The DIAD Approach to Correlative Synchrotron X-ray Imaging and Diffraction Analysis of Human Enamel.

The Dual Imaging and Diffraction (DIAD) beamline at Diamond Light Source (Didcot, U.K.) implements a correlative approach to the dynamic study of materials based on concurrent analysis of identical sample locations using complementary X-ray modalities to reveal structural detail at various length scales. Namely, the underlying beamline principle and its practical implementation allow the collocation of chosen regions within the sample and their interrogation using real-space imaging (radiography and tomography) and reciprocal space scattering (diffraction). The switching between the two principal modes is made smooth and rapid by design, so that the data collected is interlaced to obtain near-simultaneous multimodal characterization. Different specific photon energies are used for each mode, and the interlacing of acquisition steps allows conducting static and dynamic experiments. Building on the demonstrated realization of this state-of-the-art approach requires further refining of the experimental practice, namely, the methods for gauge volume collocation under different modes of beam-sample interaction. To address this challenge, experiments were conducted at DIAD devoted to the study of human dental enamel, a hierarchical structure composed of hydroxyapatite mineral nanocrystals, as a static sample previously affected by dental caries (tooth decay) as well as under dynamic conditions simulating the process of acid demineralization. Collocation and correlation were achieved between WAXS (wide-angle X-ray scattering), 2D (radiographic), and 3D (tomographic) imaging. While X-ray imaging in 2D or 3D modes reveals real-space details of the sample microstructure, X-ray scattering data for each gauge volume provided statistical nanoscale and ultrastructural polycrystal reciprocal-space information such as phase and preferred orientation (texture). Careful registration of the gauge volume positions recorded during the scans allowed direct covisualization of the data from two modalities. Diffraction gauge volumes were identified and visualized within the tomographic data sets, revealing the underlying local information to support the interpretation of the diffraction patterns. The present implementation of the 4D microscopy paradigm allowed following the progression of demineralization and its correlation with time-dependent WAXS pattern evolution in an approach that is transferable to other material systems.

Advanced Time-Stepping Interpretation of Fly-Scan Continuous Rotation Synchrotron Tomography of Dental Enamel Demineralization.

High-resolution spatial and temporal analysis and 3D visualization of time-dependent processes, such as human dental enamel acid demineralization, often present a challenging task. Overcoming this challenge often requires the development of special methods. Dental caries remains one of the most important oral diseases that involves the demineralization of hard dental tissues as a consequence of acid production by oral bacteria. Enamel has a hierarchically organized architecture that extends down to the nanostructural level and requires high resolution to study its evolution in detail. Enamel demineralization is a dynamic process that is best investigated with the help of in situ experiments. In previous studies, synchrotron tomography was applied to study the 3D enamel structure at certain time points (time-lapse tomography). Here, another distinct approach to time-evolving tomography studies is presented, whereby the sample image is reconstructed as it undergoes continuous rotation over a virtually unlimited angular range. The resulting (single) data set contains the data for multiple (potentially overlapping) intermediate tomograms that can be extracted and analyzed as desired using time-stepping selection of data subsets from the continuous fly-scan recording. One of the advantages of this approach is that it reduces the amount of time required to collect an equivalent number of single tomograms. Another advantage is that the nominal time step between successive reconstructions can be significantly reduced. We applied this approach to the study of acidic enamel demineralization and observed the progression of demineralization over time steps significantly smaller than the total acquisition time of a single tomogram, with a voxel size smaller than 0.5 µm. It is expected that the approach presented in this paper can be useful for high-resolution studies of other dynamic processes and for assessing small structural modifications in evolving hierarchical materials.

Multi-resolution Correlative Ultrastructural and Chemical Analysis of Carious Enamel by Scanning Microscopy and Tomographic Imaging.

Caries, a major global disease associated with dental enamel demineralization, remains insufficiently understood to devise effective prevention or minimally invasive treatment. Understanding the ultrastructural changes in enamel is hampered by a lack of nanoscale characterization of the chemical spatial distributions within the dental tissue. This leads to the requirement to develop techniques based on various characterization methods. The purpose of the present study is to demonstrate the strength of analytic methods using a correlative technique on a single sample of human dental enamel as a specific case study to test the accuracy of techniques to compare regions in enamel. The science of the different techniques is integrated to genuinely study the enamel. The hierarchical structures within carious tissue were mapped using the combination of focused ion beam scanning electron microscopy with synchrotron X-ray tomography. The chemical changes were studied using scanning X-ray fluorescence (XRF) and X-ray wide-angle and small-angle scattering using a beam size below 80 nm for ångström and nanometer length scales. The analysis of XRF intensity gradients revealed subtle variations of Ca intensity in carious samples in comparison with those of normal mature enamel. In addition, the pathways for enamel rod demineralization were studied using X-ray ptychography. The results show the chemical and structural modification in carious enamel with differing locations. These results reinforce the need for multi-modal approaches to nanoscale analysis in complex hierarchically structured materials to interpret the changes of materials. The approach establishes a meticulous correlative characterization platform for the analysis of biomineralized tissues at the nanoscale, which adds confidence in the interpretation of the results and time-saving imaging techniques. The protocol demonstrated here using the dental tissue sample can be applied to other samples for statistical study and the investigation of nanoscale structural changes. The information gathered from the combination of methods could not be obtained with traditional individual techniques.

Time-Lapse In Situ 3D Imaging Analysis of Human Enamel Demineralisation Using X-ray Synchrotron Tomography.

Caries is a chronic disease that causes the alteration of the structure of dental tissues by acid dissolution (in enamel, dentine and cementum) and proteolytic degradation (dentine and cementum) and generates an important cost of care. There is a need to visualise and characterise the acid dissolution process on enamel due to its hierarchical structure leading to complex structural modifications. The process starts at the enamel surface and progresses into depth, which necessitates the study of the internal enamel structure. Artificial demineralisation is usually employed to simulate the process experimentally. In the present study, the demineralisation of human enamel was studied using surface analysis carried out with atomic force microscopy as well as 3D internal analysis using synchrotron X-ray tomography during acid exposure with repeated scans to generate a time-lapse visualisation sequence. Two-dimensional analysis from projections and virtual slices and 3D analysis of the enamel mass provided details of tissue changes at the level of the rods and inter-rod substance. In addition to the visualisation of structural modifications, the rate of dissolution was determined, which demonstrated the feasibility and usefulness of these techniques. The temporal analysis of enamel demineralisation is not limited to dissolution and can be applied to other experimental conditions for the analysis of treated enamel or remineralisation.

Synchrotron X-ray Studies of the Structural and Functional Hierarchies in Mineralised Human Dental Enamel: A State-of-the-Art Review.

Hard dental tissues possess a complex hierarchical structure that is particularly evident in enamel, the most mineralised substance in the human body. Its complex and interlinked organisation at the Ångstrom (crystal lattice), nano-, micro-, and macro-scales is the result of evolutionary optimisation for mechanical and functional performance: hardness and stiffness, fracture toughness, thermal, and chemical resistance. Understanding the physical-chemical-structural relationships at each scale requires the application of appropriately sensitive and resolving probes. Synchrotron X-ray techniques offer the possibility to progress significantly beyond the capabilities of conventional laboratory instruments, i.e., X-ray diffractometers, and electron and atomic force microscopes. The last few decades have witnessed the accumulation of results obtained from X-ray scattering (diffraction), spectroscopy (including polarisation analysis), and imaging (including ptychography and tomography). The current article presents a multi-disciplinary review of nearly 40 years of discoveries and advancements, primarily pertaining to the study of enamel and its demineralisation (caries), but also linked to the investigations of other mineralised tissues such as dentine, bone, etc. The modelling approaches informed by these observations are also overviewed. The strategic aim of the present review was to identify and evaluate prospective avenues for analysing dental tissues and developing treatments and prophylaxis for improved dental health.

Increased connectivity of hiPSC-derived neural networks in multiphase granular hydrogel scaffolds.

To reflect human development, it is critical to create a substrate that can support long-term cell survival, differentiation, and maturation. Hydrogels are promising materials for 3D cultures. However, a bulk structure consisting of dense polymer networks often leads to suboptimal microenvironments that impedes nutrient exchange and cell-to-cell interaction. Herein, granular hydrogel-based scaffolds were used to support 3D human induced pluripotent stem cell (hiPSC)-derived neural networks. A custom designed 3D printed toolset was developed to extrude hyaluronic acid hydrogel through a porous nylon fabric to generate hydrogel granules. Cells and hydrogel granules were combined using a weaker secondary gelation step, forming self-supporting cell laden scaffolds. At three and seven days, granular scaffolds supported higher cell viability compared to bulk hydrogels, whereas granular scaffolds supported more neurite bearing cells and longer neurite extensions (65.52 ± 11.59 µm) after seven days compared to bulk hydrogels (22.90 ± 4.70 µm). Long-term (three-month) cultures of clinically relevant hiPSC-derived neural cells in granular hydrogels supported well established neuronal and astrocytic colonies and a high level of neurite extension both inside and beyond the scaffold. This approach is significant as it provides a simple, rapid and efficient way to achieve a tissue-relevant granular structure within hydrogel cultures.

Finite Element Modelling and Experimental Validation of the Enamel Demineralisation Process at the Rod Level.

In the past years, a significant amount of effort has been directed at the observation and characterisation of caries using experimental techniques. Nevertheless, relatively little progress has been made in numerical modelling of the underlying demineralisation process. The present study is the first attempt to provide a simplified calculation framework for the numerical simulation of the demineralisation process at the length scale of enamel rods and its validation by comparing the data with statistical analysis of experimental results. FEM model was employed to simulate a time-dependent reaction-diffusion equation process in which H ions diffuse and cause demineralisation of the enamel. The local orientation of the hydroxyapatite crystals was taken into account. Experimental analysis of the demineralising front was performed using advanced high-resolution synchrotron X-ray micro-Computed Tomography. Further experimental investigations were conducted by means of SEM and STEM imaging techniques. Besides establishing and validating the new modelling framework, insights into the role of the etchant solution pH level were obtained. Additionally, some light was shed on the origin of different types of etching patterns by simulating the demineralisation process at different etching angles of attack. The implications of this study pave the way for simulations of enamel demineralisation within different complex scenarios and across the range of length scales. Indeed, the framework proposed can incorporate the presence of chemical species other than H ions and their diffusion and reaction leading to dissolution and re-precipitation of hydroxyapatite. It is the authors' hope and aspiration that ultimately this work will help identify new ways of controlling and preventing caries.

On the Structural Peculiarities of Self-Reinforced Composite Materials Based on UHMWPE Fibers.

The structure of self-reinforced composites (SRCs) based on ultra-high molecular weight polyethylene (UHMWPE) was studied by means of Wide-Angle X-ray Scattering (WAXS), X-ray tomography, Raman spectroscopy, Scanning Electron Microscopy (SEM) and in situ tensile testing in combination with advanced processing tools to determine the correlation between the processing conditions, on one hand, and the molecular structure and mechanical properties, on the other. SRCs were fabricated by hot compaction of UHMWPE fibers at different pressure and temperature combinations without addition of polymer matrix or softener. It was found by WAXS that higher compaction temperatures led to more extensive melting of fibers with the corresponding reduction of the Herman's factor reflecting the degree of molecular orientation, while the increase of hot compaction pressure suppressed the melting of fibers within SRCs at a given temperature. X-ray tomography proved the absence of porosity while polarized light Raman spectroscopy measurements for both longitudinal and perpendicular fiber orientations showed qualitatively the anisotropy of SRC samples. SEM revealed that the matrix was formed by interlayers of molten polymer entrapped between fibers in SRCs. Moreover, in situ tensile tests demonstrated the increase of Young's modulus and tensile strength with increasing temperature.

Acid-induced demineralisation of human enamel as a function of time and pH observed using X-ray and polarised light imaging.

Acid-induced enamel demineralisation affects many individuals either by exposure to acidic diets, acidic gas pollution (dental erosion) or to dental plaque acids (dental caries). This study aimed to develop in situ X-ray and light imaging methods to determine progression of enamel demineralisation and the dynamic relationship between acid pH and mineral density. Hourly digital microradiograph time-lapse sequences showed the depth of enamel demineralisation in 500 µm thick sections progressed with time from the surface towards the dentine following a power-law function, which was 21% faster than the lateral demineralisation progression after exposure for 85 h to lactic acid (10%, pH 2.2). The minimum greyscale remaining (mineral content) within the induced enamel lesion followed an exponential decay, while the accumulated total greyscale loss with time was linear, which showed a constant anisotropic mineral release within the enamel architecture. This 85 h demineralisation method studied by polarised light microscopy time-lapse sequences showed that once the demineralisation front reached the enamel Hunter-Schreger bands, there was preferential demineralisation along those bands. Mineral density loss was linear with increasing pH acidity between pH 5.2 and pH 4.0 (with 0.4 pH increments) when incubated over a 3-week period exposed to 0.5% lactic acid. At pH 4.0, there was complete mineral loss in the centre of the demineralised area after the 3-week period and the linear function intercepted the x-axis at ~ pH 5.5, near the critical pH for hydroxyapatite (HAp). These observations showed how intrinsic enamel structure and pH affected the progression of demineralisation. STATEMENT OF SIGNIFICANCE: Hydroxyapatite crystallites (HAp) in human enamel dissolve when exposed to an acidic environment but little is known about how the intrinsic structures in enamel and pH influence the demineralisation kinetics. We have developed a time-lapse in situ microradiography method to quantify microscopic anisotropic mineral loss dynamics in response to an acid-only caries model. Correlation with polarised light microscopy time-lapse sequences showed that larger structures in enamel also influence demineralisation progression as demineralisation occurred preferentially along the Hunter-Schreger bands (decussating prismatic enamel). The pH-controlled enamel mineral release in a linear manner quantifying the relationship between HAp orientation and acid solubility. These findings should direct the development of improved anti-demineralisation/ remineralisation treatments to retain/ restore the natural intrinsic enamel structure.

Multi-Scale Digital Image Correlation Analysis of In Situ Deformation of Open-Cell Porous Ultra-High Molecular Weight Polyethylene Foam.

Porous ultra-high molecular weight polyethylene (UHMWPE) is a high-performance bioinert polymer used in cranio-facial reconstructive surgery in procedures where relatively low mechanical stresses arise. As an alternative to much stiffer and more costly polyether-ether-ketone (PEEK) polymer, UHMWPE is finding further wide applications in hierarchically structured hybrids for advanced implants mimicking cartilage, cortical and trabecular bone tissues within a single component. The mechanical behaviour of open-cell UHMWPE sponges obtained through sacrificial desalination of hot compression-moulded UHMWPE-NaCl powder mixtures shows a complex dependence on the fabrication parameters and microstructural features. In particular, similarly to other porous media, it displays significant inhomogeneity of strain that readily localises within deformation bands that govern the overall response. In this article, we report advances in the development of accurate experimental techniques for operando studies of the structure-performance relationship applied to the porous UHMWPE medium with pore sizes of about 250 µm that are most well-suited for live cell proliferation and fast vascularization of implants. Samples of UHMWPE sponges were subjected to in situ compression using a micromechanical testing device within Scanning Electron Microscope (SEM) chamber, allowing the acquisition of high-resolution image sequences for Digital Image Correlation (DIC) analysis. Special masking and image processing algorithms were developed and applied to reveal the evolution of pore size and aspect ratio. Key structural evolution and deformation localisation phenomena were identified at both macro- and micro-structural levels in the elastic and plastic regimes. The motion of pore walls was quantitatively described, and the presence and influence of strain localisation zones were revealed and analysed using DIC technique.

Synchrotron X-ray Scattering Analysis of Nylon-12 Crystallisation Variation Depending on 3D Printing Conditions.

Nylon-12 is an important structural polymer in wide use in the form of fibres and bulk structures. Fused filament fabrication (FFF) is an extrusion-based additive manufacturing (AM) method for rapid prototyping and final product manufacturing of thermoplastic polymer objects. The resultant microstructure of FFF-produced samples is strongly affected by the cooling rates and thermal gradients experienced across the part. The crystallisation behaviour during cooling and solidification influences the micro- and nano-structure, and deserves detailed investigation. A commercial Nylon-12 filament and FFF-produced Nylon-12 parts were studied by differential scanning calorimetry (DSC) and wide-angle X-ray scattering (WAXS) to examine the effect of cooling rates under non-isothermal crystallisation conditions on the microstructure and properties. Slower cooling rates caused more perfect crystallite formation, as well as alteration to the thermal properties.

Usefulness of Routine Fractional Flow Reserve for Clinical Management of Coronary Artery Disease in Patients With Diabetes.

Importance: Approximately one-third of patients considered for coronary revascularization have diabetes, which is a major determinant of clinical outcomes, often influencing the choice of the revascularization strategy. The usefulness of fractional flow reserve (FFR) to guide treatment in this population is understudied and has been questioned. Objective: To evaluate the usefulness and rate of major adverse cardiovascular events (MACE) of integrating FFR in management decisions for patients with diabetes who undergo coronary angiography. Design, Setting, and Participants: This cross-sectional study used data from the PRIME-FFR study derived from the merger of the POST-IT study (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease [March 2012-November 2013]) and R3F study (French Study of FFR Integrated Multicenter Registries Implementation of FFR in Routine Practice [October 2008-June 2010]), 2 prospective multicenter registries that shared a common design. A population of all-comers for whom angiography disclosed ambiguous lesions was analyzed for rates, patterns, and outcomes associated with management reclassification, including revascularization deferral, in patients with vs without diabetes. Data analysis was performed from June to August 2018. Main Outcomes and Measures: Death from any cause, myocardial infarction, or unplanned revascularization (MACE) at 1 year. Results: Among 1983 patients (1503 [77%] male; mean [SD] age, 65 [10] years), 701 had diabetes, and FFR was performed for 1.4 lesions per patient (58.2% of lesions in the left anterior descending artery; mean [SD] stenosis, 56% [11%]; mean [SD] FFR, 0.81 [0.01]). Reclassification by FFR was high and similar in patients with and without diabetes (41.2% vs 37.5%, P = .13), but reclassification from medical treatment to revascularization was more frequent in the former (142 of 342 [41.5%] vs 230 of 730 [31.5%], P = .001). There was no statistical difference between the 1-year rates of MACE in reclassified (9.7%) and nonreclassified patients (12.0%) (P = .37). Among patients with diabetes, FFR-based deferral identified patients with a lower risk of MACE at 12 months (25 of 296 [8.4%]) compared with those undergoing revascularization (47 of 257 [13.1%]) (P = .04), and the rate was of the same magnitude of the observed rate among deferred patients without diabetes (7.9%, P = .87). Status of insulin treatment had no association with outcomes. Patients (6.6% of the population) in whom FFR was disregarded had the highest MACE rates regardless of diabetes status. Conclusions and Relevance: Routine integration of FFR for the management of coronary artery disease in patients with diabetes may be associated with a high rate of treatment reclassification. Management strategies guided by FFR, including revascularization deferral, may be useful for patients with diabetes.

Fabrication of Hemin-Doped Serum Albumin-Based Fibrous Scaffolds for Neural Tissue Engineering Applications.

Neural tissue engineering (TE) represents a promising new avenue of therapy to support nerve recovery and regeneration. To recreate the complex environment in which neurons develop and mature, the ideal biomaterials for neural TE require a number of properties and capabilities including the appropriate biochemical and physical cues to adsorb and release specific growth factors. Here, we present neural TE constructs based on electrospun serum albumin (SA) fibrous scaffolds. We doped our SA scaffolds with an iron-containing porphyrin, hemin, to confer conductivity, and then functionalized them with different recombinant proteins and growth factors to ensure cell attachment and proliferation. We demonstrated the potential for these constructs combining topographical, biochemical, and electrical stimuli by testing them with clinically relevant neural populations derived from human induced pluripotent stem cells (hiPSCs). Our scaffolds could support the attachment, proliferation, and neuronal differentiation of hiPSC-derived neural stem cells (NSCs), and were also able to incorporate active growth factors and release them over time, which modified the behavior of cultured cells and substituted the need for growth factor supplementation by media change. Electrical stimulation on the doped SA scaffold positively influenced the maturation of neuronal populations, with neurons exhibiting more branched neurites compared to controls. Through promotion of cell proliferation, differentiation, and neurite branching of hiPSC-derived NSCs, these conductive SA fibrous scaffolds are of broad application in nerve regeneration strategies.

Impact of Routine Fractional Flow Reserve on Management Decision and 1-Year Clinical Outcome of Patients With Acute Coronary Syndromes: PRIME-FFR (Insights From the POST-IT [Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease] and R3F [French FFR Registry] Integrated Multicenter Registries - Implementation of FFR [Fractional Flow Reserve] in Routine Practice).

BACKGROUND: Fractional flow reserve (FFR) is not firmly established as a guide to treatment in patients with acute coronary syndromes (ACS). Primary goals were to evaluate the impact of integrating FFR on management decisions and on clinical outcome of patients with ACS undergoing coronary angiography, as compared with patients with stable coronary artery disease. METHODS AND RESULTS: R3F (French FFR Registry) and POST-IT (Portuguese Study on the Evaluation of FFR-Guided Treatment of Coronary Disease), sharing a common design, were pooled as PRIME-FFR (Insights From the POST-IT and R3F Integrated Multicenter Registries - Implementation of FFR in Routine Practice). Investigators prospectively defined management strategy based on angiography before performing FFR. Final decision after FFR and 1-year clinical outcome were recorded. From 1983 patients, in whom FFR was prospectively used to guide treatment, 533 sustained ACS (excluding acute ST-segment-elevation myocardial infarction). In ACS, FFR was performed in 1.4 lesions per patient, mostly in left anterior descending (58%), with a mean percent stenosis of 58±12% and a mean FFR of 0.82±0.09. In patients with ACS, reclassification by FFR was high and similar to those with non-ACS (38% versus 39%; P=NS). The pattern of reclassification was different, however, with less patients with ACS reclassified from revascularization to medical treatment compared with those with non-ACS (P=0.01). In ACS, 1-year outcome of patients reclassified based on FFR (FFR against angiography) was as good as that of nonreclassified patients (FFR concordant with angiography), with no difference in major cardiovascular event (8.0% versus 11.6%; P=0.20) or symptoms (92.3% versus 94.8% angina free; P=0.25). Moreover, FFR-based deferral to medical treatment was as safe in patients with ACS as in patients with non-ACS (major cardiovascular event, 8.0% versus 8.5%; P=0.83; revascularization, 3.8% versus 5.9%; P=0.24; and freedom from angina, 93.6% versus 90.2%; P=0.35). These findings were confirmed in ACS explored at the culprit lesion. In patients (6%) in whom the information derived from FFR was disregarded, a dire outcome was observed. CONCLUSIONS: Routine integration of FFR into the decision-making process of ACS patients with obstructive coronary artery disease is associated with a high reclassification rate of treatment (38%). A management strategy guided by FFR, divergent from that suggested by angiography, including revascularization deferral, is safe in ACS.

Primary angioplasty: Effect of deferred stenting on stent size.

BACKGROUND: Primary angioplasty with immediate stenting (IS) is the gold standard for ST-segment elevation myocardial infarction (STEMI). Deferred stenting (DS) has been proposed to limit periprocedural complications, and may influence stent size because of thrombus and spasm alleviation. AIM: We sought to study the effect of DS on stent size. METHODS: Over the study period, 258 patients underwent primary angioplasty for STEMI (DS, n=84; IS, n=174). An informative coronary angiogram run - i.e. allowing for proper lesion analysis - was selected and anonymized by an independent operator. Two experienced operators randomly analysed these runs, and proposed stent dimensions after having measured vessel diameter and lesion length by quantitative coronary analysis. The primary objective was the variation in stent size between the two coronary angiograms. RESULTS: The median delay between the two coronary angiograms was 2 days. Overall, the stent length was shorter (-1.64mm; P=0.030) and its diameter was larger (+0.13mm; P<0.001) during the second coronary angiogram, especially in the right coronary arteries. CONCLUSIONS: DS led to the implantation of a larger and shorter stent; this is probably because DS allows for more accurate assessment of the residual lesion after relief of spasm and thrombus, and may have clinical consequences in terms of stent thrombosis and restenosis.

Deferred vs immediate stenting in ST elevation myocardial infarction: Potential interest in selected patients.

BACKGROUND: Slow flow, no reflow and distal embolization often occur during primary angioplasty in ST segment elevation myocardial infarction (STEMI), compromising optimal myocardial reperfusion. AIMS: This study aimed at assessing the impact of deferred stenting (DS) on periprocedural events as compared to immediate stenting (IS). The second objective was to gather the reasons advocated by the physicians for deferring stenting. METHODS: All consecutive patients referred for primary angioplasty were included between September 2010 and November 2011. Physicians were free to choose the strategy between DS and IS but had to justify their choice. DS patients underwent a coronary angiogram control in a delay > 24h. RESULTS: Ninety-eight patients were included. Forty patients underwent DS and 58 IS. DS strategy involved thrombus management by thromboaspiration (33 patients 82.5%) and by the use of AntiGpIIbIIIa (23 patients 62.2%). This strategy could be achieved with a low complication rate. In particular, one patient had a reocclusion leading to a rapid reintervention and one had a distal embolization. In comparison, 11 periprocedural events occurred in the IS subgroup. In addition, among DS patients, 7 were treated medically because of a non-significant stenosis. The major criteria considered by the operator to prefer DS in the presence of a TIMI 3 flow concerned thrombotic load. CONCLUSION: This mono-centric experience confirmed the feasibility and the safety of DS. On top of reducing periprocedural events, it may allow for other treatment options in selected STEMI patients, e.g. surgery or medical treatment. The reasons leading physicians to choose DS were large thrombus burden on top of resolution of chest pain and normalization of the ECG. These criteria could help selecting situations in which DS may be of particular value as compared to IS.

Outcome impact of coronary revascularization strategy reclassification with fractional flow reserve at time of diagnostic angiography: insights from a large French multicenter fractional flow reserve registry.

BACKGROUND: There is no large report of the impact of fractional flow reserve (FFR) on the reclassification of the coronary revascularization strategy on individual patients referred for diagnostic angiography. METHODS AND RESULTS: The Registre Français de la FFR (R3F) investigated 1075 consecutive patients undergoing diagnostic angiography including an FFR investigation at 20 French centers. Investigators were asked to define prospectively their revascularization strategy a priori based on angiography before performing the FFR. The final revascularization strategy, reclassification of the strategy by FFR, and 1-year clinical follow-up were prospectively recorded. The strategy a priori based on angiography was medical therapy in 55% and revascularization in 45% (percutaneous coronary intervention, 38%; coronary artery bypass surgery, 7%). Patients were treated according to FFR in 1028/1075 (95.7%). The applied strategy after FFR was medical therapy in 58% and revascularization in 42% (percutaneous coronary intervention, 32%; coronary artery bypass surgery, 10%). The final strategy applied differed from the strategy a priori in 43% of cases: in 33% of a priori medical patients, in 56% of patients undergoing a priori percutaneous coronary intervention, and in 51% of patients undergoing a priori coronary artery bypass surgery. In reclassified patients treated based on FFR and in disagreement with the angiography-based a priori decision (n=464), the 1-year outcome (major cardiac event, 11.2%) was as good as in patients in whom final applied strategy concurred with the angiography-based a priori decision (n=611; major cardiac event, 11.9%; log-rank, P=0.78). At 1 year, >93% patients were asymptomatic without difference between reclassified and nonreclassified patients (Generalized Linear Mixed Model, P=0.75). Reclassification safety was preserved in high-risk patients. CONCLUSION: This study shows that performing FFR during diagnostic angiography is associated with reclassification of the revascularization decision in about half of the patients. It further demonstrates that it is safe to pursue a revascularization strategy divergent from that suggested by angiography but guided by FFR.

An uncommon presentation of acute type A aortic dissection: left main coronary artery obstruction.

Acute aortic dissection presents with a wide range of manifestations. Sometimes an acute coronary syndrome is diagnosed instead of aortic dissection leading to inappropriate treatment. We describe a case of acute aortic dissection with the uncommon involvement of the left main coronary artery. A 64-year-old man was referred to our hospital for primary coronary intervention because ECG demonstrated ST elevation in the aVR lead with diffuse ST-segment depression. Coronary angiography was performed to treat the culprit lesion but the left main coronary artery could not be catheterized. Aortography and transesophageal echocardiography confirmed Stanford type A aortic dissection. The patient died of cardiac arrest in spite of cardiopulmonary resuscitation. This case also illustrates how Stanford type A aortic dissection can present with left main coronary artery obstruction.

Relation between respiratory variations in pulse oximetry plethysmographic waveform amplitude and arterial pulse pressure in ventilated patients.

INTRODUCTION: Respiratory variation in arterial pulse pressure is a reliable predictor of fluid responsiveness in mechanically ventilated patients with circulatory failure. The main limitation of this method is that it requires an invasive arterial catheter. Both arterial and pulse oximetry plethysmographic waveforms depend on stroke volume. We conducted a prospective study to evaluate the relationship between respiratory variation in arterial pulse pressure and respiratory variation in pulse oximetry plethysmographic (POP) waveform amplitude. METHOD: This prospective clinical investigation was conducted in 22 mechanically ventilated patients. Respiratory variation in arterial pulse pressure and respiratory variation in POP waveform amplitude were recorded simultaneously in a beat-to-beat evaluation, and were compared using a Spearman correlation test and a Bland-Altman analysis. RESULTS: There was a strong correlation (r2 = 0.83; P < 0.001) and a good agreement (bias = 0.8 +/- 3.5%) between respiratory variation in arterial pulse pressure and respiratory variation in POP waveform amplitude. A respiratory variation in POP waveform amplitude value above 15% allowed discrimination between patients with respiratory variation in arterial pulse pressure above 13% and those with variation of 13% or less (positive predictive value 100%). CONCLUSION: Respiratory variation in arterial pulse pressure above 13% can be accurately predicted by a respiratory variation in POP waveform amplitude above 15%. This index has potential applications in patients who are not instrumented with an intra-arterial catheter.