Articles: sepsis.
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Intensive care medicine · Apr 2024
ReviewChallenges for a broad international implementation of the current severe community-acquired pneumonia guidelines.
Severe community-acquired pneumonia (sCAP) remains one of the leading causes of admission to the intensive care unit, thus consuming a large share of resources and is associated with high mortality rates worldwide. The evidence generated by clinical studies in the last decade was translated into recommendations according to the first published guidelines focusing on severe community-acquired pneumonia. Despite the advances proposed by the present guidelines, several challenges preclude the prompt implementation of these diagnostic and therapeutic measures. The present article discusses the challenges for the broad implementation of the sCAP guidelines and proposes solutions when applicable.
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Journal of critical care · Apr 2024
Letter ReviewHeart involvement: A neglected manifestation of haemophagocytic syndrome associated with high mortality.
Secondary haemophagocytic lymphohistiocytosis (sHLH) proceeds from uncontrolled and inefficient immune activation leading to hyper-inflammation and multi-organ damage. sHLH proceeds from a wide panel of infectious, auto immune and malignant conditions and bears high mortality despite treatment. Literature on sHLH does not mention heart involvement. We sought to describe occurrence of reversible heart dysfunction in the setting of HLH in order to motivate larger prospective studies assessing the causality link between both conditions. ⋯ This leads us to hypothesize that heart involvement confers worse prognosis to HLH. Formal accountability of HLH in the occurrence of cardiac manifestations is difficult to establish given the numerous differential diagnoses but reversibility of myocardial dysfunction in 14 survivors and results of two necropsies supported it. These data, and the current knowledge on the pathophysiology of both HLH and heart failure lead us to suggest that such a link may exist.
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Sepsis is characterized by organ dysfunction resulting from a dysregulated inflammatory response triggered by infection, involving multifactorial and intricate molecular mechanisms. Hypoxia-inducible factor-1α (HIF-1α), a notable transcription factor, assumes a pivotal role in the onset and progression of sepsis. This review aims to furnish a comprehensive overview of HIF-1α's mechanism of action in sepsis, scrutinizing its involvement in inflammatory regulation, hypoxia adaptation, immune response, and organ dysfunction. ⋯ Furthermore, it will delve into the roles of HIF-1α in modulating the inflammatory response, including its association with inflammatory mediators, immune cell activation, and vasodilation. Additionally, attention will be directed toward the regulatory function of HIF-1α in hypoxic environments and its linkage with intracellular signaling, oxidative stress, and mitochondrial damage. Finally, the potential therapeutic value of HIF-1α as a targeted therapy and its significance in the clinical management of sepsis will be discussed, aiming to serve as a significant reference for an in-depth understanding of sepsis pathogenesis and potential therapeutic targets, as well as to establish a theoretical foundation for clinical applications.
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Sepsis is a life-threatening condition characterised by endothelial barrier dysfunction and impairment of normal microcirculatory function, resulting in a state of hypoperfusion and tissue oedema. No specific pharmacological therapies are currently used to attenuate microvascular injury. Given the prominent role of endothelial breakdown and microcirculatory dysfunction in sepsis, there is a need for effective strategies to protect the endothelium. In this review we will discuss key mechanisms and putative therapeutic agents relevant to endothelial barrier function.
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Acute kidney injury (AKI) often complicates sepsis and is associated with high morbidity and mortality. In recent years, several important clinical trials have improved our understanding of sepsis-associated AKI (SA-AKI) and impacted clinical care. ⋯ We discuss lessons learned and potential opportunities to improve the design of clinical trials and generate actionable evidence in future research. We specifically discuss the role of enrichment strategies to target populations that are most likely to derive benefit and the importance of patient-centered clinical trial endpoints and appropriate trial designs with the aim to provide guidance in designing future trials.