Impact of routine angiographic follow-up after percutaneous coronary intervention with drug-eluting stents in the SPIRIT III randomized trial at three years

Routine angiographic follow-up after bare-metal stent implantation has been associated with an increase in coronary revascularization. The impact of angiographic follow-up after drug-eluting stent placement remains poorly characterized. The prospective, randomized, single-blinded SPIRIT III trial assigned patients to the everolimus-eluting stent or the paclitaxel-eluting stent (PES). Major adverse cardiovascular events (cardiac death, myocardial infarction, and ischemia-driven target lesion revascularization [ID-TLR]) at 3 years were assessed by angiographic versus clinical-only follow-up at 8 months ± 28 days and a landmark survival analysis from 9 months to 3 years. Of 1,002 patients, 564 patients were assigned to angiographic follow-up at 8 months ± 28 days and 438 patients underwent clinical follow-up alone. Three-year major adverse cardiovascular event rates were 10.6% in the angiographic group and 12.0% in the clinical follow-up group (p = 0.64). Ischemia-driven revascularization increased twofold at 9 months, but no difference was noted in ID-TLR for either device. Non-ID-TLR was significantly higher in patients in the angiographic group (4.5% vs 1.0%, p = 0.002), a difference resulting from PES (9.1% vs 0.7%, p = 0.0007) rather than everolimus-eluting stent (2.2% vs 1.1%, p = 0.36) treatment. The landmark analysis showed no significant differences between the angiographic and clinical follow-up groups from 9 months to 3 years of major clinical outcomes. In conclusion, routine angiographic follow-up in SPIRIT III did not increase rates of ID-TLR compared to clinical follow-up alone. Despite higher nonischemia-driven revascularization rates with angiographic follow-up of patients with PESs, none of the safety end points were adversely affected.     

In vivo assessment of DNA damage induced in oral mucosa cells by fixed and removable metal prosthodontic appliances

Given long-term effect on oral tissues due to contact with dental appliances, the biocompatibility studies of casting alloys are of great importance. It has been previously documented that metal dental appliances, due to corrosion, might induce genotoxic and mutagenic effects in cells. Therefore, the aim of presented study was to examine the genotoxicity of two dental casting alloys (Co-Cr-Mo and Ni-Cr) commonly used in fixed and removable prosthodontic appliances that are in contact with the oral epithelium for 5 years or more. For that purpose, 55 age-matched subjects were included in the study; 30 wearers of prosthodontic appliances and 25 controls. Buccal cells of oral mucosa were collected and processed for further analysis. The cell viability has been assessed by trypan blue exclusion test, while genotoxic effect of metal ions on DNA in oral mucosa cells was studied by use of alkaline comet assay. Results have shown significantly higher comet assay parameters (tail length and percentage DNA in the tail) in the group wearing metal appliances. Both subjects with Co-Cr-Mo alloy and Ni-Cr alloy showed significantly higher comet assay parameters when compared with controls. It has been confirmed that metal ions released by the two base metal dental casting alloys examined in this study, might be responsible for DNA damage of oral mucosa cells. Therefore, the results of this study emphasize the importance of the in vivo evaluation of dental materials with respect to their genotoxicity, which is of major importance to ensure long-term biocompatibility.     

Peripheral blood lymphocyte/monocyte ratio at diagnosis and survival in nodular lymphocyte-predominant Hodgkin lymphoma

The pathological background in nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) consists of lymphocytes and histocytes. This study analysed the peripheral blood absolute lymphocyte count/absolute monocyte count ratio at diagnosis (ALC/AMC-DX) on the impact of survival in NLPHL. One hundred and three consecutive NLPHL patients that were followed at Mayo Clinic from 1974 to 2010 were included in the study. Receiver operating characteristic and area under the curve were used for ALC/AMC-DX cut-off value analysis and proportional-hazards models were used to compare survival based on the ALC/AMC-DX ratio. With a median follow-up of 8·9 years (range: 0·3-31 years), an ALC/AMC-DX ≥2·1 was the best cut-off value for survival with an area under the curve of 0·82, a sensitivity of 70% and specificity of 84%. After adjusting for the International Prognostic Score (IPS), ALC/AMC-DX remained an independent prognostic factor for overall survival [Hazard Ratio (HR), 0·33, 95% confidence interval (CI), 0·15-0·71%, P < 0·004]; lymphoma-specific survival (HR, 0·05; 95%CI, 0·01-0·68%, P < 0·002); progression-free survival (HR, 0·30; 95%CI, 0·14-0·60%, P < 0·006), and time to progression (HR, 0·06, 95%CI, 0·04-0·30%, P < 0·004). ALC/AMC-DX is a low cost, already standarized, biomarker to predict clinical outcomes in NLPHL.     

Hypertension induces brain β-amyloid accumulation, cognitive impairment, and memory deterioration through activation of receptor for advanced glycation end products in brain vasculature

Although epidemiological data associate hypertension with a strong predisposition to develop Alzheimer disease, no mechanistic explanation exists so far. We developed a model of hypertension, obtained by transverse aortic constriction, leading to alterations typical of Alzheimer disease, such as amyloid plaques, neuroinflammation, blood-brain barrier dysfunction, and cognitive impairment, shown here for the first time. The aim of this work was to investigate the mechanisms involved in Alzheimer disease of hypertensive mice. We focused on receptor for advanced glycation end products (RAGE) that critically regulates Aβ transport at the blood-brain barrier and could be influenced by vascular factors. The hypertensive challenge had an early and sustained effect on RAGE upregulation in brain vessels of the cortex and hippocampus. Interestingly, RAGE inhibition protected from hypertension-induced Alzheimer pathology, as showed by rescue from cognitive impairment and parenchymal Aβ deposition. The increased RAGE expression in transverse aortic coarctation mice was induced by increased circulating advanced glycation end products and sustained by their later deposition in brain vessels. Interestingly, a daily treatment with an advanced glycation end product inhibitor or antioxidant prevented the development of Alzheimer traits. So far, Alzheimer pathology in experimental animal models has been recognized using only transgenic mice overexpressing amyloid precursor. This is the first study demonstrating that a chronic vascular insult can activate brain vascular RAGE, favoring parenchymal Aβ deposition and the onset of cognitive deterioration. Overall we demonstrate that RAGE activation in brain vessels is a crucial pathogenetic event in hypertension-induced Alzheimer disease, suggesting that inhibiting this target can limit the onset of vascular-related Alzheimer disease.     

Prediction of a Good Response to Cardiac Resynchronization Therapy in Patients with Severe Dilated Cardyomyopathy: Could Conventional Echocardiography Be the Answer after All?

Objectives: The aim of this study was to assess the performance of echocardiographic parameters to predict response to cardiac resynchronization therapy (CRT). Background: CRT reduces morbidity and mortality due to the proper selection of candidates for CRT. Methods: The 12‐month trial was performed on 70 optimally medicated patients with standard inclusion criteria: NYHA class III or IV heart failure, left ventricular ejection fraction (LVEF) ≤ 35%, and QRS ≥ 120 ms. All parameters were evaluated by conventional and tissue Doppler‐based methods. Indicator of positive CRT response was more than 20% in improvement of LVEF. Results: LVEF increased >20% in 42 patients. Out of 43 tested baseline echocardiographic parameters, 12 showed statistical difference between responders and nonresponders. Out of these 12 parameters, six (LVSV, LVSI, LVFS, RVd, VPMR, and PISA) had modest to moderately good ability to predict LVEF response with sensitivity ranging from 62.2% to 82.4%, and specificity ranging from 56.5% to 81.2%. For those parameters, the area under the receiver‐operating characteristic curve for positive response to CRT was ≤0.76. Multivariate regression analysis resulted in selection of LVSI and LVFS as possible predictive independent parameters for a good response. The cutoff value for LVSI was 38.7 mL/m² (P = 0.045) and for LVFS was 13% (P = 0.032). Conclusions: Contribution of LVSI and LVFS is to be confirmed in larger trials. Simplicity of their assessment by conventional echocardiography could be an argument for adding them to the inclusion criteria for CRT in severe heart failure patients. (Echocardiography 2012;29:267‐275)     

Joint attention in autism: Teaching smiling coordinated with gaze to respond to joint attention bids

Children with autism demonstrate early deficits in joint attention and expressions of affect. Interventions to teach joint attention have addressed gaze behavior, gestures, and vocalizations, but have not specifically taught an expression of positive affect such as smiling that tends to occur during joint attention interactions. Intervention was applied to teach smile and gaze shift with eye contact to respond to others’ joint attention instructions. All targeted responses increased during intervention, with generalized performance as well as maintenance of performance during follow-up. Related measures of joint attention and characteristics of autism showed overall improvements from pre- to post-intervention.