Marco Fiore

Septic shock of abdominal origin remains one of the most challenging conditions in critical care, with a substantial proportion of patients progressing to a refractory state despite adequate source control and standard resuscitative measures. Molecular biomarkers are established tools for early diagnosis and prognostic stratification and have been proposed as candidate tools for individualizing therapeutic decisions. This narrative review examines the evidence on biomarkers relevant to abdominal sepsis-associated septic shock—including procalcitonin, presepsin, lactate, interleukin-6 and gut-derived markers of intestinal barrier dysfunction—and examines how far they may inform the timing of source control, vasopressor escalation and the use of adjunctive therapies. Every marker is classified as diagnostic, prognostic, treatment-monitoring or predictive (treatment-selection), since a marker associated with outcome is not thereby a marker that predicts benefit from an intervention. We report turnaround time and availability for each assay, and the effect of acute kidney injury and kidney replacement therapy on its interpretation. The review offers a practical, evidence-informed framework and identifies the gaps that warrant investigation. No biomarker-guided strategy in this population has been prospectively validated; biomarkers remain adjuncts to clinical, radiological and surgical assessment and must never delay source control.

Background: Sepsis-associated encephalopathy (SAE) is among the most frequent neurological complications of sepsis, contributing independently to mortality, prolonged mechanical ventilation and intensive care unit stay and long-term cognitive disability. The gut–brain axis has been proposed as a key mediator, through dysbiosis, intestinal barrier failure, bacterial translocation and neuroinflammation. This review synthesises the evidence on this axis in SAE and appraises whether nutritional and microbiome-directed strategies can be regarded as modulators of it, or should be framed as a testable hypothesis. Methods: A narrative review was conducted and reported according to the SANRA criteria. PubMed/MEDLINE, Scopus and Web of Science were searched from inception to September 2026 for preclinical and clinical studies on gut microbiota, intestinal permeability, neuroinflammation, blood–brain barrier dysfunction and nutritional or microbiome-directed strategies in sepsis. Results: Four communication pathways are described: neural (vagal), immune/humoral, metabolic (short-chain fatty acids, tryptophan-derived indoles, host kynurenines) and neuroendocrine. Evidence that nutritional or microbiome-directed interventions act on them is almost entirely preclinical and derives from rodent models of limited translational validity. Randomised trials of feeding route and dose, immunonutrients and probiotics were designed around mortality, infection and respiratory outcomes—endpoints of the gut–immune and gut–lung axes—and, apart from one negative cognitive follow-up in acute lung injury, none has reported SAE, delirium or cognition. This is an absence of evidence rather than heterogeneous evidence. Conversely, microbial composition and metabolites are emerging as candidate predictors of SAE and intensive care unit delirium. Conclusions: The gut–brain axis in SAE remains an unproven hypothesis. Nutrition should be regarded as a biologically plausible but untested modulator rather than an established therapy. Prospective studies with standardised neurological endpoints, and microbiota-based risk stratification, are required before any gut-directed intervention can be recommended for brain protection in sepsis.

Background: Abdominal sepsis is associated with profound pharmacokinetic (PK) alterations that make standard beta-lactam dosing regimens potentially inadequate in critically ill patients. Increased volume of distribution, hypoalbuminemia, augmented renal clearance (ARC), acute kidney injury (AKI) and the PK complexity of the peritoneal compartment collectively impair the ability of conventional dosing to achieve pharmacodynamic (PD) targets. These PK derangements are clinically relevant but incompletely characterized in intra-abdominal infections (IAI)- specific cohorts, as most available data derive from broader critically ill populations. Beta-lactam antibiotics, the cornerstone therapy in IAIs, are particularly susceptible to these alterations, especially in the context of multidrug-resistant (MDR) pathogens. Methods: We conducted a structured narrative review of the literature published between 2010 and 2026, searching PubMed and Embase using terms related to pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, beta-lactam antibiotics, abdominal sepsis, and intra-abdominal infection in critically ill patients. Additional references were identified through manual bibliography screening, including seminal studies predating the search window. No formal systematic review methodology was applied. Results: PK/PD optimization in abdominal sepsis can be organized around four proposed domains: extended or continuous infusion of beta-lactams to maximize the time above the minimum inhibitory concentration; therapeutic drug monitoring (TDM) to guide individualized dose adjustment in the presence of ARC, AKI, or continuous renal replacement therapy (CRRT); tailored dose optimization during CRRT; and target attainment analysis against MDR organisms. Extended and continuous infusions improve PD target attainment and are associated with improved outcomes in some observational studies, although prospective IAI-specific evidence is lacking and the evidence supporting these strategies derives largely from broader intensive care unit populations. Conclusions: In abdominal sepsis, integrating PK/PD principles and TDM-guided dosing represents a pharmacologically rational strategy to optimize beta-lactam exposure and improve target attainment against MDR pathogens. Rigorous IAI-specific prospective studies are needed to establish definitive TDM-guided dosing protocols and translate these pharmacological strategies in this high-acuity setting.

Introduction: Perioperative pain is a major determinant of patients’ experience and may influence long-term outcomes. Artificial intelligence (AI) is applied to perioperative datasets to predict acute postoperative pain, opioid requirements, analgesic-related adverse events, chronic postsurgical pain and pain trajectories. However, the evidence is dispersed across perioperative phases, clinical outcomes, data modalities and AI methodologies, while the extent to which current models address validation, interpretability, uncertainty and clinical implementation remains unclear. This scoping review protocol aims to characterise the existing evidence on AI applications related to perioperative pain to identify methodological features that affect its clinical credibility and implementation. Methods and analysis: This protocol will follow the Joanna Briggs Institute methodology for scoping reviews and will be reported in line with Preferred Reporting Items for Systematic Reviews and Meta-Analysis Extension for Scoping Reviews (PRISMA-ScR) guidance. Eligible studies will include human research evaluating AI methods in relation to pain-related perioperative outcomes, including observational studies, interventional studies and predictive modelling studies. AI approaches include machine learning, deep learning, natural language processing, computer vision, large language models and hybrid or ensemble methods. Searches will be conducted from PubMed/MEDLINE, Embase, the Cochrane Library, medRxiv, arXiv and ClinicalTrials.gov, with supplementary screening of reference lists. Results will be synthesised descriptively. The formal literature searches are planned for September 2026, with completion of study selection, data charting, evidence synthesis and preparation of the final review expected by December 2026. Ethics and dissemination: We will chart ethical aspects reported in included studies, such as governance of retrospective electronic health record use, consent waivers and privacy protections, where available. Findings will be disseminated through submission to a peer-reviewed journal, presentation at scientific meetings and open sharing of search strategies on the Open Science Framework. PROSPERO registration number: This protocol was prospectively registered on the Open Science Framework in March 2026: Cascella M et al ‘Artificial intelligence in perioperative pain: a scoping review protocol’. DOI: 10.17605/OSF.IO/SYZH8.

Background: Abdominal sepsis is associated with profound pharmacokinetic (PK) alterations that make standard beta-lactam dosing regimens potentially inadequate in critically ill patients. Increased volume of distribution, hypoalbuminemia, augmented renal clearance (ARC) and acute kidney injury (AKI) collectively impair the ability of conventional dosing to achieve pharmacodynamic (PD) targets. Beta-lactam antibiotics, the cornerstone therapy in intra-abdominal infections (IAIs), are particularly susceptible to these alterations, especially in the context of multidrug-resistant (MDR) pathogens. Methods: We conducted a structured narrative review of the literature published between 2010 and 2026, searching PubMed and Embase using terms related to pharmacokinetics, pharmacodynamics, therapeutic drug monitoring, beta-lactam antibiotics, abdominal sepsis, and intra-abdominal infection in critically ill patients. Additional references were identified through manual bibliography screening, including seminal studies predating the search window. No formal systematic review methodology was applied. Results: PK/PD optimization in abdominal sepsis relies on four pillars: extended or continuous infusion of beta-lactams to maximize the time above the minimum inhibitory concentration; therapeutic drug monitoring (TDM) to guide individualized dose adjustment in the presence of ARC, AKI, or continuous renal replacement therapy (CRRT); dose optimization during CRRT; and target attainment analysis against MDR organisms. Current evidence suggests combining real-time TDM with emerging bi-omarkers provides a rational framework for safe de-escalation and stewardship. Conclusions: In abdominal sepsis, integrating PK/PD principles and TDM-guided dosing represents an evidence-based strategy to optimize beta-lactam exposure, improve target attainment against MDR pathogens, and potentially reduce treatment failure and resistance selection. Prospective studies specifically designed for the IAI population are needed to establish definitive TDM-guided dosing protocols in this high-acuity setting.

Background: Major spine surgery carries an inherent risk of hemodynamic instability due to prone positioning, significant blood loss, and the strict necessity to maintain adequate spinal cord perfusion. Hemodynamic management mainly relies on a reactive approach, treating hypotension only after it occurs, which increases the risk of postoperative complications such as acute kidney injury and ischemic events. This narrative review evaluates the clinical impact, current evidence, and future perspectives of integrating Artificial Intelligence (AI) and Machine Learning (ML) algorithms into perioperative hemodynamic care. Methods: A comprehensive literature search was conducted through PubMed, EMBASE, and the Cochrane Library, spanning from inception to January 2026. The search strategy employed combinations of Medical Subject Headings terms and keywords related to “Artificial Intelligence,” “Machine Learning,” “Hypotension Prediction Index,” “hemodynamic monitoring,” and “major spine surgery.” Studies were selected based on their relevance to predictive hemodynamic algorithms, goal-directed fluid therapy (GDFT), and automated closed-loop systems within the perioperative setting of complex spinal interventions. Results: Five studies show that AI/ML tools can improve hemodynamic management in spine surgery: an hypotension prediction index (HPI)-guided algorithm reduced intraoperative hypotension during prone spinal fusion; a machine learning model accurately predicted massive blood loss in metastatic spinal disease; an AutoML framework linked intraoperative hypertension to worse neurological recovery after spinal cord injury (SCI); a case report showed HPI-guided goal-directed therapy enabled safe, transfusion-free major spine surgery; and topological network analysis identified a narrow optimal mean arterial pressure (MAP) range for neurological recovery after SCI. Collectively, these preliminary findings suggest a potential role for AI/ML in reducing hemodynamic instability and enabling more individualized perioperative management in spine surgery. Rather than converging on a single verdict, these five studies fall into three distinct evidentiary categories when appraised using a structured model-validation (V1–V4) and clinical-translation (T0–T4) framework applied within each category: a real-time monitoring technology (HPI) with a substantial extra-spinal evidence base but a limited spine-specific replication record; a single, externally validated but clinically unproven preoperative prediction model; and two retrospective, hypothesis-generating discovery frameworks that remain exploratory irrespective of surgical domain. Conclusions: The evidence identified does not support a single, unified statement about “AI/ML in spine surgery.” Instead, it points to three distinct situations that warrant separate research priorities: consolidating spine-specific replication of an otherwise mature monitoring technology (HPI); externally confirming the clinical utility, rather than only the discriminative accuracy, of a single preoperative prediction model; and prospectively testing the retrospectively derived targets generated by discovery-oriented analytic frameworks. Considered together, these findings should inform hypothesis-driven research design rather than a single implementation-readiness judgment.

Background/Objectives: Abdominal sepsis remains a major contributor to morbidity and mortality among surgical and critically ill patients worldwide. Timely diagnosis is frequently hindered by the overlapping clinical and biochemical features of postoperative inflammatory responses and evolving intra-abdominal infections, which may resemble systemic sepsis. Conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT), are widely implemented in clinical practice but demonstrate suboptimal specificity in differentiating infectious from sterile inflammatory conditions in the early postoperative phase. Presepsin (soluble CD14 subtype, sCD14-ST), a circulating fragment released during monocyte–macrophage activation in response to bacterial endotoxins, has emerged as a biomarker reflecting innate immune engagement. This review aims to critically evaluate the current evidence regarding the diagnostic accuracy, prognostic relevance, and potential clinical role of presepsin in abdominal sepsis. Methods: A comprehensive narrative review of the biomedical literature was performed using MEDLINE (via PubMed) and supplementary academic sources. Studies assessing the diagnostic performance, prognostic associations, and clinical applicability of presepsin in abdominal infections, postoperative infectious complications, and sepsis were systematically examined. Where available, comparative analyses with established biomarkers such as CRP and PCT were evaluated to contextualize its incremental value within existing diagnostic frameworks. Results: The accumulated evidence indicates that presepsin concentrations increase early during bacterial infections and correlate with validated severity indices, organ dysfunction scores, and mortality outcomes. Across multiple surgical and intensive care settings, presepsin demonstrated moderate-to-high diagnostic performance, frequently comparable to and occasionally exceeding that of traditional inflammatory biomarkers, particularly in distinguishing septic from non-septic inflammatory states. Moreover, dynamic changes in circulating levels appear to provide additional prognostic information and may support longitudinal clinical assessment. Nonetheless, substantial heterogeneity in study design, patient populations, sampling strategies, and reported cut-off values limits direct cross-study comparability and constrains definitive clinical recommendations. Conclusions: Presepsin represents a biologically plausible and clinically promising biomarker for the early identification and risk stratification of abdominal sepsis. Although current findings are encouraging, further large-scale, methodologically standardized prospective investigations are required to define optimal diagnostic thresholds and to clarify their role within multimodal biomarker strategies in contemporary sepsis management.

Background/Objectives: Abdominal sepsis remains a major contributor to morbidity and mortality among surgical and critically ill patients worldwide. Timely diagnosis is frequently hindered by the overlapping clinical and biochemical features of postoperative inflammatory responses and evolving intra-abdominal infections, which may resemble systemic sepsis. Conventional biomarkers, including C-reactive protein (CRP) and procalcitonin (PCT), are widely implemented in clinical practice but demonstrate suboptimal specificity in differentiating infectious from sterile inflammatory conditions in the early postoperative phase. Presepsin (soluble CD14 subtype, sCD14-ST), a circulating fragment released during monocyte–macrophage activation in response to bacterial endotoxins, has emerged as a biomarker reflecting innate immune engagement. This review aims to critically evaluate the current evidence regarding the diagnostic accuracy, prognostic relevance, and potential clinical role of presepsin in abdominal sepsis. Methods: A comprehensive narrative review of the biomedical literature was performed using MEDLINE (via PubMed) and supplementary academic sources. Studies assessing the diagnostic performance, prognostic associations, and clinical applicability of presepsin in abdominal infections, postoperative infectious complications, and sepsis were systematically examined. Where available, comparative analyses with established biomarkers such as CRP and PCT were evaluated to contextualize its incremental value within existing diagnostic frameworks. Results: The accumulated evidence indicates that presepsin concentrations increase early during bacterial infections and correlate with validated severity indices, organ dysfunction scores, and mortality outcomes. Across multiple surgical and intensive care settings, presepsin demonstrated moderate-to-high diagnostic performance, frequently comparable to and occasionally exceeding that of traditional inflammatory biomarkers, particularly in distinguishing septic from non-septic inflammatory states. Moreover, dynamic changes in circulating levels appear to provide additional prognostic information and may support longitudinal clinical assessment. Nonetheless, substantial heterogeneity in study design, patient populations, sampling strategies, and reported cut-off values limits direct cross-study comparability and constrains definitive clinical recommendations. Conclusions: Presepsin represents a biologically plausible and clinically promising biomarker for the early identification and risk stratification of abdominal sepsis. Although current findings are encouraging, further large-scale, methodologically standardized prospective investigations are required to define optimal diagnostic thresholds and to clarify its role within multimodal biomarker strategies in contemporary sepsis management.

Background and Objectives: Communication gaps contribute substantially to anxiety, depression, and post-traumatic stress disorder (PTSD) among relatives of critically ill patients. This study evaluated whether supplementing routine bedside meetings with a concise, co-designed informational brochure was associated with reduced psychological distress and improved satisfaction among family members in the intensive care unit (ICU). Materials and Methods: We conducted a single-centre prospective before–after observational study in a mixed medical–surgical ICU in Naples, Italy. Relatives of adult patients with an ICU length of stay >72 h completed the Hospital Anxiety and Depression Scale (HADS) and the Short Screening Scale for PTSD (SSS-PTSD) at ICU discharge. The pre-intervention phase enrolled 12 relatives (May–September 2018); following a co-design and staff training period, the post-intervention phase enrolled 23 relatives (April–October 2019). Primary outcomes were the prevalence of anxiety (HADS-A ≥8), depression (HADS-D ≥8), and probable PTSD (SSS-PTSD ≥4). Groups were compared using Fisher’s exact test and the Mann–Whitney U test. Results: Anxiety remained highly prevalent (100% pre vs. 95.7% post; p = 1.00). Depression severity decreased, with median HADS-D scores declining from 13 (IQR 10–18) to 9 (IQR 7–12) (p = 0.021), while the prevalence of HADS-D ≥8 was lower post-intervention (91.7% vs. 73.9%; p = 0.38). The prevalence of probable PTSD was numerically reduced from 58.3% to 30.4% (p = 0.116). Perceived comprehension improved (7.9 ± 1.1 vs. 8.6 ± 0.9; p = 0.037), whereas objective comprehension remained unchanged. Overall family satisfaction increased (FS-ICU-24: 66 ± 15 vs. 75 ± 12; p = 0.041). Staff depersonalization decreased from 35% to 10% (p = 0.048). Conclusions: In this real-world before–after study, integrating a low-cost, co-designed brochure into clinician–family communication was associated with reduced depressive symptom severity, a numerical reduction in PTSD prevalence, and improved satisfaction, without adverse effects on staff well-being. These findings support the use of structured written information in family-centred ICU care.

Background/Objectives: Flexible bronchoscopy (FB) enables airway exploration and diagnosis of various respiratory pathologies, but the sedation and instrumentation required during the procedure raise oxygen demand while reducing ventilation, which can lead to hypoxemia. Conventional oxygen therapy (COT) may not adequately prevent desaturations in high-risk groups, as patients with moderate respiratory deficiency. High-flow nasal cannula (HFNC) can deliver heated, humidified oxygen at high flow rates, generating low-level positive airway pressure, improving oxygenation, reducing dead-space, and enhancing procedure tolerance. Prior studies have shown that HFNC can improve gas exchange and reduce desaturations during bronchoscopy. However, evidence remains limited for patients with moderate respiratory deficiency, who are particularly vulnerable. Evaluating the feasibility and safety of HFNC in this population is essential to guide safe procedural practice. Methods: A retrospective observational study including patients undergoing FB with HFNC support between January and May 2025. Inclusion criteria were BMI between 18 and 30; age > 18 years old; moderate respiratory dysfunction, defined by pulse oximetry, Pulmonary Functional Tests (PFTs) and Arterial Blood Gas (ABG) analysis. Exclusion criteria were intolerance/contraindication to HFNC. Procedures were performed under basic monitoring. Primary outcome was occurrence of severe hypoxemia (SpO2 < 90%). Secondary outcomes were needed for rescue maneuvers, interruption for conversion to other ventilatory strategies, and hemodynamic instability. Results: No severe desaturations were recorded, all procedures were completed without rescue maneuvers or other ventilatory strategies, and no hypoxemia occurred. Mean duration of the procedure was 9 min. Vital parameters were maintained within the normal ranges, with a mean SpO₂ during bronchoscopy of 98%. Conclusions: HFNC enables oxygenation and ventilation without adverse events in sedations for FB in patients with moderate respiratory deficiency.