Obesity is a multidimensional condition characterized by autonomic imbalance, metabolic inflexibility, impaired physical resilience, and ectopic adiposity, pathophysiological alterations that arise long before overt cardiometabolic disease becomes clinically detectable. Despite this, current cardiometabolic risk scores continue to rely predominantly on biochemical and anthropometric variables, such as BMI, waist circumference, glucose, and lipid levels. While these markers are practical, inexpensive, and validated across large population cohorts, growing evidence shows that they offer limited incremental predictive value and fail to capture early functional and structural abnormalities. The recent literature highlights the prognostic importance of autonomic dysfunction, reduced metabolic flexibility, diminished cardiorespiratory fitness, impaired muscular strength, and ectopic fat depots including visceral and epicardial adiposity, independently of the traditional anthropometric indices. The domains remain absent from traditional algorithms such as the Metabolic Syndrome criteria, the Framingham Risk Score, and SCORE2. As a result, cardiometabolic risk is frequently underestimated in key subgroups, including young adults with obesity, individuals with high visceral adiposity but normal BMI, those with subclinical myocardial dysfunction, and metabolically unhealthy normal-weight phenotypes. This narrative review synthesizes current evidence on obesity-related cardiometabolic impairment, highlights major gaps in established risk scores, and supports the conceptual development of the C.O.R.E. (Cardio-Obesity Risk Evaluation) Indicator Model-a hypothesis-generating, non-validated multidomain framework integrating autonomic, metabolic, functional, and structural markers to enable earlier risk phenotyping in future studies.

Background: Obesity has evolved from a morphometric descriptor to a chronic, relapsing, multisystem disease in which low-grade adipose-tissue inflammation, insulin resistance, endothelial dysfunction, and a prothrombotic, pro-tumorigenic milieu coexist. Venous thromboembolism (VTE) and malignancy share this substrate through a well-established bidirectional link: within twelve months of an unprovoked deep vein thrombosis (DVT), 6-15% of patients are diagnosed with occult cancer, a substantial proportion of which are already locally advanced or metastatic at detection. In this context, obesity acts as a dual amplifier of both thrombotic and oncologic risk, making the post-DVT patient with an incidentally diagnosed cancer a paradigmatic candidate for integrated management. Objective: To propose an evidence-based, unifying cardiometabolic and antithrombotic clinical framework that reconciles (i) risk-stratified screening for occult malignancy after unprovoked DVT, (ii) contemporary pharmacotherapy of obesity, and (iii) cancer-associated thrombosis (CAT) management, in the light of evidence published through 2025. Methods: Narrative synthesis based on a structured literature search (PubMed/MEDLINE, Embase, Scopus; 2000-March 2025) of current guidelines (ISTH, ASH, ESC Cardio-Oncology, EASO) and pivotal randomized evidence on GLP-1 and dual GLP-1/GIP receptor agonists (semaglutide, tirzepatide), SGLT2 inhibitors (empagliflozin, dapagliflozin), and direct oral anticoagulants (DOACs), with critical interpretation of recent meta-analytic data on oncologic signals, cardiovascular outcomes, and bleeding safety. Results: Three evidence-based pillars emerge: (1) limited screening complemented by age- and sex-specific testing in patients ≥ 50 years with unprovoked DVT, enhanced by FDG-PET/CT for high-risk phenotypes in which obesity itself degrades the sensitivity of clinical examination and conventional imaging; (2) GLP-1/GIP receptor agonist-based anti-obesity pharmacotherapy, associated in observational cohorts with a 17% relative reduction in overall cancer incidence (HR 0.83; 95% CI 0.76-0.91) and neutral-to-reassuring oncologic signals, but requiring cautious, case-by-case use in patients with active cancer because of the risk of accelerating sarcopenia and cachexia; and (3) apixaban as the preferred DOAC for cancer-associated thrombosis, with a superior efficacy-to-bleeding ratio in network meta-analyses and a reduced-dose extended strategy now validated by the API-CAT trial. Conclusions: Patients with obesity presenting with unprovoked DVT and an incidentally detected cancer embody a cardiometabolic-antithrombotic continuum. A framework integrating structured occult-cancer screening, judicious obesity pharmacotherapy, and apixaban-preferred anticoagulation-coordinated by a multidisciplinary team and illustrated here by a case-based pathway-offers the most rational, evidence-aligned approach. Prospective, dedicated trials in this specific phenotype are urgently warranted.

Treating autosomal dominant polycystic kidney disease (ADPKD) has always been a challenge because the disease is too complex for single-target drugs, which are often held back by side effects. This narrative review explores a different strategy: using plant-derived polyphenols to target multiple disease pathways at the same time. Looking at research from 2005 to 2026, we break down how key compounds like resveratrol, curcumin, naringenin, quercetin, and epigallocatechin-3-gallate (EGCG) actually work. Preclinical studies show these molecules can slow down cyst growth by tackling inflammation, rapid cell division, and tissue scarring all at once, while also resetting the skewed energy metabolism of cystic cells. Some mechanisms are strikingly specific, such as naringenin’s direct interaction with polycystin-2 and quercetin’s ability to clear senescent cells. Yet, the real-world hurdle is poor absorption; a recent clinical trial with standard curcumin fell short simply because the compound could not reach the kidneys in high enough concentrations. Moving forward, the field needs to focus on testing these compounds in realistic animal models, designing smart nanoformulations to improve bioavailability, and exploring combinations that could safely complement current therapies like tolvaptan.

Unattended blood pressure (BP) measurement was introduced following the results of the SPRINT study. Conflicting results have been reported in relation to the concordance between unattended BP, attended BP and 24-hour ambulatory monitoring (ABPM). To evaluate the concordance between measurements of BP in unattended, attended and ABPM modes, and to analyse sex differences in the diagnostic accuracy in relation to the 24h ABPM. 307 patients were enrolled in 6 hypertension centers belonging to the Italian Society of Hypertension. Patients underwent BP measurement in unattended and attended modes before ABPM. BP was defined as controlled if the 24-hour average blood pressure was <130/80 mmHg on ABPM. Patients with 59.6 ±13.6 years, with a female prevalence of 48

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.

Background: Right ventricular (RV) dysfunction is increasingly recognized in acute respiratory failure. Hypoxaemia, hypercapnia, acidosis, pulmonary vascular involvement and positive-pressure respiratory support may increase pulmonary vascular resistance (PVR) and RV afterload, thereby impairing RV performance. However, the haemodynamic effects of non-invasive respiratory support strategies in severe community-acquired pneumonia (CAP) outside the ICU remain insufficiently characterized. Objectives: To assess, in patients with severe CAP (Pneumonia Severity Index - PSI - IV and V): (1) the association between oxygenation mode and RV systolic performance (Tricuspid Annular Plane Systolic Excursion - TAPSE, and lateral Tissue Doppler imaging - TDI) and (2) the relationship between oxygenation mode and Length of hospital stay (LOS). Methods: Single-centre prospective observational study with consecutive enrolment of adult patients with severe CAP (PSI IV-V, according to ATS/IDSA - American Thoracic Society/Infectious Diseases Society of America - severity criteria) hospitalized in an internal medicine ward. The initial respiratory support strategy was selected in the emergency setting among NIV-PSV [Pressure Support Ventilation], HFNC, and Venturi Mask according to the patient's gas-exchange and acid-base profile; complete transthoracic echocardiography was then performed on ward admission while patients remained on the initially assigned device and settings, before any ward-driven modification of respiratory settings. The diagnostic etiological work-up comprised blood and sputum samples for cultures and multiplex nasopharyngeal viral/atypical PCR assays. Results: A total of 70 patients were enrolled (NIV = 21, HFNC = 22, Venturi mask = 27). All patients had bilateral multilobar consolidations and pleural effusions. The predominant etiology was viral/atypical bacteria: human metapneumovirus A/B (30%), rhinovirus (30%), HPIV - Human parainfluenza virus − (20%), Mycoplasma pneumoniae (20%). RV systolic parameters significantly varied between oxygenation modalities (p < 0.001). Patients on NIV showed the worst RV performance (TAPSE 1.16 ± 0.19 cm; TDI 6.02 ± 0.73 cm/s), while patients on a Venturi mask had better RV systolic performance (TAPSE 1.74 ± 0.33 cm; TDI 10.12 ± 2.28 cm/s). LOS was considerably longer in NIV and HFNC patients than in Venturi mask patients (28.4 ± 3.0 vs 27.4 ± 2.9 vs 14.7 ± 3.7 days; p < 0.001). In multivariate linear regression analysis, age and pattern of respiratory support (NIV/HFNC vs Venturi) were both independently associated with prolonged LOS. Conclusions: In this cohort, pressure-generating respiratory support modalities were associated with poorer RV systolic indices and longer hospitalization. Because the study specifically evaluated RV systolic function - and not RV failure or RV-pulmonary artery uncoupling - and because echocardiography was performed after respiratory support had already been selected and started, these findings should be interpreted as hypothesis-generating associations that may reflect both underlying disease severity and support-related haemodynamic effects.

Cardiometabolic diseases remain the leading cause of morbidity and mortality worldwide, despite major advances in pharmacological and lifestyle interventions. Exercise training is a cornerstone of prevention and treatment; however, adherence to traditional aerobic programs remains suboptimal. Isometric handgrip (IHG) training has emerged as a simple, time-efficient, and potentially effective strategy for improving cardiovascular and metabolic outcomes. This state-of-the-art review synthesizes current evidence on the physiological mechanisms underlying IHG training, including autonomic modulation, vascular function improvement, endothelial adaptation, and metabolic regulation. We summarize clinical data regarding its effects on blood pressure, arterial stiffness, endothelial function, insulin sensitivity, and inflammatory markers. Special attention is given to its applicability in specific populations, including hypertensive patients, individuals with metabolic syndrome, heart failure patients, and cancer survivors. We also discuss methodological heterogeneity across studies, safety considerations, and knowledge gaps. Finally, we outline future research directions needed to define optimal protocols and clarify long-term cardiometabolic benefits. IHG training represents a promising adjunctive strategy within cardiometabolic prevention and rehabilitation programs.

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.

Traditional anthropometric indices reflect total body adiposity, whereas novel shape-based indices capture fat distribution and unfavorable adiposity. How these measures relate to hepatic steatosis and fibrosis risk across the spectrum of metabolic dysfunction–associated steatotic liver disease (MASLD) remains unclear. In this cross-sectional study, 222 patients with MASLD were included. Body mass index (BMI), waist circumference (WC), a body shape index (ABSI) and body roundness index (BRI) were evaluated. Hepatic steatosis was assessed by ultrasonography using the Bright Liver Echo Pattern (BLEP), while fibrosis risk was estimated using the Fibrosis-4 (FIB-4) index. BMI, WC, and BRI were higher in individuals with moderate-to-severe hepatic steatosis (BLEP ≥ 2), whereas ABSI did not differ according to steatosis severity. In multivariable logistic regression, BMI was independently associated with BLEP ≥ 2 (OR 1.19; 95

This scoping review aims to map prospective evidence on the vascular effects of major smoking cessation therapies, including pharmacotherapy, nicotine replacement therapy and exclusive switching to electronic cigarettes, in adult smokers. A comprehensive search of PubMed, Scopus and Web of Science was conducted on December 2, 2025. Eligible studies included randomized controlled trials, quasi-experimental designs and prospective cohort studies reporting quantitative or narrative findings on vascular function following smoking cessation or exclusive electronic cigarette use. Only studies with at least 1 week of follow-up and resting vascular measurements were included. Data were charted using a standardized extraction template and synthesized narratively, consistent with scoping review methodology. Twenty-two prospective studies met the inclusion criteria. Pharmacotherapy-assisted cessation, nicotine replacement therapy and exclusive switching to electronic cigarettes were all associated with improvements in vascular outcomes among participants who fully abstained from combustible cigarettes. Increases in flow-mediated dilation were observed across treatment categories, with several studies reporting measurable gains within the first 3 to 12 months. Reductions in pulse-wave velocity and augmentation index also emerged in most cohorts, although effect sizes varied according to study design, follow-up duration and population characteristics. Evidence from studies on exclusive electronic cigarette use, although limited in number, showed improvements in endothelial function and arterial stiffness comparable to those observed with conventional cessation therapies. Prospective evidence indicates that multiple smoking cessation therapies, including exclusive switching to electronic cigarettes, may be associated with early improvements in vascular function when combustible cigarette exposure is fully eliminated. The evidence base remains constrained by heterogeneity, small sample sizes and short follow-up, particularly within studies on electronic cigarette switching. Larger and long-term prospective studies are needed to clarify the durability and clinical implications of these early vascular changes.

Respiratory symptoms are common among smokers without COPD, yet symptom instruments are often optimized for established disease and may under-capture early changes relevant to cessation and tobacco harm reduction. We conducted a repeatability and replicability study of the Respiratory Symptom Experience Scale (RSES) in a rigorously phenotyped cohort to confirm both measurement stability and reproducible discrimination by smoking status. Healthy adults were recruited at a UK hospital and classified as current, former, or never smokers using self-report, exhaled CO, and a comprehensive panel of biomarkers of exposure. RSES was administered at Visit 1 and repeated after 7 ± 3 days at Visit 2 to assess test–retest repeatability. Known-group validity (discriminability by smoking status) was evaluated by comparing RSES scores across biochemically verified groups using non-parametric tests, with ANCOVA for exploratory covariate adjustment. True replicability across independent datasets was not formally tested in the present study. Of 180 enrolled participants, 170 were included (55 current smokers, 60 former smokers, 55 never smokers) after excluding clinical ineligibility and biomarker-inconsistent smoking status. RSES demonstrated high repeatability (Pearson r = 0.87; Spearman ρ = 0.85) with minimal bias (− 0.07) and good agreement. RSES also showed consistent known-group discrimination by smoking status, differing between current and never smokers (p < 0.0001) and across all three groups (p < 0.0001). Current smokers reported higher scores than never (median 2.0 vs. 1.0) and former smokers (2.0 vs. 1.2), whereas former and never smokers did not differ (p = 0.686). Covariate adjustment did not materially alter results. RSES shows strong repeatability and consistent known-group discrimination by smoking status, supporting its use as a patient-relevant endpoint for cessation, and harm-reduction trials, as well as for clinical respiratory and regulatory research.

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.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is highly prevalent worldwide and represents the hepatic manifestation of a systemic cardiometabolic-inflammatory syndrome rather than an isolated organ disease. In parallel, anticancer therapies carry a well-recognised burden of cancer therapy-related cardiovascular toxicity (CTR-CVT). Evidence suggests that the metabolic-inflammatory cascade driving steatosis → steatohepatitis → fibrosis may also contribute to endothelial dysfunction, myocardial remodelling and cardiomyocyte vulnerability to chemotherapy-induced oxidative stress. This narrative review proposes a unifying conceptual framework in which MASLD may act as a potential amplifier of cardiotoxicity in oncology patients and examines whether lifestyle and dietary interventions could mitigate this cumulative risk. Methods: A structured literature search of PubMed, Scopus and Web of Science was performed, prioritising systematic reviews, meta-analyses, randomised controlled trials, large cohort studies and recent international guidelines on MASLD, cardio-oncology and nutritional interventions. Results: Four converging molecular axes were identified as plausible links between MASLD and cardiomyocyte susceptibility to anticancer therapy: mitochondrial dysfunction with reactive oxygen species overproduction, NLRP3 inflammasome activation and metaflammation, endothelial nitric oxide impairment, and pro-fibrotic TGF-β/hepatic stellate cell signalling. Mediterranean-style dietary patterns, selected micronutrients and emerging metabolic therapies modulate the same network and may offer translational opportunities. Conclusions: Reframing MASLD as a potentially modifiable amplifier of CTR-CVT supports the integration of hepatic phenotyping into baseline cardio-oncology risk stratification and the use of personalised nutrition as a precision tool acting on shared mitochondrial, inflammatory, endothelial and fibrotic pathways. Multidisciplinary framework and prospective interventional studies, adopting composite hepato-cardio-oncological endpoints, are warranted.

Background: Cigarette smoking is a widely recognized risk factor for several diseases and a crucial problem in global health, as it contributes to the development and worsening of various diseases, resulting in an increase in both morbidity and mortality. One of the strategies to reduce the impact of tobacco damage is based on the transition from flammable to non-flammable nicotine products. Objectives: The aim of this narrative review is to summarize the effects of traditional cigarette smoking and non-combustible nicotine products on kidney function. Conclusions: The evidence shows that both combustible and non-combustible nicotine products have harmful effects on kidney health and may promote the onset and progression of kidney dysfunction, leading to chronic kidney disease (CKD).

Background: Glucagon-like peptide-1 receptor agonists and dual glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 (GIP/GLP-1) receptor agonists have substantially improved the management of obesity and cardiometabolic disease, providing significant benefits on weight reduction, glycemic control, and cardiovascular outcomes. Despite these advances, gastrointestinal (GI) adverse events remain a major cause of dose reduction, treatment interruption, and poor long-term adherence. Increasing evidence suggests that interactions between incretin-based therapies and the intestinal microenvironment may contribute to GI tolerability and influence treatment persistence. Methods: We conducted a narrative review of the literature examining the relationship between incretin-based therapies, gut microbiota, intestinal barrier function, and microbial metabolites. Evidence from randomized clinical trials, observational studies, systematic reviews, and mechanistic investigations was evaluated to explore potential gut-directed supportive strategies during incretin-based treatment. Results: Preclinical and mechanistic evidence suggests possible bidirectional interactions between incretin pharmacology and the intestinal microenvironment, whereas direct human evidence remains limited and inconsistent. Alterations in gastrointestinal motility induced by GLP-1 receptor agonists could theoretically influence microbial composition and fermentation dynamics, although human studies have not consistently demonstrated significant microbiota changes. Based on these observations, we propose the Incretin-Microbiota Tolerance Axis (IMTA) as a conceptual framework linking gut homeostasis, GI tolerability, and treatment adherence. Among potential supportive interventions, partially hydrolyzed guar gum (PHGG) may promote SCFA-producing microbiota and improve bowel function, whereas simethicone may provide symptomatic relief of gas-related discomfort during dose escalation. SCFA-supportive nutritional approaches may further contribute to maintenance of intestinal homeostasis. Conclusions: Optimization of the intestinal microenvironment may represent a complementary strategy to improve GI tolerability and support long-term adherence during incretin-based therapy. Although the IMTA framework is supported by biological plausibility and emerging evidence, prospective clinical studies are required to determine whether microbiota-targeted interventions improve treatment persistence and cardiometabolic outcomes in patients receiving GLP-1 receptor agonists or dual GIP/GLP-1 receptor agonists.

Pulmonary hypertension (PH) is a heterogeneous clinical syndrome in which similar haemodynamic abnormalities may arise from distinct vascular, cardiac, pulmonary, thromboembolic, and molecular mechanisms. This complexity limits the ability of conventional classifications and risk scores to fully capture individual disease trajectories and treatment responses. Artificial intelligence (AI) offers a framework for integrating clinical data, electrocardiography, multimodal imaging, invasive haemodynamics, biomarkers, and multi-omics information across the PH care pathway. This review summarises current applications of machine learning and deep learning in early detection, diagnostic referral, right ventricular and pulmonary vascular phenotyping, molecular endotyping, risk stratification, and therapeutic decision support. Available studies show promising results for AI-assisted electrocardiographic screening, automated echocardiographic and cardiac magnetic resonance analysis, CT-based phenotyping, and multimodal prognostic modelling. Multi-omics approaches may further identify immune, transcriptomic, proteomic, metabolic, and genetic signatures relevant to biological endotyping and biomarker-driven trial enrichment. However, most evidence remains retrospective, derives from selected referral populations, and lacks robust external or prospective validation. No AI-based model currently supports routine drug selection or autonomous clinical decision-making. Future progress will require harmonised multicentre datasets and standardised acquisition protocols, transparent and interpretable models, and prospective studies demonstrating meaningful clinical benefit. AI should therefore be viewed as an emerging decision-support tool that may strengthen precision medicine in PH while complementing clinical expertise across diagnosis, phenotyping, risk assessment, and therapeutic stratification pathways.

Non-communicable diseases (NCDs) are the leading cause of death worldwide and are among the major drivers of healthcare expenditure, particularly in societies undergoing progressive population aging [...].

Background: The 2022 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines suggest the use of Renin-angiotensin-aldosterone system inhibitors (RAASIs) in chronic Kidney Disease (CKD) stages IV-V, in contrast to the 2012 KDIGO guidelines, which discouraged it. This study aims to assess the impact of RAASIs on kalemia and mortality in a large sample of dialysis patients, where longitudinal data remain scarce, comparing traditional statistical methods with machine learning (ML) algorithms. Methods: This observational longitudinal analysis included 4764 hemodialysis (HD) patients from the Sicilian Registry of Nephrology, Dialysis and Transplantation, with a total of 56,964 longitudinal measurements. We evaluated the impact of RAASIs on serum potassium levels and all-cause mortality in the dialysis setting, comparing traditional statistics and ML. Linear Mixed Models (LMM) and Cox models with mixed effects were used for longitudinal and survival analyses. These were compared with ML approaches, including Random Forest (RF) for potassium variability and Lasso-regularized models for mortality, using four-fold cross-validation. Results: The study included 4764 patients, of whom 1207 (25%) were treated with RAASis. The mean age was 66 ± 15 years, 62% were male, 33% were diabetic, and a history of arterial hypertension was reported in 74% of patients. Hyperkalaemia at baseline was present in 1848 patients. The longitudinal model showed a statistically significant increase in kalemia [adjβ = 0.10 mmol/L, 95%CI 0.05/0.15, p < 0.001], but it was clinically negligible. Indeed, RF did not detect RAASIS as a relevant variable. Association between RAASIs and mortality was not detected either with Cox or ML models. Furthermore, the RF model outperformed traditional LMMs in explaining total potassium variability (56% vs. 43%). Conclusions: RAASI therapy in HD patients is associated with a minimal, non-clinically significant increase in serum potassium and does not impact all-cause mortality. The integration of ML reinforces the robustness of these findings, supporting the safety of RAASIs in the dialysis setting.

OBJECTIVES:This systematic review aims to evaluate the effects of smoking cessation or switching to exclusive electronic cigarette (EC) use on vascular function in adult smokers, using prospective evidence from clinical studies. METHODS:A comprehensive literature search was conducted in PubMed, Scopus, Web of Science and Embase on Oct 13, 2025. Eligible studies included randomized controlled trials (RCTs), quasi-experimental designs, and prospective cohort studies reporting quantitative or narrative data on vascular outcomes (i.e., pulse wave velocity (PWV), augmentation index (AIx), and flow-mediated dilation (FMD)), after smoking cessation or switching to ECs. Risk of bias was assessed using the Joanna Briggs Institute tools. Results were synthesized qualitatively. Certainty of the evidence was determined using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation). RESULTS:Twenty-three studies involving a total of 11,702 participants were included: 14 cohort studies, 5 quasi-experimental and 4 RCTs. Overall, smoking cessation was consistently associated with improvements in PWV, AIx, and FMD, with some effects observable within one month and sustained up to 24 months. The overall certainty of evidence was very low, except for a moderate level of certainty derived from RCTs investigating FMD. Improvements were seen across different cessation methods, including pharmacotherapy and ECs. RCTs on ECs reported significant improvements in FMD irrespective of nicotine content, suggesting that combustion rather than nicotine may be the primary driver of vascular impairment. Sensitivity analyses excluding lower-quality RCTs confirmed the primary findings. CONCLUSIONS:Smoking cessation appears to improve vascular function, as reflected by early favorable changes in endothelial and arterial stiffness markers; however, the overall certainty varies from moderate to very low, according to the outcome. These findings are consistent with the biological plausibility of cardiovascular benefit from sustained smoking abstinence.

Type 2 diabetes (T2D) exhibits substantial phenotypic heterogeneity, resulting in diverse cardiovascular (CV) outcomes driven by multiple pathophysiological mechanisms beyond hyperglycemia alone. T2D should be recognized as a systemic cardiometabolic condition in which insulin resistance, chronic inflammation, oxidative stress, and endothelial and microvascular dysfunction promote a broad spectrum of cardiovascular diseases. The traditional “one-size-fits-all” approach to cardiovascular risk management has been proven insufficient, as individuals with T2D display marked variability in clinical presentation, disease trajectory, treatment response, and cardiovascular phenotype. In this context, personalized medicine strategies integrating clinical phenotyping, individualized risk stratification, and tailored therapeutic interventions offer the potential to optimize cardiometabolic outcomes while minimizing treatment burden and adverse effects. This narrative review examines the rationale and current evidence supporting personalized cardiovascular risk management in T2D. We discuss the heterogeneity of diabetes-related CV phenotypes, encompassing both atherosclerotic and non-atherosclerotic complications. We further examine the major cardiometabolic risk factors closely linked to diabetes, including dyslipidemia, hypertension, obesity, chronic kidney disease, and metabolic liver disease, which act synergistically to accelerate vascular damage and end-organ injury, and are essential for defining personalized prognostic and therapeutic programs. Finally, we present structured approaches to cardiovascular assessment and highlight contemporary management strategies that prioritize integrated, phenotype-driven risk reduction using cardioprotective glucose-lowering therapies together with optimized lipid-lowering, antihypertensive, antithrombotic, and weight-modifying interventions. The transition from population-based guidelines to individualized, patient-centered care represents a paradigm shift in diabetes management, with the potential to substantially reduce the excess CV burden associated with this condition.