Woodshaas2103

9% and 72.3% of mice, respectively. Plaque volume, macrophage accumulation, and phenotype switching of vascular smooth muscle cells were advanced in the IR group. Irradiated samples showed increased persistent DNA damage response (53BP1 [p53 binding protein 1]), upregulated cyclin-dependent kinase inhibitors (p16INK4a and p21), and elevated inflammatory chemokines expression (monocyte chemotactic protein-1, keratinocyte-derived chemokine, and macrophage inflammatory protein 2). Conclusions IR promoted plaque growth in murine carotid arteries. Our findings support the possibility that senescence-associated secretory phenotype aggravates atherogenesis in irradiated artery. This mice model might contribute to mechanism elucidation of radiation-induced atherosclerosis.Background Guidelines recommend mineralocorticoid receptor antagonist (MRA) use in patients with left ventricular ejection fraction ≤40% following a myocardial infarction plus heart failure or diabetes mellitus, based on mortality benefit in the EPHESUS (Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study) trial. see more The objective of this study was to evaluate the real-world utilization of MRAs for patients with ST-segment-elevation myocardial infarction (STEMI) with left ventricular dysfunction. Methods and Results The prospective, population-based, Vancouver Coastal Health Authority STEMI database was linked with local outpatient cardiology records from 2007 to 2018. EPHESUS criteria were used to define post-STEMI MRA eligibility (left ventricular ejection fraction ≤40% plus clinical heart failure or diabetes mellitus, and no dialysis-dependent renal dysfunction). The primary outcome was MRA prescription among eligible patients at discharge and the secondary outcome was MRA prescription within 3 months postdischarge. Of 2691 patients with STEMI, 317 (12%) were MRA eligible, and 70 (22%) eligible patients were prescribed an MRA at discharge. Among eligible patients with no MRA at discharge, 12/126 (9.5%) with documented postdischarge follow-up were prescribed an MRA within 3 months. In multivariable analysis, left ventricular ejection fraction (odds ratio [OR], 1.55 per 5% left ventricular ejection fraction decrease; 95% CI, 1.26-1.90) and calendar year (OR, 1.23 per year, 95% CI, 1.11-1.37) were associated with MRA prescription at discharge. Other prespecified variables were not associated with MRA prescription. link2 Conclusions In this contemporary STEMI cohort, only 1 in 4 MRA-eligible patients were prescribed an MRA within 3 months following hospitalization despite high-quality evidence for use. Novel decision-support tools are required to optimize pharmacotherapy decisions during hospitalization and follow-up to target this gap in post-STEMI care.Despite the remarkable achievements in treating metastatic prostate cancer over the last two decades, castrate-resistant status is still considered the lethal stage of the disease. Theranostics combines a targeting compound (ligand) with a therapeutic radioisotope (radioactive particle) injected into the blood to target the cancer cells. The most studied radioligand is 177Lu-PSMA-617, which targets PSMA, a protein found in prostate cancer cells. This new approach has shown promising results in treating metastatic castration-resistant prostate cancer. Currently, many trials are using PSMA-targeting radioligands in combination with conventional therapies in advanced prostate cancer or even in the earlier stages of the disease. link3 Other preclinical trials are exploring the possibility of using newer ligands or radioisotopes to treat prostate cancer to increase the specificity and efficacy of this treatment.Background It is known that dietary intake of polyunsaturated fatty acids may improve cardiac function. However, relatively high daily doses are required to achieve sufficient cardiac concentrations of beneficial omega-3 fatty acids. The liver X receptor (LXR) is a nuclear hormone receptor and a crucial regulator of lipid homeostasis in mammals. LXR activation has been shown to endogenously reprogram cellular lipid profiles toward increased polyunsaturated fatty acids levels. Here we studied whether LXR lipid reprogramming occurs in cardiac tissue and exerts cardioprotective actions. Methods and Results Male 129SV mice were treated with the LXR agonist AZ876 (20 µmol/kg per day) for 11 days. From day 6, the mice were injected with the nonselective β-agonist isoproterenol for 4 consecutive days to induce diastolic dysfunction and subendocardial fibrosis while maintaining systolic function. Treatment with isoproterenol led to a marked impairment of global longitudinal strain and the E/e' ratio of transmitral flow to mitral annular velocity, which were both significantly improved by the LXR agonist. Histological examination showed a significant reduction in isoproterenol-induced subendocardial fibrosis by AZ876. Analysis of the cardiac lipid composition by liquid chromatography-high resolution mass spectrometry revealed a significant increase in cardiac polyunsaturated fatty acids levels and a significant reduction in saturated fatty acids by AZ876. Conclusions The present study provides evidence that the LXR agonist AZ876 prevents subendocardial damage, improves global longitudinal strain and E/e' in a mouse model of isoproterenol-induced cardiac damage, accompanied by an upregulation of cardiac polyunsaturated fatty acids levels. Cardiac LXR activation and beneficial endogenous cardiac lipid reprogramming may provide a new therapeutic strategy in cardiac disease with diastolic dysfunction.Aim HCV diagnosis will become the bottleneck in eliminating hepatitis C. Simple, accurate and cost-effective testing strategies are urgently needed to improve hepatitis C screening and diagnosis. Materials & methods Performance of seven rapid diagnostic tests (RDT) have been assessed in a large series (n = 498) of serum or plasma specimens collected in France and in Cameroon. Results Specificity varied from 96.1 to 100%. The clinical sensitivity, compared with immunoassays as the reference, was high for all seven RDT (97.2-100%). The Multisure HCV antibody assay and OraQuick HCV rapid antibody test reached sensitivity ≥99%. Conclusion A number of RDT may be suitable for WHO prequalification and may be implemented in the framework of large-scale low-cost treatment programs to achieve the WHO viral hepatitis objectives by 2030.Background This retrospective, observational study examined real-world treatment patterns and effectiveness outcomes in 450 patients with stage II-IIIB early-stage triple-negative breast cancer treated in the community oncology setting. Methods Kaplan-Meier methods were used to evaluate event-free survival (EFS), time to recurrence and overall survival (OS). Cox regression models were used to evaluate predictors of EFS and OS by pathological complete response (pCR) status. Results Among patients receiving neoadjuvant systemic therapy only, pCR was a predictor of EFS and OS. Conclusion These results highlight the unmet need for therapies that improve outcomes for patients with early-stage triple-negative breast cancer including increasing rates of pCR among patients receiving neoadjuvant therapy.Desmoid fibromatosis is a locally aggressive tumor with an unpredictable clinical course. Surgery was once the mainstay of treatment, but the treatment protocol has been constantly evolving and currently active surveillance is the front-line approach. There have been significant insights into the molecular biology with the addition of mutational analysis of CTNNB1 adding to prognostic information. We present a review of the literature with current practice guidelines, also including novel therapeutic targets and ongoing clinical trials, to unravel the next step in the management of sporadic desmoid fibromatosis.Background Although beta-blockers are recommended following myocardial infarction (MI), the benefits of long-term treatment have not been established. The study's aim was to evaluate beta-blocker efficacy by dose in 1-year post-MI survivors. Methods and Results The OBTAIN (Outcomes of Beta-Blocker Therapy After Myocardial Infarction) registry included 7057 patients with acute MI, with 6077 one-year survivors. For this landmark analysis, beta-blocker dose status was available in 3004 patients and analyzed by use (binary) and dose at 1 year after MI. Doses were classified as no beta-blocker and >0% to 12.5%, >12.5% to 25%, >25% to 50%, and >50% of target doses used in randomized clinical trials. Age was 63 to 64 years, and approximately two thirds were men. Median follow-up duration was 1.05 years (interquartile range, 0.98-1.22). When analyzed dichotomously, beta-blocker therapy was not associated with improved survival. When analyzed by dose, propensity score analysis showed significantly increased mortality in the no-beta-blocker group (hazard ratio,1.997; 95% CI, 1.118-3.568; P12.5% to 25% of the target dose used in prior randomized clinical trials beyond 1 year after MI may have enhanced survival compared with no beta-blocker and other beta-blocker doses. A new paradigm for post-MI beta-blocker therapy is needed that addresses which patients should be treated, for how long, and at what dose.Background Cardiogenic shock (CS) is a heterogeneous syndrome with varied presentations and outcomes. We used a machine learning approach to test the hypothesis that patients with CS have distinct phenotypes at presentation, which are associated with unique clinical profiles and in-hospital mortality. Methods and Results We analyzed data from 1959 patients with CS from 2 international cohorts CSWG (Cardiogenic Shock Working Group Registry) (myocardial infarction [CSWG-MI; n=410] and acute-on-chronic heart failure [CSWG-HF; n=480]) and the DRR (Danish Retroshock MI Registry) (n=1069). Clusters of patients with CS were identified in CSWG-MI using the consensus k means algorithm and subsequently validated in CSWG-HF and DRR. Patients in each phenotype were further categorized by their Society of Cardiovascular Angiography and Interventions staging. The machine learning algorithms revealed 3 distinct clusters in CS "non-congested (I)", "cardiorenal (II)," and "cardiometabolic (III)" shock. Among the 3 cohorts (CSWG-MI versus DDR versus CSWG-HF), in-hospital mortality was 21% versus 28% versus 10%, 45% versus 40% versus 32%, and 55% versus 56% versus 52% for clusters I, II, and III, respectively. The "cardiometabolic shock" cluster had the highest risk of developing stage D or E shock as well as in-hospital mortality among the phenotypes, regardless of cause. Despite baseline differences, each cluster showed reproducible demographic, metabolic, and hemodynamic profiles across the 3 cohorts. Conclusions Using machine learning, we identified and validated 3 distinct CS phenotypes, with specific and reproducible associations with mortality. These phenotypes may allow for targeted patient enrollment in clinical trials and foster development of tailored treatment strategies in subsets of patients with CS.Trainees represent the medical practice of tomorrow. Interactions and collaborations at the early stage in career will strengthen the future of our specialties, clinical microbiology and infectious diseases. Trainee networks at the national level help access the best education and career opportunities. The aim of this collaborative white paper between the Trainee Association of European Society of Clinical Microbiology and Infectious Diseases (ESCMID) and four national trainee networks is to discuss the motivation for building such networks and offer guidance for their creation and sustainability even during a health crisis.