Obesity, body adiposity, and intracranial aneurysms: A narrative review of clinical evidence beyond body mass index Luca Ruggeri, Rita Lipani, Giuliano Cassataro, Valentina Paternò, Nicola Sinatra, Caterina Carollo, Giuseppe Cuttone, Riccardo Polosa, Pietro Ferrara, Giulio Geraci Obesity Research and Clinical Practice, 2026 Intracranial aneurysms are a prevalent cerebrovascular condition and a leading cause of aneurysmal subarachnoid hemorrhage (aSAH). Beyond established risk factors, increasing attention has been focused on metabolic conditions that may modulate vascular inflammation and endothelial function. In this context, obesity has been proposed as potential modifiers of intracranial aneurysm vulnerability. However, clinical evidence remains inconsistent and, in some cases, counterintuitive. Most studies rely on body mass index (BMI) as a proxy for adiposity. Across population-based cohorts and clinical series, BMI has not consistently emerged as an independent risk factor for aneurysm formation or rupture after adjustment for major confounders. Conversely, several studies have reported inverse associations between higher BMI and the risk of aSAH or post-hemorrhagic mortality, findings that have contributed to the concept of an "obesity paradox." Nevertheless, these associations vary widely by study design, population characteristics, and clinical endpoints, and do not show a consistent linear response pattern. Interpretation of these findings is limited by substantial methodological constraints. BMI does not reflect body composition, fat distribution, or the biological activity of adipose tissue, and may instead capture overall health status or nutritional reserve. Overall, current clinical evidence does not support a consistent or independent role of BMI-defined obesity in intracranial aneurysm risk or prognosis. Reported inverse associations should be interpreted with caution, as they may reflect methodological constraints rather than true biological effects. Future research should incorporate direct and biologically meaningful measures of adiposity to better clarify the relationship between metabolic factors and aneurysm disease.
Novel adiposity indices and their role in identifying left ventricular hypertrophy among hypertensive individuals undergoing echocardiography Giulio Geraci, Pietro Ferrara, Tommaso Piticchio, Rosario Le Moli, Valentina Paternò, Vincenzo Calabrese, Giuseppe Cuttone, Francesco Pallotti, Marco Barbanti, Emilio Nardi, Costantino Mancusi, Riccardo Polosa, Giuseppe Mulè, Caterina Carollo Nutrition Metabolism and Cardiovascular Diseases, 2026 Background and aims.While body mass index (BMI) is the most used measure of adiposity, it does not account for fat distribution.Novel indices, such as A Body Shape Index (ABSI) and Body Roundness Index (BRI), may better reflect cardiometabolic risk.However, their association with subclinical cardiac damage, particularly left ventricular hypertrophy (LVH), remains unclear.The aim of this study was to evaluate the association between novel adiposity indices (ABSI and BRI) and left ventricular mass (LVM) assessed by echocardiography in a large cohort of patients with hypertensive. Methods and Results. We conducted a cross-sectional study including 724 hypertensive adults who underwent standardized anthropometric and echocardiographic assessments.Adiposity indices (BMI, waist circumference, ABSI, and BRI) were calculated, and left ventricular mass was indexed to body surface area and height 2.7 .Correlations and multivariate analyses were performed, and receiver operating characteristic (ROC) curves were used to assess diagnostic performance.All adiposity indices were significantly higher in individuals with LVH.BRI showed the strongest correlation with LVMH 2.7 (r = 0.423), particularly in women.In multivariate analysis, BRI remained significantly associated with LVMH 2.7 in both sexes, while ABSI was not independently associated in men.ROC curve analysis demonstrated that BRI had the highest diagnostic accuracy for identifying LVH, outperforming BMI and ABSI, especially when LVH was defined using LVMH 2.7 .Conclusions.BRI outperformed traditional and novel adiposity indices in identifying LVH in hypertensive patients, particularly when LVM was indexed to height 2.7 .Given its superior diagnostic performance, BRI may represent a valuable tool in cardiovascular risk stratification, though further studies are warranted.
Strategies for a Rational Use of Opioids in Critical Care Settings Giovanni Misseri, Matteo Piattoli, Alice Mirasola, Lorenzo Guarrera, Carla Evangelista, Giuseppe Cuttone, Luigi La Via, Cesare Gregoretti Journal of Clinical Medicine, 2026 Opioids play a central role in pain management and sedation in Intensive Care Units (ICUs), where critically ill patients frequently experience moderate-to-severe pain due to illness and invasive procedures or devices. Uncontrolled pain exacerbates stress responses, contributing to clinical deterioration and adverse outcomes. Although analgesics and sedatives can mitigate these effects, their use must be carefully individualized to avoid complications such as delirium, prolonged mechanical ventilation, and increased mortality. Evidence now shows that excessive or poorly controlled analgosedation can prolong ICU length of stay and delay recovery. Current guidelines recommend opioids as first-line agents for severe acute pain in the ICU, preferably within a multimodal analgesia framework to optimize pain control while minimizing adverse effects. Opioids are also essential for improving tolerance to invasive and noninvasive mechanical ventilation. Modern ICU practice emphasizes an analgesia-first or “analgosedation” strategy, prioritizing pain control with intravenous opioids before adding sedatives. This approach aims to achieve light sedation, reduce ventilator days, and improve overall outcomes. Commonly used opioids include fentanyl, morphine, hydromorphone, sufentanil, and remifentanil, with short-acting agents favored when rapid titration is required. Our narrative review aims to evaluate the clinical impact of opioid use in critically ill patients, including post-ICU outcomes, and to explore the role of opioid stewardship in optimizing patient care.
Artificial Nutrition Support in Acute Liver Failure in Intensive Care Unit: A Practical Approach Cristian Deana, Andrea De Gasperi, Francesco Alessandri, Giuseppe Cuttone, Vittorio Cherchi, Yaroslava Longhitano, Luigi Vetrugno Journal of Intensive Care Medicine, 2026 Acute liver failure (ALF) is a life-threatening clinical syndrome characterized by the rapid onset of severe hepatic dysfunction, coagulopathy, and hepatic encephalopathy in patients without preexisting chronic liver disease. ALF remains associated with high morbidity and mortality, largely driven by profound metabolic instability, systemic inflammation, and multiorgan dysfunction. The liver's central role in carbohydrate, protein, and lipid metabolism makes metabolic derangements an early and defining feature of ALF. Hypoglycemia, hyperlactatemia, and hyperammonemia reflect impaired hepatic bioenergetic and detoxifying capacity and directly contribute to cerebral edema, intracranial hypertension, and neurological deterioration. Simultaneously, a cytokine-mediated hypercatabolic state promotes accelerated skeletal muscle wasting and alters amino acid homeostasis, further complicating nutritional management. Lipid metabolism is also profoundly disrupted, with reduced lipoprotein synthesis, altered fatty acid profiles, and impaired innate immune functions. In parallel, intestinal barrier dysfunction and gut microbiota dysbiosis exacerbate systemic inflammation through bacterial translocation and endotoxemia, reinforcing the gut–liver axis as a key modulator of disease severity. Nutritional support therefore represents a cornerstone of intensive care management in ALF, extending beyond caloric provision to influence metabolic control, immune competence, and neurological safety. This review provides a practical, evidence-based framework for nutritional management of patients with ALF admitted to the intensive care unit. Key aspects discussed include assessment of energy expenditure, timing and route of nutritional support, macronutrient composition, and the management of micronutrient deficiencies. Particular attention is given to balancing protein delivery against the risk of hyperammonemia, optimizing glucose control to avoid neurological harm, and selecting lipid formulations that minimize proinflammatory effects. Nutritional therapy in ALF must be individualized, dynamically reassessed, and closely integrated with hemodynamic stabilization, renal replacement therapy, and neuroprotective strategies. A systematic and multidisciplinary approach to nutrition is essential to reduce metabolic and infectious complications and to improve outcomes in this critically ill population.
Chloremia Disturbances in Critical Care: A Narrative Review of Pathophysiology, Clinical Impact and Management Strategies Nicola Sinatra, Giuseppe Cuttone, Tarek Senussi Testa, Luigi La Via, Francesca Maria Rubulotta, Maurizio Giuseppe Abrignani, Carmelo Zumbino, Giuseppe Mulè, Giulio Geraci, Caterina Carollo Life, 2026 Chloride, the leading extracellular anion, plays a crucial role in acid-base balance, fluid homeostasis, and neuromuscular function. Despite historical underrecognition, emerging evidence demonstrates significant associations between chloremia disturbances and critical care outcomes. This paper aims to narratively review the pathophysiology, clinical features, and management strategies of chloremia disturbances in critically ill patients. Chloremia disturbances are common in ICU patients, with both hypochloremia (<96 mEq/L) and hyperchloremia (>106 mEq/L) independently associated with increased mortality, prolonged ICU length of stay, and organ dysfunction. In sepsis, chloride levels exhibit a prognostic value, with threshold effects around 105 mEq/L. Hyperchloremia particularly increases acute kidney injury risk, while hypochloremia correlates with prolonged mechanical ventilation. The choice of resuscitation fluids significantly influences clinical outcomes, with balanced crystalloids potentially reducing adverse events if compared to normal saline solutions. Recent large-scale trials demonstrate lower rates of major adverse kidney events with chloride-restrictive strategies. Optimal management requires careful patient monitoring along with acid-base assessment. Treatment approaches must identify underlying causes to avoid complications. Prevention strategies include protocol-based fluid therapy, medication selection consideration, and early intervention in high-risk patients. Emerging technologies, including continuous monitoring systems and machine learning algorithms, offer promising advances for predicting and managing chloride disturbances.
Finerenone in Cardiorenal Disease: A Narrative Review of Molecular Mechanisms, Clinical Evidence, and Emerging Therapeutic Roles Giulio Geraci, Nicola Sinatra, Valentina Paternò, Vincenzo Calabrese, Giuliano Cassataro, Giuseppe Cuttone, Calogero Geraci, Roberta Esposito, Costantino Mancusi, Giacomo Pucci, Luca Zanoli, Giuseppe Mulè, Riccardo Polosa, Pietro Ferrara, Caterina Carollo Cardiovascular Drugs and Therapy, 2026 Cardiorenal disease reflects a tightly interconnected pathophysiological continuum driven by neurohormonal activation, inflammation, oxidative stress, and progressive fibrosis. Among these mechanisms, mineralocorticoid receptor (MR) overactivation has emerged as a central mediator of cardiac and renal injury independent of blood pressure effects. Finerenone, a non-steroidal selective MR antagonist, exhibits distinct pharmacological properties compared with steroidal MR antagonists, including enhanced receptor selectivity, balanced cardiac and renal tissue distribution, and differential cofactor modulation that translates into potent anti-inflammatory and antifibrotic activity with an improved safety profile. Large outcome trials have established finerenone as an effective cardiorenal protective therapy. The FIDELIO-DKD and FIGARO-DKD trials demonstrated significant reductions in kidney disease progression and cardiovascular events in patients with type 2 diabetes and chronic kidney disease, with consistent benefits confirmed in the pooled FIDELITY analysis. More recently, the FINEARTS-HF trial extended these benefits to patients with heart failure with mildly reduced or preserved ejection fraction regardless of diabetes status. Across trials, hyperkalemia was infrequent when structured monitoring strategies were applied. Beyond established indications, emerging data suggest potential systemic effects on retinal and hepatic outcomes, while ongoing studies are evaluating finerenone in non-diabetic chronic kidney disease. Subgroup analyses consistently demonstrate preserved efficacy and favorable safety when finerenone is combined with sodium–glucose cotransporter-2 inhibitors, supporting complementary disease-modifying strategies. This review integrates molecular mechanisms, clinical trial evidence, systemic effects, and therapeutic positioning of finerenone within contemporary cardiorenal care, highlighting its expanding role in multidrug approaches targeting the cardiovascular–renal–metabolic axis.
Personalized Parenteral Nutrition in Critically Ill Patients Undergoing Continuous Renal Replacement Therapy: A Comprehensive Framework for Clinical Practice Nicola Sinatra, Antonino Maniaci, Giuseppe Cuttone, Tarek Senussi Testa, Simona Tutino, Daniele Salvatore Paternò, Alessandro Girombelli, Giovanni Ippati, Giorgia Caputo, Massimiliano Sorbello, Luigi La Via Journal of Personalized Medicine, 2025 Critically ill patients receiving continuous renal replacement therapy (CRRT) face distinct nutritional challenges requiring specialized parenteral nutrition (PN) strategies. This review synthesizes current evidence with clinical expertise to provide a comprehensive nutritional framework for this population. Key findings reveal that CRRT significantly impacts nutrient homeostasis through daily losses of amino acids (14–22 g), water-soluble vitamins, and trace elements via the extracorporeal circuit. Results from observational studies demonstrate that higher protein targets (1.8–2.5 g/kg/day) are necessary to achieve positive nitrogen balance, while energy prescriptions must subtract “hidden” calories from citrate anticoagulation (3–4 kcal/mmol) and propofol (1.1 kcal/mL). Clinical outcome data, though primarily observational, indicate that achieving nutritional adequacy correlates with reduced ICU stays (average reduction 2.1–3.4 days), shorter mechanical ventilation duration, and improved functional recovery. Evidence supports that early PN prescription when indicated, coupled with systematic consideration of therapy modality, extracorporeal losses, oral intake capacity, and mobilization status, optimizes nutritional support. We conclude that successful implementation requires: (1) dynamic adjustment based on CRRT parameters, (2) integration with enteral nutrition when feasible, (3) regular metabolic monitoring, (4) multidisciplinary collaboration, and (5) structured protocols. Future research using point-of-care analysis and AI-driven support systems is needed to establish evidence-based guidelines in this specialized population.
Correlation Between Hypophosphatemia and Hyperventilation in Critically Ill Patients: Causes, Clinical Manifestations, and Management Strategies Nicola Sinatra, Giuseppe Cuttone, Giulio Geraci, Caterina Carollo, Michele Fici, Tarek Senussi Testa, Luigi La Via Biomedicines, 2025 Hypophosphatemia, defined as serum phosphate levels below 2.5 mg/dL, is a common yet underrecognized electrolyte disturbance in critically ill patients, with prevalence estimates reaching up to 80%. This review explores the intricate bidirectional relationship between hypophosphatemia and hyperventilation, emphasizing its profound implications for respiratory function and critical care management. Hypophosphatemia impairs oxygen delivery by depleting 2,3-diphosphoglycerate (2,3-DPG), disrupts central respiratory drive, and weakens respiratory muscles, leading to hyperventilation, ventilatory failure, and prolonged mechanical ventilation. Conversely, hyperventilation exacerbates hypophosphatemia through respiratory alkalosis, triggering intracellular phosphate shifts and metabolic cascades that rapidly deplete serum levels. This cycle creates significant challenges for ventilator weaning and increases morbidity and mortality. Underlying mechanisms include impaired ATP synthesis, altered chemoreceptor sensitivity, and systemic inflammatory responses. Hypophosphatemia-induced hyperventilation manifests as unexplained tachypnea and respiratory alkalosis, often misdiagnosed as anxiety or pain, while hyperventilation-induced hypophosphatemia contributes to diaphragmatic dysfunction and poor ventilatory performance. Common precipitating factors include refeeding syndrome, diabetic ketoacidosis, continuous renal replacement therapy, and malnutrition. Complications extend beyond respiratory dysfunction to include cardiac depression, immune dysfunction, prolonged ICU stays, and increased healthcare costs. Current diagnostic approaches rely on serum phosphate measurements, which poorly reflect total body stores due to significant intracellular shifts. Emerging biomarkers such as fibroblast growth factor 23 (FGF23) and advanced monitoring technologies, including continuous phosphate tracking, may enhance recognition. Treatment strategies emphasize targeted phosphate repletion based on severity, with intravenous supplementation and ventilatory support tailored to minimize complications. Preventive measures, including risk stratification, prophylactic supplementation, and ventilator management, are critical for high-risk populations. Despite advances, knowledge gaps persist in optimizing monitoring and repletion protocols, understanding genetic variations, and identifying ideal phosphate targets for improved respiratory outcomes. This review provides a comprehensive framework for recognizing and managing hypophosphatemia’s impact on respiratory dysfunction in critically ill patients. Adopting evidence-based interventions and leveraging emerging technologies can significantly improve clinical outcomes, reduce ICU complications, and enhance recovery in this vulnerable population.
The Burden of Sepsis and Septic Shock in the Intensive Care Unit Luigi La Via, Antonino Maniaci, Mario Lentini, Giuseppe Cuttone, Salvatore Ronsivalle, Simona Tutino, Francesca Maria Rubulotta, Giuseppe Nunnari, Andrea Marino Journal of Clinical Medicine, 2025
Critical Care Pharmacology of Antiretroviral Therapy in Adults Luigi La Via, Andrea Marino, Giuseppe Cuttone, Giuseppe Nunnari, Cristian Deana, Manfredi Tesauro, Antonio Voza, Raymond Planinsic, Yaroslava Longhitano, Christian Zanza European Journal of Drug Metabolism and Pharmacokinetics, 2025
Neurological and Olfactory Disturbances After General Anesthesia Antonino Maniaci, Mario Lentini, Rosario Trombadore, Loris Gruppuso, Santo Milardi, Rosario Scrofani, Giuseppe Cuttone, Massimiliano Sorbello, Rodolfo Modica, Jerome R. Lechien, Paolo Boscolo-Rizzo, Daniele Salvatore Paternò, Luigi La Via Life, 2025
Perioperative intravenous lidocaine infusion for postsurgical pain management in bariatric surgery patients Gilberto Duarte-Medrano, Natalia Nuño-Lámbarri, Analucia Dominguez-Franco, Yazmin Lopez-Rodriguez, Marissa Minutti-Palacios, Adrian Palacios-Chavarria, Luigi La Via, Daniele Salvatore Paternò, Giovanni Misseri, Giuseppe Cuttone, Massimiliano Sorbello, Guillermo Dominguez-Cherit, Diego Escarramán Journal of Anesthesia Analgesia and Critical Care, 2024
