Congestion is a key clinical feature of heart failure (HF), contributing to hospitalizations, disease progression, and poor outcomes. While traditionally considered a hemodynamic issue, congestion is now recognized as a systemic process affecting multiple organs. Renal dysfunction arises from impaired perfusion and sodium retention, leading to maladaptive left ventricular remodeling. Hepatic congestion contributes to cholestatic liver injury, while metabolic disturbances drive anemia, muscle wasting, and systemic inflammation. Additionally, congestion disrupts the intestinal barrier and immune function, exacerbating HF progression. Given its widespread impact, effective congestion management requires a shift from a cardiovascular-centered approach to a comprehensive, multidisciplinary strategy. Targeted decongestive therapy, metabolic and nutritional optimization, and immune modulation are crucial in mitigating congestion-related organ dysfunction. Early recognition and intervention are essential to slow disease progression, preserve functional capacity, and improve survival. Addressing HF congestion through personalized, evidence-based strategies is vital for optimizing long-term care and advancing treatment paradigms.

Heart failure (HF) remains a major global health challenge, driven by multifactorial pathophysiological processes, such as systemic congestion, endothelial dysfunction, and inflammation. While natriuretic peptides are well-established biomarkers for diagnosing and monitoring HF, they do not fully capture the complexity of vascular involvement. CD146, also known as melanoma cell adhesion molecule (MCAM), is a transmembrane glycoprotein primarily expressed on endothelial cells and involved in cell adhesion, vascular permeability, and angiogenesis. Its soluble form (sCD146), released in response to multiple pathophysiological stimuli, including venous and arterial endothelial stretch, oxidative stress, and inflammatory cytokine activation, has emerged as a promising biomarker reflecting both hemodynamic congestion and systemic endothelial stress. This review synthesizes current knowledge on the structure, regulation, and release mechanisms of CD146 and explores its clinical utility in HF. Elevated sCD146 levels have been associated with echocardiographic and radiological indicators of congestion, as well as with adverse outcomes. While promising, its application is limited by variability, lack of standardization, and confounding elevations in non-cardiac conditions, including malignancy.

Heart failure (HF) remains a major global health challenge, driven by multifactorial pathophysiological processes such as systemic congestion, endothelial dysfunction, and inflammation. While natriuretic peptides are well-established biomarkers for diagnosing and monitoring HF, they do not fully capture the complexity of vascular involvement. CD146, also known as melanoma cell adhesion molecule (MCAM), is a transmembrane glycoprotein primarily expressed on endothelial cells and involved in cell adhesion, vascular permeability, and angiogenesis. Its soluble form (sCD146), released in response to multiple pathophysiological stimuli, including venous and arterial endothelial stretch, oxidative stress, and inflammatory cytokine activation, has emerged as a promising biomarker reflecting both hemodynamic congestion and systemic endothelial stress. This review synthesizes current knowledge on the structure, regulation, and release mechanisms of CD146 and explores its clinical utility in HF. Elevated sCD146 levels have been associated with echocardiographic and radiological indicators of congestion, as well as with adverse outcomes. While promising, its application is limited by variability, lack of standardization, and confounding elevations in non-cardiac conditions, including malignancy.

Chronic obstructive pulmonary disease (COPD) is a chronic progressive respiratory disease, characterized by respiratory symptoms and airflow limitation, and is one of the leading causes of morbidity and mortality worldwide. The evolution of the disease is associated with episodes of acute exacerbations (AECOPD), characterized by worsening symptoms and accelerated deterioration of lung function. Acute exacerbations of COPD have different severity, being mild, moderate or severe depending on how aggravated the patients’ symptoms are, but also depending on the pulmonary functional and biological changes. Around 70% of AECOPD are infectious in nature, through upper or lower respiratory tract infections. Often, exacerbations associated with lower respiratory tract infections are more severe and have a higher risk of unfavorable outcome compared to AECOPD associated with upper respiratory tract infections. Severe exacerbations require hospital management, most of them being treated in the intensive care unit (ICU). In this narrative review, we evaluated the frequency of different bacterial pathogens involved in severe COPD exacerbations associated with lower respiratory tract infections and the need for treatment in the ICU. Identifying patients with exacerbated COPD at high risk of respiratory infections especially with gram-negative bacilli is extremely important to choose the optimal treatment, thus reducing the risk of death.

The introduction of respiratory multiplex PCR in the post-pandemic world has improved the detection of viral infections, whose clinical relevance is still being characterized. Patients with diabetes mellitus (DM) exhibit altered innate immune responses, yet the effect of concurrent viral infection on their inflammatory trajectory and clinical outcomes remains poorly characterized. This study examined whether diabetes is associated with a more pronounced inflammatory response, delayed resolution, and worse multi-organ outcomes during viral respiratory infections. A prospective, longitudinal cohort of 430 hospitalized adults (DM: n = 211; non-DM: n = 219) with PCR-confirmed viral respiratory infections was stratified into four groups by diabetes and co-infection status using a respiratory multiplex PCR panel. Serum IL-6, CRP, NLR, procalcitonin, and urea were measured at admission (Day 1) and at clinical stabilization (Day 6). All variables failed normality testing (Shapiro–Wilk p < 0.0001); non-parametric methods were applied. Receiver operating characteristic (ROC) analysis was used to identify candidate biomarker cutoffs for mortality prediction. SARS-CoV-2 was the predominant pathogen (29.1%). In an exploratory comparison limited by small subgroup sizes (n = 8 vs. n = 14), co-infected diabetic patients had higher baseline inflammatory markers than co-infected non-diabetic patients: median IL-6 32.87 vs. 6.20 pg/mL (Mann–Whitney p = 0.0006) and median CRP 103.83 vs. 23.03 mg/L (p = 0.0012). At the Day 6 checkpoint, co-infected diabetic survivors had higher IL-6 (12.01 vs. 6.13 pg/mL, p = 0.0183) and showed little within-group NLR change (Wilcoxon p = 0.2367); these Day 6 estimates are subject to survivor selection and should be interpreted accordingly. In-hospital mortality was 25.6% in diabetic vs. 3.7% in non-diabetic patients (p < 0.0001). Diabetic patients more frequently required orotracheal intubation (6.4% vs. 1.0%, p = 0.0207) and high-flow nasal oxygen (HFNO) support (7.9% vs. 1.8%, p = 0.0166). In an internal ROC analysis, baseline IL-6 showed the highest discriminatory performance for in-hospital mortality (AUC 0.812, 95% CI 0.772–0.848), with a candidate cutoff of > 55.78 pg/mL (sensitivity 71.0%, specificity 79.1%); IL-6 outperformed CRP (AUC 0.706, DeLong p = 0.0029) and NLR (AUC 0.656, DeLong p = 0.0001). As this cutoff was derived and evaluated in the same cohort, it is reported as exploratory and requires external validation. In this single-center cohort, diabetes was associated with a more pronounced baseline inflammatory profile, slower resolution of the neutrophil-to-lymphocyte ratio, and greater multi-organ involvement during viral respiratory infection, including in the small co-infected subgroup. In the full cohort, diabetes remained associated with higher mortality, IL-6, and CRP after adjustment for age, sex, and BMI; however, the small co-infected subgroups could not be adjusted, so those specific comparisons should be regarded as hypothesis-generating and need confirmation in larger, adequately powered multi-center cohorts.

Chronic obstructive pulmonary disease (COPD) is a chronic progressive respiratory disease characterized by respiratory symptoms and airflow limitation and is one of the leading causes of morbidity and mortality worldwide. The evolution of the disease is associated with episodes of acute exacerbations (AECOPD), characterized by worsening symptoms and accelerated deterioration of lung function. Acute exacerbations of COPD have different severity, being mild, moderate or severe depending on how aggravated the patients’ symptoms are, but they also depend on pulmonary functional and biological changes. Around 70% of AECOPD cases are infectious in nature, through upper or lower respiratory tract infections. Often, exacerbations associated with lower respiratory tract infections are more severe and have a higher risk of unfavorable outcome compared to AECOPD associated with upper respiratory tract infections. Severe exacerbations require hospital management, with most of them being treated in the intensive care unit (ICU). In this narrative review, we evaluated the frequency of different bacterial pathogens involved in severe COPD exacerbations associated with lower respiratory tract infections and the need for treatment in the ICU. Identifying patients with exacerbated COPD at high risk of respiratory infections, especially with Gram-negative bacilli, is extremely important to choose the optimal treatment, thus reducing the risk of death.