Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation in the treatment of primary great saphenous vein incompetence (MARADONA):Study protocol for a randomized controlled trial

BACKGROUND: Radiofrequency ablation (RFA) is associated with an excellent outcome in the treatment of great saphenous vein (GSV) incompetence. The use of thermal energy as a treatment source requires the instillation of tumescence anesthesia. Mechanochemical endovenous ablation (MOCA) combines mechanical endothelial damage, using a rotating wire, with the infusion of a liquid sclerosant. Tumescence anesthesia is not required. Preliminary experiences with MOCA showed good results and low post-procedural pain. METHODS/DESIGN: The MARADONA (Mechanochemical endovenous Ablation versus RADiOfrequeNcy Ablation) trial is a multicenter randomized controlled trial in which 460 patients will be randomly allocated to MOCA or RFA. All patients with primary GSV incompetence who meet the eligibility criteria will be invited to participate in this trial. The primary endpoints are anatomic and clinical success at a one-year follow-up, and post-procedural pain. The secondary endpoints are technical success, complications, operation time, procedural pain, disease-specific quality of life, time taken to return to daily activities and/or work, and cost-efficiency analyses after RFA or MOCA. Both groups will be evaluated on an intention to treat base. DISCUSSION: The MARADONA trial is designed to show equal results in anatomic and clinical success after one year, comparing MOCA with RFA. In our hypothesis MOCA has an equal anatomic and clinical success compared with RFA, with less post-procedural pain. TRIAL REGISTRATION: Clinicaltrials NCT0193616

Serial [F-18]-FDHT-PET to predict bicalutamide efficacy in patients with androgen receptor positive metastatic breast cancer

Background: The androgen receptor (AR) is a potential target in metastatic breast cancer (MBC), and 16 beta-[F-18]-fluoro-5 alpha-dihydrotestosterone positron emission tomography ([F-18]-FDHT-PET) can be used for noninvasive visualisation of AR. [F-18]-FDHT uptake reduction during AR-targeting therapy reflects AR occupancy and might be predictive for treatment response. We assessed the feasibility of [F-18]-FDHT-PET to detect changes in AR availability during bicalutamide treatment and correlated these changes with treatment response. Patients and methods: Patients with AR thorn MBC, regardless of oestrogen receptor status, received an [F-18]-FDHT-PET at baseline and after 4-6 weeks bicalutamide treatment. Baseline [F-18]-FDHT uptake was expressed as maximum standardised uptake value. Percentage change in tracer uptake, corrected for background activity (SUVcor), between baseline and follow-up PET scan (% reduction), was assessed per-patient and lesion. Clinical benefit was determined in accordance with Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 or clinical evaluation (absence of disease progression for >= 24 weeks). Results: Baseline [F-18]-FDHT-PET in 21 patients detected 341 of 515 lesions found with standard imaging and 21 new lesions. Follow-up [F-18]-FDHT- PET was evaluable in 17 patients with 349 lesions, showing a decrease in median SUVcor from 1.3 to 0.7 per-patient and lesion (P <0.001). Median % reduction per-patient was - 45% and per-lesion -39%. In patients with progressive disease (n Z 11), median % reduction was -30% versus -53% for patients who showed clinical benefit (in accordance with RECIST (n = 3) or clinical evaluation (n = 3); P Z 0.338). Conclusion: In this feasibility study, a bicalutamide-induced reduction in [F-18]-FDHT uptake could be detected by follow-up [F-18]-FDHT-PET in patients with AR thorn MBC. However, this change could not predict bicalutamide response. (C) 2020 The Authors. Published by Elsevier Ltd

Current discharge management of acute coronary syndromes: data from the Rijnmond Collective Cardiology Research (CCR) study

BACKGROUND: Medical discharge management of acute coronary syndromes (ACS) remains suboptimal outside randomised trials and constitutes an essential quality benchmark for ACS. We sought to evaluate the rates of key guideline-recommended pharmacological agents after ACS and characteristics associated with optimal treatment at discharge. METHODS: The Rijnmond Collective Cardiology Research (CCR) registry is an ongoing prospective, observational study in the Netherlands that aims to enrol 4000 patients with ACS. We examined discharge and 1-month follow-up medication use among the first 1000 patients enrolled in the CCR registry. Logistic regression was performed to identify patient and hospital characteristics associated with collective guideline-recommended pharmacotherapy at hospital discharge. RESULTS: At discharge, 94 % of patients received aspirin, 100 % thienopyridines, 80 % angiotensin-converting enzyme inhibitors/angiotensin-II receptor blockers, 87 % β-blockers, 96 % statins, and 65 % the combination of all 5 agents. ST-segment elevation myocardial infarction, hypertension, hypercholesterolaemia, and enrolment in an interventional centre were positive independent predictors of 5-drug combination therapy at discharge. Negative independent predictors were unstable angina and advanced age. CONCLUSION: Current data from the CCR registry reflect a high quality of care for ACS discharge management in the Rotterdam-Rijnmond region. However, potential still remains for further optimisation

Distribution of Matrix Metalloproteinases in Human Atherosclerotic Carotid Plaques and Their Production by Smooth Muscle Cells and Macrophage Subsets

In this study, the potential of matrix metalloproteinase (MMP) sense for detection of atherosclerotic plaque instability was explored. Secondly, expression of MMPs by macrophage subtypes and smooth muscle cells (SMCs) was investigated. Twenty-three consecutive plaques removed during carotid endarterectomy were incubated in MMPSense (TM) 680 and imaged with IVISA (R) Spectrum. mRNA levels of MMPs, macrophage markers, and SMCs were determined in plaque specimens, and in in vitro differentiated M1 and M2 macrophages. There was a significant difference between autofluorescence signals and MMPSense signals, both on the intraluminal and extraluminal sides of plaques. MMP-9 and CD68 messenger RNA (mRNA) expression was higher in hot spots, whereas MMP-2 and alpha SMA expression was higher in cold spots. In vitro M2 macrophages had higher mRNA expression of MMP-1, MMP-9, MMP-12, and TIMP-1 compared to M1 macrophages. MMP-9 is most dominantly MMP present in atherosclerotic plaques and is produced by M2 rather than M1 macrophages

Occupational exposure to gases/fumes and mineral dust affect DNA methylation levels of genes regulating expression

Many workers are daily exposed to occupational agents like gases/fumes, mineral dust or biological dust, which could induce adverse health effects. Epigenetic mechanisms, such as DNA methylation, have been suggested to play a role. We therefore aimed to identify differentially methylated regions (DMRs) upon occupational exposures in never-smokers and investigated if these DMRs associated with gene expression levels. To determine the effects of occupational exposures independent of smoking, 903 never-smokers of the LifeLines cohort study were included. We performed three genome-wide methylation analyses (Illumina 450 K), one per occupational exposure being gases/fumes, mineral dust and biological dust, using robust linear regression adjusted for appropriate confounders. DMRs were identified using comb-p in Python. Results were validated in the Rotterdam Study (233 never-smokers) and methylation-expression associations were assessed using Biobank-based Integrative Omics Study data (n = 2802). Of the total 21 significant DMRs, 14 DMRs were

Investigation of the Exclusive 3He(e,e'pp)n Reaction

Cross sections for the 3He(e,e'pp)n reaction were measured over a wide range of energy and three- momentum transfer. At a momentum transfer q=375 MeV/c, data were taken at transferred energies omega ranging from 170 to 290 MeV. At omega=220 MeV, measurements were performed at three q values (305, 375, and 445 MeV/c). The results are presented as a function of the neutron momentum in the final-state, as a function of the energy and momentum transfer, and as a function of the relative momentum of the two-proton system. The data at neutron momenta below 100 MeV/c, obtained for two values of the momentum transfer at omega=220 MeV, are well described by the results of continuum-Faddeev calculations. These calculations indicate that the cross section in this domain is dominated by direct two-proton emission induced by a one-body hadronic current. Cross section distributions determined as a function of the relative momentum of the two protons are fairly well reproduced by continuum-Faddeev calculations based on various realistic nucleon-nucleon potential models. At higher neutron momentum and at higher energy transfer, deviations between data and calculations are observed that may be due to contributions of isobar currents.Comment: 14 pages, 1 table, 17 figure

Spin-Momentum Correlations in Quasi-Elastic Electron Scattering from Deuterium

We report on a measurement of spin-momentum correlations in quasi-elastic scattering of longitudinally polarized electrons with an energy of 720 MeV from vector-polarized deuterium. The spin correlation parameter $A^V_{ed}$ was measured for the $^2 \vec{\rm H}(\vec e,e^\prime p)n$ reaction for missing momenta up to 350 MeV/$c$ at a four-momentum transfer squared of 0.21 (GeV/c)$^2$. The data give detailed information about the spin structure of the deuteron, and are in good agreement with the predictions of microscopic calculations based on realistic nucleon-nucleon potentials and including various spin-dependent reaction mechanism effects. The experiment demonstrates in a most direct manner the effects of the D-state in the deuteron ground-state wave function and shows the importance of isobar configurations for this reaction.Comment: 4 pages, 3 figures, submitted to Phys. Rev. Lett. for publicatio