Biodegradable polymer drug-eluting stents reduce the risk of stent thrombosis at 4 years in patients undergoing percutaneous coronary intervention: a pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials

Aims The efficacy of durable polymer drug-eluting stents (DES) is delivered at the expense of delayed healing of the stented vessel. Biodegradable polymer DES aim to avoid this shortcoming and may potentially improve long-term clinical outcomes, with benefit expected to accrue over time. We sought to compare long-term outcomes in patients treated with biodegradable polymer DES vs. durable polymer sirolimus-eluting stents (SES). Methods and results We pooled individual patient data from three large-scale multicentre randomized clinical trials (ISAR-TEST 3, ISAR-TEST 4, and LEADERS) comparing biodegradable polymer DES with durable polymer SES and assessed clinical outcomes during follow-up through 4 years. The efficacy endpoint of interest was target lesion revascularization and the safety endpoint of interest was definite stent thrombosis. Out of 4062 patients included in the present analysis, 2358 were randomly assigned to treatment with biodegradable polymer DES (sirolimus-eluting, n= 1501; biolimus-eluting, n= 857) and 1704 patients to durable polymer SES. No heterogeneity across the trials was observed in analyses of the primary and secondary endpoints. At 4 years, the risk of target lesion revascularization was significantly lower among patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.82, 95% CI 0.68-0.98, P= 0.029). In addition, the risk of stent thrombosis was significantly reduced with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.56, 95% CI 0.35-0.90, P= 0.015), driven by a lower risk of very late stent thrombosis (hazard ratio 0.22, 95% CI 0.08-0.61, P= 0.004). In keeping with this, in landmark analysis between 1 and 4 years, the incidence of myocardial infarction was lower for patients treated with biodegradable polymer DES vs. durable polymer SES (hazard ratio 0.59, 95% CI 0.73-0.95, P= 0.031). Conclusion Biodegradable polymer DES improve safety and efficacy compared with durable polymer SES during long-term follow-up to 4 year

Protocol for an economic evaluation of the randomised controlled trial of culprit lesion only PCI versus immediate multivessel PCI in acute myocardial infarction complicated by cardiogenic shock: CULPRIT-SHOCK trial

CULPRIT-SHOCK is a Collaboration Project funded by the European Union under the 7th Framework Programme under grant agreement no 602202)

A randomized comparison of novel bioresorbable polymer sirolimus-eluting stent and durable polymer everolimus-eluting stent in patients with acute coronary syndromes : the CENTURY II high risk ACS substudy

AbstractBackgroundTo investigate clinical outcomes of percutaneous coronary intervention using a sirolimus-eluting stent with bioresorbable polymer, Ultimaster (BP-SES) compared with a permanent polymer everolimus-eluting stent, Xience (PP-EES) in patients with high risk (ST-segment elevation and non-ST-segment elevation myocardial infarction) acute coronary syndromes (ACS) enrolled in the CENTURY II trial.MethodsCENTURY II is a prospective, multicenter, randomized, single blind, controlled trial comparing BP-SES and PP-EES, with primary endpoint of target lesion failure (TLF) at 9month post-stent implantation. Out of 1123 patients enrolled in CENTURY II trial, 264 high risk ACS patients were included in this subgroup analysis, and the clinical outcomes including target lesion failure (TLF), target vessel failure (TVF), cardiac death, myocardial infarction, and stent thrombosis were evaluated at 24months.ResultsThe baseline clinical, angiographic and procedural characteristics were similar between two groups. At 24months, TLF occurred in 6.3% of patients receiving a BP-SES and 6.5% of patients receiving a PP-EES (P=0.95); TVF was 6.3% in patients receiving a BP-SES and 9.4% in patients receiving a PP-EES (P=0.36). There were no significant differences in cardiac death, myocardial infarction and stent thrombosis rate.ConclusionsBP-SES achieved similar safety and efficacy outcomes as PP-EES in this ACS subgroup of CENTURY II study, at 24-month follow-up. This finding is hypothesis-generating and needs to be confirmed in larger trials with longer follow-up

Cardiac magnetic resonance imaging parameters as surrogate endpoints in clinical trials of acute myocardial infarction

Cardiac magnetic resonance (CMR) offers a variety of parameters potentially suited as surrogate endpoints in clinical trials of acute myocardial infarction such as infarct size, myocardial salvage, microvascular obstruction or left ventricular volumes and ejection fraction. The present article reviews each of these parameters with regard to the pathophysiological basis, practical aspects, validity, reliability and its relative value (strengths and limitations) as compared to competitive modalities. Randomized controlled trials of acute myocardial infarction which have used CMR parameters as a primary endpoint are presented

Nuclear FABP7 immunoreactivity is preferentially expressed in infiltrative glioma and is associated with poor prognosis in EGFR-overexpressing glioblastoma

BACKGROUND: We previously identified brain type fatty acid-binding protein (FABP7) as a prognostic marker for patients with glioblastoma (GBM). Increased expression of FABP7 is associated with reduced survival. To investigate possible molecular mechanisms underlying this association, we compared the expression and subcellular localization of FABP7 in non-tumor brain tissues with different types of glioma, and examined the expression of FABP7 and epidermal growth factor receptor (EGFR) in GBM tumors. METHODS: Expression of FABP7 in non-tumor brain and glioma specimens was examined using immunohistochemistry, and its correlation to the clinical behavior of the tumors was analyzed. We also analyzed the association between FABP7 and EGFR expression in different sets of GBM specimens using published DNA microarray datasets and semi-quantitative immunohistochemistry. In vitro migration was examined using SF763 glioma cell line. RESULTS: FABP7 was present in a unique population of glia in normal human brain, and its expression was increased in a subset of reactive astrocytes. FABP7 immunoreactivity in grade I pilocytic astrocytoma was predominantly cytoplasmic, whereas nuclear FABP7 was detected in other types of infiltrative glioma. Nuclear, not cytoplasmic, FABP7 immunoreactivity was associated with EGFR overexpression in GBM (N = 61, p = 0.008). Expression of the FABP7 gene in GBM also correlated with the abundance of EGFR mRNA in our previous microarray analyses (N = 34, p = 0.016) and an independent public microarray dataset (N = 28, p = 0.03). Compared to those negative for both markers, nuclear FABP7-positive/EGFR-positive and nuclear FABP7-positive/EGFR-negative GBM tumors demonstrated shortest survival, whereas those only positive for EGFR had intermediate survival. EGFR activation increased nuclear FABP7 immunoreactivity in a glioma cell line in vitro, and inhibition of FABP7 expression suppressed EGF-induced glioma-cell migration. Our data suggested that in EGFR-positive GBM the presence of nuclear FABP7 immunoreactivity increases the risk of poor prognosis CONCLUSION: In this study, we identified a possible mechanism as the basis of the association between nuclear FABP7 and poor prognosis of GBM. FABP7 expression can be found in all grades of astrocytoma, but neoplastic cells with nuclear FABP7 were only seen in infiltrative types of tumors. Nuclear FABP7 may be induced by EGFR activation to promote migration of GBM tumor cells. Positive nuclear FABP7 and EGFR overexpression correlated with short survival in EGFR-positive GBM patients. Therefore, nuclear FABP7 immunoreactivity could be used to monitor the progression of EGFR-overexpressed GBM

О перспективе извлечения йода из продукта утилизации окислителя ракетного топлива

Crop models are essential tools for assessing the threat of climate change to local and global food production. Present models used to predict wheat grain yield are highly uncertain when simulating how crops respond to temperature. Here we systematically tested 30 different wheat crop models of the Agricultural Model Intercomparison and Improvement Project against field experiments in which growing season mean temperatures ranged from 15 degrees C to 32 degrees C, including experiments with artificial heating. Many models simulated yields well, but were less accurate at higher temperatures. The model ensemble median was consistently more accurate in simulating the crop temperature response than any single model, regardless of the input information used. Extrapolating the model ensemble temperature response indicates that warming is already slowing yield gains at a majority of wheat-growing locations. Global wheat production is estimated to fall by 6% for each degree C of further temperature increase and become more variable over space and time

Loss of chromosome 10 is an independent prognostic factor in high-grade gliomas

Loss of heterozygosity (LOH) for chromosome 10 is the most frequent genetic abnormality observed in high-grade gliomas. We have used fluorescent microsatellite markers to examine a series of 83 patients, 34 with anaplastic astrocytoma (grade 3) and 49 with glioblastoma multiforme (grade 4), for LOH of chromosome 10. Genotype analysis revealed LOH for all informative chromosome 10 markers in 12 (35%) of patients with grade 3 and 29 (59%) grade 4 tumours respectively, while partial LOH was found in a further eight (24%) grade 3 and ten (20%) grade 4 tumours. Partial LOH, was confined to the long arm (10q) in six and the short arm (10p) in three cases, while alleles from both arms were lost in four cases. Five tumours (one grade 3 and four grade 4) showed heterogeneity with respect to loss at different loci. There was a correlation between any chromosome 10 loss and poorer performance status at presentation (χ2P = 0.005) and with increasing age at diagnosis (Mann–Whitney U-test P = 0.034) but not with tumour grade (χ2P = 0.051). A Cox multivariate model for survival duration identified age (proportional hazards (PH), P = 0.004), grade (PH, P = 0.012) and any loss of chromosome 10 (PH, P = 0.009) as the only independent prognostic variables. Specifically, LOH for chromosome 10 was able to identify a subgroup of patients with grade 3 tumours who had a significantly shorter survival time. We conclude that LOH for chromosome 10 is an independent, adverse prognostic variable in high-grade glioma. © 1999 Cancer Research Campaig

The International Heat Stress Genotype Experiment for modeling wheat response to heat: field experiments and AgMIP-Wheat multi-model simulations

The data set contains a portion of the International Heat Stress Genotype Experiment (IHSGE) data used in the AgMIP-Wheat project to analyze the uncertainty of 30 wheat crop models and quantify the impact of heat on global wheat yield productivity. It includes two spring wheat cultivars grown during two consecutive winter cropping cycles at hot, irrigated, and low latitude sites in Mexico (Ciudad Obregon and Tlaltizapan), Egypt (Aswan), India (Dharwar), the Sudan (Wad Medani), and Bangladesh (Dinajpur). Experiments in Mexico included normal (November-December) and late (January-March) sowing dates. Data include local daily weather data, soil characteristics and initial soil conditions, crop measurements (anthesis and maturity dates, anthesis and final total above ground biomass, final grain yields and yields components), and cultivar information. Simulations include both daily in-season and end-of-season results from 30 wheat models

The 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial: study protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Second-generation drug-eluting stents (DES) have raised the bar of clinical performance. These stents are mostly made from cobalt chromium alloy. A newer generation DES has been developed from platinum chromium alloy, but clinical data regarding the efficacy and safety of the platinum chromium-based everolimus-eluting stent (PtCr-EES) is limited, with no comparison data against the cobalt chromium-based zotarolimus-eluting stent (CoCr-ZES). In addition, an antiplatelet regimen is an integral component of medical therapy after percutaneous coronary intervention (PCI). A 1-week duration of doubling the dose of clopidogrel (double-dose antiplatelet therapy (DDAT)) was shown to improve outcome at 1 month compared with conventional dose in acute coronary syndrome (ACS) patients undergoing PCI. However in Asia, including Korea, the addition of cilostazol (triplet antiplatelet therapy (TAT)) is used more commonly than doubling the dose of clopidogrel in high-risk patients.</p> <p>Methods</p> <p>In the 'Harmonizing Optimal Strategy for Treatment of coronary artery stenosis - sAfety & effectiveneSS of drug-elUting stents & antiplatelet REgimen' (HOST-ASSURE) trial, approximately 3,750 patients are being prospectively and randomly assigned in a 2 × 2 factorial design according to the type of stent (PtCr-EES vs CoCr-ZES) and antiplatelet regimen (TAT vs DDAT). The first primary endpoint is target lesion failure at 1 year for the stent comparison, and the second primary endpoint is net clinical outcome at 1 month for comparison of antiplatelet therapy regimen.</p> <p>Discussion</p> <p>The HOST-ASSURE trial is the largest study yet performed to directly compare the efficacy and safety of the PtCr-EES versus CoCr-ZES in an 'all-comers' population. In addition, this study will also compare the clinical outcome of TAT versus DDAT for 1-month post PCI.</p> <p>Trial registration</p> <p>ClincalTrials.gov number <a href="http://www.clinicaltrials.gov/ct2/show/NCT01267734">NCT01267734</a>.</p

AgMIP-Wheat multi-model simulations on climate change impact and adaptation for global wheat, SDATA-20-01059

The climate change impact and adaptation simulations from the Agricultural Model Intercomparison and Improvement Project (AgMIP) for wheat provide a unique dataset of multi-model ensemble simulations for 60 representative global locations covering all global wheat mega environments. The multi-model ensemble reported here has been thoroughly benchmarked against a large number of experimental data, including different locations, growing season temperatures, atmospheric CO2 concentration, heat stress scenarios, and their interactions. In this paper, we describe the main characteristics of this global simulation dataset. Detailed cultivar, crop management, and soil datasets were compiled for all locations to drive 32 wheat growth models. The dataset consists of 30-year simulated data including 25 output variables for nine climate scenarios, including Baseline (1980-2010) with 360 or 550 ppm CO2, Baseline +2oC or +4oC with 360 or 550 ppm CO2, a mid-century climate change scenario (RCP8.5, 571 ppm CO2), and 1.5°C (423 ppm CO2) and 2.0oC (487 ppm CO2) warming above the pre-industrial period (HAPPI). This global simulation dataset can be used as a benchmark from a well-tested multi-model ensemble in future analyses of global wheat. Also, resource use efficiency (e.g., for radiation, water, and nitrogen use) and uncertainty analyses under different climate scenarios can be explored at different scales. The DOI for the dataset is 10.5281/zenodo.4027033 (AgMIP-Wheat, 2020), and all the data are available on the data repository of Zenodo (doi: 10.5281/zenodo.4027033).Two scientific publications have been published based on some of these data here