Assessment of Stent Strut Endothelialization in Iliac Arteries of Rabbits

Background: Fast post-implantation stent endothelialization is desirable for theoretically reducing the possibility of stent thrombosis. Objective: To evaluate the extent of sirolimus-eluting stent strut endothelialization (delivered from the luminal and abluminal aspects or abluminal aspect only) in the iliac arteries of rabbits. Methods: The iliac arteries of 10 rabbits were implanted with four sirolimus-eluting stents in the luminal and abluminal aspects, three sirolimus-eluting stents in the abluminal aspect, six polymer-coated stents, and four uncoated stents. After four weeks, the rabbits were euthanized and scanning electron microscopy was performed to quantify the area of exposed stent strut as well as the percentage of endothelialization. Results: The area (mean +/- SD) (mm(2)) of exposed uncoated stent struts, polymer-coated stents, sirulimus-eluting stent in the abluminal and luminal aspects and sirolimus-eluting stent in the abluminal aspect was 0.12 +/- 0.08, 0.09 +/- 0.12, 0.60 +/- 0.67 and 0.05 +/- 0.04, respectively (p = 0.120). The percentage of endothelialization (mean +/- SD) (%) of uncoated stents, polymer-coated stents, sirolimus-eluting stents in the luminal and abluminal aspects and sirolimus-eluting stents in the abluminal aspect was 99 +/- 01, 99 +/- 0. 97 +/- 03 and 99 +/- 0, respectively (p = 0.133). Conclusion: After four weeks of implantation in the iliac arteries of rabbits, both the sirolimus-eluting stents in the luminal plus abluminal aspects and those in the abluminal aspect only showed stent strut endothelialization rates similar to those of the other types of non-drug eluting stents. (Arq Bras Cardiol 2012;99(6):1123-1128)

Freeze-drying microscopy in mathematical modeling of a biomaterial freeze-drying

Transplantation brings hope for many patients. A multidisciplinary approach on this field aims at creating biologically functional tissues to be used as implants and prostheses. The freeze-drying process allows the fundamental properties of these materials to be preserved, making future manipulation and storage easier. Optimizing a freeze-drying cycle is of great importance since it aims at reducing process costs while increasing product quality of this time-and-energy-consuming process. Mathematical modeling comes as a tool to help a better understanding of the process variables behavior and consequently it helps optimization studies. Freeze-drying microscopy is a technique usually applied to determine critical temperatures of liquid formulations. It has been used in this work to determine the sublimation rates of a biological tissue freeze-drying. The sublimation rates were measured from the speed of the moving interface between the dried and the frozen layer under 21.33, 42.66 and 63.99 Pa. The studied variables were used in a theoretical model to simulate various temperature profiles of the freeze-drying process. Good agreement between the experimental and the simulated results was found.

Procedura di progettazione di protesi a basso costo per l'arto inferiore

L'attività di ricerca descritta in questa tesi fornisce linee guida per la progettazione di arti protesici inferiori, con particolare riferimento alla progettazione di protesi a basso costo. La necessità di efficienti protesi a basso costo risulta infatti sentita nei Paesi in via di sviluppo ma anche dalle fasce meno abbienti dei paesi occidentali. Al fine di comprendere le strategie adottate dall'apparato locomotorio per muoversi con le protesi sono analizzati il cammino fisiologico, le protesi presenti sul mercato ed infine le modalità con cui le loro prestazioni sono valutate. Con il presente lavoro, dopo aver osservato la presenza di una scarsa strutturazione della metodologia di progettazione che riguarda specialmente il settore del basso costo, si propone una metodologia il più possibile oggettiva e ripetibile tesa ad individuare quali sono gli aspetti essenziali di una protesi per garantire al paziente una buona qualità di vita. Solo questi aspetti dovranno essere selezionati al fine di ottenere la massima semplificazione della protesi e ridurre il più possibile i costi. Per la simulazione delle attività di locomozione, in particolare del cammino, è stato elaborato un apposito modello spaziale del cammino. Il modello proposto ha 7 membri rigidi (corrispondenti a piedi, tibie, femori e bacino) e 24 gradi di libertà. Le articolazioni e l'appoggio dei piedi al suolo sono modellati con giunti sferici. La pianta del piede consente tre possibili punti di appoggio. I criteri di realizzazione delle simulazioni possono comprendere aspetti energetici, cinematici e dinamici considerati come obiettivo dall'apparato locomotorio. In questa tesi vengono trattati in particolare gli aspetti cinematici ed è mostrata un'applicazione della procedura nella quale vengono dapprima identificati i riferimenti fisiologici del cammino e quindi simulato il cammino in presenza di una menomazione al ginocchio (eliminazione della flessione in fase di appoggio). Viene quindi lasciato a sviluppi futuri il completamento della procedura e la sua implementazione in un codice di calcolo.

Chapter IV: Treatment of critical limb ischaemia

Recommendations stated in the TASC II guidelines for the treatment of peripheral arterial disease (PAD) regard a heterogeneous group of patients ranging from claudicants to critical limb ischaemia (CLI) patients. However, specific considerations apply to CLI patients. An important problem regarding the majority of currently available literature that reports on revascularisation strategies for PAD is that it does not focus on CLI patients specifically and studies them as a minor part of the complete cohort. Besides the lack of data on CLI patients, studies use a variety of endpoints, and even similar endpoints are often differentially defined. These considerations result in the fact that most recommendations in this guideline are not of the highest recommendation grade. In the present chapter the treatment of CLI is not based on the TASC II classification of atherosclerotic lesions, since definitions of atherosclerotic lesions are changing along the fast development of endovascular techniques, and inter-individual differences in interpretation of the TASC classification are problematic. Therefore we propose a classification merely based on vascular area of the atherosclerotic disease and the lesion length, which is less complex and eases the interpretation. Lesions and their treatment are discussed from the aorta downwards to the infrapopliteal region. For a subset of lesions, surgical revascularisation is still the gold standard, such as in extensive aorto-iliac lesions, lesions of the common femoral artery and long lesions of the superficial femoral artery (>15 cm), especially when an applicable venous conduit is present, because of higher patency and limb salvage rates, even though the risk of complications is sometimes higher than for endovascular strategies. It is however more and more accepted that an endovascular first strategy is adapted in most iliac, superficial femoral, and in some infrapopliteal lesions. The newer endovascular techniques, i.e. drug-eluting stents and balloons, show promising results especially in infrapopliteal lesions. However, most of these results should still be confirmed in large RCTs focusing on CLI patients. At some point when there is no possibility of an endovascular nor a surgical procedure, some alternative non-reconstructive options have been proposed such as lumbar sympathectomy and spinal cord stimulation. But their effectiveness is limited especially when assessing the results on objective criteria. The additional value of cell-based therapies has still to be proven from large RCTs and should therefore still be confined to a research setting. Altogether this chapter summarises the best available evidence for the treatment of CLI, which is, from multiple perspectives, completely different from claudication. The latter also stresses the importance of well-designed RCTs focusing on CLI patients reporting standardised endpoints, both clinical as well as procedural.

Tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent vs. a fluoropolymer-coated everolimus-eluting stent at 13-month follow-up: an optical coherence tomography substudy from the RESOLUTE All Comers trial

Aims To compare the tissue coverage of a hydrophilic polymer-coated zotarolimus-eluting stent (ZES) vs. a fluoropolymer-coated everolimus-eluting stent (EES) at 13 months, using optical coherence tomography (OCT) in an ‘all-comers' population of patients, in order to clarify the mechanism of eventual differences in the biocompatibility and thrombogenicity of the devices. Methods and results Patients randomized to angiographic follow-up in the RESOLUTE All Comers trial (NCT00617084) at pre-specified OCT sites underwent OCT follow-up at 13 months. Tissue coverage and apposition were assessed strut by strut, and the results in both treatment groups were compared using multilevel logistic or linear regression, as appropriate, with clustering at three different levels: patient, lesion, and stent. Fifty-eight patients (30 ZES and 28 EES), 72 lesions, 107 stents, and 23 197 struts were analysed. Eight hundred and eighty-seven and 654 uncovered struts (7.4 and 5.8%, P= 0.378), and 216 and 161 malapposed struts (1.8 and 1.4%, P= 0.569) were found in the ZES and EES groups, respectively. The mean thickness of coverage was 116 ± 99 µm in ZES and 142 ± 113 µm in EES (P= 0.466). No differences in per cent neointimal volume obstruction (12.5 ± 7.9 vs. 15.0 ± 10.7%) or other areas–volumetric parameters were found between ZES and EES, respectively. Conclusion No significant differences in tissue coverage, malapposition, or lumen/stent areas and volumes were detected by OCT between the hydrophilic polymer-coated ZES and the fluoropolymer-coated EES at 13-month follow-up.

Prosthetic considerations

Implants have changed prosthodontics more than any other innovation in dentistry. Replacement of lost teeth by a fixed or removable prosthesis is considered to be a restitutio ad similem, while implants may provide a feeling of restitutio ad integrum. Implant prosthodontics means restoring function, aesthetics, and providing technology; biology and technology are combined. Placement of implants is a reconstructive, preprosthetic surgical intervention and is therefore different from most goals in oral surgery that consist of tooth extraction, treating infection and removing pathology from soft or hard tissues. Thus, implants are part of the final prosthetic treatment which encompasses functional, aesthetic and social rehabilitation. The patient's needs and functional status determine the goal of prosthetic treatment. Treatment outcomes in implant prosthodontics are survival of implants and prostheses, impact on physiological and psychological status, oral health-related impact on quality of life, and initial and maintenance costs. A variety of prosthetic solutions are available to restore the partially and completely edentulous jaw and more recently specific methods have been developed such as computer guided planning and CAD-CAM technologies. These should allow more uniform quality and passive fit of prostheses, and simultaneously enables processing of biologically well-accepted materials.

Influence of stent type on hemodynamic depression after carotid artery stent placement

PURPOSE: To assess the effect of stent type on hypotension and bradycardia after carotid artery stent placement. MATERIALS AND METHODS: A retrospective analysis on a prospectively maintained database was conducted in 256 patients (126 men; mean age, 71.8 years +/- 8.6; 194 de novo lesions) undergoing carotid artery stent placement between January 1996 and January 2007 by using self-expanding stents. Braided Elgiloy stents (Wallstents) were used in 44 of the 256 patients (17.2%) and slotted-tube nitinol stents were deployed in 212 (82.8%). Bivariate and multivariable logistic regression models were used to determine the influence of stent design on procedural and 24-hour hypotension and bradycardia. RESULTS: Procedural hemodynamic depression (HD) was encountered in 73 of the 256 patients (28.5%) due to hypotension in 24 (9.4%), bradycardia in 12 (4.7%), or both in 37 (14.5%) patients. Rates of procedural hypotension were 11.3% with nitinol stents and 0% with braided Elgiloy stents (P = .0188). Persistent postprocedural HD occurred in 91 of the 256 patients (35.5%) due to hypotension in 40 patients (15.6%), bradycardia in 23 (9.0%), or both in 28 (10.9%). Within a multivariable analysis adjusted for clinically relevant factors affecting rates of HD, the use of braided Elgiloy stents was associated with a decreased rate of procedural hypotension (odds ratio: 0.165; 95% confidence interval: 0.038, 0.721; P = .017). Procedural hypotension and bradycardia were not correlated to incidence of major adverse events but were associated with an increased duration of hospital stay (P = .0059 and P = .0335, respectively). CONCLUSIONS: Nitinol stents are associated with a higher risk of hypotension as compared to braided Elgiloy stents during carotid artery stent placement.

Simultaneous subacute coronary drug-eluting stent thrombosis in two different vessels of a patient with factor V Leiden mutation

We review the case of a 46-year-old man who underwent elective percutaneous coronary intervention and stenting of the left anterior descending artery and right coronary artery with two sirolimus- and paclitaxel-eluting stents. Four days after angioplasty, he was readmitted with cardiogenic shock due to acute anterior and inferior myocardial infarction. Coronary angiography revealed subacute thrombosis of both stents, and balloon dilation was performed successfully thereafter. The follow-up investigations revealed that the patient was a carrier of factor V Leiden. We hereby discuss the importance of factor V Leiden as the most common cause of hypercoagulable state and its probable role in acute and subacute coronary stent thrombosis in drug-eluting stents.

Correlation of intravascular ultrasound findings with histopathological analysis of thrombus aspirates in patients with very late drug-eluting stent thrombosis

BACKGROUND: Intravascular ultrasound of drug-eluting stent (DES) thrombosis (ST) reveals a high incidence of incomplete stent apposition (ISA) and vessel remodeling. Autopsy specimens of DES ST show delayed healing and hypersensitivity reactions. The present study sought to correlate histopathology of thrombus aspirates with intravascular ultrasound findings in patients with very late DES ST. METHODS AND RESULTS: The study population consisted of 54 patients (28 patients with very late DES ST and 26 controls). Of 28 patients with very late DES ST, 10 patients (1020+/-283 days after implantation) with 11 ST segments (5 sirolimus-eluting stents, 5 paclitaxel-eluting stents, 1 zotarolimus-eluting stent) underwent both thrombus aspiration and intravascular ultrasound investigation. ISA was present in 73% of cases with an ISA cross-sectional area of 6.2+/-2.4 mm(2) and evidence of vessel remodeling (index, 1.6+/-0.3). Histopathological analysis showed pieces of fresh thrombus with inflammatory cell infiltrates (DES, 263+/-149 white blood cells per high-power field) and eosinophils (DES, 20+/-24 eosinophils per high-power field; sirolimus-eluting stents, 34+/-28; paclitaxel-eluting stents, 6+/-6; P for sirolimus-eluting stents versus paclitaxel-eluting stents=0.09). The mean number of eosinophils per high-power field was higher in specimens from very late DES ST (20+/-24) than in those from spontaneous acute myocardial infarction (7+/-10), early bare-metal stent ST (1+/-1), early DES ST (1+/-2), and late bare-metal stent ST (2+/-3; P from ANOVA=0.038). Eosinophil count correlated with ISA cross-sectional area, with an average increase of 5.4 eosinophils per high-power field per 1-mm(2) increase in ISA cross-sectional area. CONCLUSIONS: Very late DES thrombosis is associated with histopathological signs of inflammation and intravascular ultrasound evidence of vessel remodeling. Compared with other causes of myocardial infarction, eosinophilic infiltrates are more common in thrombi harvested from very late DES thrombosis, particularly in sirolimus-eluting stents, and correlate with the extent of stent malapposition.

Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P<0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Biocompatibility assessment of biosorbable polymer coated nitinol alloys

Owing to an increased risk of aging population and a higher incidence of coronary artery disease (CAD), there is a need for more reliable and safer treatments. Numerous varieties of durable polymer-coated drug eluting stents (DES) are available in the market in order to mitigate in-stent restenosis. However, there are certain issues regarding their usage such as delayed arterial healing, thrombosis, inflammation, toxic corrosion by-products, mechanical stability and degradation. As a result, significant amount of research has to be devoted to the improvement of biodegradable polymer-coated implant materials in an effort to enhance their bioactive response. ^ In this investigation, magneto-electropolished (MEP) and a novel biodegradable polymer coated ternary Nitinol alloys, NiTiTa and NiTiCr were prepared to study their bio and hemocompatibility properties. The initial interaction of a biomaterial with its surroundings is dependent on its surface characteristics such as, composition, corrosion resistance, work of adhesion and morphology. In-vitro corrosion tests such as potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) studies were conducted to determine the coating stability and longevity. In-vitro hemocompatibility studies and HUVEC cell growth was performed to determine their thrombogenic and biocompatibility properties. Critical delamination load of the polymer coated Nitinol alloys was determined using Nano-scratch analysis. Sulforhodamine B (SRB) assays were performed to elucidate the effect of metal ions leached from Nitinol alloys on the viability of HUVEC cells. Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), contact angle meter and X-ray diffraction (XRD) were used to characterize the surface of the alloys. ^ MEP treated and polymer coated (PC) Nitinol alloys displayed a corrosion resistant polymer coating as compared to uncoated alloys. MEP and PC has resulted in reduced Ni and Cr ion leaching from NiTi5Cr and subsequently low cytotoxicity. Thrombogenicity tests revealed significantly less platelet adhesion and confluent endothelial cell growth on polymer coated and uncoated ternary MEP Nitinol alloys. Finally, this research addresses the bio and hemocompatibility of MEP + PC ternary Nitinol alloys that could be used to manufacture blood contacting devices such as stents and vascular implants which can lead to lower U.S. healthcare spending.^

Biocompatibility Assessment of Biosorbable Polymer Coated Nitinol Alloys

Owing to an increased risk of aging population and a higher incidence of coronary artery disease (CAD), there is a need for more reliable and safer treatments. Numerous varieties of durable polymer-coated drug eluting stents (DES) are available in the market in order to mitigate in-stent restenosis. However, there are certain issues regarding their usage such as delayed arterial healing, thrombosis, inflammation, toxic corrosion by-products, mechanical stability and degradation. As a result, significant amount of research has to be devoted to the improvement of biodegradable polymer-coated implant materials in an effort to enhance their bioactive response. In this investigation, magneto-electropolished (MEP) and a novel biodegradable polymer coated ternary Nitinol alloys, NiTiTa and NiTiCr were prepared to study their bio and hemocompatibility properties. The initial interaction of a biomaterial with its surroundings is dependent on its surface characteristics such as, composition, corrosion resistance, work of adhesion and morphology. In-vitro corrosion tests such as potentiodynamic polarization and electrochemical impedance spectroscopic (EIS) studies were conducted to determine the coating stability and longevity. In-vitro hemocompatibility studies and HUVEC cell growth was performed to determine their thrombogenic and biocompatibility properties. Critical delamination load of the polymer coated Nitinol alloys was determined using Nano-scratch analysis. Sulforhodamine B (SRB) assays were performed to elucidate the effect of metal ions leached from Nitinol alloys on the viability of HUVEC cells. Scanning Electron Microscopy (SEM), X-ray Photoelectron Spectroscopy (XPS), contact angle meter and X-ray diffraction (XRD) were used to characterize the surface of the alloys. MEP treated and polymer coated (PC) Nitinol alloys displayed a corrosion resistant polymer coating as compared to uncoated alloys. MEP and PC has resulted in reduced Ni and Cr ion leaching from NiTi5Cr and subsequently low cytotoxicity. Thrombogenicity tests revealed significantly less platelet adhesion and confluent endothelial cell growth on polymer coated and uncoated ternary MEP Nitinol alloys. Finally, this research addresses the bio and hemocompatibility of MEP + PC ternary Nitinol alloys that could be used to manufacture blood contacting devices such as stents and vascular implants which can lead to lower U.S. healthcare spending.

Trends in Primary Angioplasty in Portugal From 2002 to 2013 According to the Portuguese National Registry of Interventional Cardiology

INTRODUCTION AND OBJECTIVES: The aim of the present paper was to report trends in coronary angioplasty for the treatment of ST-elevation myocardial infarction (STEMI) in Portugal. METHODS: Prospective multicenter data from the Portuguese National Registry of Interventional Cardiology (RNCI) and official data from the Directorate-General for Health (DGS) were studied to analyze percutaneous coronary intervention (PCI) procedures for STEMI from 2002 to 2013. RESULTS: In 2013, 3524 primary percutaneous coronary intervention (p-PCI) procedures were performed (25% of all procedures), an increase of 315% in comparison to 2002 (16% of all interventions). Between 2002 and 2013 the rate increased from 106 to 338 p-PCIs per million population per year. Rescue angioplasty decreased from 70.7% in 2002 to 2% in 2013. During this period, the use of drug-eluting stents grew from 9.9% to 69.5%. After 2008, the use of aspiration thrombectomy increased, reaching 46.7% in 2013. Glycoprotein IIb-IIIa inhibitor use decreased from 73.2% in 2002 to 23.6% in the last year of the study. Use of a radial approach increased steadily from 8.3% in 2008 to 54.6% in 2013. CONCLUSION: During the reporting period there was a three-fold increase in primary angioplasty rates per million population. Rescue angioplasty has been overtaken by p-PCI as the predominant procedure since 2006. New trends in the treatment of STEMI were observed, notably the use of drug-eluting stents and radial access as the predominant approach.

Candida albicans in patients with oronasal communication and obturator prostheses

Patients using obturator prostheses often present denture-induced stomatitis. In order to detect the presence of oral Candida albicans in patients with oronasal communications and to evaluate the effectiveness of a topical antifungal treatment, cytological smears obtained from the buccal and palatal mucosa of 10 adult patients, and from the nasal acrylic surface of their obturator prostheses were examined. A therapeutic protocol comprising the use of oral nystatin (Mycostatin®) and prosthesis disinfection with sodium hypochlorite was prescribed for all patients. Seven patients were positive for C. albicans in the mucosa, with 1 negative result for the prosthetic surface in this group of patients. Post-treatment evaluation revealed the absence of C. albicans on prosthesis surface and on the oral mucosa of all patients. The severity of the candidal infection was significantly higher in the palatal mucosa than in the buccal mucosa, but similar in the palatal mucosa and prosthesis surface, indicating that the mucosa underlying the prosthesis is more susceptible to infection. The therapeutic protocol was effective in all cases, which emphasizes the need for denture disinfection in order to avoid reinfection of the mucosa.

Mock circulatory system for the evaluation of left ventricular assist devices, endoluminal prostheses, and vascular diseases

A new digital computer mock circulatory system has been developed in order to replicate the physiologic and pathophysiologic characteristics of the human cardiovascular system. The computer performs the acquisition of pressure, flow, and temperature in an open loop system. A computer program has been developed in Labview programing environment to evaluate all these physical parameters. The acquisition system was composed of pressure, flow, and temperature sensors and also signal conditioning modules. In this study, some results of flow, cardiac frequencies, pressures, and temperature were evaluated according to physiologic ventricular states. The results were compared with literature data. In further works, performance investigations will be conducted on a ventricular assist device and endoprosthesis. Also, this device should allow for evaluation of several kinds of vascular diseases.