Establishing comprehensive, quantitative criteria for detection of restenosis and remodeling after percutaneous transluminal coronary angioplasty

To establish comprehensive criteria for detecting restenosis and remodeling, inter- and intraobserver reproducibiltty of quantitative arteriography in the analysis of 20 lesions immediately after and 6 months after percutaneous transluminal coronary angioplasty (PTCA) were assessed. Geometric single-plane (minimum, maximum, mean diameter and percent diameter stenosis), biplane (absolute and relative cross-sectional area stenosis), relative densitometric area stenosis and the average of densitometric area stenosis in orthogonal views were compared. A high intra- and interobserver reproducibility of all absolute measurements was found, with the highest correlations for minimum diameter and cross-sectional area (interobserver, R = 0.85 and 0.85; intraobserver, R = 0.93, and 0.95 for minimum diameter and cross-sectional area, respectively). Of the relative measurements, biplane geometric percent crosssectional area stenosis was the most reliable and percent densitometric area stenosis was the most variable (Interobserver, R = 0.67; intraobserver, R = 0.71). Only small differences were demonstrated for the absolute measurements between the analysis of lesions immediately after PTCA and after follow-up, whereas a greater variability was found for relative measurements, especially videodensitometry. In both circumstances, a poor correlation between relative densitometric crosssectional area from orthogonal views was found, whereas geometric elliptical cross-sectional area correlated quite well with the average of densitometric percent cross-sectional area in orthogonal views (interobserver, R = 0.86; intraobserver, R = 0.84). Thus, data in this study support the suitability of geometric quantitative analysis for the assessment of PTCA results. Densitometry was the least reliable quantitative parameter.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30287/1/0000689.pd

Clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy

AbstractTo define the clinical, angiographic and procedural correlates of quantitative coronary dimensions after directional coronary atherectomy, 400 lesions in 378 patients were analyzed with use of qualitative morphologic and quantitative angiographic methods. Successful atherectomy, defined by a <75% residual area stenosis, tissue retrieval and the absence of in-hospital ischemic complications, was performed in 351 lesions (87.7%). After atherectomy, minimal cross-sectional area increased from 1.2 ± 1.1 to 6.6 ± 4.4 mm2(p < 0.001) and percent area stenosis was reduced from 87 ± 10% to 31 ± 42% (p < 0.001).By univariate analysis, device size (p < 0.001) and left circumflex artery lesion location (p = 0.004) were associated with a larger final minimal cross-sectional area. Conversely, restenotic lesion (p = 0.002), lesion length ≥ 10 mm (p = 0.018) and lesion calcification (p = 0.035) were quantitatively associated with a smaller final minimum cross-sectional area. With use of stepwise multivariate analysis to control for the reference area, atherectomy device size (p = 0.003) and left circumflex lesion location (p = 0.007) were independently associated with a larger final minimal cross-sectional area, whereas restenotic lesion (p = 0.010), diffuse proximal disease (p = 0.033), lesion length ≥ 10 mm (p = 0.026) and lesion calcification (p = 0.081) were significantly correlated with a smaller final minimal cross-sectional area. The number of specimens excised, the number of atherectomy passes and atherectomy balloon inflation pressure did not correlate with the final minimal cross-sectional area.Thus, directional atherectomy results in marked improvement of coronary lumen dimensions, at least in part correlated with the presence of certain clinical, angiographic and procedural factors at the time of atherectomy

Zotarolimus-Eluting Versus Bare-Metal Stents in Uncertain Drug-Eluting Stent Candidates

BACKGROUND The use of drug-eluting stents (DES) in patients at high risk of bleeding or thrombosis has not been prospectively studied; limited data are available in patients who have a low restenosis risk. OBJECTIVES This study sought to compare a hydrophilic polymer-based, second-generation zotarolimus-eluting stent (ZES) with a unique drug fast-release profile versus bare-metal stents (BMS) under similar durations of dual-antiplatelet therapy (DAPT). METHODS We randomly assigned 1,606 patients with stable or unstable symptoms, and who on the basis of thrombotic bleeding or restenosis risk criteria, qualified as uncertain candidates for DES, to receive ZES or BMS. DAPT duration was on the basis of patient characteristics, rather than stent characteristics, and allowed for a personalized 1-month dual antiplatelet regimen. The primary endpoint was the risk of 1-year major adverse cardiovascular events (MACE), which included death, myocardial infarction (MI), or target vessel revascularization (TVR). RESULTS Median DAPT duration was 32 days (interquartile range [IQR]: 30 to 180 days) and did not differ between the groups. In the ZES group, 140 patients (17.5%) reached the primary endpoint, compared with 178 patients (22.1%) in the BMS group (hazard ratio: 0.76; 95% confidence interval: 0.61 to 0.95; p = 0.011) as a result of lower MI (2.9% vs. 8.1%; p < 0.001) and TVR rates (5.9% vs. 10.7%; p = 0.001) in the ZES group. Definite or probable stent thrombosis was also significantly reduced in ZES recipients (2.0% vs. 4.1%; p = 0.019). CONCLUSIONS Compared with BMS, DES implantation using a stent with a biocompatible polymer and fast drug-eluting characteristics, combined with an abbreviated, tailored DAPT regimen, resulted in a lower risk of 1-year MACE in uncertain candidates for DES implantation. (Zotarolimus-eluting Endeavor Sprint Stent in Uncertain DES Candidates [ZEUS] Study; NCT01385319) (C) 2015 by the American College of Cardiology Foundation

Phase II Randomized Study of Vandetanib Plus Gemcitabine or Gemcitabine Plus Placebo as First-Line Treatment of Advanced Non–Small-Cell Lung Cancer in Elderly Patients

Introduction:The aim of the present study was to evaluate the efficacy and tolerability of vandetanib plus gemcitabine (V/G) compared with gemcitabine alone in elderly patients with untreated advanced non–small-cell lung cancer.Methods:This was a phase II, randomized, double-blind study. A total of 124 elderly patients (mean age, 75 yr; age range, 70–84 yr; 73% men) received V/G (n = 61) or placebo plus gemcitabine (n = 63). Progression-free survival (PFS) was the primary endpoint. Secondary endpoints were overall survival, objective response rate, duration of response, disease control rate, time to deterioration of performance status, and safety outcomes.Results:PFS was significantly prolonged with V/G (median, 183 days; 95% confidence interval, 116–214) compared with placebo plus gemcitabine (median, 169 days; 95% confidence interval, 95–194; p = 0.047). No statistically significant differences between arms were observed in all secondary endpoints, including overall survival. The addition of vandetanib to gemcitabine was well tolerated. The rate of patients with ≥1 treatment-related adverse event was comparable in the two arms, pyrexia, dyspnea, and neutropenia being the most common adverse events.Conclusions:V/G combination was associated with a statistically significant prolongation of PFS compared with gemcitabine alone in untreated elderly patients with advanced non–small-cell lung cancer, with an acceptable safety profile

Clinical angiographic and histologic correlates of eetasia after directional coronary atherectomy

Directional coronary atherectomy can cause ectasia (final area stenosis = 75%, was present in 50% of patients without procedural ectasia and in 70% of patients with marked ectasia (residual area stenosis &lt;-20%; P = 0.12). It is concluded that excision beyond the normal arterial lumen may occur after directional coronary atherectomy, related, in part, to angiographic and procedural features noted at the time of atherectomy. Restenosis tends to occur more often in patients with marked ectasia after coronary atherectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30232/1/0000626.pd

Quantitative analysis of factors influencing late lumen loss and restenosis after directional coronary atherectomy

Although encouraging initial results have been demonstrated after directional atherectomy, the mechanisms and predictors of late lumen loss and restenosis after this procedure have not been evaluated. To examine these issues, clinical and angiographic follow-up were obtained in 262 (96%) and 212 (77%) of 274 patients undergoing successful directional coronary atherectomy. Symptom recurrence developed in 87 (33%) patients and angiographic restenosis was found in 93 (44%). Restenosis was highest in restenotic lesions in saphenous vein grafts (78% [95% confidence interval (CI): 56 to 100%]) and lowest in new-onset lesions in the left anterior descending (27% [95% CI: 15 to 39%]) and circumflex (14% [95% CI: 0 to 43%]) coronary arteries. Residual lumen diameter immediately after atherectomy was smaller in re-stenotic lesions (p = 0.002) and in lesions &gt;=10 mm in length (p = 0.02). Late lumen loss was associated with the minimal lumen diameter immediately after atherectomy (p =10 mm in length (p = 0.018), saphenous vein graft lesion location (p = 0.025) and male gender (p = 0.045) were independent predictors for restenosis. It is concluded that restenosis after directional atherectomy is related both to factors resulting in a suboptimal initial result and to factors contributing to excessive late lumen loss. These results may have implications for lesion selection in patients undergoing directional coronary atherectomy.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/30957/1/0000629.pd

A zinc, copper and citric acid biocomplex shows promise for control of Xylella fastidiosa subsp. pauca in olive trees in Apulia region (southern Italy)

The bacterium Xylella fastidiosa subsp. pauca is associated with the “olive quick decline syndrome” in the Apulia region of southern Italy. To investigate control of this phytopathogen, a compound containing zinc and copper complexed with citric-acid hydracids (Dentamet®) was evaluated for in vitro and in planta bactericidal activity. Confocal laser scanning microscopy, fluorescent quantification and atomic emission spectroscopy were then used to determine if the compound reached the xylem networks of leaves, twigs and branches of olive, to release zinc and copper within the xylem. A 3-year field trial in an olive orchard containing mature Cellina di Nardò and Ogliarola salentina olive trees, and officially declared infected by X. fastidiosa subsp. pauca,was also carried out o to determine if the compound affected severity of the disease. Each year, from early April to October (excluding July and August), six spray treatments of 0.5% (v:v) Dentamet® were applied on the olive tree crowns. The compound reduced severity of symptoms in both cultivars. Most untreated trees died by the end of the trial, whereas all treated trees survived with good vegetative status as assessed by a normalized difference vegetation index. Quantitative real-time PCR was performed from June 2016 to September 2017, following the official procedures established by the European and Mediterranean Plant Protection Organization. The analysis revealed a statistically significant reduction of X. fastidiosa cell densities within the leaves of treated trees. These promising results suggest that integrated management to reduce severity of X. fastidiosa that includes regular pruning and soil harrowing with spring and summer spray treatments with Dentamet®, is likely to effectively control the disease.

A chemical survey of exoplanets with ARIEL

Thousands of exoplanets have now been discovered with a huge range of masses, sizes and orbits: from rocky Earth-like planets to large gas giants grazing the surface of their host star. However, the essential nature of these exoplanets remains largely mysterious: there is no known, discernible pattern linking the presence, size, or orbital parameters of a planet to the nature of its parent star. We have little idea whether the chemistry of a planet is linked to its formation environment, or whether the type of host star drives the physics and chemistry of the planet’s birth, and evolution. ARIEL was conceived to observe a large number (~1000) of transiting planets for statistical understanding, including gas giants, Neptunes, super-Earths and Earth-size planets around a range of host star types using transit spectroscopy in the 1.25–7.8 μm spectral range and multiple narrow-band photometry in the optical. ARIEL will focus on warm and hot planets to take advantage of their well-mixed atmospheres which should show minimal condensation and sequestration of high-Z materials compared to their colder Solar System siblings. Said warm and hot atmospheres are expected to be more representative of the planetary bulk composition. Observations of these warm/hot exoplanets, and in particular of their elemental composition (especially C, O, N, S, Si), will allow the understanding of the early stages of planetary and atmospheric formation during the nebular phase and the following few million years. ARIEL will thus provide a representative picture of the chemical nature of the exoplanets and relate this directly to the type and chemical environment of the host star. ARIEL is designed as a dedicated survey mission for combined-light spectroscopy, capable of observing a large and well-defined planet sample within its 4-year mission lifetime. Transit, eclipse and phase-curve spectroscopy methods, whereby the signal from the star and planet are differentiated using knowledge of the planetary ephemerides, allow us to measure atmospheric signals from the planet at levels of 10–100 part per million (ppm) relative to the star and, given the bright nature of targets, also allows more sophisticated techniques, such as eclipse mapping, to give a deeper insight into the nature of the atmosphere. These types of observations require a stable payload and satellite platform with broad, instantaneous wavelength coverage to detect many molecular species, probe the thermal structure, identify clouds and monitor the stellar activity. The wavelength range proposed covers all the expected major atmospheric gases from e.g. H2O, CO2, CH4 NH3, HCN, H2S through to the more exotic metallic compounds, such as TiO, VO, and condensed species. Simulations of ARIEL performance in conducting exoplanet surveys have been performed – using conservative estimates of mission performance and a full model of all significant noise sources in the measurement – using a list of potential ARIEL targets that incorporates the latest available exoplanet statistics. The conclusion at the end of the Phase A study, is that ARIEL – in line with the stated mission objectives – will be able to observe about 1000 exoplanets depending on the details of the adopted survey strategy, thus confirming the feasibility of the main science objectives.Peer reviewedFinal Published versio

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London