The Role of Vasospasm and Microcirculatory Dysfunction in Fluoropyrimidine-Induced Ischemic Heart Disease

Cardiovascular diseases and cancer are the leading cause of morbidity and mortality globally. Cardiotoxicity from chemotherapeutic agents results in substantial morbidity and mortality in cancer survivors and patients with active cancer. Cardiotoxicity induced by 5-fluorouracil (5-FU) has been well established, yet its incidence, mechanisms, and manifestation remain poorly defined. Ischemia secondary to coronary artery vasospasm is thought to be the most frequent cardiotoxic effect of 5-FU. The available evidence of 5-FU-induced epicardial coronary artery spasm and coronary microvascular dysfunction suggests that endothelial dysfunction or primary vascular smooth muscle dysfunction (an endothelial-independent mechanism) are the possible contributing factors to this form of cardiotoxicity. In patients with 5-FU-related coronary artery vasospasm, termination of chemotherapy and administration of nitrates or calcium channel blockers may improve ischemic symptoms. However, there are variable results after administration of nitrates or calcium channel blockers in patients treated with 5-FU presumed to have myocardial ischemia, suggesting mechanisms other than impaired vasodilatory response. Clinicians should investigate whether chest pain and ECG changes can reasonably be attributed to 5-FU-induced cardiotoxicity. More prospective data and clinical randomized trials are required to understand and mitigate potentially adverse outcomes from 5-FU-induced cardiotoxicity

Coronary revascularisation in stable patients after an acute coronary syndrome: a propensity analysis of early invasive versus conservative management in a register-based cohort study

OBJECTIVES: To compare the effectiveness of in-hospital medical therapy versus coronary revascularisation added to medical therapy in patients who stabilised after an acute coronary syndrome (ACS). DESIGN: Propensity score-matched cohort study from the database of the Tampere ACS registry. SETTING: A single academic hospital in Finland. PARTICIPANTS: 1149 patients with a recent ACS, but no serious coexisting conditions: recurrent ischaemic episodes despite adequate medical therapy, haemodynamic instability, overt congestive heart failure and serious ventricular arrhythmias. PRIMARY AND SECONDARY OUTCOME MEASURES: The composite endpoint of major acute cardiovascular events (MACEs): unstable angina requiring rehospitalisation, stroke, myocardial infarction and all-cause mortality, at 6-month follow-up. RESULTS: Compared with standard medical treatment, revascularisation was associated with a lower rate of MACEs at 6 months in patients of the first quintile (HR 0.81; 95% CI 0.66 to 0.99), but a higher rate of MACEs in the fifth quintile (HR 4.74, CI 1.36 to 16.49; p=0.014). There were no significant differences in the rates of MACEs in the remaining three quintiles. Patients of the first quintile were the oldest (79.7\ub18.3 years) and had a more significant (p<0.001) history of prior myocardial infarction (37%) and poor renal function (creatine, \ub5mol/l: 114.9\ub170.7). They also showed the highest C reactive protein (7.3\ub19.5 mg/l) levels. CONCLUSIONS: Our findings suggest that in-hospital coronary revascularisation did not lead to any advantage with signal of possible harm in the great majority of patients who stabilised after an ACS. An early invasive management strategy may be best reserved for elderly patients having high-risk clinical features and biochemical evidence of a strong inflammatory activity

Delayed Care and Mortality Among Women and Men with Myocardial Infarction

Background-Women with ST-segment-elevation myocardial infarction (STEMI) have higher mortality rates than men. We investigated whether sex-related differences in timely access to care among STEMI patients may be a factor associated with excess risk of early mortality in women. Methods and Results-We identified 6022 STEMI patients who had information on time of symptom onset to time of hospital presentation at 41 hospitals participating in the ISACS-TC (International Survey of Acute Coronary Syndromes in Transitional Countries) registry (NCT01218776) from October 2010 through April 2016. Patients were stratified into time-delay cohorts. We estimated the 30-day risk of all-cause mortality in each cohort. Despite similar delays in seeking care, the overall time from symptom onset to hospital presentation was longer for women than men (median: 270 minutes [range: 130-776] versus 240 minutes [range: 120-600]). After adjustment for baseline variables, female sex was independently associated with greater risk of 30-day mortality (odds ratio: 1.58; 95% confidence interval, 1.27-1.97). Sex differences in mortality following STEMI were no longer observed for patients having delays from symptom onset to hospital presentation of (odds ratio: 0.77; 95% confidence interval, 0.29-2.02). Conclusions-Sex difference in mortality following STEMI persists and appears to be driven by prehospital delays in hospital presentation. Women appear to be more vulnerable to prolonged untreated ischemia

Aspirin for primary prevention of ST segment elevation myocardial infarction in persons with diabetes and multiple risk factors

Controversy exists as to whether low-dose aspirin use may give benefit in primary prevention of cardiovascular (CV) events. We hypothesized that the benefits of aspirin are underevaluated. We investigated 12,123 Caucasian patients presenting to hospital with acute coronary syndromes as first manifestation of CV disease from 2010 to 2019 in the ISACS-TC multicenter registry (ClinicalTrials.gov, NCT01218776). Individual risk of ST segment elevation myocardial infarction (STEMI) and its association with 30-day mortality was quantified using inverse probability of treatment weighting models matching for concomitant medications. Estimates were compared by test of interaction on the log scale. The risk of STEMI was lower in the aspirin users (absolute reduction: 6·8%; OR: 0·73; 95%CI: 0·65-0·82) regardless of sex (p for interaction=0·1962) or age (p for interaction=0·1209). Benefits of aspirin were seen in patients with hypertension, hypercholesterolemia, and in smokers. In contrast, aspirin failed to demonstrate a significant risk reduction in STEMI among diabetic patients (OR:1·10;95%CI:0·89-1·35) with a significant interaction (p: <0·0001) when compared with controls (OR:0·64,95%CI:0·56-0·73). Stratification of diabetes in risk categories revealed benefits (p interaction=0·0864) only in patients with concomitant hypertension and hypercholesterolemia (OR:0·87, 95% CI:0·65-1·15), but not in smokers. STEMI was strongly related to 30-day mortality (OR:1·93; 95%CI:1·59-2·35) Low-dose aspirin reduces the risk of STEMI as initial manifestation of CV disease with potential benefit in mortality. Patients with diabetes derive substantial benefit from aspirin only in the presence of multiple risk factors. In the era of precision medicine, a more tailored strategy is required

Integrazione di tecniche di agricoltura biologica e conservativa in sistemi colturali con crescente intensità ecologica: il progetto F.I.R.B. SMOCA

Il progetto SMOCA (Smart Management of Organic Conservative Agriculture) (2014- 2017) mira ad incrementare la sostenibilità dei sistemi colturali integrati/biologici mediante l’introduzione di tecniche di agricoltura conservativa, finalizzate alla riduzione dei consumi energetici e al miglioramento della fertilità del terreno. In SMOCA saranno sviluppate macchine e strategie agronomiche innovative che permettano di applicare le tecniche di lavorazione ridotta anche in assenza di mezzi chimici di sintesi

Spintronic Majority Gates

In this paper we present an overview of two types of majority gate devices based on spintronic phenomena. We compare the spin torque majority gate and the spin wave majority gate and describe work on these devices. We discuss operating conditions for the two device concepts, circuit implication and how these reflect on materials choices for device implementation

Consensus standards for acquisition, measurement, and reporting of intravascular optical coherence tomography studies

Objectives: The purpose of this document is to make the output of the International Working Group for Intravascular Optical Coherence Tomography (IWG-IVOCT) Standardization and Validation available to medical and scientific communities, through a peer-reviewed publication, in the interest of improving the diagnosis and treatment of patients with atherosclerosis, including coronary artery disease. Background: Intravascular optical coherence tomography (IVOCT) is a catheter-based modality that acquires images at a resolution of ∼10 μm, enabling visualization of blood vessel wall microstructure in vivo at an unprecedented level of detail. IVOCT devices are now commercially available worldwide, there is an active user base, and the interest in using this technology is growing. Incorporation of IVOCT in research and daily clinical practice can be facilitated by the development of uniform terminology and consensus-based standards on use of the technology, interpretation of the images, and reporting of IVOCT results. Methods: The IWG-IVOCT, comprising more than 260 academic and industry members from Asia, Europe, and the United States, formed in 2008 and convened on the topic of IVOCT standardization through a series of 9 national and international meetings. Results: Knowledge and recommendations from this group on key areas within the IVOCT field were assembled to generate this consensus document, authored by the Writing Committee, composed of academicians who have participated in meetings and/or writing of the text. Conclusions: This document may be broadly used as a standard reference regarding the current state of the IVOCT imaging modality, intended for researchers and clinicians who use IVOCT and analyze IVOCT data

Inferring causal molecular networks: empirical assessment through a community-based effort

Inferring molecular networks is a central challenge in computational biology. However, it has remained unclear whether causal, rather than merely correlational, relationships can be effectively inferred in complex biological settings. Here we describe the HPN-DREAM network inference challenge that focused on learning causal influences in signaling networks. We used phosphoprotein data from cancer cell lines as well as in silico data from a nonlinear dynamical model. Using the phosphoprotein data, we scored more than 2,000 networks submitted by challenge participants. The networks spanned 32 biological contexts and were scored in terms of causal validity with respect to unseen interventional data. A number of approaches were effective and incorporating known biology was generally advantageous. Additional sub-challenges considered time-course prediction and visualization. Our results constitute the most comprehensive assessment of causal network inference in a mammalian setting carried out to date and suggest that learning causal relationships may be feasible in complex settings such as disease states. Furthermore, our scoring approach provides a practical way to empirically assess the causal validity of inferred molecular networks