Sodium-glucose cotransporter 2 inhibitors and the cancer patient: from diabetes to cardioprotection and beyond.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i), a new drug class initially designed and approved for treatment of diabetes mellitus, have been shown to exert pleiotropic metabolic and direct cardioprotective and nephroprotective effects that extend beyond their glucose-lowering action. These properties prompted their use in two frequently intertwined conditions, heart failure and chronic kidney disease. Their unique mechanism of action makes SGLT2i an attractive option also to lower the rate of cardiac events and improve overall survival of oncological patients with preexisting cardiovascular risk and/or candidate to receive cardiotoxic therapies. This review will cover biological foundations and clinical evidence for SGLT2i modulating myocardial function and metabolism, with a focus on their possible use as cardioprotective agents in the cardio-oncology settings. Furthermore, we will explore recently emerged SGLT2i effects on hematopoiesis and immune system, carrying the potential of attenuating tumor growth and chemotherapy-induced cytopenias.

Atherosclerotic Coronary Plaque Features in Patients With Chronic Obstructive Pulmonary Disease and Acute Coronary Syndrome.

Previous studies reported a robust relation between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD). Systemic inflammation has been proposed as possible pathogenetic mechanism linking these 2 entities, although data on atherosclerotic coronary features in COPD patients are lacking. We studied atherosclerotic coronary plaque features in COPD patients presenting with acute coronary syndrome (ACS) using optical coherence tomography (OCT). ACS patients who underwent intracoronary OCT imaging of the culprit vessel were enrolled. Coronary plaque characteristics and OCT-defined macrophage infiltration (MØI) were assessed by OCT. ACS patients were divided into 2 groups according to the presence of an established diagnosis of COPD, and plaque features at the culprit site and along the culprit vessel were compared between the groups. Of 146 ACS patients (mean age:66.1 ± 12.7 years, 109 men), 47 (32.2%) had COPD. Patients with COPD had significantly higher prevalence of MØI (78.7% vs 54.5%, p = 0.005) and thin cap fibroatheroma (TCFA) (48.9% vs 22.2%, p = 0.001) at the culprit site. In the multivariate logistic regression, COPD was independently associated with MØI (odds ratio [OR] 21.209, 95% confidence interval [CI] 1.679 to 267.910, p = 0.018) and TCFA at the culprit site (OR 5.345, 95% CI 1.386 to 20.616, p = 0.015). Similarly, COPD was independently associated with both MØI (OR 3.570, 95% CI 1.472 to 8.658, p = 0.005) and TCFA (OR 4.088, 95% CI 1.584 to 10.554, p = 0.004) along the culprit vessel. In conclusion, in ACS patients who underwent OCT imaging of the culprit vessel, COPD was an independent predictor of plaque inflammation and vulnerability. These results may suggest that a higher inflammatory milieu in COPD patients might enhance local coronary inflammation, promoting CAD development and plaque vulnerability.

Predicting the response to acetylcholine in ischemia or infarction with non-obstructive coronary arteries: The ABCD score.

BACKGROUND AND AIMS: Acetylcholine (ACh) provocation testing can detect vasomotor disorders in patients with ischemia and non-obstructed coronary arteries (INOCA) or myocardial infarction and non-obstructed coronary arteries (MINOCA). We aimed to derive and validate a simple risk score to predict a positive ACh test response. METHODS: We prospectively enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. Patients were split in two cohorts (derivation and validation) according to time of enrolment. The score was derived in 386 patients (derivation cohort) and then validated in 165 patients (validation cohort). RESULTS: 551 patients were enrolled, 371 (67.3%) INOCA and 180 (32.7%) MINOCA. ACh test was positive in 288 (52.3%) patients. MINOCA, myocardial bridge (MB), C-reactive protein (CRP) and dyslipidaemia were independent predictors of a positive ACh test in the derivation cohort. The ABCD (Acute presentation, Bridge, CRP, Dyslipidaemia) score was derived: 2 points were assigned to MINOCA, 3 to MB, 1 to elevated CRP and 1 to dyslipidaemia. The ABCD score accurately identified patients with a positive ACh test response with an AUC of 0.703 (CI 95% 0.652-0.754,p < 0.001) in the derivation cohort, and 0.705 (CI 95% 0.626-0.784, p < 0.001) in the validation cohort. In the whole population, an ABCD score ≥4 portended 94.3% risk of a positive ACh test and all patients with an ABCD score ≥6 presented a positive test. CONCLUSIONS: The ABCD score could avoid the need of ACh provocation testing in patients with a high score, reducing procedural risks, time, and costs, and allowing the implementation of a tailored treatment strategy. These results are hypothesis generating and further research involving larger cohorts and multicentre trials is needed to validate and refine the ABCD score.

The irrepressible influence of vocal stereotypes on trust.

There is a reciprocal relationship between trust and vocal communication in human interactions. On one hand, a predisposition towards trust is necessary for communication to be meaningful and effective. On the other hand, we use vocal cues to signal our own trustworthiness and to infer it from the speech of others. Research on trustworthiness attributions to vocal characteristics is scarce and contradictory, however, being typically based on explicit judgements which may not predict actual trust-oriented behaviour. We use a game theory paradigm to examine the influence of speaker accent and prosody on trusting behaviour towards a simulated game partner, who responds either trustworthily or untrustworthily in an investment game. We found that speaking in a non-regional standard accent increases trust, as does relatively slow articulation rate. The effect of accent persists over time, despite the accumulation of clear evidence regarding the speaker's level of trustworthiness in a negotiated interaction. Accents perceived as positive for trust can maintain this benefit even in the face of behavioural evidence of untrustworthiness.

Exploring the Effectiveness of Sustainability Measurement: Which ESG Metrics Will Survive COVID-19?

This paper aims to investigate the current state of play on Environmental Social and Governance (ESG) integration and check the validity of the current metrics system by assessing if it will survive the COVID-19 crisis. By adopting a qualitative research approach through semi-structured anonymous interviews with 14 senior managers of six European listed companies we use a framework by assessing the mechanisms of reactivity on the effectiveness of ESG measures in times of COVID-19. By interpreting the practitioners' points of view through the lens of the sociological framework by Espeland and Sauder (Am J Sociol 113:1-40, 2007) our findings show different mechanisms of reactivity by companies on the effectiveness of ESG measures in times of COVID-19, i.e., active and passive conformity and active resistance. We also identified the main Corporate Social Responsibility (CSR) institutional factors that affect managers' reactivity. An extensive re-formulation of the ESG metrics is required in the light of times of crisis, given that accountability and transparency are strongly linked to quantitative measures which can play a critical role in the financial system and investors' engagement. Particularly, the strict distinction between "E", "S" and "G" issues should be abandoned claiming a different holistic re-design of sustainability measures by considering the increasing relevance of the Social dimension in time of COVID-19. This study provides a valuable contribution to the existing literature on the measurement of sustainability within the link of accountability and crisis by highlighting new corporate needs to re-design the ESG metrics system.

The influence of perceived vocal traits on trusting behaviours in an economic game.

When presented with voices, we make rapid, automatic judgements of social traits such as trustworthiness-and such judgements are highly consistent across listeners. However, it remains unclear whether voice-based first impressions actually influence behaviour towards a voice's owner, and-if they do-whether and how they interact over time with the voice owner's observed actions to further influence the listener's behaviour. This study used an investment game paradigm to investigate (1) whether voices judged to differ in relevant social traits accrued different levels of investment and/or (2) whether first impressions of the voices interacted with the behaviour of their apparent owners to influence investments over time. Results show that participants were responding to their partner's behaviour. Crucially, however, there were no effects of voice. These findings suggest that, at least under some conditions, social traits perceived from the voice alone may not influence trusting behaviours in the context of a virtual interaction.