Role of Lung Ultrasound in the Detection of Lung Sequelae in Post-COVID-19 Patients: A Systematic Review and Meta-Analysis.

Background: During the COVID-19 pandemic, several studies demonstrated the effectiveness of lung ultrasound (LUS) as a frontline tool in diagnosing and managing acute SARS-CoV-2 pneumonia. However, its role in detecting post-COVID-19 lung sequelae remains to be fully determined. This study aims to evaluate the diagnostic accuracy of LUS in identifying lung parenchymal damage, particularly fibrotic-like changes, following COVID-19 pneumonia, comparing its performance to that of CT. Methods: Relevant studies published before July 2024 were identified through a comprehensive search of PubMed, Embase, and Cochrane library. The search terms were combinations of the relevant medical subject heading (MeSH) terms, key words and word variants for "lung", "post-COVID", "long-COVID", and "ultrasound". The pooled sensitivity, specificity, diagnostic odds ratio (DOR), and summary receiver-operating characteristic (SROC) curve were used to examine the accuracy of CEUS. The selected works used different thresholds for the detection and counting of B-lines by ultrasound. This led to dividing our analysis into two models, the first based on the lower thresholds for detection of B-lines found in the works, and the second on data obtained using a higher detection threshold. Results: In terms of the diagnostic accuracy of LUS in detecting residual fibrotic-like changes in patients post-COVID-19 infection, a low-threshold model displayed a pooled sensitivity of 0.98 [95% confidence interval (CI): 0.95-0.99] and a pooled specificity of 0.54 (95% CI: 0.49-0.59). The DOR was 44.9 (95% CI: 10.8-187.1). The area under the curve (AUC) of SROC was 0.90. In the second analysis, the model with the higher threshold to detect B-lines showed a pooled sensitivity of 0.90 (95% CI: 0.85-0.94) and a pooled specificity of 0.88 (95% CI: 0.84-0.91). The DOR was 50.4 (95% CI: 15.9-159.3). The AUC of SROC was 0.93. Conclusions: In both analyses (even using the high threshold for the detection of B-lines), excellent sensitivity (98% in model 1 and 90% in model 2) is maintained. The specificity has a significant variation between the two models from 54 (model 1) to 87% (model 2). The model with the highest threshold for the detection of B-lines displayed the best diagnostic accuracy, as confirmed by the AUC values of the SROC (0.93).

Predictive role of microvesicles in cirrhotic patients: A promised land or a land of confusion? A narrative review.

Mammalian cells release several membrane-enclosed vesicles called extracellular vesicles. Those vesicles can contain several molecules such as proteins, DNA and various RNA. Therefore, extracellular vesicles can act as a target delivery system and exert multiple biological effects. Several works demonstrated that extracellular vesicles are increased or dysregulated in patients with cirrhosis, and they can be predictive of disease progression, complications and mortality. This review aims to summarize and highlight the role of extracellular vesicles in the cirrhotic patient and how they correlate with the degree of disease and with complications, particularly with the development of portal thrombosis and hepatocellular carcinoma.

RANK-RANKL-OPG Axis in MASLD: Current Evidence Linking Bone and Liver Diseases and Future Perspectives.

Metabolic dysfunction-associated steatotic liver disease (MASLD)-and its worse form, metabolic-associated steatohepatitis (MASH), characterised by inflammation and liver damage-corresponds to the liver's involvement in metabolic syndrome, which constitutes an economic burden for healthcare systems. However, the biomolecular pathways that contribute to steatotic liver disease are not completely clear. Abnormalities of bone metabolism are frequent in people affected by metabolic liver disease, with reduced bone density and an increased risk of fracture. Receptor activator of NF-κB (RANK), receptor activator of NF-κB ligand (RANKL), and osteoprotegerin(OPG) are critical regulators of bone metabolism, performing pleiotropic effects, and may have potential involvement in metabolic disorders like MASLD, resulting in a topic of great interest and intrigue. This narrative review aims to investigate this potential role and its implications in MASLD development and progression and in hepatocellular carcinoma, which represents its worst complication.

High bone fracture risk in a large modern cohort of liver transplant recipients.

Liver transplantation (LT) has historically been associated with a high prevalence of osteoporosis, but most of the available data date back to late 1990s-early 2000s with limited sample size. Our aim was to assess the prevalence of bone fragility fractures and contributing factors in a large modern cohort of liver transplant recipients. Retrospective study of 429 consecutive patients receiving liver transplantation from 1/1/2010 to 31/12/2015. Final cohort included 366 patients. Electronic radiological images (lateral views of spine X-rays or Scout CT abdominal scans) performed within 6 months from LT, were blinded reviewed to screen for morphometric vertebral fractures. Symptomatic clinical fragility fractures were recorded from the medical records. Patients with fragility fractures in the cohort were 155/366 (42.3%), with no significant differences between sexes. Most sustained vertebral fractures (145/155, 93.5%), mild or moderate wedges, with severe fractures more frequently observed in women. Multiple vertebral fractures were common (41.3%). Fracture rates were similar across different etiologies of cirrhosis and independent of diabetes or glucocorticoids exposure. Kidney function was significantly worse in women with fractures. Independently of age, sex, alcohol use, eGFR, and etiology of liver disease, low BMI was significantly associated with an increased risk for fractures (adjusted OR 1.058, 95%CI 1.001-1.118, P = 0.046). Our study shows a considerable fracture burden in a large and modern cohort of liver transplant recipients. Given the very high prevalence of bone fractures, a metabolic bone disease screening should be implemented in patients awaiting liver transplantation.

Beta-Blockers Lower First Decompensation in Patients With Cirrhosis and Enduring Portal Hypertension After Etiological Treatment.

BACKGROUND AND AIMS: Nonselective beta-blockers (NSBBs) can lower the risk of first decompensation in patients with cirrhosis and clinically significant portal hypertension (CSPH) (identified by a hepatic venous pressure gradient ≥10 mm Hg) with active etiology. Our aim was to examine the effect of NSBBs on first decompensation occurrence in patients with cirrhosis and enduring CSPH after etiological treatment. METHODS: Patients with compensated cirrhosis and clinical evidence of CSPH (gastroesophageal varices [GEVs] and/or spontaneous portosystemic collaterals [SPSSs]) after 2 years from etiological treatment. The primary endpoint was first decompensation (occurrence of variceal bleeding, ascites, or hepatic encephalopathy) in patients on NSBBs vs off NSBBs. RESULTS: The final cohort included 406 patients. Baseline characteristics of patients on NSBBs (n = 187) and off NSBBs (n = 219) were comparable, except for signs of portal hypertension that were more pronounced in the on-NSBB group. During a mean follow-up of 32 months, 127 (31%) patients decompensated, with ascites being the most common (77%) decompensating event. Decompensation rates were lower in patients on NSBBs (16% vs 44%; P < .0001). The benefit of NSBBs on decompensation was maintained in patients with small GEVs (17% vs 43%; P < .0001), in those with spontaneous portosystemic shunt only (8% vs 43%; P = .003), and in each different etiology, including hepatitis C virus-cured cirrhosis (9% vs 32%; P < .0001). At Cox regression analysis, hemoglobin, Child-Pugh, Model for End-Stage Liver Disease-Sodium, diabetes at baseline, and previous bacterial infections were independent predictors of decompensation, while NSBB use had a protective effect (hazard ratio, 0.32; 95% confidence interval, 0.20-0.49; P < .0001). NSBB use significantly reduced bacterial infection rates (hazard ratio, 0.36; 95% confidence interval, 0.22-0.58; P < .0001). CONCLUSION: NSBBs decrease the risk of first decompensation in patients with cirrhosis and enduring CSPH after etiological treatment.

Suboptimal outcomes of sorafenib as a second-line treatment after atezolizumab-bevacizumab for unresectable hepatocellular carcinoma.

BACKGROUND: Most patients receiving atezolizumab-bevacizumab (AB) for hepatocellular carcinoma will eventually experience disease progression. Randomized clinical trials (RCTs) are undergoing to identify second-line treatments. Where RCTs are unavailable or patients are non-eligible, sorafenib is often prescribed based on approval and reimbursement policies. However, evidence supporting this approach is minimal. OBJECTIVE: To assess the efficacy and safety of sorafenib in patients who permanently discontinued AB. METHODS: The ARTE database prospectively collects patients treated with AB in a real-life setting. We analysed the outcome of patients who received sorafenib as second-line treatment. RESULTS: Amongst 213 patients, 130 (61.0 %) permanently discontinued AB. Of them, 54 received second- line treatments, and sorafenib was prescribed in 40 patients. The disease control rate (DCR) was 10.0 %. The median progression-free (PFS) and overall survival were 3.3 (95 % confidence interval [CI] 2.7-3.9) and 6.9 months (95 % CI 2.7-11.1), respectively. CONCLUSIONS: In patients progressing under AB, the efficacy of sorafenib on different outcomes is limited.

Circulating microRNAs as biomarkers for stratifying different phases of liver cancer progression and response to therapy.

Hepatocellular carcinoma (HCC) is the most common liver cancer and is among the leading causes of cancer-related death worldwide. There is no reliable biomarker for the early diagnosis of HCC. Circulating microRNAs (miRNAs) have attracted attention as potential biomarkers of disease. By small-RNA next-generation sequencing, the analysis of serum miRNAs led to the identification of molecular signatures able to discriminate advanced HCC from early HCC (n = 246); advanced HCC from CIRRHOSIS (n = 299); advanced HCC from HEALTHY (n = 320); HEALTHY from early HCC (n = 343); and HEALTHY from CIRRHOSIS (n = 414). Cirrhotic patients and early HCC patients exhibited similar serum miRNA profiles, yet a small number of miRNAs (n = 57) were able to distinguish these two classes of patients. A second objective of the study was to identify serum miRNAs capable of predicting the response to therapy in patients with advanced HCC. All patients were treated with sorafenib as first-line therapy: 24 were nonresponsive and 24 responsive. Analysis of circulating miRNAs revealed a 54 miRNAs signature able to separate the two subgroups. This study suggested that circulating miRNAs could be useful biomarkers for monitoring patients with liver diseases ranging from cirrhosis to advanced HCC and possibly predicting susceptibility to first-line treatment based on sorafenib.

Use of sodium oxybate for the treatment of alcohol withdrawal syndrome in patients with acute alcohol-associated hepatitis: A 4-patient case report.

INTRODUCTION: During the treatment of alcohol use disorder, alcohol withdrawal syndrome (AWS) can occur. Benzodiazepines remain the "gold standard" for the pharmacological treatment of AWS. However, other drugs have been approved in some European Countries for the treatment of AWS: namely, clomethiazole in Spain and Germany and sodium oxybate in Italy and Austria. Acute alcohol-associated hepatitis (AAH) is a distinct clinical syndrome characterized by the recent onset of jaundice with or without other signs of liver decompensation in patients with ongoing alcohol consumption. RATIONALE: We report 4 paradigmatic clinical cases to analyze the efficacy, safety, and tolerability of the very short half-life (30-45 minutes) sodium oxybate (SO) in the management of AWS with moderate to severe AAH. Compared to SO, "as needed" short-acting benzodiazepines, currently prescribed to treat AWS in patients with AAH, have a much longer half-life (5-25 hours) which increases the risk of drug accumulation. The very short half-life of SO provides a fixed dose approach allowing for a more effective control of AWS than "as needed" therapy throughout the 24 hours. PATIENT CONCERNS: Patients reported anxiety, agitation, diffuse abdominal pain, loss of appetite, and nausea with elevation in serum bilirubin and 2 of them had abdomen distension due to ascites. DIAGNOSIS: Patients were affected by moderate or severe AWS and moderate or severe AAH on alcohol-related liver cirrhosis. INTERVENTIONS: In order to suppress AWS, all patients were treated with oral sodium oxybate at a dose of 25 mg/kg/day, progressively increased to 50 to 100 mg/kg/day, divided into 3 to 5 administrations. OUTCOMES: SO was efficient, safe and tolerable in suppressing AWS even in patients with severe AAH. All treated patients showed a rapid improvement of all symptom (via the Clinical Institute of Withdrawal Assessment for Alcohol Scale) and liver test scores (Model for End-Stage Liver Disease). CONCLUSION: Because of its short half-life, SO can be considered a safe and effective pharmacological option for the AWS in patients with moderate to severe AAH even in comparison to short-acting benzodiazepines, thus avoiding the risk of accumulation. Notably, SO guarantees a fixed approach to cover the possible onset of AWS throughout the 24 hours.

Liver and spleen shear-wave elastography in the diagnosis and severity staging of myeloproliferative diseases and myelofibrosis.

AIMS: Spleen and liver stiffness, investigated by VCTE (Vibration-Controlled Transient Elastography), have been associated with marrow fibrosis in patients with myeloproliferative neoplasms (MPNs). Tissue stiffness can be assessed by shear wave point (pSWE) and bidimensional elastography (2DSWE). Spleen stiffness (SS) values were higher in Myelofibrosis (MF) and Polycythemia Vera (PV) compared to Essential Thrombocythemia (ET). We aimed to identify SWE differences between MPN patients and healthy volunteers; to evaluate specific SWE features in patients with MF, PV and ET; to establish a correlation with bone marrow fibrosis in patients with myeloproliferative disease. METHODS: Patients with myeloproliferative disease and healthy volunteers performed evaluation of spleen and liver stiffness (LS) by pSWE and 2DSWE. RESULTS: A total of 218 subjects were included: 143 with myeloproliferative disease (64 MF, 29.4%, 33 PV, 15.1% and 46 ET, 21.1%), and 75 (34.4%) healthy volunteers. Compared to volunteers, MF patients had greater spleen (pSWE 40.9 vs. 26.3 kPa, p < 0.001; 2DSWE 34.9 vs. 20.1 kPa, p < 0.001), and liver stiffness (pSWE 7.72 vs. 5.52 kPa, p < 0.001; 2DSWE 6.96 vs. 5.01 kPa, p < 0.001). In low (0-1) (n = 81, 60.4%) versus high-grade bone marrow fibrosis (2-3) (n = 42, 39.6%), is evident a higher median stiffness in patients with higher grades of fibrosis both for liver (pSWE 5.2 vs. 6.65 kPa; 2DSWE 5.1 vs. 6.05 kPa) and spleen (pSWE 27.2 vs. 37.9 kPa, 2DSWE 21.7 vs 30.75 kPa-p < 0.001 in both). CONCLUSION: SWE evaluation distinguishes MF patients from HV and ET/PV and may help in MPN diagnosis. LS and SS values are associated with bone marrow fibrosis grade.

The importance of ultrasound-guided biopsy: lesson from a case of liver metastasis from uveal melanoma.

Melanoma is an extremely aggressive malignant neoplasm. Uveal melanoma is the most common primary intraocular malignancy in adults, representing 3-5% of all melanomas. Liver metastases can be clinically detected in 10-20% of patients with metastatic disease from cutaneous melanoma. However, while liver is typically not the first site of disease spread in cutaneous melanoma, ocular melanoma has been showed to primarily metastasize from the eye to the liver; indeed, liver metastases are detected in approximately 87% of patients with metastatic uveal melanoma. Therefore, liver metastasis can be challenging to identify in early stages, thus being essentially asymptomatic until the disease has advanced. Here we report the case of a patient who came to our ultrasound unit reporting a large liver mass. Both contrast-enhanced abdominal computed tomography and magnetic resonance imaging did not establish a definitive diagnosis. The final diagnosis was made only through an ultrasound-guided biopsy of the mass, thus revealing a uveal melanoma metastasis. This is followed by a review of the literature on imaging follow-up of patients with melanoma.

Ultrasound-Assisted and Ultrasound-Guided Thoracentesis: An Educational Review.

Thoracentesis is one of the most important invasive procedures in the clinical setting. Particularly, thoracentesis can be relevant in the evaluation of a new diagnosed pleural effusion, thus allowing for the collection of pleural fluid so that laboratory tests essential to establish a diagnosis can be performed. Furthermore, thoracentesis is a maneuver that can have therapeutic and palliative purposes. Historically, the procedure was performed based on a physical examination. In recent years, the role of ultrasound has been established as a valuable tool for assistance and guidance in the thoracentesis procedure. The use of ultrasound increases success rates and significantly reduces complications. The aim of this educational review is to provide a detailed and sequential examination of the procedure, focusing on the two main modalities, the ultrasound-assisted and ultrasound-guided form.

Liver Imaging Reporting and Data System Contrast-Enhanced US Nonradiation Treatment Response Assessment Version 2024.

The American College of Radiology Liver Imaging Reporting and Data System (LI-RADS) standardizes the imaging technique, reporting lexicon, disease categorization, and management for patients with or at risk for hepatocellular carcinoma (HCC). LI-RADS encompasses HCC surveillance with US; HCC diagnosis with CT, MRI, or contrast-enhanced US (CEUS); and treatment response assessment (TRA) with CT or MRI. LI-RADS was recently expanded to include CEUS TRA after nonradiation locoregional therapy or surgical resection. This report provides an overview of LI-RADS CEUS Nonradiation TRA v2024, including a lexicon of imaging findings, techniques, and imaging criteria for posttreatment tumor viability assessment. LI-RADS CEUS Nonradiation TRA v2024 takes into consideration differences in the CEUS appearance of viable tumor and posttreatment changes within and in close proximity to a treated lesion. Due to the high sensitivity of CEUS to vascular flow, posttreatment reactive changes commonly manifest as areas of abnormal perilesional enhancement without washout, especially in the first 3 months after treatment. To improve the accuracy of CEUS for nonradiation TRA, different diagnostic criteria are used to evaluate tumor viability within and outside of the treated lesion margin. Broader criteria for intralesional enhancement increase sensitivity for tumor viability detection. Stricter criteria for perilesional enhancement limit miscategorization of posttreatment reactive changes as viable tumor. Finally, the TRA algorithm reconciles intralesional and perilesional tumor viability assessment and assigns a single LI-RADS treatment response (LR-TR) category: LR-TR nonviable, LR-TR equivocal, or LR-TR viable.

Incidence and Predictors of Esophagogastric Varices Bleeding in Patients with Hepatocellular Carcinoma in Lenvatinib.

Introduction: Lenvatinib is indicated for the forefront treatment of advanced hepatocellular carcinoma (aHCC), but its use may be limited by the risk of esophagogastric varices (EGV) bleeding. This study assessed the prevalence, predictors, and complications of EGV in aHCC patients treated with lenvatinib. Methods: In this multicenter international retrospective study, cirrhotic patients treated with lenvatinib for aHCC, were enrolled if upper-gastrointestinal endoscopy was available within 6 months before treatment. Primary endpoint was the incidence of EGV bleeding during lenvatinib therapy; secondary endpoints were predictors for EGV bleeding, prevalence, and risk factors for the presence of EGV and high-risk EGV at baseline, as well as impact of EGV bleeding on patients' survival. Results: 535 patients were enrolled in the study (median age: 72 years, 78% male, 63% viral etiology, 89% Child-Pugh A, 16% neoplastic portal vein thrombosis [nPVT], 56% Barcelona Clinic Liver Cancer-C): 234 had EGV (44%), 70 (30%) were at high risk and 59 were on primary prophylaxis. During lenvatinib treatment, 17 patients bled from EGV (3 grade 5), the 12-month cumulative incidence being 3%. The only baseline independent predictor of EGV bleeding was the presence of baseline high-risk EGV (hazard ratio: 6.94, 95% confidence interval [CI]: 2.23-21.57, p = 0.001). In these patients the 12-month risk was 17%. High-risk varices were independently associated with Child-Pugh B score (odds ratio [OR]: 2.12; 95% CI: 1.08-4.17, p = 0.03), nPVT (OR: 2.54; 95% CI: 1.40-4.61, p = 0.002), and platelets <150,000/µL (OR: 2.47; 95% CI: 1.35-4.50, p = 0.003). Conclusion: In hepatocellular carcinoma patients treated with lenvatinib, the risk of EGV bleeding was mostly low but significant only in patients with high-risk EGV at baseline.

Ultrasound diagnosis of a pseudoaneurysm of the internal right mammary artery.

One of the principles of managing trauma patients is that of their continuous re-evaluation over the hours and days. Even if the execution of the computed tomography method is classically recommended, especially in the most serious cases and in polytraumas with major dynamics, the clinician can use or request an ultrasound examination, especially in subsequent re-evaluations. Here we report a clinical case demonstrating how an ultrasound re-evaluation after the acute event can lead to a correct diagnosis of a rare complication of thoracic trauma. The findings were suggestive for a pseudoaneurysm of the internal right mammary artery. Subsequently, an ultrasound-guided injection of thrombin was carried out until complete interruption of the flow within the formation. At subsequent follow-up, no arterial or venous blush was highlighted.

Portal Vein Thrombosis: State-of-the-Art Review.

Background: Portal vein thrombosis (PVT) is a rare disease with an estimated incidence of 2 to 4 cases per 100,000 inhabitants. The most common predisposing conditions for PVT are chronic liver diseases (cirrhosis), primary or secondary hepatobiliary malignancy, major infectious or inflammatory abdominal disease, or myeloproliferative disorders. Methods: PVT can be classified on the basis of the anatomical site, the degree of venous occlusion, and the timing and type of presentation. The main differential diagnosis of PVT, both acute and chronic, is malignant portal vein invasion, most frequently by hepatocarcinoma, or constriction (typically by pancreatic cancer or cholangiocarcinoma). Results: The management of PVT is based on anticoagulation and the treatment of predisposing conditions. The aim of anticoagulation in acute thrombosis is to prevent the extension of the clot and enable the recanalization of the vein to avoid the development of complications, such as intestinal infarction and portal hypertension. Conclusions: The treatment with anticoagulant therapy favors the reduction of portal hypertension, and this allows for a decrease in the risk of bleeding, especially in patients with esophageal varices. The anticoagulant treatment is generally recommended for at least three to six months. Prosecution of anticoagulation is advised until recanalization or lifelong if the patient has an underlying permanent pro-coagulant condition that cannot be corrected or if there is thrombosis extending to the mesenteric veins.

Platelet, Antiplatelet Therapy and Metabolic Dysfunction-Associated Steatotic Liver Disease: A Narrative Review.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is not only related to traditional cardiovascular risk factors like type 2 diabetes mellitus and obesity, but it is also an independent risk factor for the development of cardiovascular disease. MASLD has been shown to be independently related to endothelial dysfunction and atherosclerosis. MASLD is characterized by a chronic proinflammatory response that, in turn, may induce a prothrombotic state. Several mechanisms such as endothelial and platelet dysfunction, changes in the coagulative factors, lower fibrinolytic activity can contribute to induce the prothrombotic state. Platelets are players and addresses of metabolic dysregulation; obesity and insulin resistance are related to platelet hyperactivation. Furthermore, platelets can exert a direct effect on liver cells, particularly through the release of mediators from granules. Growing data in literature support the use of antiplatelet agent as a treatment for MASLD. The use of antiplatelets drugs seems to exert beneficial effects on hepatocellular carcinoma prevention in patients with MASLD, since platelets contribute to fibrosis progression and cancer development. This review aims to summarize the main data on the role of platelets in the pathogenesis of MASLD and its main complications such as cardiovascular events and the development of liver fibrosis. Furthermore, we will examine the role of antiplatelet therapy not only in the prevention and treatment of cardiovascular events but also as a possible anti-fibrotic and anti-tumor agent.

The Role of Contrast-Enhanced Ultrasound in the Differential Diagnosis of Malignant and Benign Subpleural Lung Lesions.

Background: The application of transthoracic contrast-enhanced ultrasound (CEUS) to the study of peripheral lung lesions is still a topic of debate. The main objective of this review was to evaluate the diagnostic accuracy of CEUS in the diagnosis of malignant subpleural pulmonary consolidations and, therefore, differentiate them from benign ones. Methods: Papers published before December 2023 were detected through a search of PubMed, Cochrane library, and Embase. The pooled specificity and sensitivity, summary receiver operating characteristic (SROC) curve and diagnostic odds ratio (DOR) were used. Results: CEUS is characterized by a pooled sensitivity of 0.95 (95% CI: 0.93-0.97) and a pooled specificity of 0.93 (95% CI: 0.90-0.95) in differentiating benign and malignant subpleural lung diseases; the AUC of SROC was 0.97. Homogeneous CE was characterized by a pooled sensitivity of 0.43 (95% CI: 0.40-0.45) and the pooled specificity of 0.49 (95% CI: 0.46-0.52). Non-homogeneous CE displayed a pooled sensitivity of 0.57 (95% CI: 0.55-0.60) and a pooled specificity of 0.51 (95% CI: 0.48-0.54). The lack of CE displayed a pooled sensitivity of 0.01 (95% CI: 0.00-0.06) and a pooled specificity of 0.76 (95% CI: 0.64-0.85). Marked CE displayed a pooled sensitivity of 0.41 (95% CI: 0.37-0.44) and a pooled specificity of 0.54 (95% CI: 0.50-0.58). Non-marked CE displayed a pooled sensitivity of 0.59 (95% CI: 0.56-0.63) and a pooled specificity of 0.46 (95% CI: 0.42-0.50). The early AT displayed a pooled sensitivity of 0.04 (95% CI: 0.02-0.08) and a pooled specificity of 0.83 (95% CI: 0.77-0.87). The early wash out displayed a pooled sensitivity of 0.61 (95% CI: 0.48-0.72) and a pooled specificity of 0.98 (95% CI: 0.92-1.00). The delayed wash out displayed a pooled sensitivity of 0.15 (95% CI: 0.10-0.20) and a pooled specificity of 0.69 (95% CI: 0.62-0.75). Conclusions: CEUS is characterized by excellent diagnostic accuracy for the diagnosis of the malignancy of subpleural lung lesions. By separately analyzing the CEUS findings, the diagnostic accuracy values are considerably lower and not significant in some cases. The simultaneous evaluation of multiple CEUS features allows us to reach an excellent diagnostic accuracy. Non-homogeneous CE with early wash out are the most indicative features of malignancy of a lung lesion.

Prediction of cardiovascular risk in patients with hepatocellular carcinoma receiving anti-angiogenic drugs: lessons from sorafenib.

Antiangiogenics are associated with an increased risk of major adverse cardiac and cerebrovascular events (MACE). The identification of at-risk subjects is relevant in the case of hepatocellular carcinoma (HCC), for which anti-angiogenic TKIs and bevacizumab are used in first and subsequent lines of therapy, to select alternative drugs for patients with excessive risk. We verified the ability to predict MACE in sorafenib-treated patients of the 2022 European Society of Cardiology (ESC-2022) score for anti-angiogenics and the recently proposed CARDIOSOR score. A retrospective analysis was conducted of prospectively collected data of the ARPES and ITA.LI.CA databases. All patients received sorafenib for unresectable HCC from 2008 to 2018. Baseline information to calculate the ESC-2022 and CARDIOSOR scores and registration of evolutive events (including MACE) were available for all patients. The predictive ability of both scores was verified using competing risk regressions and tests for goodness of fit. This study included 843 patients (median follow-up 11.3 months). Thirty-four (4.0%) patients presented a MACE. The four-tier ESC-2022 classification showed a progressive risk increase for every class (cumulative risk 1.7%, 2.7%, 4.3%, and 15.0% in the low, medium, high, and high-risk tiers, respectively). The dichotomous CARDIOSOR scale identified a high-risk group with a fourfold increased risk of MACE (sHR 4.66, p = 0.010; cumulative risk 3.8% and 16.4%). ESC-2022 showed a better goodness of fit compared to the CARDIOSOR score [C-index 0.671 (0.583-0.758) vs 0.562 (0.501-0.634), p = 0.021], but this gap was eliminated using the linear version of CARDIOSOR. Both the ESC-2022 and CARDIOSOR scores discriminated patients at increased risk for MACE. The use of these scores in clinical practice should be encouraged, since therapeutic measures can mitigate the cardiovascular risk.

Intermediate-stage hepatocellular carcinoma: refining substaging or shifting paradigm?

This review explores the evolution of cancer staging, focusing on intermediate hepatocellular carcinoma (HCC), and the challenges faced by physicians. The Barcelona Clinic Liver Cancer (BCLC) staging system, introduced in 1999, was designed to address the limitations associated with providing accurate prognostic information for HCC and allocating specific treatments, to avoid overtreatment. However, criticism has emerged, particularly regarding the intermediate stage of HCC (BCLC-B) and its heterogeneous patient population. To overcome this limitation, various subclassification systems, such as the Bolondi and Kinki criteria, have been proposed. These systems are aimed at refining categorizations within the intermediate stage and have demonstrated varying degrees of success in predicting outcomes through external validation. This study discusses the shift in treatment paradigms, emphasizing the need for a more personalized approach rather than strictly adhering to cancer stages, without dismissing the relevance of staging systems. It assesses the available treatment options for intermediate-stage HCC, highlighting the importance of considering surgical and nonsurgical options alongside transarterial chemoembolization for optimal outcomes. In conclusion, the text advocates for a paradigm shift in staging systems prioritizing treatment suitability over cancer stage. This reflects the evolving landscape of HCC management, where a multidisciplinary approach is crucial for tailoring treatments to individual patients, ultimately aiming to improve overall survival.