Sepsis is a complex and heterogeneous condition, arising from a disrupted immune response to infection that can progress to organ failure and carries a high risk of death. In recent years, growing attention has been paid to the role of epigenetic mechanisms—including DNA methylation, histone modifications, non-coding RNAs, and RNA methylation—in shaping immune activity during sepsis. These processes affect immune functions such as macrophage polarization, cytokine release, and the exhaustion of immune cells, and they help explain the shift from an initial phase of overwhelming inflammation to a later state of immune suppression. Epigenetic alterations also contribute to tissue-specific damage, notably in the lungs, kidneys, and heart, and have been linked to disease severity and clinical prognosis. Advances in transcriptomic and epigenetic profiling have made it possible to distinguish molecular subtypes of septic patients, each with distinct immune features and varied responses to treatments such as corticosteroids and metabolic therapies. Emerging biomarkers—like AQP5 methylation, histone lactylation (H3K18la), and m⁶A RNA methylation—are opening new options for patient classification and more tailored therapeutic strategies. This review examines the current understanding of how epigenetic regulation contributes to the pathophysiology of sepsis and considers its implications for developing more individualized approaches to care.

Peripheral arterial disease (PAD) is a prevalent medical condition associated with high mortality and morbidity rates. Despite the high clinical burden, sex-based differences among PAD patients are not well defined yet, in contrast to other atherosclerotic diseases. This study aimed to describe sex-based differences in clinical characteristics and outcomes among hospitalized patients affected by PAD. This was a retrospective study evaluating all patients with a diagnosis of PAD admitted to the Emergency Department from 1 December 2013 to 31 December 2021. The primary endpoint of the study was the difference between male and female PAD patients in cumulative occurrence of Major Adverse Cardiovascular Events (MACEs) and Major Adverse Limb Events. A total of 1640 patients were enrolled. Among them, 1103 (67.3%) were males while females were significantly older (median age of 75 years vs. 71 years; p =< 0.001). Females underwent more angioplasty treatments for revascularization than men (29.8% vs. 25.6%; p = 0.04); males were treated with more amputations (19.9% vs. 15.3%; p = 0.012). A trend toward more MALEs and MACEs reported in the male group did not reach statistical significance (OR 1.27 [0.99–1.64]; p = 0.059) (OR 0.75 [0.50–1.11]; p = 0.153). However, despite lower extremity PAD severity seeming similar between the two sexes, among these patients males had a higher probability of undergoing lower limb amputations, of cardiovascular death and of myocardial infarction. Among hospitalized patients affected by PAD, even if there was not a sex-based significant difference in the incidence of MALEs and MACEs, adverse clinical outcomes were more common in males.

Sepsis is a life-threatening condition that requires early recognition and intervention to improve patient outcomes. Optimizing hemodynamic management is crucial, and clinicians must utilize all available tools to guide therapy effectively. Echocardiography is a rapid, non-invasive, and repeatable method that has emerged as a valuable tool in the management of septic patients. Studying its role can provide insights into both therapeutic guidance and prognostic assessment. The primary aim of this review is to highlight the importance of echocardiography in the hemodynamic management of patients with sepsis. The secondary objective is to assess its prognostic value, as echocardiography can inform both the immediate management of critically ill patients and their overall prognosis. A narrative review of the literature published in the last 15 years was conducted using PubMed, and references were managed with Mendeley. Articles focusing on adult and pediatric patients, as well as relevant animal studies, which evaluated echocardiographic assessment of cardiac function, fluid responsiveness, or hemodynamic management were included. Multiple studies demonstrate that echocardiography is a reliable, non-invasive, and easily repeatable tool for assessing fluid responsiveness in septic patients. It allows for dynamic monitoring of stroke volume, VTI, and other hemodynamic parameters, supporting tailored fluid and vasoactive therapy. Additionally, echocardiography provides prognostic insights, with right ventricular dysfunction emerging as a strong predictor of increased mortality. Other parameters, including global longitudinal strain and left ventricular diastolic function, further contribute to risk stratification. Echocardiography is an indispensable tool in the management of sepsis, offering both real-time guidance for hemodynamic optimization and valuable prognostic information. Its routine use can enhance personalized care and improve clinical outcomes in critically ill septic patients.

Mild traumatic brain injury (mTBI) remains a clinical challenge, particularly in cases with normal computed tomography (CT) findings but persistent or evolving symptoms. Conventional diagnostic approaches relying solely on clinical criteria and neuroimaging often lack adequate sensitivity and may lead to unnecessary radiation exposure. Recent advances in biomarker research have identified several blood-based proteins such as glial fibrillary acidic protein (GFAP), ubiquitin carboxy-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), Tau protein, neuron-specific enolase (NSE), and neurofilament light chain (NFL) as potential tools for improving diagnostic precision and guiding clinical decisions. In this study, we synthesize current evidence evaluating the diagnostic and prognostic utility of these biomarkers using sensitivity, specificity, negative predictive value (NPV), and area under the receiver operating characteristic curve (AUC). GFAP and UCH-L1 have shown high sensitivity in detecting intracranial lesions and are now FDA-cleared for emergency department triage within 12 h of injury. While S100B remains widely investigated, its low specificity limits its application beyond select clinical scenarios (i.e., in patients without polytrauma). Additionally, Tau, NSE, and NFL are emerging as prognostic markers, with studies suggesting associations with persistent symptoms and long-term neurocognitive outcomes. Overall, the integration of biomarker-based data into clinical workflows may enhance early mTBI diagnosis, reduce reliance on imaging, and enable individualized follow-up and prognostic stratification. Future research should refine optimal sampling windows and explore multimarker panels to maximize diagnostic and prognostic performance.

This retrospective analysis at a major Italian university hospital (January 2018–September 2022) assessed the prognostic significance of fever in patients with bloodstream infections (BSIs). Of the 1299 patients with positive blood cultures, a comparison between febrile and afebrile patients at emergency department admission was conducted. This study particularly focused on the mortality rates associated with these two groups. Notably, afebrile patients exhibited a higher mortality rate. The odds ratio for mortality in afebrile patients was significantly higher compared to febrile patients. This suggests that the absence of fever might be an indicator of increased mortality risk, highlighting the complexity of diagnosing bloodstream infections based on fever presence. This study contributes to the understanding of fever as a diagnostic marker in emergency settings.

Liver involvement is closely related to the progression and prognosis of heart failure (HF). This review evaluates the role of FIB-4, a non-invasive and easily calculable index of hepatic fibrosis, as a prognostic biomarker across different HF phenotypes, compared with other established biomarkers of HF. Current evidence demonstrates that elevated FIB-4 scores are closely associated with systemic venous congestion and right ventricular dysfunction and represent a strong independent predictor of adverse cardiovascular events, particularly in HFpEF. In contrast, in HFrEF and HFmrEF, its prognostic value appears less pronounced and more strongly influenced by concomitant primary liver disease, such as MASLD. In acute heart failure, FIB-4 reflects congestion severity and its dynamic reduction during hospitalization carries independent prognostic significance. Compared with NT-proBNP, FIB-4 provides complementary or superior prognostic information in HFpEF, particularly in the presence of predominant right ventricular dysfunction. Additionally, FIB-4 may serve as a screening tool to identify subjects at risk for HFpEF. In conclusion, FIB-4 is a promising tool for risk stratification in HF. However, further prospective studies are needed to establish standardized cut-off values, support its incorporation into clinical guidelines, and clarify its response to SGLT2 inhibitor therapy. Moreover, emerging cardio-metabolic therapies targeting both HF and hepatic fibrosis may further increase the clinical relevance of FIB-4 as a dynamic biomarker of the cardio–hepatic axis.