Mitochondrial dysfunction has emerged as a central pathomechanism in the setting of obesity and diabetes mellitus, linking these intertwined pathologies that share insulin resistance as a common denominator. High-resolution respirometry (HRR) is a state-of-the-art research method currently used to study mitochondrial respiration and its impairment in health and disease. Tissue samples, cells or isolated mitochondria are exposed to various substrate-uncoupler-inhibitor-titration protocols, which allows the measurement and calculation of several parameters of mitochondrial respiration. In this review, we discuss the alterations of mitochondrial bioenergetics in the main dysfunctional organs that contribute to the development of the obese and diabetic phenotypes in both animal models and human subjects. Herein we review data regarding the impairment of oxidative phosphorylation as integrated mitochondrial function assessed by means of HRR. We acknowledge the critical role of this method in determining the alterations in oxidative phosphorylation occurring in the early stages of metabolic pathologies. We conclude that there is a mutual two-way relationship between mitochondrial dysfunction and insulin insensitivity that characterizes these diseases.

Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

Sodium–glucose cotransporter 2 inhibitors (SGLT2i), a novel class of glucose-lowering drugs, have revolutionized the management of heart failure with reduced and preserved ejection fraction, regardless of the presence of diabetes, and are currently incorporated in the heart failure guidelines. While these drugs have consistently demonstrated their ability to decrease heart failure hospitalizations in several landmark clinical trials, their cardioprotective effects are far from having been completely elucidated. In the past decade, a growing body of experimental research has sought to address the molecular and cellular mechanisms of SGLT2i in order to provide a better understanding of the off-target acute and chronic cardiac benefits, beyond the on-target renal effect responsible for blood glucose reduction. The present narrative review addresses the direct cardioprotective effects of SGLT2i, delving into the off-target mechanisms of the drugs currently approved for heart failure therapy, and provides insights into future perspectives.

Background/Objectives: According to the European Centre for Disease Prevention and Control, improved antimicrobial stewardship programs (ASPs) combined with rapid diagnostic tests could potentially prevent thousands of deaths caused by multidrug-resistant organisms annually. This study aimed to compare the results obtained using the Unyvero system/hospital-acquired pneumonia (HPN) panel with those obtained using classic microbiological diagnostic methods to evaluate the potential of introducing this rapid diagnostic test into routine diagnosis and improving local ASPs. Methods: A single-center, observational, cross-sectional, analytical study was performed; it included patients admitted to the intensive care unit (ICU) with the presumptive diagnosis of community- or hospital-acquired pneumonia. One hundred non-repetitive endotracheal aspirates were collected and subjected to analysis using both methods. The concordance between the results obtained via the standard-of-care (SoC) culture and Unyvero was analyzed. Results: Of the results generated using Unyvero/HPN, 51% were fully concordant with those obtained via culture, 48% were partially concordant, and only 1% represented failure. It was also more efficient in identifying multiple organisms in a single sample than the SoC culture (1.32 versus 1.1 per sample). The three most common isolates identified via both methods were Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The most common resistance markers identified with Unyvero were sul1 (41%), tem and ndm (25%), and kpc, imp, vim, and gyrA87 (2% of results). Conclusions: Unyvero/HPN, if associated with appropriate diagnostic stewardship, could be used to manage critically ill patients to ensure an appropriate ASP.