Genomics correlates of brain metastasis and progression in colorectal cancer.

Background: Brain metastasis (BM) in colorectal cancer (CRC) is a rare event that undermines longevity and neurocognitive function. However, the molecular basis of BM in CRC is poorly understood. We analyzed next-generation sequencing (NGS) from patients with CRC to identify genomic features associated with BM and intracranial progression (IP).

Interleukin-6 in Cardiogenic Shock.

Purpose Of Review: Cardiogenic shock (CS) is one of the leading causes of mortality in patients with acute cardiac disease, and systemic inflammation plays a critical role in its pathophysiology. This review explores the role of interleukin-6 (IL-6) in CS, with a focus on its biological pathways, prognostic value, and potential as a therapeutic target, highlighting the importance of addressing inflammation in this context.

Recent Findings: Recent evidence highlights systemic inflammation implied in CS progression.

[Surgical and percutaneous treatment of hypertrophic obstructive cardiomyopathy: state-of-the-art review].

Hypertrophic cardiomyopathy is a heterogeneous and complex disease. It is an autosomal dominant genetic disease caused by a missense mutation in one of at least 12 genes that code for cardiac sarcomere proteins. There are various approaches used today for the treatment of this pathology, but the "gold standard" remains the surgical treatment of septal myectomy according to Morrow, in which the hypertrophic septum is surgically excised.

[Kidney protection: role of sodium-glucose co-transporter 2 inhibitors and finerenone].

Chronic kidney disease, diabetes mellitus and heart failure represent three chronic conditions closely linked to each other from a pathophysiological and prognostic point of view. This link has led to an ever-increasing emphasis in recent years on the need for a holistic approach to patients who are affected by optimizing the therapeutic management of what has recently been defined as cardio-kidney-metabolic syndrome. The cardiorenal and metabolic approach has gained relevance thanks to recent studies on new drug classes.

Right ventricular global work efficiency: A reliable non-invasive estimate of right ventricular contractility.

Background: Right ventricular (RV) myocardial work (RVMW) recently emerged as a non-invasive alternative for the assessment of RV contractility. However, none of the prior studies assessed its variations under different haemodynamic conditions. We aimed to evaluate the variations of the components of RVMW in heart failure (HF) patients with pulmonary hypertension (PH) undergoing a reversibility test.

[ISMETT experience with long-term left ventricular assist devices].

Background: Advanced heart failure is a condition where pharmacological therapies have a limited impact on prognosis. Left ventricular assist devices (LVAD) have been shown to improve survival and quality of life in well-selected patients in this setting. LVAD technology has evolved over time, leading to more efficient devices with fewer complications.

Transcatheter Aortic Valve Replacement With Intra-Annular Self-Expanding or Balloon-Expandable Valves: The Multicenter International NAVULTRA Registry.

Background: No comparative data exist with the self-expanding Navitor (NAV) and the balloon-expandable SAPIEN 3 Ultra (ULTRA) transcatheter heart valves (THVs).

Objectives: This study sought to investigate the 1-year outcomes of transcatheter aortic valve replacement using the intra-annular NAV and the ULTRA THVs.

Methods: The NAVULTRA (Navitor and SAPIEN 3 Ultra) registry included consecutive patients who underwent transfemoral transcatheter aortic valve replacement at 16 centers with NAV or ULTRA between November 2018 and April 2024.

Targeting the MAP Kinase Pathway in Colorectal Cancer: A Journey in Personalized Medicine.

The anti-EGFR agents cetuximab and panitumumab were the first targeted agents to be licensed for colorectal cancer and marked a significant advancement in personalized care. Initial biomarkers provided poor discrimination between responders and nonresponders. Through hypothesis-led translational studies, tumor genomic negative predictive markers were identified, and treatment is now limited to patients with RAS and BRAF wild-type disease.

[Diagnosis and treatment of iron deficiency in heart failure].

Patients with heart failure (HF) frequently experience iron deficiency, with an estimated prevalence of sideropenia around 50%. In HF patients, iron deficiency is associated with reduced functional capacity, lower quality of life, and an increased risk of hospitalizations and mortality. Therefore, timely diagnosis and treatment of sideropenia are essential to improve clinical outcomes in HF patients with reduced or mildly reduced ejection fraction, while data on the benefits of iron supplementation in HF patients with preserved ejection fraction remain limited.

Gaps and Knowledge in the Contemporary Management of Acute Right Ventricular Failure.

Acute right ventricular failure (ARVF) is commonly seen in the intensive care unit and constitutes a significant clinical challenge, with associated high in-hospital mortality. Recently, the treatment of ARVF has significantly changed, with the progressive implementation of mechanical circulatory support devices that now represent important tools for clinicians in treating this condition. However, despite recent advancements, the optimal approach for ARVF remains elusive, and precise treatment algorithms and comprehensive management protocols are still lacking.

Epidemiology, pathogenesis, biology and evolving management of MSI-H/dMMR cancers.

Deficiency in DNA mismatch repair (dMMR) is a common pathway of carcinogenesis across different tumour types and confers a characteristic microsatellite instability-high (MSI-H) molecular phenotype. The prevalence of the MSI-H/dMMR phenotype is highest in endometrial and colorectal cancers, and this phenotype is associated with a distinct tumour biology, prognosis and responsiveness to various anticancer treatments. In a minority of patients, MSI-H/dMMR cancers result from an inherited pathogenic variant in the context of Lynch syndrome, which has important implications for familial genetic screening.

The role of left atrio-ventricular coupling index and left atrial ejection fraction in predicting onset of atrial fibrillation and adverse cardiac events in hypertrophic cardiomyopathy.

Background: Several predictors of atrial fibrillation (AF) onset in patients with hypertrophic cardiomyopathy (HCM) have been proposed, however, all of them showed limited accuracy. This study aims to assess the role of new echographic parameters in predicting AF onset and major adverse cardiovascular outcomes (cardiovascular death or heart transplantation).

Methods: Clinical and imaging data from 141 patients with HCM and without a history of AF were retrospectively analyzed over a 5-year period.

[Follow-up of patients with acute and chronic heart failure: risk stratification to diversify the pathway].

Heart failure is a syndrome with a high clinical and healthcare impact. Currently, the incidence in Europe is approximately 5/1000 people/year in the adult population, with a prevalence of 1-2%. The prognosis is burdened by a still high mortality and hospitalization rate.

[Role of inflammation in heart failure with preserved ejection fraction: from nephro-metabolic interactions to future therapeutic implications].

Heart failure with preserved ejection fraction (HFpEF) is a complex clinical entity frequently associated with chronic kidney disease (CKD). Recent studies indicate that 50-60% of HFpEF patients also have CKD, and the prevalence of HFpEF among CKD patients is similarly high. Chronic low-grade systemic inflammation is common to both conditions and is linked to risk factors such as obesity, insulin resistance, and diabetes.

A Nanostring gene expression approach identifies aggressive clinical behavior related genes in dedifferentiated liposarcoma.

Dedifferentiated liposarcoma (DDLPS) is one of the most common subtypes of soft tissue sarcoma with a highly variable clinical behavior. Despite advanced molecular approaches are exploring the genetic panorama of DDLPS progression, to date the driver genes of the aggressive clinical behavior in DDLPS have not been identified yet. Here, we used a Nanostring nCounter approach to study the gene expression profile of 60 selected genes involved in DDLPS progression, in a cohort of DDLPS with aggressive clinical behavior, in comparison to a cohort of DDLPS with indolent clinical behavior.

Functional Mitral Valve Regurgitation, Pathophysiology, Leaflet ReModeling, and the Role of Imaging.

Functional mitral regurgitation (FMR) is a complex left ventricle (LV) and left atrium (LA) disorder in which mitral valve regurgitation is just the "tip of the iceberg." Unlike primary mitral cvalve regurgitation, in which regurgitation occurs due to anatomic abnormalities of the valve itself, the etiology of FMR is multifactorial. Regional and global LV dysfunction, extent and location of fibrotic myocardium (subendocardial/transmural scar), and annulus enlargement are the leading causes of valve regurgitation.

[Worsening heart failure: definition, management and treatment].

Heart failure (HF) is a clinical syndrome with high morbidity and mortality, characterized by periods of relative clinical stability and exacerbations of HF, known as worsening heart failure (WHF). WHF is currently defined as a deterioration of HF signs and symptoms, necessitating an intensification of medical therapy, often identified by an increase in diuretic therapy. Episodes of WHF, whether they result in patient hospitalization or outpatient management, suggest clinical progression of HF with significant worsening of the prognosis.

Biomarkers for Congestion in Heart Failure: State-of-the-art and Future Directions.

Congestion in patients with heart failure (HF) predicts adverse outcomes and is a leading cause of hospitalisation. Understanding congestion mechanisms helps in HF management and underscores the importance of tailored therapies to treat vascular and tissue congestion, improving patient outcomes. In this setting, several tools are available to detect congestion.

MAD or MADness?

Mitral valve prolapse (MVP) is a common condition affecting approximately 3% of the population, typically with a benign clinical course. However, a small subset of patients (5-10%) may develop severe mitral regurgitation or arrhythmias, which can lead to sudden cardiac death (SCD). Among the morphological features of MVP, mitral annular disjunction (MAD) has emerged as a potential marker of malignant MVP, with some studies suggesting an association with ventricular arrhythmias and SCD.

[Mineralocorticoid receptor antagonists in heart failure with preserved/mildly reduced ejection fraction: from TOPCAT to FINEARTS-HF].

Mineralocorticoid receptor antagonists (MRAs) represent one of the cornerstones of treatment for heart failure with reduced ejection fraction. Post-hoc data from the TOPCAT trial, conducted in patients with heart failure mildly reduced or preserved ejection fraction (HFmrEF/HFpEF), suggest the possible clinical benefit of MRAs, particularly for slightly reduced ejection fraction values. The advent of non-steroidal MRAs, including finerenone, seems to represent a turning point in the treatment for HFmrEF/HFpEF.

The Prostaglandin EP4 Antagonist Vorbipiprant Combined with PD-1 Blockade for Refractory Microsatellite-Stable Metastatic Colorectal Cancer: A Phase Ib/IIa Trial.

Purpose: Novel combinations are required to overcome resistance to immune checkpoint inhibitors in proficient mismatch repair (pMMR) or microsatellite-stable (MSS) metastatic colorectal cancer (mCRC). We aimed to determine whether vorbipiprant, a prostaglandin E2 receptor EP4 subtype antagonist, can convert immune-resistant mCRC into a tumor responsive to anti-PD-1 inhibition.

Patients And Methods: This phase Ib/IIa prospective, open-label, single-arm trial followed a 3 + 3 dose-escalation and dose-optimization design.

SGLT2 inhibitor therapy in patients with advanced heart failure and reduced ejection fraction.

Aims: Sodium-glucose cotransporter inhibitors (SGLT2-i) improve outcomes in patients with heart failure (HF) and reduced ejection fraction (HFrEF). However, evidence in patients with advanced HF is lacking. We aimed to determine the effect of SGLT2-i in advanced HFrEF compared to their effect on a non-advanced population.