Development and validation of a 6-point grading scale in patients undergoing correction of nasolabial folds with a collagen implant.

BACKGROUND: Various scoring techniques prone to subjective interpretation have been used to evaluate soft tissue augmentation of nasolabial folds (NLFs). OBJECTIVE: To design and validate a reliable wrinkle assessment scoring scale. MATERIALS AND METHODS: Six photographed wrinkles of varying severity were electronically copied onto the same facial image to become a 6-point grading scale (GGS). A pilot training program (13 investigators) determined reliability, and a 12-week multicenter survey study validated the GGS scoring method. RESULTS: Pilot study inter- and intrarater scoring reliability were high (weighted kappa scores of 0.85 and 0.86, respectively). Seventy-five percent of survey investigators and independent review panel (IRP) members considered a GGS score difference of 0.5 to be a minimally perceivable difference. Interrater weighted kappa scores were 0.91 for the IRP and 0.80 for investigators. Intrarater agreements after repeat testing were 0.91 and 0.89, respectively. The baseline "live" assessment GGS mean score was 3.34, and the baseline blinded photographic assessment GGS mean score was 2.00 for the IRP and 2.16 for the investigators. CONCLUSIONS: The GGS is a reproducible method of grading the severity of NLF wrinkles. Treatment effectiveness of a dermal filler can be reliably evaluated using the GGS by comparing "live" assessments with the standard GGS photographic panel.

Comparison of inflammatory response after implantation of sirolimus- and paclitaxel-eluting stents in porcine coronary arteries.

BACKGROUND: Although both sirolimus (CYPHER) and paclitaxel (TAXUS) drug-eluting stents have demonstrated efficacy and safety in clinical trials, human autopsy data have raised concerns about long-term healing and the potential for local inflammatory reactions. METHODS AND RESULTS: Overlapping stents (CYPHER drug-eluting stents, Bx SONIC bare metal stents, TAXUS drug-eluting stents, and Liberté bare metal stents) were implanted in noninjured coronary arteries of 58 domestic swine. Histopathological evaluation of proximal, overlapped, and distal stented segments was determined with emphasis on inflammation at 30, 90, and 180 days. Circumferential granulomatous inflammation in all stented segments was defined as inflammation consisting of macrophages, multinucleated giant cells, lymphocytes, and granulocytes, including many eosinophils, adjacent to almost all struts. Circumferential granulomatous inflammation was more prevalent in CYPHER (9 of 23, 39%) compared with TAXUS (1 of 21, 5%; P=0.01) and control bare metal stents (0 of 44) in the combined 90- and 180-day cohorts. Only CYPHER specimens showed marked adventitial inflammation (P=0.0025) and fibrosis (P=0.0055) accompanied by extensive remodeling. Fibrin deposition within neointima and medial smooth muscle cell death were greater (both P<0.001) in TAXUS than CYPHER at 30 days, with more fibrin in TAXUS than CYPHER through 90 days (P<0.05). CONCLUSIONS: Although these data cannot be directly extrapolated to humans, the high prevalence in this porcine model of diffuse granulomatous inflammation seen with CYPHER stents, persisting at 180 days and associated with extensive remodeling of the artery, and persistent para-strut fibrin deposition with TAXUS stents emphasize the need for further investigation of biocompatibility with these and other novel combination drug/polymer drug-eluting stents.

Time dependent vascular and myocardial responses of a second generation, small vessel, paclitaxel-eluting stent platform.

OBJECTIVES: The purpose of this study was to evaluate the time-dependent vascular and myocardial responses to a second-generation, small vessel (< or =2.5 mm) paclitaxel-eluting stent (PES) platform. BACKGROUND: Small caliber coronary vessels present complex challenges for percutaneous coronary intervention (PCI) and are associated with lower technical success and inferior long-term efficacy. A next-generation, highly deliverable PES may improve clinical outcomes in small vessels. METHODS: Sixty single stents were implanted in noninjured coronary arteries in 30 domestic swine (one TAXUS Liberté small vessel PES (svPES) and one Liberté small vessel bare metal stent (svBMS) in each animal). Ten animals each were allocated to 30-, 90-, and 180-day follow-up groups; final quantitative angiography and necropsy were performed. Samples of myocardium, liver, and kidney were processed and evaluated for pathology. Radiography and either histopathology or scanning electron microscopy were performed on all the explanted stented vessels. RESULTS: There were no stent-related deaths or downstream myocardial pathology. Both the svPES stent and its svBMS control demonstrated complete strut tissue coverage and complete endothelialization at all timepoints, and there was no evidence of macro- or microscopic thrombus or stent fracture. Medial smooth muscle cell content was markedly reduced in all the svPES groups compared with that in the svBMS controls. CONCLUSIONS: The small diameter paclitaxel-eluting TAXUS Liberté stent has a safe and predictable biologic vascular response in the noninjured swine model. This device warrants further investigation targeting the currently poorly met clinical need for small vessel PCI.

Early vascular response to overlapped paclitaxel-eluting stents in swine coronary arteries.

BACKGROUND: The early response to the TAXUS Express2 paclitaxel-eluting stent (PES) system was compared to the response to the Express2 bare metal stent (BMS) system in porcine arteries. METHODS: Swine coronary arteries were implanted with overlapping PES or BMS and examined at 1, 2, 4, 10, and 20 days postimplantation using scanning electron microscopy or light microscopy. RESULTS: Vascular healing in terms of strut coverage, reendothelialization, degree of inflammation, and absence of thrombus was equivalent in both groups from 1 to 20 days. Interstrut member spaces were unaffected by stent deployment and remained covered with endothelium from Day 1. In both groups at 2 days, small patches of endothelial cells covered approximately 5-10% of the stent surface. At 4 days, endothelial cell coverage progressed to nearly 50% in both groups. After 10 days, endothelial cell strut coverage was nearly complete (>90%), with regions of incomplete coverage located primarily in strut overlap regions in both groups. BMS exhibited a fibrocellular neointima and no parastrut fibrin, whereas PES exhibited a developing but immature fibrocellular neointima and prominent parastrut fibrin. By Day 20, an endothelialized neointima was present in both groups, with comparable coverage of proximal and distal stented regions. The neointima of PES was more fibrocellular and parastrut fibrin was still comparable to that at 10 days. CONCLUSION: Early vascular response was comparable for both PES and BMS, with similar rates of reendothelialization, limited inflammatory response, and absence of thrombus, but differed parastrut fibrin clearance and neointimal maturation rate.

Overlapping paclitaxel-eluting stents: long-term effects in a porcine coronary artery model.

OBJECTIVE: At 4-year follow-up, paclitaxel-eluting stents (PES, TAXUS) have demonstrated clinical effectiveness in reducing restenosis without increasing death or myocardial infarction. Concerns remain with all drug-eluting stents, however, regarding potential interference with long-term healing, particularly in zones with adjacent stent overlap due to theoretical doubling in both drug release and tissue contact with coating polymer. Therefore, we evaluated long-term healing of overlapped TAXUS stents in an accepted animal model. METHODS: Seventy-one non-injured swine underwent coronary artery placement of 138 overlapping stent-pairs (91 PES TAXUS Liberté 1 microg/mm(2) slow release formulation, 3.0 or 3.5 mm diameter pairs and 47 control bare metal Liberté pairs) deployed at a 1.1:1 to 1.2:1 target stent-to-artery diameter ratio. Pathological analysis was performed at 30 (9 bare, 10 paclitaxel), 90 (9 bare, 10 paclitaxel), 180 (10 bare, 16 paclitaxel), 360 (10 bare, 21 paclitaxel), and 580 (9 bare, 22 paclitaxel) days. RESULTS: At all time intervals overlapped TAXUS stents were consistently endothelialized and free of luminal thrombus or vascular dilatation. Full healing, however, was delayed compared to control, with macrophage processed para-strut fibrin and cellular debris still present, but reduced and sequestered from blood flow by an endothelialized neointima at 360 and 580 days. While neointimal thickness in TAXUS overlap zones was significantly less than control at 30 days, greater neointima formation was observed with TAXUS at > or =90 days, but was stable and did not progress further from 90 to 580 days. CONCLUSION: In this porcine model TAXUS stents demonstrated safety and acceptable healing with prolonged time to resolution of para-strut deposits, and did not produce the sustained neointimal suppression seen clinically.