Imaging of the unstable plaque: how far have we got?

Rupture of unstable plaques may lead to myocardial infarction or stroke and is the leading cause of morbidity and mortality in western countries. Thus, there is a clear need for identifying these vulnerable plaques before the rupture occurs. Atherosclerotic plaques are a challenging imaging target as they are small and move rapidly, especially in the coronary tree. Many of the currently available imaging tools for clinical use still provide minimal information about the biological characteristics of plaques, because they are limited with respect to spatial and temporal resolution. Moreover, many of these imaging tools are invasive. The new generation of imaging modalities such as magnetic resonance imaging, nuclear imaging such as positron emission tomography and single photon emission computed tomography, computed tomography, fluorescence imaging, intravascular ultrasound, and optical coherence tomography offer opportunities to overcome some of these limitations. This review discusses the potential of these techniques for imaging the unstable plaque.

Off-resonance angiography: a new method to depict vessels--phantom and rabbit studies.

PURPOSE: To evaluate the utility of inversion recovery with on-resonant water suppression (IRON) in combination with injection of the long-circulating monocrystalline iron oxide nanoparticle (MION)-47 for contrast material-enhanced magnetic resonance (MR) angiography. MATERIALS AND METhods: Experiments were approved by the institutional animal care committee. Eleven rabbits were imaged at baseline before injection of a contrast agent and then serially 5-30 minutes, 2 hours, 1 day, and 3 days after a single intravenous bolus injection of 80 micromol of MION-47 per kilogram of body weight (n = 6) or 250 micromol/kg MION-47 (n = 5). Conventional T1-weighted MR angiography and IRON MR angiography were performed on a clinical 3.0-T imager. Signal-to-noise and contrast-to-noise ratios were measured in the aorta of rabbits in vivo. Venous blood was obtained from the rabbits before and after MION-47 injection for use in phantom studies. RESULTS: In vitro blood that contained MION-47 appeared signal attenuated on T1-weighted angiograms, while characteristic signal-enhanced dipolar fields were observed on IRON angiograms. In vivo, the vessel lumen was signal attenuated on T1-weighted MR angiograms after MION-47 injection, while IRON supported high intravascular contrast by simultaneously providing positive signal within the vessels and suppressing background tissue (mean contrast-to-noise ratio, 61.9 +/- 12.4 [standard deviation] after injection vs 1.1 +/- 0.4 at baseline, P < .001). Contrast-to-noise ratio was higher on IRON MR angiograms than on conventional T1-weighted MR angiograms (9.0 +/- 2.5, P < .001 vs IRON MR angiography) and persisted up to 24 hours after MION-47 injection (76.2 +/- 15.9, P < .001 vs baseline). CONCLUSION: IRON MR angiography in conjunction with superparamagnetic nanoparticle administration provides high intravascular contrast over a long time and without the need for image subtraction.

Validation of rotational thromboelastometry during cardiopulmonary bypass : a prospective, observational in-vivo study

Le ROTEM est un test de coagulation réalisable au près du malade qui permet d'objectiver la coagulopathie, de distinguer la contribution des différents éléments du système de coagulation et de cibler les produits procoagulants comme le plasma frais congelé (PFC), les plaquettes, le fibrinogène et les facteurs de coagulation purifiés ou les antifibrinolytiques. 3 des tests disponibles pour le ROTEM sont: EXTEM, INTEM, HEPTEM. Le premier test est stable sous hautes doses d'héparine alors que le deuxième est très sensible à sa présence. Dans le dernier test on rajoute de l'héparinase pour mettre en évidence l'éventuel effet résiduel de l'héparine en le comparant à l'INTEM. Idéalement, le ROTEM devrait être effectué avant la fin du bypass cardiopulmonaire (CEC), donc sous anticoagulation maximale pas héparine, afin de pouvoir administrer des produits pro¬coagulants dans les délais les plus brefs et ainsi limiter au maximum les pertes sanguines. En effet la commande et la préparation de certains produits procoagulants peut prendre plus d'une heure. Le but de cette étude est de valider l'utilisation du ROTEM en présence de hautes concentrations d'héparine. Il s'agit d'une étude observationnelle prospective sur 20 patients opérés électivement de pontages aorto-coronariens sous CEC. Méthode : l'analyse ROTEM a été réalisée avant l'administration d'héparine (TO), 10 minutes après l'administration d'héparine (Tl), à la fin de la CEC (T2) et 10 minutes après la neutralisation de l'anticoagulation avec la protamine (T3). L'état.d'héparinisation a été évalué par l'activité anti-Xa à T1,T2,T3. Résultats : Comparé à TO, la phase de polymérisation de la cascade de coagulation et l'interaction fibrine-plaquettes sont significativement détériorées par rapport à Tl pour les canaux EXTEM et HEPTEM. A T2 l'analyse EXTEM et INTEM sont comparables à celles de EXTEM et HEPTEM à T3. Conclusion: les hautes doses d'héparine utilisées induisent une coagulopathie qui reste stable durant toute la durée de la CEC et qui persiste même après la neutralisation de l'anticoagulation. Les mesures EXTEM et HEPTEM sont donc valides en présence de hautes concentrations d'héparine et peuvent être réalisés pendant la CEC avant l'administration de protamine.

Histoplasma capsulatum var. duboisii infection in a patient with AIDS: rapid diagnosis using polymerase chain reaction-sequencing.

We describe an original case of disseminated infection with Histoplasma capsulatum (Hc) var. duboisii in an African patient with AIDS who migrated to Switzerland. The diagnosis of histoplasmosis was suggested using direct examination of tissues and confirmed in 24 h with a panfungal polymerase chain reaction assay. The variety duboisii of Hc was established using DNA sequencing of the polymorphic genomic region OLE. Molecular tools allow diagnosis of histoplasmosis in 24 h, which is drastically shorter than culture procedures.

ESCMID* guideline for the diagnosis and management of Candida diseases 2012: diagnostic procedures.

As the mortality associated with invasive Candida infections remains high, it is important to make optimal use of available diagnostic tools to initiate antifungal therapy as early as possible and to select the most appropriate antifungal drug. A panel of experts of the European Fungal Infection Study Group (EFISG) of the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) undertook a data review and compiled guidelines for the clinical utility and accuracy of different diagnostic tests and procedures for detection of Candida infections. Recommendations about the microbiological investigation and detection of candidaemia, invasive candidiasis, chronic disseminated candidiasis, and oropharyngeal, oesophageal, and vaginal candidiasis were included. In addition, remarks about antifungal susceptibility testing and therapeutic drug monitoring were made.

Transcatheter aortic valve implantation (TAVI): state of the art techniques and future perspectives.

Transcatheter aortic valve therapies are the newest established techniques for the treatment of high risk patients affected by severe symptomatic aortic valve stenosis. The transapical approach requires a left anterolateral mini-thoracotomy, whereas the transfemoral method requires an adequate peripheral vascular access and can be performed fully percutaneously. Alternatively, the trans-subclavian access has been recently proposed as a third promising approach. Depending on the technique, the fine stent-valve positioning can be performed with or without contrast injections. The transapical echo-guided stent-valve implantation without angiography (the Lausanne technique) relies entirely on transoesophageal echocardiogramme imaging for the fine stent-valve positioning and it has been proved that this technique prevents the onset of postoperative contrast-related acute kidney failure. Recent published reports have shown good hospital outcomes and short-term results after transcatheter aortic valve implantation, but there are no proven advantages in using the transfemoral or the transapical technique. In particular, the transapical series have a higher mean logistic Euroscore of 27-35%, a procedural success rate above 95% and a mean 30-day mortality between 7.5 and 17.5%, whereas the transfemoral results show a lower logistic Euroscore of 23-25.5%, a procedural success rate above 90% and a 30-day mortality of 7-10.8%. Nevertheless, further clinical trials and long-term results are mandatory to confirm this positive trend. Future perspectives in transcatheter aortic valve therapies would be the development of intravascular devices for the ablation of the diseased valve leaflets and the launch of new stent-valves with improved haemodynamic, different sizes and smaller delivery systems.

Krypton laser photocoagulation induces retinal vascular remodeling rather than choroidal neovascularization.

The purpose of this study is to analyze the retina and choroid response following krypton laser photocoagulation. Ninety-two C57BL6/Sev129 and 32 C57BL/6J, 5-6-week-old mice received one single krypton (630 nm) laser lesion: 50 microm, 0.05 s, 400 mW. On the following day, every day thereafter for 1 week and every 2-3 days for the following 3 weeks, serial sections throughout the lesion were systematically collected and studied. Immunohistology using specific markers or antibodies for glial fibrillary acidic protein (GFAP) (astrocytes, glia and Muller's cells), von Willebrand (vW) (vascular endothelial cells), TUNEL (cells undergoing caspase dependent apoptosis), PCNA (proliferating cell nuclear antigen) p36, CD4 and F4/80 (infiltrating inflammatory and T cells), DAPI (cell nuclei) and routine histology were carried out. Laser confocal microscopy was also performed on flat mounts. Temporal and spatial observations of the created photocoagulation lesions demonstrate that, after a few hours, activated glial cells within the retinal path of the laser beam express GFAP. After 48 h, GFAP-positive staining was also detected within the choroid lesion center. "Movement" of this GFAP-positive expression towards the lasered choroid was preceded by a well-demarcated and localized apoptosis of the retina outer nuclear layer cells within the laser beam path. Later, death of retinal outer nuclear cells and layer thinning at this site was followed by evagination of the inner nuclear retinal layer. Funneling of the entire inner nuclear and the thinned outer nuclear layers into the choroid lesion center was accompanied by "dragging" of the retinal capillaries. Thus, from days 10 to 14 after krypton laser photocoagulation onward, well-formed blood capillaries (of retinal origin) were observed within the lesion. Only a few of the vW-positive capillary endothelial cells stained also for PCNA p36. In the choroid, dilatation of the vascular bed occurred at the vicinity of the photocoagulation site and around it. Confocal microscopy demonstrates that the vessels throughout the path lesion are located within the neuroretina while in the choroid (after separation of the neural retina) only GFAP-positive but no lectin-positive cells can be seen. The involvement of infiltrating inflammatory cells in these remodeling and healing processes remained minimal throughout the study period. During the 4 weeks following krypton laser photocoagulation in the mouse eye, processes of wound healing and remodeling appear to be driven by cells (and vessels) originating from the retina.

Allergo-immunologie. 1. Nouveautés dans le traitement des crises aiguës d'angioedème héréditaire [Allergy-immunology. New therapies for acute attacks in hereditary angioedema].

Hereditary angioedema is a disease which develops as a result of a deficiency or dysfonction of C1-inhibitor, a key regulator of the complement, coagulation and contact cascades, resulting among others in excessive release of bradykinin. This disease mortality rate is high in absence of immediate and effective treatment, in particular in presence of acute attacks of the upper respiratory tract (laryngeal edema). Until now only administration of a purified C1-inhibitor extract was effective against these symptoms. This paper aims to synthesise essentials knowledge concerning news drugs, in particular icatibant, a selective bradykinin B2- receptor antagonist whose use should be widened to the treatment of angioedema with ACE-inhibitors intolerance.

Sociedad de la información y del conocimiento: personas, tecnología y cambio social

La Humanidad siempre ha trasladado, almacenado y difundido información; en este sentido podríamos afirmar que la sociedad de la información es una característica de la sociedad humana. Lo que ha cambiado en los últimos años es fruto de la incorporación de nuevas tecnologías en el tratamiento de la información. La separación que, tradicionalmente, existía entre una época para aprender y una época para trabajar ha terminado. En un momento en que la información es tan caduca, lo que necesitan los ciudadanos no es tanto acumular información como saber obtener buena información. A todos los cambios hay que incorporar, además, el hecho de que las personas cada vez recibimos más información por medios audiovisuales que escritos. Esto conlleva también cambios en la forma de incorporar la información, de entenderla y producirla.

Feasibility of a knowledge translation CME program: courriels Cochrane.

INTRODUCTION: Systematic literature reviews provide best evidence, but are underused by clinicians. Thus, integrating Cochrane reviews into continuing medical education (CME) is challenging. We designed a pilot CME program where summaries of Cochrane reviews (Courriels Cochrane) were disseminated by e-mail. Program participants automatically received CME credit for each Courriel Cochrane they rated. The feasibility of this program is reported (delivery, participation, and participant evaluation). METHOD: We recruited French-speaking physicians through the Canadian Medical Association. Program delivery and participation were documented. Participants rated the informational value of Courriels Cochrane using the Information Assessment Method (IAM), which documented their reflective learning (relevance, cognitive impact, use for a patient, expected health benefits). IAM responses were aggregated and analyzed. RESULTS: The program was delivered as planned. Thirty Courriels Cochrane were delivered to 985 physicians, and 127 (12.9%) completed at least one IAM questionnaire. Out of 1109 Courriels Cochrane ratings, 973 (87.7%) conta-ined 1 or more types of positive cognitive impact, while 835 (75.3%) were clinically relevant. Participants reported the use of information for a patient and expected health benefits in 595 (53.7%) and 569 (51.3%) ratings, respectively. DISCUSSION: Program delivery required partnering with 5 organizations. Participants valued Courriels Cochrane. IAM ratings documented their reflective learning. The aggregation of IAM ratings documented 3 levels of CME outcomes: participation, learning, and performance. This evaluation study demonstrates the feasibility of the Courriels Cochrane as an approach to further disseminate Cochrane systematic literature reviews to clinicians and document self-reported knowledge translation associated with Cochrane reviews.

Structure-function characterization and optimization of a plant-derived antibacterial peptide.

Crushed seeds of the Moringa oleifera tree have been used traditionally as natural flocculants to clarify drinking water. We previously showed that one of the seed peptides mediates both the sedimentation of suspended particles such as bacterial cells and a direct bactericidal activity, raising the possibility that the two activities might be related. In this study, the conformational modeling of the peptide was coupled to a functional analysis of synthetic derivatives. This indicated that partly overlapping structural determinants mediate the sedimentation and antibacterial activities. Sedimentation requires a positively charged, glutamine-rich portion of the peptide that aggregates bacterial cells. The bactericidal activity was localized to a sequence prone to form a helix-loop-helix structural motif. Amino acid substitution showed that the bactericidal activity requires hydrophobic proline residues within the protruding loop. Vital dye staining indicated that treatment with peptides containing this motif results in bacterial membrane damage. Assembly of multiple copies of this structural motif into a branched peptide enhanced antibacterial activity, since low concentrations effectively kill bacteria such as Pseudomonas aeruginosa and Streptococcus pyogenes without displaying a toxic effect on human red blood cells. This study thus identifies a synthetic peptide with potent antibacterial activity against specific human pathogens. It also suggests partly distinct molecular mechanisms for each activity. Sedimentation may result from coupled flocculation and coagulation effects, while the bactericidal activity would require bacterial membrane destabilization by a hydrophobic loop.

Haemophilia registry of the Medical Committee of the Swiss Hemophilia Society. Update and annual survey 2010-2011.

The Haemophilia Registry of the Swiss Haemophilia Society was created in the year 2000. The latest records from October 31st 2011 are presented here. Included are all patients with haemophilia A or B and other inherited coagulation disorders (including VWD patients with R-Co activity below 10%) known and followed by the 11 paediatric and 12 adult haemophilia treatment or reference centers. Currently there are 950 patients registered, the majority of which (585) having haemophilia A. Disease severity is graded according to ISTH criteria and its distribution between mild, moderate and severe haemophilia is similar to data from other European and American registries. The majority (about two thirds) of Swiss patients with haemophilia A or B are treated on-demand, with only about 20% of patients being on prophylaxis. The figure is different in paediatrics and young adults (1st and 2nd decades), where 80 to 90% of patients with haemophilia A are under regular prophylaxis. Interestingly enough, use of factor concentrates, although readily available, is rather low in Switzerland, especially when taking the country's GDP into account: The total amount of factor VIII and IX was 4.94 U pro capita, comparable to other European countries with distinctly lower incomes (Poland, Slovakia, Hungary). This finding is mainly due to the afore mentioned low rate of prophylactic treatment of haemophilia in our country. Our registry remains an important instrument of quality control of haemophilia therapy in Switzerland.

Consultoria del procés de logística interna del laboratori d'anàlisis clíniques a l'Hospital General de Vic

Com a resultat de les politiques i estratègies de col·laboració entre la universitat de Vic i de l’hospital i de la voluntat de realitzar activitats formatives conjuntes , s’estableix un línia de treball orientada a l’estudi i anàlisi de la situació logística interna actual del laboratori d’anàlisis clíniques de l’Hospital General de Vic. El treball es centra en el procés intern del laboratori i l’abast de l’estudi es troba limitat a les àrees especifiques d’hematologia i coagulació i bioquímica. D’aquestes dues àrees el treball realitza un estudi exhaustiu del seu procés intern, identifica les seves activitats i la seva metodologia de treball amb l’objectiu d’elaborar el Value Stream Map de cadascuna de les àrees. Les àrees de Microbiologia, Banc de Sang i Urgències resten fora d’aquest estudi exhaustiu tot i que són presents en el treball per la inevitable interacció que tenen en la globalitat del procés. El treball es centra bàsicament en els processos automatitzats tot i que els processos que es duen a terme en el laboratori són tant automatitzats com manuals. També es limita al sistema productiu intern del laboratori tot i la interacció que té aquest sistema intern amb altres centres productius del sistema com ara són els centres d’atenció primària, els diversos hospitals i centres d’atenció sociosanitària. El laboratori es troba immers en el moment de l’elaboració d’aquest treball en un situació de canvi i millora del seus processos interns que consisteixen principalment en la substitució de part la maquinària actual que obliguen a la definició d’un nou layout i d’una nova distribució de la producció a cada màquina. A nivell extern també s’estan produint millores en el sistema informàtic de gestió que afecten a part del seu procés. L’objectiu del treball és donar visibilitat total al procés de logística interna actual del laboratori, identificant clarament com són i quina seqüència tenen els processos logístics interns i els mètodes de treball actuals, tant de recursos màquina com recursos persona, per poder identificar sota una perspectiva de generació de valor, aquells punts concrets de la logística interna que poden ser millorats en quant a eficiència i productivitat amb l’objectiu que un cop identificats es puguin emprendre accions i/o projectes de millora. El treball finalitza amb un anàlisis final del procés logística interna des d’una òptica Lean. Per fer-ho, identifica aquelles activitats que no aporten valor al procés o MUDA i les classifica en set categories i es realitzen diverses propostes de millora com són la implantació d’un flux continu , anivellat i basat en un concepte pull , identifica activitats que poden ser estandarditzades i/o simplificades i proposa modificacions en les infraestructures físiques per donar major visibilitat al procés. L’aspecte humà del procés es planteja des d’un punt de vist de metodologia, formació, comunicació i aplicació de les 5S.

Apport de l'angiographie au vert d'indocyanine (ICG) dans la localisation des néovascularisations chororoidiennes occultes [Value of indocyanine green angiography in localization of occult choroid neovascularization]

PURPOSE: To determine the role of Indocyanin Green (ICG) angiography in localizing occult new vessels associated with age-related macular degeneration (ARMD) and assess the possibilities of ICG guided laser photocoagulations. PATIENTS AND METHODS: Fluorescein and ICG angiographies (IMAGEnet system) of 62 patients with occult new vessels (ONV), serous (SPED) or vascular (VPED) pigment epithelium detachment have been studied. RESULTS: Based on fondoscopic examination and fluorescein angiography, 43 eyes (69%) disclosed ONV, 8 (13%) SPED and 11 (18%) VPED. Choroidal neovascularisation was confirmed by ICG angiography in 37 ONV cases (86%), in 8 (72%) VPED cases, but in no SPED. Conversion of ONV in classical neovascular membranes was possible in 19 ONV cases (44%) and in 6 (54%) VPED cases, making a laser photocoagulation possible in 9 eyes (36%). CONCLUSION: ICG angiography plays an important role in the evaluation, classification and laser treatment of patients with ONV secondary to ARMD.