[Controlling risks in healthcare institutions]. / Maîtriser les risques dans les établissements de santé.

The management of a healthcare institution generates risks through the very hazards of the management process. The management of these risks is integrated into the global safety management process and into the strategic thinking of geriatric hospitals.

[Assessment of nursing needs and risk management in geriatric oncology]. / Evaluation des besoins en soins et gestion des risques en oncogériatrie.

In France, the incidence and rate of mortality of cancer increase with age. For elderly patients suffering from cancer, the standard geriatric assessment, together with an oncological assessment aims to optimise the treatment. This geriatric oncology assessment enables the priorities to be identified and the cancer treatment to be adapted by anticipating the risks and organising the support care.

[Implementation of a procedure for nominating a health care surrogate]. / Mise en oeuvre d'une procédure de désignation d'une personne de confiance.

A procedure for the systematic nomination of a health care surrogate was put in place following a multi-disciplinary approach within an acute care geriatric unit at Ambroise-Paré hospital in Boulogne-Billancourt. Its originality lies in the way the whole team, on the initiative of a doctor, prepared the procedure, implemented it and assessed it. A review.

Stereoscopically observed deformations of a compliant abdominal aortic aneurysm model.

A new experimental setup has been implemented to precisely measure the deformations of an entire model abdominal aortic aneurysm (AAA). This setup addresses a gap between the computational and experimental models of AAA that have aimed at improving the limited understanding of aneurysm development and rupture. The experimental validation of the deformations from computational approaches has been limited by a lack of consideration of the large and varied deformations that AAAs undergo in response to physiologic flow and pressure. To address the issue of experimentally validating these calculated deformations, a stereoscopic imaging system utilizing two cameras was constructed to measure model aneurysm displacement in response to pressurization. The three model shapes, consisting of a healthy aorta, an AAA with bifurcation, and an AAA without bifurcation, were also evaluated with computational solid mechanical modeling using finite elements to assess the impact of differences between material properties and for comparison against the experimental inflations. The device demonstrated adequate accuracy (surface points were located to within 0.07 mm) for capturing local variation while allowing the full length of the aneurysm sac to be observed at once. The experimental model AAA demonstrated realistic aneurysm behavior by having cyclic strains consistent with reported clinical observations between pressures 80 and 120 mm Hg. These strains are 1-2%, and the local spatial variations in experimental strain were less than predicted by the computational models. The three different models demonstrated that the asymmetric bifurcation creates displacement differences but not cyclic strain differences within the aneurysm sac. The technique and device captured regional variations of strain that are unobservable with diameter measures alone. It also allowed the calculation of local strain and removed rigid body motion effects on the strain calculation. The results of the computations show that an asymmetric aortic bifurcation created displacement differences but not cyclic strain differences within the aneurysm sac.

Side-dependent effect in the response of valve endothelial cells to bidirectional shear stress.

Endothelial cells covering the aortic and ventricular sides of the aortic valve leaflets are exposed to different stresses, in particular wall shear stress (WSS). Biomechanical stimuli actively regulate valve tissue structure and induce remodeling events leading to valve dysfunction. Endothelial to mesenchymal transformation (EndMT), for example, has been associated with aortic valve disease. The biomechanical response of cells at different sides of the leaflets has not been clearly characterized. To analyze the mechanical response of valve endothelial cells (VECs) we developed a unique fluid activation device that applies physiologically relevant pulsatile WSS. We characterized the morphology and function of adult porcine aortic VECs derived from the opposite sides of aortic valve leaflets following exposure to different pulsatile WSS. We found that elongation and orientation of cells in response to pulsatile WSS depends on their side of origin. Quantification of gene expression confirms phenotypic differences between aortic and ventricular VECs. Aortic VECs exposed to pulsatile WSS similar to that in vivo at the tip of aortic side of the valve leaflet upregulated pro-EndMT (ACTA2, Snail, TGFß1) and inflammation (ICAM-1, VCAM-1) genes, whereas expression of endothelial markers like PECAM-1 was decreased. Conversely, ventricular-VECs showed strong increase of PECAM-1 expression and no activation of pro-EndMT marker. Finally, we found that stress-induced genes are upregulated in both cell types, at higher levels in ventricular compared to aortic VECs. Application of physiological shear stress levels using a fluid activation device therefore reveals functional differences in VECs derived from opposite sides of the aortic valve leaflets.

[Mapping hazardous situations with regard to fall risk]. / Cartographie des situations dangereuses dans le risque de chute.

The mapping of hazardous situations aims to provide a practical representation of the ranking of vulnerabilities in patient care. While there is no universally recognised method, a task force working on fall risk at Ambroise Paré hospital in Boulogne (AP-HP, Hauts-de-Seine) has drawn up a map charting the a posteriori and a priori identification and analysis of risks. Mobilising the professionals involved is essential in order to achieve as comprehensive a map as possible. The possibility of generalising this approach remains to be assessed.

Biophotonics applied to proteomics.

Since the completion of the human genome sequencing, our understanding of gene and protein function and their involvement in physiopathological states has increased dramatically, partly due to technological developments in photonics. Photonics is a very active area where new developments occur on a weekly basis, while established tools are adapted to fulfill the needs of other disciplines like genomics and proteomics. Biophotonics emerged at the interface of photonics and biology as a very straightforward and efficient approach to observe and manipulate living systems. In this chapter, we review the current applications of photonics and imaging to proteomics from 2D gels analysis to molecular imaging.

Flow behaviour in an asymmetric compliant experimental model for abdominal aortic aneurysm.

An experimental study was carried out on asymmetrical abdominal aortic aneurysm (AAA) to analyse the physiological flows involved. Velocity measurements were performed using particle image velocimetry. Resting and exercise flow rates were investigated in models with rigid and compliant walls to assess the parameters affecting the flow behaviour. The secondary flow patterns, and especially the evolution of the vortices within the AAA, were found to be highly dependent on both the flow waveforms and the wall behaviour. Vortices impacts on the distal walls of the AAA occur in the compliant model and can increase the local pressure on the AAA walls and thus increase the wall stresses; AAA wall stresses are one of the most important factors contributing to ruptured aneurysm.

Biaxial tensile tests of the porcine ascending aorta.

One of the aims of this work is to develop an original custom built biaxial set-up to assess mechanical behavior of soft tissues. Stretch controlled biaxial tensile tests are performed and stereoscopic digital image correlation (SDIC) is implemented to measure the 3D components of the generated displacements. Using this experimental device, the main goal is to investigate the mechanical behavior of porcine ascending aorta in the more general context of human ascending aorta pathologies. The results highlight that (i) SDIC arrangement allows accurate assessment of displacements and so stress strain curves, (ii) porcine ascending aorta has a nearly linear and anisotropic mechanical behavior until 30% of strain, (iii) porcine ascending aorta is stiffer in the circumferential direction than in the longitudinal one, (iv) the material coefficient representing the interaction between the two loading directions is thickness dependent, (v) taking into account the variability of the samples the stress values are independent of the stretch rate in the range of values from 10(-3) to 10(-1)s(-1) and finally, (vi) unlike other segments of the aorta, 4-month-old pigs ascending aorta is definitely not a relevant model to investigate the mechanical behavior of the human ascending aorta.

In vitro atrial flow dynamics: normal conditions versus atrial fibrillation.

AIMS: The flow dynamics in the atrium is poorly described. The reasons are principally due to the complicated geometry of the cavity and its contractility. The present in vitro study focuses on the description of the flow in the left atrium in normal conditions (NC) and in atrial fibrillation (AF). The final objective is to give leads to understand, from the hemodynamic point of view, complications in case of AF. METHODS AND RESULTS: An atrio-ventricular dual activation system is used to simulate physiological flow in the left atrium. The cavities are compliant and transparent. Velocity measurements are performed with Particle Image Velocimetry. Systolic peak of the pulmonary venous flow is about 0.4 m s(-1) and diastolic peak 0.6 m s(-1) in magnitude. Vortices appear during diastasis and systole and are of normal size and duration. In early and late diastole, the ventricular filling (in NC and AF) and the atrial contraction (in NC only) create a characteristic flow pattern that consists in directed flow towards the mitral valve. In AF an increased resident time (500 ms versus 300 ms) and a slow helical flow pattern (about 0.1 m s(-1)), similar to what is measured using ultrasound echocardiography are observed. CONCLUSION: This study uses atrial flow dynamics description to help understand why thromboembolisms occur in AF.

Flow of a blood analogue fluid in a compliant abdominal aortic aneurysm model: experimental modelling.

The aim of this work is to develop a unique in vitro set-up in order to analyse the influence of the shear thinning fluid-properties on the flow dynamics within the bulge of an abdominal aortic aneurysm (AAA). From an experimental point of view, the goals are to elaborate an analogue shear thinning fluid mimicking the macroscopic blood behaviour, to characterise its rheology at low shear rates and to propose an experimental device able to manage such an analogue fluid without altering its feature while reproducing physiological flow rate and pressure, through compliant AAA. Once these experimental prerequisites achieved, the results obtained in the present work show that the flow dynamics is highly dependent on the fluid rheology. The main results point out that the propagation of the vortex ring, generated in the AAA bulge, is slower for shear thinning fluids inducing a smaller travelled distance by the vortex ring so that it never impacts the anterior wall in the distal region, in opposition to Newtonian fluids. Moreover, scalar shear rate values are globally lower for shear thinning fluids inducing higher maximum stress values than those for the Newtonian fluids. Consequently, this work highlights that a Newtonian fluid model is finally inadequate to obtain a reliable prediction of the flow dynamics within AAA.

Risk management of excreta in a cancer unit.

Although many legal and clinical requirements are in effect for the preparation and administration of the antineoplasic drugs, limited data exist on the potential cytotoxic risk to healthcare personnel from exposure of excreta (urine, feces, expectorations, saliva, perspiration, and vomiting) from patients. A preliminary risk analysis was conducted with a multidisciplinary work group. The objectives were to identify all potential hazards and accidental events that may lead to an accident related to the excreta management and to implement a global risk reduction and quality improvement policy. The findings revealed the potential risks of excreta contamination in health service and led to recommendations for the healthcare team to optimize working conditions, ensure public protection and occupational health, and promote environmental and employee safety.

New insights into the understanding of flow dynamics in an in vitro model for abdominal aortic aneurysms.

An in vitro dynamics set-up of the flow in a compliant abdominal aortic aneurysm (AAA) model with an anterior posterior asymmetry, aorto-iliac bifurcation, and physiological inlet flow rate and outlet pressure waveforms was developed. The aims were first to show that the structural mechanical behavior of the used material to mimic the AAA wall was similar to this of patients with AAA and then to study the influence of the aorto-iliac bifurcation presence and to study the influence of the imbalanced flow rate in the iliac branches on the AAA flow field. 3D visualizations, never performed in the literature, have clearly put into evidence the development of a vortex ring generated at the AAA proximal neck during the decelerating phase of flow rate, which detaches and progresses downstream during the cardiac cycle, impinges on the anterior wall in the distal AAA region, breaks up, and separates into two vortices of which one rolls on upstream along the anterior wall. 2D particle image velocimetry measurements, swirling strength and enstrophy calculations allowed quantification of the vorticity, vortex trajectory and energy for the different geometrical and hydrodynamical conditions. The main results show that the instant and the intensity of the vortex ring impingement depend on the presence of the aorto-iliac bifurcation, with higher intensity, by about 90%, for an AAA without bifurcation. The imbalance of the flow rates into the iliac branches induces different propagation velocities of the vortex ring and lowers the intensity of the vortex impact by about 60%. The potential influence of the AAA dynamics is discussed in terms of AAA remodeling and rupture.

Numerical and experimental study of blood flow through a patient-specific arteriovenous fistula used for hemodialysis.

Arteriovenous fistula (AVF) pathologies related to blood flow necessitate valid calculation tools for local velocity and wall shear stress determination to overcome the clinical diagnostic limits. To illustrate this issue, a reconstructed patient-specific AVF was investigated, using computational fluid dynamics (CFDs) and particle image velocimetry (PIV). The aim of this study was to validate the methodology from medical images to numerical simulations of an AVF by comparing numerical and experimental data. Two numerical grids were presented with a refinement difference of a factor of four. A mold of the same volume was created and mounted on an experimental bench with similar boundary conditions. The patient's acquired echo D006Fppler flow waveform was injected at the arterial inlet. Experimental and numerical velocity vector cartography qualitatively produced similar flow fields. Quantification with a point-to-point approach thoroughly investigated the velocity profiles using the mean difference between both results. The finest mesh generated CFD results with a mean percentage of the difference in velocity magnitude, taking the PIV as reference, did not exceed 10%. At specific zones, the coarse mesh required adaptive meshing to improve fitting with experimental data. Meshing refinement was necessary to improve velocity accuracy at wide diameters and wall shear stress at narrow diameters. Provided that these criteria were properly respected, we show through this difficult example the validity of using CFD to properly describe flow patterns in image-based reconstructed blood vessels.

Two-dimensional intraventricular flow mapping by digital processing conventional color-Doppler echocardiography images.

Doppler echocardiography remains the most extended clinical modality for the evaluation of left ventricular (LV) function. Current Doppler ultrasound methods, however, are limited to the representation of a single flow velocity component. We thus developed a novel technique to construct 2D time-resolved (2D+t) LV velocity fields from conventional transthoracic clinical acquisitions. Combining color-Doppler velocities with LV wall positions, the cross-beam blood velocities were calculated using the continuity equation under a planar flow assumption. To validate the algorithm, 2D Doppler flow mapping and laser particle image velocimetry (PIV) measurements were carried out in an atrio-ventricular duplicator. Phase-contrast magnetic resonance (MR) acquisitions were used to measure in vivo the error due to the 2D flow assumption and to potential scan-plane misalignment. Finally, the applicability of the Doppler technique was tested in the clinical setting. In vitro experiments demonstrated that the new method yields an accurate quantitative description of the main vortex that forms during the cardiac cycle (mean error for vortex radius, position and circulation). MR image analysis evidenced that the error due to the planar flow assumption is close to 15% and does not preclude the characterization of major vortex properties neither in the normal nor in the dilated LV. These results are yet to be confirmed by a head-to-head clinical validation study. Clinical Doppler studies showed that the method is readily applicable and that a single large anterograde vortex develops in the healthy ventricle while supplementary retrograde swirling structures may appear in the diseased heart. The proposed echocardiographic method based on the continuity equation is fast, clinically-compliant and does not require complex training. This technique will potentially enable investigators to study of additional quantitative aspects of intraventricular flow dynamics in the clinical setting by high-throughput processing conventional color-Doppler images.

Validation of a numerical 3-D fluid-structure interaction model for a prosthetic valve based on experimental PIV measurements.

A numerical 3-D fluid-structure interaction (FSI) model of a prosthetic aortic valve was developed, based on a commercial computational fluid dynamics (CFD) software program using an Arbitrary Eulerian Lagrangian (ALE) formulation. To make sure of the validity of this numerical model, an equivalent experimental model accounting for both the geometrical features and the hydrodynamic conditions was also developed. The leaflet and the flow behaviours around the bileaflet valve were investigated numerically and experimentally by performing particle image velocimetry (PIV) measurements. Through quantitative and qualitative comparisons, it was shown that the leaflet behaviour and the velocity fields were similar in both models. The present study allows the validation of a fully coupled 3-D FSI numerical model. The promising numerical tool could be therefore used to investigate clinical issues involving the aortic valve.

Analysis of blood flow behaviour in custom stent grafts.

Endovascular aneurysm repair (EVAR) is an attractive alternative to open surgery for treating abdominal aortic aneurysms (AAAs). However, the implantation of stent grafts into AAAs can result in post-operative complications such as stent graft migration, rupture or endoleak. EVAR has therefore been carried out only on selected patients. Stent grafts are usually standard commercial stent grafts (CSGs); however, custom made stent grafts (cmSGs) of various shapes and sizes are sometimes used to fit patients' anatomies. In the present study, the cmSGs were specially designed and fabricated by the surgeons at the Pitié-Salpétriére hospital in Paris. Two patients carrying cmSGs with unfavourable geometries showing tortuous shapes, angulation, widening, narrowing, curvature and kinking and one patient with a cmSG with a more favourable geometry resembling a straight tube were examined. These three clinical cases were investigated using three-dimensional numerical simulations, and the results showed that even when the cmSG geometries are unfavourable, the drag forces to which they are subjected are of a similar magnitude to those exerted on CSGs, or even smaller. The hemodynamic analysis carried out on the two unfavourable cmSGs showed the occurrence of low velocity values in the main trunk of the cmSGs, high velocities linked to recirculation areas downstream from kinking and strong distal narrowing. These flow patterns are liable to induce thrombus. However, since cmSG implantation can save the lives of patients for whom neither classical stent grafts nor open surgery are indicated, it can be concluded that these devices are useful in some cases.

Antibody-based proteomics: analysis of signaling networks using reverse protein arrays.

Protein kinases drive the cellular signal transduction networks that underlie the regulation of growth, survival and differentiation. To repair the deregulations of signaling cascades that are associated with numerous disease states, therapeutic strategies, based on controlling aberrant protein kinase activity, are emerging. To develop such therapies it is crucial to have knowledge of the full complexity of signaling networks at a molecular level in order to understand the information flow through signaling cascades and their cell and tissue specificity. Antibody-based proteomic approaches (such as reverse-phase protein microarrays) are a powerful tool for using to obtain those signaling maps, through the study of phosphorylation states of pathway components using antibodies that specifically recognize the phosphorylated form of kinase substrates.

[Misoprostol for treating postpartum hemorrhages]. / Le misoprostol dans le traitement curatif des hémorragies du post-partum.

Postpartum hemorrhage is defined by bleeding > 500 mL through the vagina. It is one of the obstetrical complications that obstetricians fear most. It is the leading cause of maternal mortality in the world, especially in developing countries. The reference treatments in France are parenteral oxytocin and sulprostone. Sulprostone involves sometimes fatal side effects, and must be administered only in appropriate health care facilities. It also has the major disadvantage of requiring refrigeration. Misoprostol has uterotonic properties that have led to its occasional off-label use in the treatment of postpartum hemorrhage, by rectal or sublingual administration, as an alternative to sulprostone. A careful review of the literature on this particular use of misoprostol is essential.

Identification of apolipoprotein A-I as a "STOP" signal for myopia.

Good visual acuity requires that the axial length of the ocular globe is matched to the refractive power of the cornea and lens to focus the images of distant objects onto the retina. During the growth of the juvenile eye, this is achieved through the emmetropization process that adjusts the ocular axial length to compensate for the refractive changes that occur in the anterior segment. A failure of the emmetropization process can result in either excessive or insufficient axial growth, leading to myopia or hyperopia, respectively. Emmetropization is mainly regulated by the retina, which generates two opposite signals: "GO/GROW" signals to increase axial growth and "STOP" signals to block it. The presence of GO/GROW and STOP signals was investigated by a proteomics analysis of the retinas from chicken with experimental myopia and hyperopia. Of 18 differentially expressed proteins that were identified, five displayed an expression profile corresponding to GO/GROW signals, and two corresponded to STOP signals. Western blotting confirmed that apolipoprotein A-I (apoA-I) has the characteristics of a STOP signal both in the retina as well as in the fibrous sclera. In accordance with this, intraocular application of the peroxisome proliferator-activated receptor alpha agonist GW7647 resulted in up-regulation of apoA-I levels and in a significant reduction of experimental myopia. In conclusion, using a comprehensive functional proteomics analysis of chicken ocular growth models we identified targets for ocular growth control. The correlation of elevated apoA-I levels with reduced ocular axial growth points toward a functional relationship with the observed morphological changes of the eye.