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Background Heart transplant rejection, particularly acute cellular rejection (ACR), remains a critical post-operative concern, despite declining incidence rates. Current diagnostic standards rely on invasive endomyocardial biopsy, which presents limitations in sensitivity and reproducibility. There is an unmet need for noninvasive, accurate biomarkers that can detect and monitor rejection. This study aims to evaluate whether extracellular vesicle (EV) surface antigens, analyzed through flow cytometry and interpreted with artificial intelligence (AI), can serve as reliable biomarkers for ACR detection and monitoring in heart transplant recipients. Methods We conducted a prospective longitudinal cohort study involving 24 heart transplant recipients over a median follow-up of 303 days. A total of 285 blood samples were analyzed for EV surface antigens exploiting two flow cytometry-based protocols. An adaptive AI model (random forest regressor) was developed to interpret EV antigen profiles, dynamically calibrating thresholds per patient. Results Here we show that 14 EV surface antigens progressively increase with ACR severity. These changes are evident even before histological diagnosis. The AI model achieves an accuracy of 93.3% at leave-one-out testing (AUC 0.968), and 78.9% at validation in an independent cohort (AUC 0.832), with high specificity and negative predictive value. EV profiling outperforms conventional biochemical markers and provides anticipatory insight into rejection dynamics. Conclusions EV profiling, enhanced by patient-specific AI modeling, offers a powerful noninvasive method for early detection and monitoring of ACR. This approach holds the potential to reduce reliance on biopsies and tailor immunosuppressive strategies more precisely. Plain language summary Heart transplant patients are at risk of their body rejecting the new heart, which can lead to serious health problems. Current methods to detect rejection often rely on invasive procedures and may not catch the problem early enough. This study looked at whether tiny particles in the blood, called extracellular vesicles, could help detect rejection earlier and more accurately. Researchers analyzed blood samples from heart transplant patients and used artificial intelligence to interpret the data. They found that changes in these particles could signal rejection even before traditional tests did. This non-invasive method could help doctors treat rejection sooner, reduce the need for risky procedures, and improve long-term outcomes for transplant patients. Burrello et al. combine extracellular vesicle profiling with adaptive artificial intelligence to monitor cell rejection after heart transplant. Heart transplant rejection is detected with high accuracy, outperforming biopsy and anticipating rejection before histological signs, offering a promising noninvasive tool for timely intervention and personalized monitoring.

Objective: To evaluate the efficacy and safety of osilodrostat in patients with Cushing’s disease (CD). Methods: A retrospective, multicenter, real-world study of patients with CD. The main efficacy endpoint was the proportion of patients who were complete responders (urinary free cortisol [UFC] < the upper limit of normal and/or with adrenal insufficiency development). Results: Thirty-seven CD patients were enrolled. There were 33 patients who initially received osilodrostat in monotherapy and 4 in combination. However, 3 patients of the monotherapy group were switched to combination therapy. The median duration of osilodrostat treatment was 5 months (range 1–93). All the patients were classified as responders: 33 (89.2%) had complete response and 4 partial response. A positive correlation was detected between the percentage of UFC decrease and the maximum (r = 0.481, p = 0.006) and the maintenance doses (r = 0.440, p = 0.011). The initial doses of osilodrostat were a predictor of complete response (vs. partial) (Odds ratio [OR] 2.82, p = 0.030). The median time to UFC normalization in the group of complete responders was 4 weeks (range 1–20) and UFC normalized before or at month 1 in 67% (n = 20/30) of the patients. Osilodrostat led to a significant decrease in systolic and diastolic blood pressure in parallel with a reduction of antihypertensive medications. Conclusions: Osilodrostat leads to a complete UFC normalization in up to 90% of the patients with CD, in parallel with an improvement in the cardiometabolic profile. A proper titration of osilodrostat is important to achieve a complete response since a positive correlation between the doses and the UFC reduction was observed.

Primary aldosteronism (PA) is the most common cause of endocrine arterial hypertension, and the suggested screening test for case detection is the aldosterone-to-renin ratio (ARR) or aldosterone-to-direct renin ratio (ADRR) based on radio-immunoassay (RIA) and chemiluminescence assay (CLIA), respectively. The objective of our study was to evaluate the reliability of CLIA for aldosterone and renin measurement and the diagnostic performance of ADRR. A prospective cohort of 1110 patients referred to a single laboratory medicine center underwent measurement of aldosterone and direct renin concentration (DRC) by CLIA and measurement of aldosterone and plasma renin activity (PRA) by RIA. Of 1110 patients, 640 obtained a final diagnosis of hypertension, and 90 of these patients were diagnosed with PA. Overall, between-method correlation was highly significant for aldosterone concentrations (R = 0.945, p < 0.001) and less strong but significant for DRC/PRA (R = 0.422, p < 0.001). Among hypertensive patients, in PA cases, the areas under the receiver operator characteristics (ROC) curves were 0.928 (95% confidence interval 0.904–0.954) for ADRR and 0.943 (95% confidence interval 0.920–0.966) for ARR and were comparable and not significantly different. The highest accuracy was obtained with an ADRR cut-off of 25 (ng/L)/(mIU/L), displaying a sensitivity of 91% and a specificity of 85%. The chemiluminescence assay for aldosterone and DRC is a reliable method for PA diagnosis compared to the classical RIA method.

Purpose The delayed or missed diagnosis of secondary hypertension contributes to the poor blood pressure control worldwide. This study aimed to assess the diagnostic approach to primary aldosteronism (PA) and pheochromocytoma (PHEO) among Italian centers associated to European and Italian Societies of Hypertension. Methods Between July and December 2023, a 10-items questionnaire was administered to experts from 82 centers of 14 Italian regions and to cardiologists from the ARCA (Associazioni Regionali Cardiologi Ambulatoriali) Piemonte. Results were stratified for geographical area, specialty, and center category (excellence vs. non-excellence centers). Results Each center diagnosed an average of 2 cases of PA and 0.2 cases of PHEO annually, with higher figures in excellence centers. PA screening is performed mainly in patients with resistant hypertension (73.2%) or hypertension and spontaneous hypokalemia (84.1%), while only 17.1% and 35.4% of centers screen patients with grade 2–3 hypertension. Screening rate is lower for cardiologists compared to other specialists. The main barriers to wider testing were challenges in interpreting the aldosterone/renin ratio under interfering medications and switching to non-interfering drugs. Clinical scores to predict the likelihood of PA and the definition of Standard Operating Procedures were identified as potential tools to boost screening rates. Testing for PHEO was mostly conducted in patients with typical symptoms (75.6%) and/or hypertensive crisis (74.4%). Only 37.8% of centers screened all patients with adrenal incidentaloma. Conclusion This study highlights significant gaps in the screening and diagnosis of PA and PHEO across Italian centers and underscores the need for widespread and standardized diagnostic protocols.

IntroductionRenovascular hypertension (RVH) remains underdiagnosed despite its significant cardiovascular and renal morbidity.AimThis survey investigated screening and management practices for RVH among hypertensive patients in Italian hypertension centres in a real-life setting. Secondary, we analysed the current spread of renal denervation (RDN) and the criteria used for its eligibility.MethodsA 12 item-questionnaire was sent to hypertension centres belonging to the European Society of Hypertension and to the Italian Society of Hypertension (SIIA) in Italy. Data concerning the screening and management of RVH and of RDN were analysed according to the type of centre (excellence vs non-excellence centres), geographical area and medical specialty.ResultsEighty-two centres participated to the survey. The number of patients diagnosed in each centre with RVH and fibromuscular dysplasia during the last five years was 3 [1;6] and 1 [0;2], respectively. Despite higher rates of RVH diagnosis in excellence centres (p = 0.017), overall numbers remained unacceptably low, when compared to expected prevalence estimates. Screening rates were inadequate, particularly among young hypertensive patients, with only 28% of the centres screening for RVH in such population. Renal duplex ultrasound was underused, with computed tomographic angiography or magnetic resonance angiography reserved for confirming a RVH diagnosis (76.8%) rather than for screening (1.9–32.7%, according to patients’ characteristics). Scepticism and logistical challenges limited RDN widespread adoption.ConclusionsThese findings underscore the need for improving RVH screening strategies and for a wider use of related diagnostic tools. Enhanced awareness and adherence to guidelines are crucial to identifying renovascular hypertension and mitigating associated cardiovascular and renal risks.

Extracellular vesicles (EVs) offer valuable diagnostic and prognostic insights for cardiovascular (CV) diseases, but the influence of age-related chronic inflammation (“inflammaging”) and sex differences on EV profiles linked to CV risk remains unclear. This study aimed to use EV profiling to predict age and stratify patients by CV risk. We developed an EVaging index by analyzing surface antigen profiles of serum EVs from 625 participants, aged 20 to 94 years, across varying CV risk groups. The EVaging index was associated with age in healthy individuals and distinguished CV risk profiles in patients, correlating with CV outcomes and likelihood of fatal CV events according to the European Society of Cardiology (ESC) SCORE, and reflecting age-associated comorbidities. While changes in disease-related EV fingerprint adds complexity in CV patients, EV profiling may help assess biological aging and CV risk, emphasizing EVs’ roles in inflammaging.

Abstract Purpose To assess the impact of body mass index (BMI) on disease severity, cardiac remodeling, and clinical and biochemical outcomes after surgical and medical treatment in patients with primary aldosteronism (PA). Methods This international retrospective study included patients diagnosed with PA in Germany, Italy, and Spain. Patients with available BMI, serum potassium, blood pressure, and basal plasma aldosterone concentration at diagnosis were included. PA severity was classified using the Primary Aldosteronism Severity Classification. Results A total of 1752 patients were analyzed at baseline; 604 (34.5%) had obesity (BMI ≥30 kg/m2). Patients with obesity were older, more frequently male, and had a higher prevalence of cardiometabolic comorbidities, including type 2 diabetes, cardiovascular disease, left ventricular hypertrophy, and obstructive sleep apnea. PA severity according to the Primary Aldosteronism Severity Classification did not differ significantly between patients with and without obesity; however, the prevalence of severe PA increased progressively across BMI categories (MH test for linear trend: χ2(1) = 3.70, P = .054). Following adrenalectomy, the probability of complete hypertension resolution decreased with increasing BMI, whereas biochemical cure rates were similar. Among patients treated with mineralocorticoid receptor antagonists, obesity was associated with a lower likelihood of complete clinical response, without significant differences in biochemical response. Conclusion In patients with PA, obesity is associated with a higher burden of cardiometabolic comorbidities and increased prevalence of left ventricular hypertrophy at baseline, as well as with less favorable clinical outcome after both surgical and medical treatment.

AA7075-T6 is an aluminum alloy that has a high mechanical resistance; however, it shows corrosion vulnerability. A usual method to improve the corrosion resistance is anodization in acidic medium, which forms a thin barrier layer and a thicker porous oxide layer over the surface. This ultimate layer must be sealed to avoid electrolyte penetration. In the present work, a Zr-based conversion coating was investigated as a novel method of cold sealing and compared to the precipitation over bare AA7075-T6. The samples were characterized by Scan Electronic Microscopy (SEM) and Energy Dispersive X-Ray Spectroscopy (EDX) to elucidate the mechanism of reaction on both natural aluminum oxide and anodic oxide layer. The hydrophobicity properties were evaluated by contact angle measurements. The mechanism of deposition suggested for the coating over the anodic oxide was analogue to the one that takes place over the bare alloy: an initial attack by fluoride ions, local pH increase and Zr oxide precipitation. It was also possible to precipitate Zr oxide inside the pores. An increase of 125% on the contact angle was observed for the Zr coating over anodized surfaces, while the increase over the bare alloy was of 32%. Therefore, a robust coating system can be proposed involving the anodic layer and the nanometric Zr oxide.

This book covers the basics of semantic web technologies and indexing languages, and describes their contribution to improve methods of formal knowledge representation and reasoning. The methodologies included combine the specifics of indexing languages, Web representation languages and intersystem relations, and explain their contribution to search functionalities in information retrieval scenarios. An example oriented discussion, considering aspects of conceptual and semantic interoperability in processes of subject querying and knowledge exploration is provided. The book is relevant to information scientists, knowledge workers and indexers. It provides a suitable combination of theoretical foundations and practical applications.