a simulated setting, using a manikin-based simulator capable of fluid regurgitation, a - 15° head-down tilt with Sellick position reduced the amount of aspirated fluid but increased the difficulty in visualising the vocal cords and prolonged the time taken to intubate. Assessing the airway management in the identical position in healthy patients without risk of aspiration might be a promising next step to take.

Applying the human factors analysis and classification system to critical incident reports in anaesthesiology.

BACKGROUND: The Human Factors Analysis and Classification System (HFACS) was developed as a practical taxonomy to investigate and analyse the human contribution to accidents and incidents. Based on Reason's "Swiss Cheese Model", it considers individual, environmental, leadership and organizational contributing factors in four hierarchical levels. The aim of this study was to assess the applicability of a modified HFACS taxonomy to incident reports from a large, anonymous critical incident database with the goal of gaining valuable insight into underlying, more systemic conditions and recurring schemes that might add important information for future incident avoidance. METHODS: We analysed 50 reports from an anonymous, anaesthesiologic, single-centre Critical Incident Reporting System using a modified HFACS-CIRS taxonomy. The 19 HFACS categories were further subdivided into a total of 117 nanocodes representing specific behaviours or preconditions for incident development. RESULTS: On an individual level, the most frequent contributions were decision errors, attributed to inadequate risk assessment or critical-thinking failure. Communication and Coordination, mostly due to inadequate or ineffective communication, was contributory in two-thirds of reports. Half of the reports showed contributory complex interactions in a sociotechnical environment. Ratability scores were noticeably lower for categories evaluating leadership and organizational influences, necessitating careful interpretation. CONCLUSIONS: We applied the HFACS taxonomy to the analysis of CIRS reports in anaesthesiology. This constitutes a structured approach that, especially when applied to a large data set, might help guide future mitigation and intervention strategies to reduce critical incidents and improve patient safety. Improved, more structured reporting templates could further optimize systematic analysis.

Endogenous Expression of ODN-Related Peptides in Astrocytes Contributes to Cell Protection Against Oxidative Stress: Astrocyte-Neuron Crosstalk Relevance for Neuronal Survival.

Astroglial cells are important actors in the defense of brain against oxidative stress injuries. Glial cells synthesize and release the octadecaneuropeptide ODN, a diazepam-binding inhibitor (DBI)-related peptide, which acts through its metabotropic receptor to protect neurons and astrocytes from oxidative stress-induced apoptosis. The purpose of the present study is to examine the contribution of the endogenous ODN in the protection of astrocytes and neurons from moderate oxidative stress. The administration of H2O2 (50 µM, 6 h) induced a moderate oxidative stress in cultured astrocytes, i.e., an increase in reactive oxygen species, malondialdehyde, and carbonyl group levels, but it had no effect on astrocyte death. Mass spectrometry and QPCR analysis revealed that 50 µM H2O2 increased ODN release and DBI mRNA levels. The inhibition of ODN release or pharmacological blockage of the effects of ODN revealed that in these conditions, 50 µM H2O2 induced the death of astrocytes. The transfection of astrocytes with DBI siRNA increased the vulnerability of cells to moderate stress. Finally, the addition of 1 nM ODN to culture media reversed cell death observed in DBI-deficient astrocytes. The treatment of neurons with media from 50 µM H2O2-stressed astrocytes significantly reduced the neuronal death induced by H2O2; this effect is greatly attenuated by the administration of an ODN metabotropic receptor antagonist. Overall, these results indicate that astrocytes produce authentic ODN, notably in a moderate oxidative stress situation, and this glio- and neuro-protective agent may form part of the brain defense mechanisms against oxidative stress injury.

Does an electronic cognitive aid have an effect on the management of severe gynaecological TURP syndrome? A prospective, randomised simulation study.

BACKGROUND: Lack of familiarity with the content of current guidelines is a major factor associated with non-compliance by clinicians. It is conceivable that cognitive aids with regularly updated medical content can guide clinicians' task performance by evidence-based practices, even if they are unfamiliar with the actual guideline. Acute hyponatraemia as a consequence of TURP syndrome is a rare intraoperative event, and current practice guidelines have changed from slow correction to rapid correction of serum sodium levels. The primary objective of this study was to compare the management of a simulated severe gynaecological transurethral resection of the prostate (TURP) syndrome under spinal anaesthesia with either: an electronic cognitive aid, or with management from memory alone. The secondary objective was to assess the clinical relevance and participant perception of the usefulness of the cognitive aid. METHODS: Anaesthetic teams were allocated to control (no cognitive aid; n = 10) or intervention (cognitive aid provided; n = 10) groups. We identified eight evidence-based management tasks for severe TURP syndrome from current guidelines and subdivided them into acute heart failure (AHF)/pulmonary oedema tasks (5) and acute hyponatraemia tasks (3). Implementation of the treatment steps was measured by scoring task items in a binary fashion (yes/no). To assess whether or not the cognitive aid had prompted a treatment step, participants from the cognitive aid group were questioned during debriefing on every single treatment step. At the end of the simulation, session participants were asked to complete a survey. RESULTS: Teams in the cognitive aid group considered evidence-based treatment steps significantly more often than teams of the control group (96% vs. 50% for 'AHF/pulmonary oedema' p < 0.001; 79% vs. 12% for 'acute hyponatraemia' p < 0.001). Without the cognitive aid, performance would have been comparable across both groups. Nurses, trainees, and consultants derived equal benefit from the cognitive aid. CONCLUSIONS: The cognitive aid improved the implementation of evidence-based practices in a simulated intraoperative scenario. Cognitive aids with current medical content could help to close the translational gap between guideline publication and implementation in acute patient care. It is important that the cognitive aid should be familiar, in a format that has been used in practice and training.

The effect of an electronic cognitive aid on the management of ST-elevation myocardial infarction during caesarean section: a prospective randomised simulation study.

BACKGROUND: Cognitive aids have come to be viewed as promising tools in the management of perioperative critical events. The majority of published simulation studies have focussed on perioperative crises that are characterised by time pressure, rare occurrence, or complex management steps (e.g., cardiac arrest emergencies, management of the difficult airway). At present, there is limited information on the usefulness of cognitive aids in critical situations with moderate time pressure and complexity. Intraoperative myocardial infarction may be an emergency to which these limitations apply. METHODS: Anaesthetic teams were allocated to control (no cognitive aid; n = 10) or intervention (cognitive aid provided; n = 10) groups. The primary aim of this study was to compare cognitive aid versus memory for intraoperative ST-elevation myocardial infarction (STEMI) management in a simulation of caesarean delivery under spinal anaesthesia. We identified nine evidence-based metrics of essential care from current guidelines and subdivided them into mandatory (high level of evidence; no interference with surgery) and optional (lower class of recommendation; possible impact on surgery) tasks. Six clinically relevant tasks were added by consensus. Implementation of these steps was measured by scoring task items in a binary fashion (yes/no). The interval between the diagnosis of STEMI and the first contact with the cardiac catheterisation lab was measured. To determine whether or not the cognitive aid had prompted an action, participants from the cognitive aid group were interviewed during debriefing on every single treatment step. At the end of the simulation, session participants were asked to complete a survey. RESULTS: The presence of the cognitive aid did not shorten the time interval until the cardiac catheterisation lab was contacted. The availability of the cognitive aid improved task performance in the tasks identified from the guidelines (93% vs. 69%; p < 0.001) as well as overall task performance (87.5% vs. 59%; p < 0.001). The observed difference in performance can be attributed to the use of the cognitive aid, as performance from memory alone would have been comparable across both groups. Trainees appeared to derive greater benefit from the cognitive aid than did consultants and nurses. CONCLUSIONS: The management of intraoperative ST-elevation myocardial infarction can be improved if teams use a cognitive aid. Trainees appeared to derive greater benefit from the cognitive aid than did consultants and nurses.

The Autophagy Machinery: A New Player in Chemotactic Cell Migration.

Autophagy is a highly conserved self-degradative process that plays a key role in diverse cellular processes such as stress response or differentiation. A growing body of work highlights the direct involvement of autophagy in cell migration and cancer metastasis. Specifically, autophagy has been shown to be involved in modulating cell adhesion dynamics as well as epithelial-to-mesenchymal transition. After providing a general overview of the mechanisms controlling autophagosome biogenesis and cell migration, we discuss how chemotactic G protein-coupled receptors, through the repression of autophagy, may orchestrate membrane trafficking and compartmentation of specific proteins at the cell front in order to support the critical steps of directional migration.

Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis.

Chemotactic migration is a fundamental behavior of cells and its regulation is particularly relevant in physiological processes such as organogenesis and angiogenesis, as well as in pathological processes such as tumor metastasis. The majority of chemotactic stimuli activate cell surface receptors that belong to the G protein-coupled receptor (GPCR) superfamily. Although the autophagy machinery has been shown to play a role in cell migration, its mode of regulation by chemotactic GPCRs remains largely unexplored. We found that ligand-induced activation of 2 chemotactic GPCRs, the chemokine receptor CXCR4 and the urotensin 2 receptor UTS2R, triggers a marked reduction in the biogenesis of autophagosomes, in both HEK-293 and U87 glioblastoma cells. Chemotactic GPCRs exert their anti-autophagic effects through the activation of CAPNs, which prevent the formation of pre-autophagosomal vesicles from the plasma membrane. We further demonstrated that CXCR4- or UTS2R-induced inhibition of autophagy favors the formation of adhesion complexes to the extracellular matrix and is required for chemotactic migration. Altogether, our data reveal a new link between GPCR signaling and the autophagy machinery, and may help to envisage therapeutic strategies in pathological processes such as cancer cell invasion.