Mixed shock is common after cardiac arrest (CA), with dominant shock physiology sometimes changing over the course of hours. This article focuses on identifying dominant shock physiology in patients with refractory shock after CA and targeted strategies for resuscitation. The authors discuss approach to cardiogenic shock, including pharmacologic and mechanical support, as well as advanced pharmacologic therapies relevant to distributive shock.

Status epilepticus (SE) is a common neurological emergency in children, carrying significant risks of morbidity and mortality. Refractory SE (RSE) and super-refractory SE (SRSE) represent the most severe end of this spectrum and are among the most challenging clinical scenarios in pediatric neurology. This review addresses the key molecular and cellular mechanisms underlying the transition to refractoriness, including activity-dependent changes in GABAergic and glutamatergic neurotransmission and the activation of neuroinflammatory pathways, and discusses their implications for treatment. We further review current evidence on the pharmacological management of pediatric RSE and SRSE, from the rational use of sedating agents to less conventional strategies such as ketamine, the ketogenic diet, and immunomodulatory therapies. Understanding the pathophysiology of refractoriness is key to optimizing existing therapies and developing novel, mechanism-based approaches for children affected by this condition.

Ischemia and angina with non-obstructive coronary arteries (INOCA/ANOCA) have evolved into a defined clinical entity, with invasive coronary functional testing now guideline-recommended to establish the underlying endotypes. Yet diagnostic progress has outpaced pathophysiological understanding and therapeutic development. This article examines the principal unmet needs across INOCA/ANOCA: the observational nature of current registries; the unresolved molecular basis, natural history and overlap of the microvascular and vasospastic endotypes; persistent underdiagnosis and unstandardized invasive physiology; the absence of validated non-invasive tools and biomarkers; and the lack of endotype-targeted therapies proven to improve outcomes. Addressing these gaps is essential to advance mechanism-based personalized care.

Coronary dysfunction encompasses a spectrum of pathophysiologically distinct endotypes with differing therapeutic implications. The aim of this article was to provide an overview of device-based therapies targeting the various forms of coronary dysfunction. A systematic review of the available literature was performed. Multiple device-based strategies have been proposed for the treatment of angina in the absence of obstructive coronary artery disease, reflecting the heterogeneity of underlying mechanisms, and tailored approaches based on specific endotypes may improve symptom control and clinical outcomes.

Management of chronic coronary syndromes has shifted from an obstructive coronary artery disease-focused model to a phenotype-guided approach that includes angina with nonobstructive coronary arteries/ ischemia with nonobstructive coronary arteries (INOCA), vasospastic angina (VSA), and coronary microvascular dysfunction (CMD). Background therapies such as statins, angiotensin-converting enzyme inhibitors, antiplatelets, and sodium-glucose cotransporter-2 inhibitor inhibitors improve vascular health, but the WARRIOR trial highlighted the limits of intensive therapy in unselected INOCA patients. Anti-ischemic treatment should be mechanism-based: calcium channel blockers for VSA, beta-blockers and ranolazine for CMD, while nitrates may worsen microvascular disease.

Over 3 decades, invasive coronary physiology has evolved into a cornerstone of cardiovascular care. Fractional flow reserve (FFR) enabled lesion-specific assessment of epicardial stenoses, improving percutaneous coronary intervention (PCI) selection beyond angiography. Recognition of ischemia without obstructive disease expanded its role, with contemporary testing integrating adenosine-based flow assessment and acetylcholine-based evaluation of endothelial and vasomotor function, allowing identification of angina with nonobstructive coronary arteries endotypes, and tailored therapy. Physiologic pullback and post-PCI indices support procedural planning. Emerging tools, including angiography-derived indices, FFR-computed tomography, and optical coherence tomography (OCT)-based virtual flow reserve, are extending physiology-guided care toward noninvasive assessment and precision cardiovascular intervention.

Myocardial ischemia in chronic coronary syndromes extends far beyond the presence of obstructive epicardial coronary stenoses. Advanced cardiovascular imaging has emerged as a cornerstone for the identification of the diverse anatomic and functional mechanisms underlying myocardial ischemia, including atherosclerotic coronary artery disease, vasospastic angina, myocardial bridging, and coronary microvascular dysfunction. Coronary computed tomography angiography, cardiac magnetic resonance, and PET provide complementary insights. This article reviews the diagnostic performance, characteristic imaging findings, and contemporary clinical applications of these modalities, highlighting their role in refining phenotypic characterization and enabling a more precise and individualized approach to patients with chronic coronary syndromes.

Structural coronary microvascular dysfunction (CMD) is an important endotype of ischemia with nonobstructive coronary arteries (INOCA) and is characterized by adverse arteriolar remodeling and capillary rarefaction. These alterations impair coronary vasodilator capacity and increase microcirculatory resistance, all of which contribute to impaired myocardial perfusion. In this article, we aim to review the anatomic and pathophysiological basis of structural CMD, its clinical presentation and prognostic relevance, and the role of invasive physiologic indices in its identification. We also highlight new considerations about dynamic aspects of structural CMD laying the groundwork for emerging therapeutic strategies and future research directions.

Epicardial coronary disease includes dynamic disorders capable of causing myocardial ischaemia without fixed obstructive stenosis. Vasospastic angina (VSA) and myocardial bridging (MB) are paradigmatic entities characterized by transient luminal narrowing and reversible flow impairment. Although traditionally viewed as distinct, they frequently overlap, sharing mechanisms such as endothelial dysfunction, smooth muscle hyperreactivity, altered shear stress, and autonomic imbalance. VSA results from episodic coronary constriction, whereas MB involves systolic compression of an intramyocardial segment with possible diastolic flow limitation. The aim of this article is to provide a mechanistic appraisal of these conditions and their clinical implications within chronic coronary syndromes.

Persistent low-grade inflammation, oxidative stress, cellular senescence, and disturbance of cellular homeostasis are all connected with ageing and can lead to the development of age-related diseases. Ferroptosis, an iron-dependent type of controlled cell death, has been linked to these processes more and more. It may represent a key connection between inflammation, oxidative damage, and tissue failure as people age. With a focus on neurodegenerative, cardiovascular, metabolic, pulmonary, and musculoskeletal problems, this study explores the new idea of a ferroptosis-inflammaging axis and its role in age-associated degenerative disorders. The review addresses the data supporting ferroptosis as a potential therapeutic target and summarises the current understanding on the relationship between ferroptosis and the main biological processes linked to ageing. Natural products are given particular attention as possible ferroptosis modulators, emphasizing their therapeutic significance and the growing data from experimental models. Additionally included are the translational difficulties related to ferroptosis-targeted therapies, such as the lack of clinical validation, the development of biomarkers, pharmacokinetic issues, and disease-specific treatment approaches. All things considered, comprehending the ferroptosis-inflammaging axis may offer a foundation for discovering cutting-edge therapeutic strategies to delay tissue dysfunction and enhance healthy ageing.