Alberto Barbieri

Background: Gram-negative bacterial infections represent an increasingly relevant challenge in orthopedic surgery, particularly in complex patients exposed to major trauma, revision procedures, prolonged hospitalization, previous antimicrobial therapy, and intensive care. Although Gram-positive organisms remain predominant in prosthetic joint infections (PJIs) and fracture-related infections (FRIs), the emergence of multidrug-resistant (MDR) Gram-negative pathogens has important implications for perioperative management, antimicrobial prophylaxis, and treatment. Objective: This narrative review examines the epidemiology, pathogenesis, antimicrobial resistance, and management of Gram-negative orthopedic infections, with particular emphasis on issues relevant to anesthesiologists and intensive care physicians. Methods: A structured narrative literature search was conducted in PubMed/MEDLINE, Scopus, and Web of Science from database inception to July 2026, according to the principles of the Scale for the Assessment of Narrative Review Articles (SANRA). Original studies, systematic reviews, meta-analyses, guidelines, consensus statements, and relevant narrative reviews addressing Gram-negative infections in orthopedic surgery were considered. Results: Gram-negative pathogens account for a minority of orthopedic infections but become increasingly relevant in complex PJIs, FRIs, open fractures, revision surgery, and patients with substantial healthcare exposure. Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii are among the principal pathogens involved. Their clinical relevance is amplified by biofilm formation and increasingly complex antimicrobial resistance mechanisms. Perioperative antibiotic prophylaxis should remain individualized in patients colonized or previously infected with MDR Gram-negative organisms, avoiding indiscriminate broad-spectrum prophylaxis. Once infection is established, management requires adequate microbiological sampling, surgical source control, and susceptibility-guided antimicrobial therapy. New β-lactam/β-lactamase inhibitor combinations and cefiderocol have expanded therapeutic options against resistant Gram-negative pathogens; however, evidence specifically supporting cefiderocol for bone and joint infections remains limited. Conclusions: Gram-negative orthopedic infections represent an emerging challenge at the intersection of orthopedic surgery, infectious diseases, anesthesiology, and critical care. Early recognition of high-risk patients, individualized perioperative strategies, effective source control, resistance-guided antimicrobial therapy, and multidisciplinary management are essential.

Background: In head and neck reconstructive surgery, flap loss remains a major complication and continues to represent a significant challenge in perioperative management. Although free tissue transfer is widely used, unsatisfactory outcomes are still reported across different flap procedures. Anaesthetic management plays an important role in influencing flap perfusion through its effects on systemic haemodynamics, regional blood flow, and microcirculation. However, there is currently no consensus on universally acceptable haemodynamic targets, and the impact of intraoperative strategies appears to be highly application-specific. Materials and Methods: This narrative review was conducted in accordance with the 2019 SANRA guidelines. PubMed^® was used as the primary database for literature selection. Relevant studies addressing anaesthetic management in head and neck free flap surgery were reviewed, with a particular focus on intraoperative haemodynamic control, ischemia–reperfusion injury, fluid and transfusion management, vasoactive agents, and advanced monitoring techniques. Results: Ischemia–reperfusion injury represents a major mechanism of vascular compromise in free flap surgery and has a significant impact on microcirculatory perfusion. The literature suggests that several anaesthetic strategies—including goal-directed fluid therapy, cautious use of vasopressors, and advanced haemodynamic monitoring—may support intraoperative haemodynamic stability and improve flap perfusion. Nevertheless, the magnitude of haemodynamic improvement achievable with these strategies and their effect on graft survival vary according to patient characteristics, surgical factors, and flap type. Conclusions: Current evidence indicates that anaesthetic management has the potential to contribute to improved intraoperative haemodynamic control in head and neck free flap reconstruction, thereby supporting graft viability. However, haemodynamic targets and management strategies cannot be generalised and should be interpreted within specific clinical contexts. Rather than aiming for optimisation, future research should focus on defining acceptable clinical outcomes for individual applications and on evaluating whether achievable haemodynamic improvements are sufficient to reduce flap-related complications to clinically acceptable levels.

This study investigates the influence of sevoflurane and desflurane on the electrochemical behavior of the Fe(III)-acetylacetonate (Fe(acac)₃) complex. Using cyclic voltammetry (CV), we demonstrate that while Fe(acac)₃ exhibits reversible redox behavior in an oxygen-free environment, the presence of dissolved oxygen renders the system irreversible, leading to the formation of a thick, reddish film on the electrode surface upon potential cycling. Notably, the addition of sevoflurane and desflurane restores the electrochemical reversibility and dramatically inhibits this film formation. Raman spectroscopy of the resulting films confirmed structural changes which are consistent with this inhibiting action. Furthermore, X-ray photoelectron spectroscopy (XPS) analysis reveals that the iron in the film remains predominantly in the Fe³⁺ oxidation state even after prolonged electrochemical reduction cycles. These findings suggest that the anesthetics act by inhibiting the interaction between the Fe(acac)₃ complex and oxygen, likely through a spin–decoherence mechanism. This work highlights the critical role of anesthetics in modifying the electrochemical behavior of metal-oxygen complexes, with potential implications for sensing, electrocatalysis, and bio-oriented systems.

Background: Sepsis is a life-threatening syndrome caused by a dysregulated host response to infection leading to organ dysfunction. Distinguishing sepsis from localized infection is crucial, as it guides clinical decision-making and biomarker interpretation. Biomarkers may support diagnosis, prognosis, and therapeutic choices, but their integration into practice remains debated. Methods: This narrative review was conducted in accordance with the SANRA (Scale for the Assessment of Narrative Review Articles) guidelines. A comprehensive literature search was performed in PubMed, Embase, and Cochrane CENTRAL (January 2000–September 2025). Studies evaluating sepsis-related biomarkers for diagnosis, prognostication, shock assessment, antimicrobial stewardship, and post-acute follow-up were considered. Findings: Established biomarkers such as procalcitonin (PCT), C-reactive protein (CRP), and lactate remain widely used for diagnosis, monitoring of inflammatory response, and assessment of severity. Emerging candidates include pancreatic stone protein (PSP), neutrophil gelatinase-associated lipocalin (NGAL), and monocyte HLA-DR (mHLA-DR), which may provide insights into infection dynamics, renal injury, and immune suppression, respectively. However, limitations in standardization and heterogeneous evidence hinder routine implementation. Interleukin-6 (IL-6), despite extensive study, shows limited specificity and inconsistent clinical applicability. Renin has been proposed as a marker of shock severity rather than infection. Comparative evidence highlights the need for stage-specific biomarker use across prehospital, emergency, ICU, and recovery phases. Conclusions: No single biomarker is universally applicable in sepsis. Their utility depends on timing, clinical setting, and patient phenotype. Combining classical and emerging biomarkers with point-of-care technologies and dynamic monitoring may enhance personalized management. Limitations include heterogeneity of evidence and lack of standardized thresholds. Future research should validate biomarker panels, integrate them into stewardship strategies, and explore their cost-effectiveness in clinical practice.

Background: The identification and clinical implementation of robust biomarkers are essential for improving diagnosis, prognosis, and treatment across a wide range of diseases. Pancreatic stone protein (PSP) has recently emerged as a promising candidate biomarker. Objective: This narrative review aims to provide an updated and comprehensive overview of the clinical applications of PSP in infectious, oncological, metabolic, and surgical contexts. Methods: We conducted a structured literature search using PubMed^®, applying the SANRA framework for narrative reviews. Boolean operators were used to retrieve relevant studies on PSP in a wide range of clinical conditions, including sepsis, gastrointestinal cancers, diabetes, and ventilator-associated pneumonia. Results: PSP has shown strong diagnostic and prognostic potential in sepsis, where it may outperform traditional markers such as CRP and PCT. It has also demonstrated relevance in gastrointestinal cancers, type 1 and type 2 diabetes, and perioperative infections. PSP levels appear to rise earlier than other inflammatory markers and may be less affected by sterile inflammation. Conclusion: PSP represents a versatile and clinically valuable biomarker. Its integration into diagnostic protocols could enhance early detection and risk stratification in critical care and oncology settings. However, widespread adoption is currently limited by the availability of point-of-care assay platforms.

Background/Objectives: Endovascular thrombectomy has become a mainstay in the treatment of acute ischemic stroke caused by large vessel occlusion. Among the multiple factors that influence outcomes, the choice of anesthetic technique—general anesthesia (GA), conscious sedation (CS), or local anesthesia (LA)—remains controversial. This narrative review aims to critically examine and synthesize current evidence comparing the efficacy and safety of different anesthetic strategies in endovascular stroke treatment. Methods: A structured search of the PubMed^® database was conducted using the terms “stroke treatment”, “endovascular stroke treatment”, “anesthesia”, “general anesthesia”, “conscious sedation”, and “local anesthesia”. The search focused on clinical trials involving human subjects published in English. Studies were included if they compared at least two anesthetic techniques during thrombectomy and reported outcomes such as neurological recovery, mortality, or complication rates. Reviews, case reports, and animal studies were excluded. Results: Several randomized controlled trials and observational studies show comparable functional outcomes between GA and CS, though CS may confer advantages in early neurological recovery and reduced complications. Local anesthesia, though less studied, may offer favorable outcomes in selected patients. General anesthesia appears to be associated with greater hemodynamic variability and a higher risk of post-procedural infections, particularly in unsuccessful interventions. Maintaining stable blood pressure and minimizing ventilation duration are crucial to improving patient prognosis. Conclusions: While both GA and CS are viable options during thrombectomy, CS and LA may provide a safer profile in selected patients by preserving hemodynamic stability and reducing infectious risk. Personalized anesthetic strategies and further high-quality trials are warranted.

Background: Bacterial infections are frequent complications in critically ill COVID-19 patients, and are associated with increased morbidity, antibiotic use, and healthcare burden. Early and accurate identification of infection remains challenging. Pancreatic Stone Protein (PSP) has emerged as a promising biomarker of infection. In this study, PSP was evaluated alongside C-reactive protein (CRP). Methods: We conducted a prospective study including 105 critically ill COVID-19 patients admitted to the intensive care unit (ICU). Blood samples were collected at admission to measure PSP and CRP. A LASSO Least Absolute Shrinkage and Selection Operator (LASSO) regression model was used to identify independent predictors of proven or suspected bacterial infection. Mixed-effects models were applied to account for repeated measures and clinical confounders. Results: Among 105 patients, 57 (54%) developed bacterial infections. PSP levels were significantly higher in infected patients (median 100 ng/mL) than in non-infected patients (median 37 ng/mL, p < 0.001). CRP was also elevated in infected patients (median 125 vs. 70 mg/L, p = 0.015). The LASSO model retained PSP as the most informative predictor. In mixed-effects logistic regression, PSP remained significantly associated with infection (OR 1.017, 95% CI 1.006–1.027, p = 0.001). The AUC for PSP was 0.87. Conclusion: PSP appears to be a useful biomarker for early detection of bacterial infection in critically ill COVID-19 patients. Its integration into infection surveillance protocols could support antibiotic stewardship efforts and improve clinical decision-making.

Background: Major orthopedic trauma in patients receiving anticoagulants such as ticagrelor or rivaroxaban poses a significant perioperative challenge, particularly in emergency contexts where bleeding risks are heightened and specific reversal agents may be unavailable. CytoSorb^®, a hemoadsorption device, has demonstrated efficacy in cardiac surgery for drug removal. Its potential application in trauma surgery remains unexplored. Objective: This protocol describes a prospective clinical investigation assessing the feasibility and safety of CytoSorb^® hemoadsorption for the preoperative removal of ticagrelor and rivaroxaban in trauma patients requiring urgent orthopedic surgery. Methods: The proposed intervention involves integrating CytoSorb^® into a dedicated extracorporeal circuit under normothermic conditions (37 °C) with a blood flow of 150–200 mL/min for 300 min. Serial plasma samples will be collected at predefined intervals (0, 30, 60, 120, 240, 300 min) and drug concentrations. The primary outcome is the pharmacokinetic profile of drug clearance. Secondary endpoints include procedural safety, bleeding complications, and the feasibility of timely surgery. Expected Impact: The study aims to provide real-world data on the practical integration of CytoSorb^® for anticoagulant removal in orthopedic trauma care, potentially facilitating earlier surgery and improving perioperative safety. Findings may inform future randomized trials and protocol standardization.

Background: SARS-CoV-2 clinical manifestation and progression are variable and unpredictable, hence the importance of considering biomarkers in clinical practice that can be useful for both diagnosis and prognostic evaluation. This review aims to summarize, for intensive care physicians, the most recent state of knowledge regarding known COVID-19 in critical patients. We searched PubMed^® using the Boolean operators and identified all results on the PubMed^® database of all studies regarding COVID-19 biomarkers. We selected studies regarding endothelium, cytokines, bacterial infection, coagulation, and cardiovascular biomarkers. Methods: We divided the results into four essential paragraphs: “Cytokine storm”, “Endothelium dysfunction and coagulation biomarkers in COVID-19”, “Biomarker of sepsis”, and Cardiovascular lung and new perspectives. Results: The assessments of the severe COVID-19 prognosis should monitor, over time, IL-6, soluble Von Willebrand factor (VWF), P-selectin, sCD40L, thrombomodulin, VCAM-1, endothelin- Troponin, D-dimer, LDH, CRP, and procalcitonin. Metabolomic alterations and ACE2 receptors represent new perspectives. Discussion and Conclusions: Early identification of critically ill patients has been crucial in the first COVID-19 pandemic wave for the sustainability of the healthcare emergency system and clinical management. Only through the early identification of the most severe patients can they be provided with the most appropriate treatments.

Dear Editor, Thanks for the opportunity to review and read this paper: it seems well done. The research is a retrospective study, with a detailed introduction and a correct methodology for the retrospective study. The power size is right. The resu...