IRIS UniSR (’Università Vita-Salute San Raffaele)
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MitraClip device automated localization in 3D transesophageal echocardiography via deep learning
Full text linkBackground and Objective: The MitraClip is the most widely used percutaneous treatment for mitral regurgitation, typically performed under the real-time guidance of 3D transesophageal echocardiography (TEE). However, artifacts and low image contrast in echocardiography hinder accurate clip visualization. This study presents a proof-of-concept of an automated pipeline for clip detection from 3D TEE images acquired in a controlled in vitro simulation environment. Methods: An Attention UNet was employed to segment the device, while a DenseNet classifier predicted its configuration among ten possible states, ranging from fully closed to fully open. Based on the predicted configuration, a template model derived from computer-aided design (CAD) was automatically registered to refine the segmentation and enable quantitative characterization of the device. The pipeline was trained and validated on 196 3D TEE images acquired using a heart simulator, with ground-truth annotations refined through CAD-based templates. Results: The Attention UNet achieved an average surface distance of 0.76 mm and a 95% Hausdorff distance of 2.44 mm for segmentation, while the DenseNet achieved an average weighted F1-score of 0.80 for classification. Post-refinement, segmentation accuracy improved, with average surface distance and 95% Hausdorff distance reduced to 0.69 mm and 1.83 mm, respectively. Conclusion: This pipeline enhanced clip visualization, providing fast and accurate detection with quantitative feedback, potentially improving procedural efficiency and reducing adverse outcomes
Gastrointestinal symptoms in the journey of pancreatic cancer patients
No full textIntroduction: Pancreatic ductal adenocarcinoma (PDAC) is a lethal malignancy frequently arising with nonspecific and overlooked gastrointestinal symptoms. Gastroenterologists are typically the first specialists to encounter these patients, positioning them to play a pivotal role not only in early diagnosis, but also in the ongoing management of the disease’s complex symptom burden. Areas covered: This review explored gastrointestinal symptoms in patients with PDAC (ranging from pain and diarrhea to anorexia, jaundice, and nausea) and outlined both tumor- and treatment-related causes. A literature review based on non-systematic PubMed search updated to April 2025 was conducted to summarize current diagnostic strategies, medical, endoscopic therapies, and multidisciplinary management approaches. In addition, we present original data from a single-center cohort, suggesting that the involvement of gastroenterologists leads to more comprehensive management of gastrointestinal symptom control and supportive care. Expert opinion: Collaboration among specialists is essential for optimizing patient outcomes in the multidisciplinary management of PDAC. Gastroenterologists’ ‘stewardship’ significantly contributes to prompt diagnosis, symptom control, quality of life preservation, and prognosis. Future priorities should focus on strengthening integration within care pathways, fostering interdisciplinary coordination, and implementing shared clinical tools to enhance comprehensive patient care. A well-structured team-based approach is key to advancing holistic PDAC management
TROPION-Breast04: a randomized phase III study of neoadjuvant datopotamab deruxtecan (Dato-DXd) plus durvalumab followed by adjuvant durvalumab versus standard of care in patients with treatment-naïve early-stage triple negative or HR-low/HER2− breast cancer
No full textBackground: Despite treatment advances for patients with early-stage triple-negative breast cancer (TNBC) and hormone receptor (HR)-low/human epidermal growth factor receptor 2-negative (HER2−) breast cancer, treatments that improve clinical outcomes while mitigating toxicity are needed. Datopotamab deruxtecan (Dato-DXd), a TROP2-directed antibody-drug conjugate consisting of a humanized IgG1 monoclonal antibody attached via a plasma-stable cleavable linker to a topoisomerase-I inhibitor payload, has shown efficacy alone or in combination with durvalumab, a selective, high-affinity anti-programmed cell death ligand 1 antibody, in early-phase clinical studies. Objectives: The primary objective of TROPION-Breast04 is to evaluate the efficacy and safety of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy versus standard of care in patients with previously untreated early-stage TNBC or HR-low/HER2− breast cancer. Design: This is an ongoing, international, phase III, open-label, randomized controlled study. Methods and analysis: Approximately 1728 patients (aged ⩾18 years) will be randomized 1:1 to eight cycles of neoadjuvant Dato-DXd (6 mg/kg intravenously (IV) every 3 weeks (Q3W)) plus durvalumab (1120 mg IV Q3W) followed by nine cycles of adjuvant durvalumab (1120 mg IV Q3W) with or without chemotherapy versus eight cycles of pembrolizumab (200 mg IV Q3W) plus chemotherapy followed by nine cycles of adjuvant pembrolizumab (200 mg IV Q3W) with or without chemotherapy. Dual primary endpoints are pathological complete response by blinded central review and event-free survival by investigator assessment. Secondary endpoints include overall survival (key), distant disease-free survival, patient-reported outcomes, and safety. Ethics: The study is approved by independent ethics committees and/or institutional review boards at each study site. All patients will provide written informed consent. Discussion: This study will evaluate the potential use of neoadjuvant Dato-DXd plus durvalumab followed by adjuvant durvalumab with or without chemotherapy versus standard of care in patients with previously untreated early-stage TNBC or HR-low/HER2− breast cancer. The findings of this trial could lead to promising treatment options for these patients. Trial registration: ClinicalTrials.gov identifier: NCT06112379
Atmosfere emozionali nella clinica psicoterapeutica. Alcuni dubbi sulla psichiatria atmosferologica
No full textThe fundamental points of the atmospherologically oriented phenomenological psychology are identified and discussed: if phenomenology sees the symptom within subjectivity, atmospherology shifts the emphasis of emotions outward. Atmospheres capture us so deeply that they direct our agency and our perception of places, objects and situations: in psychiatry it would be possible to organize a diagnostic criterion where the psychopathogenic agents are reconstructed following the emotional atmospheres grasped by the patient-person. The article problematizes the theoretical base of this concept, arguing that the personhood of the patient-person, in an externalizing theory of emotions, is lost. In a psychiatric instance, this is problematic as the aim of reconstructing one’s atmospherical emotions collides with emotions being all-out: it is at least paradoxical or conflicting to believe that one’s psychopathogenic atmospheres are clinically detectable if emotions are poured into air. Finally, it is supported the idea that, while preserving the possibility of having an atmospherological diagnosis, a deeper analysis of its theoretical preconditions is needed
Transcatheter Repair in Posterior, Anterior, and Bileaflet Mitral Valve Disease: 1-Year Results From EXPANDed
No full textBackground: Treating anterior and bileaflet mitral valve disease in patients with primary or degenerative mitral regurgitation (DMR) is considered more challenging than posterior leaflet repair. Objectives: The aim of this analysis was to evaluate the impact of anterior, posterior, or bileaflet disease on outcomes following mitral transcatheter edge-to-edge repair (M-TEER) in the EXPANDed studies. Methods: EXPANDed is a pooled, patient-level analysis of subjects undergoing M-TEER with the MitraClip G3 or G4 system as part of the contemporary EXPAND and EXPAND G4 studies. Subjects with DMR were categorized according to echocardiography core laboratory–assessed prolapse or flail location into posterior (prolapse or flail at P1, P2, and/or P3), anterior (prolapse or flail at A1, A2, and/or A3) or bileaflet disease (prolapse or flail at any combination of A1, A2, and A3 and P1, P2, and P3). Key outcomes assessed included procedural outcomes, 30-day major adverse events, and 1-year mitral regurgitation (MR) severity. Results: Of 2,205 subjects in EXPANDed, 556 had echocardiography core laboratory–assessed DMR and prolapse or flail location. A total of 389 had posterior, 106 had anterior, and 61 had bileaflet disease. All groups experienced low device and procedure times with high procedural success rates (defined as discharge MR ≤2+). Thirty-day major adverse events rates were low across all groups (posterior, 4.4% [17 of 388]; anterior, 3.8% [4 of 105]; bileaflet, 6.6% [4 of 61]; P = 0.65). Through 1 year, all groups showed a significant reduction in MR severity from baseline (MR ≤1+ posterior, 82% [179 of 219]; anterior, 93% [53 of 57]; bileaflet, 97% [28 of 29]). Conclusions: Results from the EXPANDed studies demonstrate that subjects with DMR treated with M-TEER experienced significant improvements in outcomes, regardless of the location of prolapse or flail
2024 update in heart failure
No full textIn the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium-glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called 'high-intensity care' strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article.In the last years, major progress has occurred in heart failure (HF) management. The 2023 ESC focused update of the 2021 HF guidelines introduced new key recommendations based on the results of the last years of science. First, two drugs, sodium–glucose co-transporter-2 (SGLT2) inhibitors and finerenone, a novel nonsteroidal, selective mineralocorticoid receptor antagonist (MRA), are recommended for the prevention of HF in patients with diabetic chronic kidney disease (CKD). Second, SGLT2 inhibitors are now recommended for the treatment of HF across the entire left ventricular ejection fraction spectrum. The benefits of quadruple therapy in patients with HF with reduced ejection fraction (HFrEF) are well established. Its rapid and early up-titration along with a close follow-up with frequent clinical and laboratory re-assessment after an episode of acute HF (the so-called ‘high-intensity care’ strategy) was associated with better outcomes in the STRONG-HF trial. Patients experiencing an episode of worsening HF might require a fifth drug, vericiguat. In the STEP-HFpEF-DM and STEP-HFpEF trials, semaglutide 2.4 mg once weekly administered for 1 year decreased body weight and significantly improved quality of life and the 6 min walk distance in obese patients with HF with preserved ejection fraction (HFpEF) with or without a history of diabetes. Further data on safety and efficacy, including also hard endpoints, are needed to support the addition of acetazolamide or hydrochlorothiazide to a standard diuretic regimen in patients hospitalized due to acute HF. In the meantime, PUSH-AHF supported the use of natriuresis-guided diuretic therapy. Further options and most recent evidence for the treatment of HF, including specific drugs for cardiomyopathies (i.e., mavacamten in hypertrophic cardiomyopathy and tafamidis in transthyretin cardiac amyloidosis), device therapies, cardiac contractility modulation and percutaneous treatment of valvulopathies, with the recent finding from the TRILUMINATE Pivotal trial, are also reviewed in this article
Emergency colon cancer diagnosis in people with mental health conditions: a population-based cohort study in northern Italy
Full text linkBackground Individuals with mental health conditions may experience disparity in cancer diagnosis and health outcomes. This study aims to examine diagnostic pathways and mortality in patients with colon cancer with pre-existing mental health conditions. Methods A population-based cohort study on colon cancer cases diagnosed in 2014-2020 in the provinces of Milan and Lodi, using linked cancer registration and health data. We examined cancer diagnostic pathways (screening, emergency presentation (EP), inpatient/outpatient visits) and short-term mortality in patients with and without pre-existing mental health conditions, accounting for physical comorbidities and sociodemographic factors. Mental health conditions were systematically categorised into distinct groups according to the International Classification of Diseases, 10th Revision. Results Out of 11 429 patients with colon cancer, 16.2% had a pre-existing mental health condition. Individuals with mental health conditions versus those without had a higher risk of cancer diagnosis following EP: 43.8% versus 33.8%, adjusted OR (aOR) 1.32, 95% CI 1.19 to 1.47. EP risk was higher for patients with diagnoses of dementia and related cognitive conditions (aOR 1.69, 95% CI 1.41 to 2.03), substance use/ behavioural syndromes/personality-related conditions (aOR 1.92, 95% CI 1.34 to 2.75) and anxiety (aOR 1.44, 95% CI 1.16 to 1.79). The likelihood of screening-detected cancer was lower (4.6% vs 9.1%; aOR 0.78, 95% CI 0.60 to 0.99), especially for dementia and related cognitive conditions (aOR 0.27, 95% CI 0.08 to 0.86). Short-term mortality was higher in patients with cancer with mental health conditions than in those without. Conclusion Mental health conditions were associated with a lower likelihood of screening and a higher risk of emergency cancer diagnosis. Tailored strategies are warranted to enhance cancer diagnosis for the non-negligible group of individuals with mental health conditions
Neoadjuvant Immunotherapy in Cutaneous Squamous Cell Carcinoma: Systematic Literature Review and State of the Art
No full textBackground/Objectives: Cutaneous squamous cell carcinoma (cSCC) is a prevalent skin cancer with increasing incidence worldwide. High-risk cSCCs often require extensive surgical treatments, which can impair anatomical function and aesthetics. Neoadjuvant immunotherapy, particularly immune checkpoint inhibitors (ICIs) such as cemiplimab and pembrolizumab, has emerged as a promising approach to enhance tumor control and surgical outcomes. We performed a systematic review to evaluate the efficacy and safety of neoadjuvant immunotherapy in high-risk cSCC. Methods: A systematic review and proportional meta-analysis focusing on neoadjuvant immunotherapy for cSCC were conducted following PRISMA guidelines. MEDLINE and Scopus databases were searched up to September 2024 using predefined terms. Recorded findings were pathological/radiological response, 1-year disease-free survival (DFS), and overall survival (OS). Data extraction and risk-of-bias assessment were independently performed by two reviewers. Statistical analysis included fixed- and random-effects models, with heterogeneity assessed using Cochran’s Q statistic and the I2 index. Results: Nine studies met the inclusion criteria. The pooled pathologic response rate was 72.2% (95% CI: 57.7–84.6), and the radiological response rate was 54.8% (95% CI: 38.6–70.5), with moderate heterogeneity. Pooled 1-year DFS and OS proportions were 91.1% (95% CI: 85.0–95.3) and 90.6% (95% CI: 85.1–95.0), respectively, demonstrating homogeneity across studies. Adverse events were consistent with previously reported immune-related toxicities, with rare severe events. Conclusions: Neoadjuvant immunotherapy is a promising therapeutic strategy for high-risk cSCC, with high pathologic response rates and high survival outcomes. However, standardization of treatment protocols and further trials are needed to optimize efficacy, ensure safety, and assess long-term benefits
Utopie progressive e regressive
No full textUtopias can have a progressive or a regressive character, depending on their conception of freedom. Humanistic utopias as that of Thomas More have a progressive characte
