The percutaneous assessment of regional and acute coronary hot unstable plaques by thermographic evaluation (PARACHUTE) study: A prospective reproducibility and prognostic clinical study using thermography to predict future ischemic cardiac events

Intravascular thermography is currently being considered as a valuable tool in assessing macrophage-rich plaques. Since it is unknown what the prognostic value is of non-obstructive atherosclerotic plaques showing temperature heterogeneity, we designed the PARACHUTE study, a prospective, reproducibility, and prognostic clinical study using thermography in patients presenting with an unstable coronary syndrome. The primary endpoint of the study is the predictive value of temperature heterogeneity towards the occurrence of ischemic coronary events and hospitalization for ischemia and/or angina. The secondary endpoints are the predictive value of high-risk plaques associated with the development of future cardiac events, assessmen

Inter- and intra-observer variability in the qualitative categorization of coronary angiograms.

The ABC classification of the American College of Cardiology and the American Heart Association is a commonly used categorization to estimate the risk and success of intracoronary intervention, as well as the probability of restenosis. To evaluate the reliability of qualitative angiogram readings, we randomly selected 200 films from single lesion angioplasty procedures. A repeated visual assessment (> or = 2 months interval) by two independent observers resulted in kappa values of inter and intra-observer variability for the ABC lesion classification and for all separate items that compile it. Variability in assessment is expressed in percentage of total agreement, and in kappa value, which is a parameter of the agreement between two or more observations in excess of the chance agreement. Percentage of total agreement and kappa value was 67.8% and 0.33 respectively for the ABC classification, indicating a poor agreement. Probably this is due to the deficiency of strict definitions. Further investigation has to demonstrate whether improvement can be achieved using complete and detailed definitions without ambiguity, and consensus after panel assessment

Normalization of Function in Pediatric Dilated Cardiomyopathy Recovery or Remission?∗

Time to publication: sensitivity analyses. (DOC 62 kb

Optimal design of multi-channel microreactor for uniform residence time distribution

Multi-channel microreactors can be used for various applications that require chemical or electrochemical reactions in either liquid, gaseous or multi phase. For an optimal control of the chemical reactions, one key parameter for the design of such microreactors is the residence time distribution of the fluid, which should be as uniform as possible in the series of microchannels that make up the core of the reactor. Based on simplifying assumptions, an analytical model is proposed for optimizing the design of the collecting and distributing channels which supply the series of rectangular microchannels of the reactor, in the case of liquid flows. The accuracy of this analytical approach is discussed after comparison with CFD simulations and hybrid analytical-CFD calculations that allow an improved refinement of the meshing in the most complex zones of the flow. The analytical model is then extended to the case of microchannels with other cross-sections (trapezoidal or circular segment) and to gaseous flows, in the continuum and slip flow regimes. In the latter case, the model is based on second-order slip flow boundary conditions, and takes into account the compressibility as well as the rarefaction of the gas flow

Clinical and Angiographic Factors Associated With Asymptomatic Restenosis After Percutaneous Coronary Intervention

BACKGROUND: Angiographic restenosis after percutaneous coronary interventional procedures is more common than recurrent angina. Clinical and angiographic factors associated with asymptomatic versus symptomatic restenosis after percutaneous coronary intervention were compared. METHODS AND RESULTS: All patients with angiographic restenosis from the BENESTENT I, BENESTENT II pilot, BENESTENT II, MUSIC, WEST 1, DUET, FINESS 2, FLARE, SOPHOS, and ROSE studies were analyzed. Multivariate analysis evaluated 46 clinical and angiographic variables, comparing those with and without angina. The 10 studies recruited 2690 patients who underwent percutaneous revascularization and 6-month follow-up angiography (86% of those eligible). Restenosis (>/=50% diameter stenosis) occurred in 607 patients and was clinically silent in 335 (55%). Male sex (P=0.008), absence of antianginal therapy with nitrates (P=0.0002) and calcium channel blockers (P=0.02) at 6 months, greater reference diameter after the procedure (P=0.04), greater reference diameter at follow-up (P=0.004), and lesser lesion severity (percent stenosis) at 6 months (P=0.0004) were univariate predictors of asymptomatic restenosis. By multivariate analysis, only male sex (P=0.04), greater reference diameter at follow-up (P=0.002), and lesser lesion severity at 6 months (P=0.0001) were associated with restenosis without angina. CONCLUSIONS: Approximately half of patients with angiographic restenosis have no symptoms. The only multivariate predictors of silent restenosis at 6 months were male sex, greater reference diameter at follow-up, and lesser lesion severity on follow-up angiography

An individual based computational model of intestinal crypt fission and its application to predicting unrestrictive growth of the intestinal epithelium.

Intestinal crypt fission is a homeostatic phenomenon, observable in healthy adult mucosa, but which also plays a pathological role as the main mode of growth of some intestinal polyps. Building on our previous individual based model for the small intestinal crypt and on in vitro cultured intestinal organoids, we here model crypt fission as a budding process based on fluid mechanics at the individual cell level and extrapolated predictions for growth of the intestinal epithelium. Budding was always observed in regions of organoids with abundant Paneth cells. Our data support a model in which buds are biomechanically initiated by single stem cells surrounded by Paneth cells which exhibit greater resistance to viscoelastic deformation, a hypothesis supported by atomic force measurements of single cells. Time intervals between consecutive budding events, as simulated by the model and observed in vitro, were 2.84 and 2.62 days, respectively. Predicted cell dynamics was unaffected within the original crypt which retained its full capability of providing cells to the epithelium throughout fission. Mitotic pressure in simulated primary crypts forced upward migration of buds, which simultaneously grew into new protruding crypts at a rate equal to 1.03 days-1 in simulations and 0.99 days-1 in cultured organoids. Simulated crypts reached their final size in 4.6 days, and required 40 6.2 days to migrate to the top of the primary crypt. The growth of the secondary crypt is independent of its migration along the original crypt. Assuming unrestricted crypt fission and multiple budding events, a maximal growth rate of the intestinal epithelium of 0.10 days-1 43 is predicted and thus approximately 22 days are required for a 10-fold increase of polyp size. These predictions are in agreement with the time reported to develop macroscopic adenomas in mice after loss of Apc in intestinal stem cells

A broad distribution of the alternative oxidase in microsporidian parasites

Microsporidia are a group of obligate intracellular parasitic eukaryotes that were considered to be amitochondriate until the recent discovery of highly reduced mitochondrial organelles called mitosomes. Analysis of the complete genome of Encephalitozoon cuniculi revealed a highly reduced set of proteins in the organelle, mostly related to the assembly of ironsulphur clusters. Oxidative phosphorylation and the Krebs cycle proteins were absent, in keeping with the notion that the microsporidia and their mitosomes are anaerobic, as is the case for other mitosome bearing eukaryotes, such as Giardia. Here we provide evidence opening the possibility that mitosomes in a number of microsporidian lineages are not completely anaerobic. Specifically, we have identified and characterized a gene encoding the alternative oxidase (AOX), a typically mitochondrial terminal oxidase in eukaryotes, in the genomes of several distantly related microsporidian species, even though this gene is absent from the complete genome of E. cuniculi. In order to confirm that these genes encode functional proteins, AOX genes from both A. locustae and T. hominis were over-expressed in E. coli and AOX activity measured spectrophotometrically using ubiquinol-1 (UQ-1) as substrate. Both A. locustae and T. hominis AOX proteins reduced UQ-1 in a cyanide and antimycin-resistant manner that was sensitive to ascofuranone, a potent inhibitor of the trypanosomal AOX. The physiological role of AOX microsporidia may be to reoxidise reducing equivalents produced by glycolysis, in a manner comparable to that observed in trypanosome

Recoil following Wiktor stent implantation for restenotic lesions of coronary arteries

The purpose of this study was to determine acute recoil of the vessel wall immediately after Wiktor stent implantation in native coronary arteries of 77 consecutive patients and to assess whether there was compression or “late recoil” of the stent itself at long-term follow-up. Furthermore, the relationship between recoil and a number of clinical, angiographic, and procedural variables was studied in addition to the relation between acute recoil renarrowing or restenosis was assessed. All angiograms were analyzed with the Cardiovascular Angiography Analysis System using automated edge detection. Acute recoil was defined by the difference between the mean diameter of the fully expanded balloon on which the stent was mounted and the mean diameter of the stented segment. Late recoil was calculated by comparing the mean diameter of the stent itself immediately after implantation and at follow-up without opacification of the vessel. Acute recoil amounted to 0.25 ± 0.32 mm or 8.2%. Multivariate analysis identified sex (coefficient = –0.20, p = 0.04) and stent/artery ratio (coefficient = 0.99, p = 0.0001) as the only independent predictors of acute recoil. “Late recoil” of the stent itself was not observed. The overall difference between the mean diameter of the stent itself immediately after implantation and at follow-up was –0.15 ± 0.33 mm, suggesting an overall increase in diameter of 5.0%. There was no relation between acute recoil and late restenosis. On the contrary, there was a trend towards a greater degree of recoil in patients without restenosis. Moreover, linear regression analysis disclosed a weak but negative correlation between acute recoil and a loss in minimal luminal diameter (coefficient: –0.55, p = 0.04). The Wiktor stent effectively scaffolds the instrumented vessel. Only a minimal amount of acute recoil was noted, which did not contribute to late luminal renarrowing or restenosis. In addition, no late compression of the stent itself was observed. These data suggest that tissue ingrowth into the lumen of the stented segment is the main cause of late luminal renarrowing after stent implantation. © 1994 Wiley-Liss,Inc.

An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study

Aims Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial. Methods and results Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference −1.4%, 95% confidence interval (CI) −3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had ≥5% of all struts uncovered (difference −33.1%, 95% CI −61.7 to −10.3, P < 0.01). Conclusion Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determine

One year cost effectiveness of sirolimus eluting stents compared with bare metal stents in the treatment of single native de novo coronary lesions: an analysis from the RAVEL trial

OBJECTIVE: To assess the balance between costs and effects of the sirolimus eluting stent in the treatment of single native de novo coronary lesions in the RAVEL (randomised study with the sirolimus eluting Bx Velocity balloon expandable stent in the treatment of patients with de novo native coronary artery lesions) study. DESIGN: Multicentre, double blind, randomised trial. SETTING: Percutaneous coronary intervention for single de novo coronary lesions. PATIENTS: 238 patients with stable or unstable angina. INTERVENTIONS: Randomisation to sirolimus eluting stent or bare stent implantation. MAIN OUTCOME MEASURES: Patients were followed up to one year and the treatment effects were expressed as one year survival free of major adverse cardiac events (MACE). Costs were estimated as the product of resource utilisation and Dutch unit costs. RESULTS: At one year, the absolute difference in MACE-free survival was 23% in favour of the sirolimus eluting stent group. At the index procedure, sirolimus eluting stent implantation had an estimated additional procedural cost of 1286. At one year, however, the estimated additional cost difference had decreased to 54 because of the reduction in the need for repeat revascularisations in the sirolimus group (0.8% v 23.6%; p < 0.01). After adjustment of actual results for the consequences of angiographic follow up (correction based on data from the BENESTENT (Belgium Netherlands stent) II study), the difference in MACE-free survival was estimated at 11.1% and the addit