Ospedale dell' Angelo

Background: Interest in inhalational anesthesia in cardiac surgery has resurged as volatile anesthetics exert biological effects extending beyond hypnosis. Sevoflurane and desflurane activate mitochondrial cytoprotective signaling pathways, modulate inflammatory and endothelial responses and may attenuate ischemia-reperfusion injury during cardiopulmonary bypass, potentially influencing postoperative organ function and recovery. Methods: This narrative review critically examines experimental and clinical evidence on the use of volatile anesthetics in cardiac anesthesia. The current literature was analyzed to elucidate mechanistic foundations of myocardial and extracardiac organ protection, hemodynamic and metabolic effects, and the influence of patient-specific vulnerability profiles on perioperative outcomes. Results: Preclinical studies consistently demonstrate that volatile anesthetics trigger mitochondrial protective pathways, including K-ATP channel activation, controlled reactive oxygen species signaling and inhibition of the mitochondrial permeability transition pore. Clinical studies suggest potential benefits in myocardial protection and modulation of systemic inflammatory and microcirculatory responses. However, translation into consistent clinical outcome improvement remains heterogeneous, influenced by variability in surgical procedures, anesthetic protocols and patient risk stratification. Conclusions: Volatile anesthetics exhibit mechanistic properties supporting a potential role in organ protection during cardiac surgery. Nevertheless, clinical evidence remains inconclusive, underscoring the need for refined patient stratification and precision-based perioperative strategies. Identifying knowledge gaps and research priorities may facilitate rational, individualized integration of inhalational anesthesia into contemporary cardiac surgical practice.

The 2025 ESC/EAS Dyslipidaemia Focused Update provides a targeted revision of the 2019 guidelines, integrating newly available evidence with the potential to influence clinical decision-making before the next full update. While LDL-C treatment targets remain unchanged, the document reshapes how they should be achieved, emphasizing faster therapeutic intensification, broader use of combination therapy and improved risk stratification with SCORE2/SCORE2-OP, lipoprotein(a) [Lp(a)] and coronary artery calcium (CAC) scoring. New evidence supporting bempedoic acid, inclisiran and evinacumab expands the therapeutic armamentarium, particularly for patients at high, very high and extreme cardiovascular risk or those with statin intolerance. In the acute coronary syndrome (ACS) setting, the update reinforces a more proactive, early-intensification approach. Overall, the Focused Update refines the operational framework of LDL-C management, promoting earlier, more personalized and more sustained lipid lowering to reduce cumulative atherosclerotic exposure.

Acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) relapse is the most frequent cause of allogeneic stem cell transplantation (allo-SCT) failure. The utility of post-relapse therapy is controversial due to the high incidence of toxicity and the low efficacy. This sub-analysis of the Gruppo Italiano Trapianto di Midollo Osseo (GITMO) AML/MDS relapse study focuses on 647 AML/MDS relapsing after allo-SCT performed between 2015 and 2021. Following the relapse, these patients were treated with either hypomethylating agents (HMAs)-based therapy (n = 308) or other treatments (n = 339), including intensive chemotherapy, FLT3-inhibitors, and second allo-SCT. HMAs-based therapies were more frequently used in older patients, transplanted not in CR following a reduced-intensity conditioning regimen. The overall response rate (ORR) with or without HMA-based salvage treatment was 33% and 40%, respectively (P = .006). The complete remission (CR) rate was 23% and 33% in the two groups, respectively (P < .001). The long-term OS and TRM of the two groups were superimposable. Independently from the type of salvage, an advantage in OS was observed when donor lymphocytes infusion (DLI) was included (P < .001). Relapse within 12 months after SCT, low disease burden at relapse, and the CR status at transplant confirmed their independent strong prognostic impact on both HMA and non-HMA-based group (HR 0.05, 0.44, and 0.49 and HR 0.19, 0.32, and 0.53, respectively). Despite the lower ORR observed with HMA-based therapy, the long-term OS was comparable to that observed with other therapies. The immune control of the disease relapse with DLI is of benefit, independently from the salvage therapy. .

Background: Hemodynamic management in veno-arterial extracorporeal membrane oxygenation (V-A ECMO) is inherently complex, as extracorporeal circulation profoundly alters preload, afterload, ventriculo-arterial coupling and tissue perfusion. This review summarizes current and emerging monitoring strategies to guide initiation, maintenance and weaning. Methods: A structured literature search was performed in PubMed and Scopus (1990–2025), including clinical studies, consensus statement and expert reviews addressing hemodynamic monitoring in V-A ECMO. Results: A multiparametric framework is required. Echocardiography remains central for assessing biventricular performance, aortic valve dynamics and ventricular unloading. Pulmonary artery catheterization provides complementary data on filling pressures, cardiac output and global oxygen balance. Metabolic indices such as lactate clearance and veno-arterial CO2 gap, together with regional oximetry (NIRS), inform the adequacy of systemic and tissue perfusion. Microcirculatory monitoring, though technically demanding, has shown prognostic value, particularly during weaning. Additional adjuncts include arterial pulse pressure, end-tidal CO2 and waveform analysis. Phenotype oriented priorities, such as detection of differential hypoxemia, prevention of left ventricular distension or surveillance for limb ischemia, require tailored monitoring strategies. Artificial intelligence and machine learning represent future avenues for integrating multiparametric data into predictive models. Conclusions: No single modality can capture the hemodynamic complexity of V-A ECMO. Precision monitoring demands a dynamic, phenotype-specific and time-dependent approach that integrates systemic, cardiac, metabolic and microcirculatory variables. Such individualized strategies hold promise to optimize outcomes, reduce complications and align V-A ECMO management with the principles of precision medicine.

The clinical pathway of a patient who experiences cardiac arrest and subsequently dies (with or without organ donation) is complex. It involves uncontrolled (u-) donation after circulatory death (DCD), controlled (c-) DCD, and donor after brain death (DBD). The present paper aims to summarize existing evidence on organ donation rates among out-of-hospital cardiac arrest (OHCA) patients, with a focus on these three donor categories (uDCD, DBD, and cDCD). Furthermore, the potential to expand each donor pathway in OHCA patients will be highlighted, based on available evidence. Among non-survivor OHCA patients, the prevalence of brain death (BD) is estimated to be low, though reported data are not uniform. The diagnosis of BD is made 3 to 6 days after return of spontaneous circulation. The implementation of uDCD is known to be quite challenging due to logistical, ethical, and resource issues. Its rationale is still well grounded, mainly considering two factors: (a) the high incidence of OHCA, such that uDCD donors can be considered an existing pool of potential donors; (b) the uDCD pathway shows feasibility both under organizational (i.e., only lung uDCD program) and clinical views (normothermic regional perfusion, ex vivo machine perfusion, and an appropriate donor-recipient match). Controlled DCDs are donors who died after a planned withdrawal of life-sustaining therapy (WLST). Data on the percentage of cDCD among OHCA patients is not uniform since the percentage of utilized cDCD has been estimated at around 10%. According to available evidence, each donor pathway in OHCA has the potential to be expanded, mainly by the identification of potential donors and the implementation of DCD programs.

Ventilator-associated bacterial pneumonia (VABP) is a common infection in critically ill patients in intensive care units (ICU), with attributable mortality of up to 13%, and its etiological diagnosis remains challenging. We conducted a multicenter, prospective, observational study within the MULTI-SITA platform to assess the impact on relevant clinical and antimicrobial stewardship outcomes of the use of a molecular syndromic panel (BIOFIRE® FILMARRAY® Pneumonia plus), in addition to a standard approach based on culture. The primary outcome measure was 30-day mortality from VABP onset. Overall, 237 patients with VABP were included in the study. In multivariable analysis, SOFA score (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.04–1.22, p = 0.003), previous isolation of carbapenem-resistant Pseudomonas aeruginosa (HR 3.02, 95% CI 1.25–7.32, p = 0.015), and solid neoplasm (HR 2.15, 95% CI 1.12–4.14, p = 0.022) were associated with increased mortality, while no association was registered for the molecular syndromic panel performed (HR 1.07, 95% CI 0.59–1.93, p = 0.825). In secondary analyses, use of the molecular syndromic panel resulted in more events of either de-escalation or initiation of appropriate antibiotic therapy at day 1 from VABP onset in comparison with a standard approach based on culture only (41.3% vs. 27.8%, p = 0.041). The use of a molecular syndromic panel in patients with VABP was able to impact antibiotic decisions, without an unfavorable effect on mortality. Further study is necessary to assess the long-term effects in terms of antimicrobial stewardship of molecular syndromic panels-based antibiotic treatment decisions.

BackgroundThe prognostic stratification is the cornerstone of treatment decision-making for mRCC. The novel Meet-URO score (IMDC score + NLR + Bone metastases) was developed in the immunotherapy era and has shown better prognostic performance compared with the IMDC score in different settings. Its application in the first-line IO-TKI setting was awaited.MethodsThe Meet-URO 33 is a multicentric prospective observational study enrolling mRCC patients receiving first-line systemic therapy. A retrospective cohort of patients treated from 01.01.2021 was included. The Meet-URO score was assessed compared with the IMDC score in predicting OS. An exploratory analysis on PFS was also conducted.ResultsA total of 1,557 patients were enrolled, 1400 (90%) were assessable. Median age was 66 years, 75% were males, 84% had clear cells, and 64% underwent nephrectomy; 20% received IO-IO, 66% IO-TKI (32% Pembrolizumab+Axitinib) and 14% TKI; 45% had NLR ≥ 3.2 and 29% bone metastases.After a mFU of 14.1 months, mOS was 40.5 months, and mPFS was 16.8 months. The Meet-URO score confirmed a better prognostic stratification compared with the IMDC score (c-index 0.714 vs 0.688) (Table 1). Although the Meet-URO score was developed as an OS model, it showed a similar PFS performance (c-index 0.62 vs 0.61).ConclusionsThe Meet-URO score confirmed its better prognostic accuracy compared with the IMDC score, also in a large-scale prospective cohort receiving first-line therapy. The adoption of the Meet-URO score should be implemented in clinical practice and as a stratification factor of clinical trials for more individualized patient management.ScoreGroup distributionHR (95%CI)P valuemOS (months)3y-OSMeet-URO 116%RefNR85% 230%2.19 (1.34-3.56).002 NR64% 322%3.62 (2.22-5.90)<.001 37.852% 424%6.76 (4.25-10.75)<.001 22.435% 58%12.59 (7.54-21.04)<.001 10.918%IMDC Favorable21%RefNR82% Intermediate57%2.97 (1.99-4.42)<.001 43.756% Poor22%8.45 (5.61-12.70)<.001 13.726%