Background and Objectives: Despite major advances in medical science and critical care, sepsis remains a leading cause of morbidity and mortality worldwide: it arises from dysregulated host response to infections and may culminate in organ dysfunction. A hallmark of its pathogenesis is the cytokine storm, in which interleukins (ILs) serve as central mediators of both protective and deleterious immune responses. This review summarizes the current knowledge on the role of ILs in sepsis, emphasizing their potential as biomarkers and therapeutic targets. Material and Methods: We analyzed recent clinical and experimental studies focusing on the most studied ILs—including IL-1, IL-6, IL-10, IL-8, IL-12, IL-18, and IL-17—in the pathophysiology of sepsis. Attention was given to mechanistic insights, prognostic significance, and therapeutic strategies targeting IL pathways. Results: IL-1 and IL-6 emerged as key pro-inflammatory mediators, amplifying vascular permeability, coagulation activation, and shock, with IL-6 validated as a robust prognostic biomarker. IL-10 was identified as a pivotal anti-inflammatory cytokine, limiting tissue injury but fostering immunosuppression and secondary infections. Other ILs, such as IL-8, IL-12, IL-18, and IL-17, contributed to neutrophil recruitment, Th1/Th17 activation, organ-specific injury, and sepsis susceptibility. Therapeutic interventions targeting ILs, including the IL-1 receptor antagonist anakinra and IL-6 receptor blockade with tocilizumab, have shown promise in selected patient subgroups. Conclusions: ILs are central to the immunopathology of sepsis, acting both as drivers of hyperinflammation and mediators of immunosuppression. Their dual role underscores the relevance of ILs as diagnostic and prognostic biomarkers, as well as context-dependent therapeutic targets. Future approaches should prioritize precision immunomodulation aligned with the principles of personalized medicine to improve clinical outcomes in sepsis.

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis < 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11 years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982. Graphical

Background: to date, there are no specific markers available for diagnosing sepsis. Diagnosis is, indeed, mainly determined by clinical suspicion and the evaluation of the patient’s overall condition. This evaluation involves assessing various inflammatory markers, such as C-reactive protein (CRP) and procalcitonin (PCT), along with markers of tissue hypoxia, such as serum lactate. Additionally, it includes scores that account for complete blood count (CBC), organ function markers, and the patient’s vital parameters, including SOFA, qSOFA, SIRS, and NEWS. Over the years, various potential biomarkers have been studied; among these presepsin appears to offer some significant advantages. Objective: Presepsin, which is the N-terminal fragment of the soluble component of CD14, is primarily elevated in infectious conditions. Its levels rise much earlier in the context of infection compared to currently used biomarkers. As a result, Presepsin shows promise for the early identification of septic patients and could aid in prognostic assessment, allowing clinicians to prioritize care for critically ill individuals. Methods: this study aims to evaluate the role of serum presepsin in the early diagnosis of sepsis in patients who present to the emergency room with a clinical suspicion of sepsis. The secondary objectives include comparing the diagnostic performance of presepsin with traditional biomarkers currently used for sepsis diagnosis and assessing its utility as a prognostic biomarker for mortality risk stratification, in comparison with validated severity prediction scores. Result: Presepsin had valuable diagnostic utility for sepsis (AUC 0.946, p < 0.001) comparable to PCT (AUC 0.905, p < 0.001). Conclusions: the combination of Presepsin, PCT, and EWS yielded the highest diagnostic accuracy for sepsis.

Traumatic brain injury (TBI) is a major global health concern and a leading cause of mortality and disability. Head computed tomography (CT) remains indispensable for the detection of intracranial hemorrhage; however, its indiscriminate use in mild trauma increases radiation exposure, cumulative oncogenic risk, and healthcare costs. Consequently, there is growing interest in tools capable of improving sensitivity in mild or early-stage TBI. Protein-based biomarkers are promising complements to conventional assessment. Molecules such as glial fibrillary acidic protein (GFAP), ubiquitin C-terminal hydrolase L1 (UCH-L1), S100 calcium-binding protein B (S100B), and neurofilament light chain (NfL) reflect astroglial activation, neuronal injury, and axonal damage, enabling objective evaluation of neurotrauma. Beyond protein biomarkers, metabolomic and lipidomic approaches capture alterations associated with early metabolic distress, oxidative stress, mitochondrial dysfunction, and membrane disruption following TBI. High-resolution mass spectrometry studies have identified reproducible metabolite and lipid signatures correlating with injury severity and functional outcomes. Longitudinal profiling further reveals dynamic metabolic trajectories that distinguish secondary injury progression from stabilization, supporting predictive modeling and risk stratification. Together, these advances pave the way toward precision medicine in neurotrauma. Nevertheless, variability in assay performance and sampling timing continues to limit widespread clinical adoption. Future research should prioritize methodological standardization, analytical validation, and the integration of multi-omic data with machine learning–based predictive models.

Familial hypercholesterolemia is a common genetic disorder with a propensity towards early onset of atherosclerotic cardiovascular disease (CVD). The main goal of therapy is to reduce the LDL cholesterol and the current treatment generally consists of statin, ezetimibe and PCSK9 inhibitors. Unfortunately, lowering LDL cholesterol may be difficult for many reasons such as the variation of response to statin therapy among the population or the high cost of some therapies (i.e., PCSK9 inhibitors). In addition to conventional therapy, additional strategies may be used. The gut microbiota has been recently considered to play a part in chronic systemic inflammation and hence in CVD. Several studies, though they are still preliminary, consider dysbiosis a risk factor for various CVDs through several mechanisms. In this review, we provide an update of the current literature about the intricate relation between the gut microbiota and the familial hypercholesterolemia.

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.