Background/Objectives: This systematic review describes a largely descriptive synthesis of studies investigating the diagnostic performance of quantitative contrast-enhanced ultrasound (CEUS) in differentiating benign from malignant peripheral pulmonary lesions. Methods: Formal quantitative pooling of effect sizes was not feasible due to variability in outcome measurements and reporting. Results: Combining CEUS parameters with real-time on-site evaluation (ROSE) substantially improved percutaneous biopsy success rates. In one comparative study, biopsy yield reached 97.62% with CEUS, versus 84% using conventional ultrasound, while complications remained minimal. Other investigations focused on the discriminatory value of specific time-based indices (e.g., AT ≥ 10 s, lesion-lung AT difference ≥ 2.5 s) or complex multi-parameter models. A notable large study demonstrated that a six-parameter logistic regression model achieved near-excellent discrimination, with C-statistics exceeding 0.97 for both development and validation cohorts, outperforming single-threshold approaches. Nevertheless, certain findings emphasize that no single indicator—particularly arrival time alone—reliably distinguishes benign from malignant lesions, given the diverse vascular patterns and histological subtypes involved. TDOA-based analyses proved more promising, as malignant lesions generally exhibit a delayed but robust bronchial arterial supply and rapid washout. Heterogeneity in ultrasound systems, operator experience, and patient populations further underscores the need for standardized protocols. Conclusions: Overall, these data suggest that CEUS, particularly when combined with additional sonographic or cytological tools, significantly enhances diagnostic precision for peripheral pulmonary lesions.

Background: Use of high-flow nasal cannula (HFNC) expanded from ICUs to internal medicine/respiratory wards during and after the COVID-19 pandemic, but safety and effectiveness in non-ICU settings remain uncertain. Methods: We performed a systematic review and meta-analysis of adults (≥18 years) initiated on HFNC in non-ICU wards. Primary outcomes were in-hospital (or 28-day) mortality and ICU transfer; where available, we compared mortality for HFNC vs. conventional oxygen therapy (COT) in do-not-intubate (DNI) cohorts. Observational studies and trials were eligible. Random-effects models synthesized proportions and risk ratios; risk of bias (ROBINS-I/RoB 2) and certainty (GRADE) were assessed. Results: Ten studies met the inclusion criteria for any-ward HFNC; subsets contributed data to pooled analyses. Across all non-ICU wards (general wards plus step-up IMCU/HDU), pooled mortality was 14.0% (95% CI 4.6–35.5; I² ≈ 92%). Pooled ICU transfer after ward/step-up HFNC start was 20.0% (95% CI 6.3–48.1; I² ≈ 97%). Restricted to internal medicine/respiratory wards, pooled mortality was 19.8% (95% CI 7.1–44.2; I² ≈ 95%) and ICU transfer 31.2% (95% CI 9.9–65.0; I² ≈ 97%). In step-up units (IMCU/HDU), ICU transfer appeared lower and less variable (22.0% [95% CI 16.5–28.8]; I² ≈ 10%), suggesting environment-dependent outcomes. In a multicenter DNI COVID-19 cohort, HFNC vs. COT showed no clear mortality difference (RR ≈ 0.90, 95% CI 0.75–1.08; adjusted OR ≈ 0.72, 95% CI 0.34–1.54). Certainty of evidence for all critical outcomes was very low due to observational design, high inconsistency, and imprecision. Conclusions: HFNC outside the ICU is feasible, but it is related to nontrivial mortality and frequent escalation—particularly on general wards—while step-up units demonstrate more reproducible trajectories. Outcomes appear strongly conditioned by care environment, staffing, monitoring, and escalation pathways. Given very low certainty and substantial heterogeneity, institutions should pair ward HFNC with protocolized reassessment and rapid response/ICU outreach, and future research should prospectively compare ward HFNC pathways against optimized COT/NIV using standardized outcomes.

Background: Contrast-enhanced ultrasound (CEUS) recently emerged as a valuable imaging modality for evaluating pleuropulmonary diseases. By combining morphological information from conventional B-mode ultrasound with real-time assessment of microvascular perfusion, CEUS can provide functional insights that improve diagnostic accuracy, guide interventions, and support patient surveillance. Methods: This review summarizes the current evidence on the use of CEUS in major pleuropulmonary disorders, including pneumonia, pleural effusion, pulmonary embolism, neoplasms, and COVID-19-related lung injury. The most relevant clinical studies and meta-analyses were analyzed, focusing on CEUS parameters, diagnostic performance, and integration with other imaging techniques. Results: CEUS enables the differentiation between inflammatory, ischemic, and malignant lesions through qualitative and quantitative analyses of enhancement patterns. Early and homogeneous enhancement is typical of inflammatory or infectious processes, whereas heterogeneous or delayed enhancement with early washout strongly suggests malignancy or ischemia. In pneumonia and pleural infections, CEUS identifies non-perfused or necrotic areas, guiding drainage and evaluating therapeutic responses. In pulmonary embolism, it reveals avascular consolidations corresponding to infarction, even when CT angiography is inconclusive. For peripheral lung tumors, CEUS assesses angiogenesis and vascular supply, correlating perfusion parameters with histopathology, and improving biopsy targeting. Furthermore, in COVID-19 pneumonia, CEUS can detect microvascular alterations related to thrombosis and fibrosis. Conclusions: CEUS is a safe, noninvasive, and radiation-free technique that provides unique real-time information on pulmonary perfusion. Its integration with conventional ultrasound enhances diagnostic precision, optimizes interventional guidance, and allows for dynamic monitoring of treatment response. Future developments in quantitative analysis, artificial intelligence, and targeted contrast agents are expected to further expand CEUS clinical applications in pleuropulmonary imaging.

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) and the dual incretin agonist tirzepatide have demonstrated cardiometabolic benefits in cardiovascular outcome trials, but their effects on limb outcomes in peripheral artery disease (PAD) remain unclear. This study evaluated whether GLP-1-based therapies reduce the risk of major adverse limb events (MALE), major adverse cardiovascular events (MACE), and mortality in real-world PAD populations. A systematic search of MEDLINE, Embase, Cochrane CENTRAL, Scopus, and grey literature identified comparative real-world studies of GLP-1-based therapies in adults with PAD. Six studies including over 240,000 patients were analyzed. GLP-1-based therapies were associated with a significant reduction in MALE (HR 0.59, 95% CI 0.39-0.90), although heterogeneity was substantial. A significant reduction in MACE was also observed (HR 0.67, 95% CI 0.53-0.85), with greater consistency in diabetic populations. Stroke was significantly reduced (HR 0.75, 95% CI 0.63-0.89), demonstrating consistent effects across studies. Myocardial infarction and all-cause mortality were also significantly reduced, although with greater variability in effect magnitude. In real-world PAD populations, GLP-1-based therapies are associated with meaningful reductions in both limb and cardiovascular outcomes. These findings support a vascular protective profile, particularly for stroke and MACE in more homogeneous populations such as patients with diabetes.

The optimal anticoagulant strategy for portal vein thrombosis (PVT) in patients with cirrhosis remains uncertain, particularly regarding the role of direct oral anticoagulants (DOACs) compared with vitamin K antagonists (VKAs), low-molecular-weight heparin, or no anticoagulation. We conducted a systematic review and meta-analysis of studies evaluating DOAC therapy in patients with cirrhosis with PVT. Random-effects models were used to estimate pooled risk ratios (RRs). A total of 21 studies including 21 506 patients with cirrhosis with PVT were analyzed. Among them, 2099 patients were treated with DOACs. Compared with VKAs, DOAC therapy was associated with higher rates of complete PVT recanalization (RR, 3.49; 95% confidence interval [CI], 2.06-5.93) and lower risk of PVT progression (RR, 0.19; 95% CI, 0.04-0.78), with no significant difference in major bleeding (RR, 1.09; 95% CI, 0.79-1.51). DOACs were also associated with a lower risk of intracranial hemorrhage (ICH; RR, 0.49; 95% CI, 0.30-0.80). Compared with no anticoagulation, DOAC therapy was associated with lower mortality (RR, 0.77; 95% CI, 0.71-0.84) without increased bleeding risk. DOAC benefit on recanalization was more pronounced in studies including only patients with Child-Pugh class A or B, whereas safety outcomes remained consistent across cirrhosis severity strata. In patients with cirrhosis with PVT, DOAC therapy is associated with improved complete recanalization and reduced PVT progression compared with VKAs, without increased bleeding risk and with lower risk of ICH. These findings support the use of DOACs in select patients, although randomized trials are needed to confirm these results.

Background: Fontan-associated liver disease (FALD) is a progressive condition resulting from chronic hepatic venous congestion following the Fontan procedure for univentricular heart defects. As survival improves in these patients, recognition and management of FALD have become increasingly important. Objective: To describe the pathophysiological mechanisms, imaging findings, and diagnostic approach to FALD, with a focus on the role of ultrasonography, including contrast-enhanced ultrasound (CEUS). Methods: This narrative review explores the evolution of FALD through a multidisciplinary lens, integrating cardiovascular and hepatic imaging data. Particular attention is paid to Doppler ultrasound and CEUS, both in early parenchymal changes and in the differential diagnosis of potential complications such as hepatic nodules. Results: FALD is characterized by progressive fibrosis due to long-standing passive congestion, resulting in a wide spectrum of imaging findings. B-mode ultrasound reveals hepatomegaly, heterogeneous parenchyma, and gallbladder wall thickening. Doppler studies show altered hepatic venous flow patterns, while CEUS provides dynamic vascular evaluation, highlighting areas of altered perfusion. In advanced stages, hypo-vascular areas in the late phase may simulate malignant lesions, emphasizing the need for careful interpretation. The role of liver biopsy, though limited by invasiveness, remains crucial in selected cases. Surveillance strategies are not standardized but require close multidisciplinary follow-up. Conclusions: FALD presents complex diagnostic challenges requiring integrated imaging and clinical assessment. CEUS emerges as a valuable, non-invasive tool in characterizing hepatic congestion and guiding management. Increased awareness and standardized protocols are essential for early detection and tailored care in this growing patient population.