PERFORMANCE 1 study: Novel carotid stent system with integrated post-dilation balloon and embolic protection device.

OBJECTIVES: The PERFORMANCE I study was designed to evaluate the safety and feasibility of the Neuroguard IEP® System, a novel carotid stent system with an integrated embolic filter and post-dilatation balloon, to treat clinically significant carotid artery stenosis. BACKGROUND: The risk of major adverse events during carotid artery stenting is comparable to carotid endarterectomy, however, the risk of minor stroke remains higher with stenting. METHODS: In total, 67 patients undergoing carotid artery stenting were enrolled at nine centers in Europe. Follow-up assessments included neurological exams, duplex ultrasound, 12-lead electrocardiogram, and cardiac enzyme analysis. The primary endpoint was the 30-day composite rate of stroke, death, and myocardial infarctions versus a prespecified performance goal. Secondary endpoints included procedure success, device success, and target lesion revascularization. RESULTS: The study population was predominantly male (74.6%) with a mean age of 69.3 ± 8.9 years and 67% of subjects met at least one criterion placing them at an elevated risk for adverse events following carotid endarterectomy. All patients were treated successfully with the study device. There were no deaths or strokes within 30 days of the index procedure. One subject (1.5%) experienced a non-ST elevation myocardial infarction at day 17. The primary endpoint was met with a 30-day major adverse events rate of 1.5% (1/67). Through 12-month follow-up, there were no strokes, neurological deaths, target lesion revascularizations, or instances of in-stent-restenosis. CONCLUSIONS: Results from this study demonstrate the Neuroguard IEP system is safe and feasible with a stroke/death rate of 0% at 30 days. A large pivotal study is currently underway.

Overview of Imaging Techniques in Immunohistochemistry.

Augmentation of digital images is almost always a necessity in order to obtain a reproduction that matches the appearance of the original. However, that augmentation can mislead if it is done incorrectly and not within reasonable limits. When procedures are in place for ensuring that originals are archived and image manipulation steps reported, scientists not only follow good laboratory practices but avoid ethical issues associated with post-processing and protect their labs from any future allegations of scientific misconduct. Also, when procedures are in place for the correct acquisition of images, the extent of post-processing is minimized or eliminated. These procedures include color balancing (for brightfield images), keeping tonal values within the dynamic range of the detector, frame averaging to eliminate noise (typically in fluorescence imaging), use of the highest bit depth when a choice is available, flatfield correction, and archiving of the image in a non-lossy format (not JPEG).When post-processing is necessary, the commonly used applications for correction include Photoshop and ImageJ, but a free program (GIMP) can also be used. Corrections to images include scaling the bit depth to higher and lower ranges, removing color casts from brightfield images, setting brightness and contrast, reducing color noise, reducing "grainy" noise, conversion of pure colors to grayscale, conversion of grayscale to colors typically used in fluorescence imaging, correction of uneven illumination and flatfield correction, blending color images (fluorescence), and extending the depth of focus. These corrections are explained in step-by-step procedures in the chapter that follows.

Double Filtration During Carotid Artery Stenting Using a Novel Post-Dilation Balloon With Integrated Embolic Protection.

OBJECTIVES: This study evaluated the safety and performance of the Paladin System, a novel angioplasty balloon with an integrated embolic protection filter designed to increase embolic protection during post-dilation. BACKGROUND: The risk of major adverse events during carotid artery stenting (CAS) is equivalent to carotid endarterectomy. However, the risk of minor stroke remains higher with CAS. Much of this risk occurs during post-stent dilation. METHODS: A total of 106 patients were enrolled in 5 centers in Germany. The study's primary endpoint was all-cause death, myocardial infarction, and stroke at 30 days post-procedure. Pre- and post-procedural diffusion-weighted magnetic resonance imaging evaluated new ischemic lesions in 30 subjects. Filter histomorphometric analysis was performed in 23 patients. Retrospective analyses compared outcome rates to historical controls. RESULTS: Device and procedural success rates were 100%. The combined major adverse event rate (death, myocardial infarction, and stroke) at discharge and at 30 days was 0% and 1.0%, respectively. The single adverse event was a stroke, which occurred at day 12 and was believed unrelated to the device or procedure. New ischemic lesions were found in 11 (36.7%) patients in the diffusion-weighted magnetic resonance imaging subset. New ipsilateral lesions were seen in 9 (30.0%) patients. Mean lesion volume per patient was 0.010 cm3. Debris was present in all filters, and approximately 90% of captured particles were <100 µm. CONCLUSIONS: Use of the Paladin System for post-stent dilation during CAS appears safe, and it may effectively decrease the number of embolic particles reaching the brain, which may help reduce the risk of procedure-related stroke. (A Multi-Center Study to Evaluate Acute Safety and Clinical Performance of Paladin® Carotid Post-Dilation Balloon System With Integrated Embolic Protection; NCT02501148).

Determination of simian immunodeficiency virus production by infected activated and resting cells.

OBJECTIVE: To determine the relative amount of virus produced by activated and resting CD4+ T cells. DESIGN: The total quantity of virus produced by an activated cell relative to a resting cell in vivo was estimated from 'snap-shots' of virus production by infected cells at one time point. METHODS: Bayesian statistical methods were used to determine a credible interval for the desired ratio. RESULTS: The posterior mean of the ratio of virus produced by a typical activated cell to a typical resting cell is 0.82 to 4.28, depending on the half-lives of the resting infected cells. Simian immunodeficiency virus-infected resting cells could accordingly be responsible for 70 to 93% of peak virus production in the acute stage of infection. CONCLUSIONS: Whereas in 'snap-shots' the infected resting cells apparently produce much less virus than infected activated CD4+ T cells, the coincidence of peak SIV production with predominant infection of resting cells along with longer half-lives for productively infected resting cells point to a major contribution to virus production in early infection.

An innovative method for obtaining consistent images and quantification of histochemically stained specimens.

Obtaining digital images of color brightfield microscopy is an important aspect of biomedical research and the clinical practice of diagnostic pathology. Although the field of digital pathology has had tremendous advances in whole-slide imaging systems, little effort has been directed toward standardizing color brightfield digital imaging to maintain image-to-image consistency and tonal linearity. Using a single camera and microscope to obtain digital images of three stains, we show that microscope and camera systems inherently produce image-to-image variation. Moreover, we demonstrate that post-processing with a widely used raster graphics editor software program does not completely correct for session-to-session inconsistency. We introduce a reliable method for creating consistent images with a hardware/software solution (ChromaCal™; Datacolor Inc., NJ) along with its features for creating color standardization, preserving linear tonal levels, providing automated white balancing and setting automated brightness to consistent levels. The resulting image consistency using this method will also streamline mean density and morphometry measurements, as images are easily segmented and single thresholds can be used. We suggest that this is a superior method for color brightfield imaging, which can be used for quantification and can be readily incorporated into workflows.

Endostatin binding to ovarian cancer cells inhibits peritoneal attachment and dissemination.

Ovarian cancer cells use integrins to attach to the peritoneal wall. Integrin alpha(5)beta(1) is also the target for the angiogenesis inhibitor, endostatin. Therefore, the ability of endostatin to competitively inhibit tumor cell seeding of the peritoneum was investigated. An imaging method was developed to determine early phases of peritoneal dissemination of ovarian cancer cells. Using this method, endostatin was found to bind ovarian cancer cells through integrin alpha(5)beta(1) and inhibit vessel cooption efficiently. Although both angiostatin and endostatin are potent inhibitors of tumor angiogenesis, peritoneal attachment and vessel cooption was blocked only by the endostatin. Knocking down the expression of integrins alpha(5) and beta(1) in ovarian cancer cells interfered with endostatin-mediated inhibition of peritoneal seeding. Furthermore, adenovirus-mediated in situ expression of endostatin either inside the peritoneum or by the ovarian tumor cells inhibited peritoneal seeding and dissemination in vivo. Endostatin treatment also prevented primary ovarian cancer cells from attaching to mouse peritoneal wall. These studies show a paraendothelial mechanism by which endostatin can inhibit peritoneal dissemination of ovarian cancer cells and raises the possibility of intraperitoneal expression of endostatin to reduce recurrence.