IRIS UniSR (’Università Vita-Salute San Raffaele)
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The prognostic value of the Dandel's index in patients undergoing tricuspid transcatheter edge-to-edge repair
No full textAims: Conventional parameters of right ventricular (RV) function are load-dependent and therefore do not accurately reflect contractility in patients with relevant tricuspid regurgitation (TR). RV adaptability to load has been characterized using the Dandel's index in patients with heart failure, but its prognostic value in patients undergoing tricuspid transcatheter edge-to-edge repair (T-TEER) has not been investigated so far. Methods and results: From the EuroTR registry (2019 to 2022), patients with complete datasets and a minimum of 2-years of follow-up were included. RV functional parameters (i.e. tricuspid annular plane systolic excursion [TAPSE], fractional area change [FAC], TAPSE/systolic pulmonary arterial pressure [sPAP]), as well as a echocardiographic RV load adaptation index (Dandel's index) were assessed and their predictive value in terms of all-cause mortality evaluated using logistic multivariate logistic regression. The majority of the 364 patients had secondary TR (96%) and were severely symptomatic (New York Heart Association class ≥III; 92%). At 2-year follow-up, 36% of patients had died. Functional RV parameters (TAPSE: hazard ratio [HR] 0.72, 95% confidence interval [CI] 0.62–0.84; FAC: HR 0.73, 95% CI 0.59–0.91), coupling index (TAPSE/sPAP: HR 0.8, 95% CI 0.65–0.99) and Dandel's index (HR 0.67, 95% CI 0.53–0.85) were all associated with mortality at 2 years in univariable analyses. In a multivariate logistic regression model, the Dandel's index maintained its predictive value (p < 0.001), along with TAPSE and absence of signs of right heart failure, with an optimal threshold of 20.5 determined by the receiver-operating characteristic analysis. This threshold also successfully predicted cardiac hospital readmission. A multivariate analysis was conducted to identify parameters linked to RV function and predicting clinical outcomes. Conclusion: Assessment of the RV capacity to adjust for changes in loading conditions predicted mortality in patients with severe symptomatic TR undergoing T-TEER. The use of a multiparametric approach including the Dandel's index to assess RV function had an incremental value for the stratification of patients into subgroups with different prognosis
Delayed cerebral infarction in poor grade subarachnoid hemorrhage. Features, predictors, and clinical impact
No full textObjectives: To investigate predictors and clinical impact of delayed cerebral infarction (CI) in a national multicentric poor grade aneurysmal subarachnoid hemorrhage (aSAH) population. Methods: Retrospective analysis of prospectively collected data from the multi-centric POGASH (Poor Grade aSAH) registry of consecutive patients treated from January 1st, 2015, to June 30th, 2023. Poor grade was defined according to the worst-pretreatment WFNS scale. CI was defined as a new ischemic lesion/s within 6 weeks of aSAH onset, not present on CT acquired within 48hrs and not related to treatment or hematoma. Clinical outcome was assessed by the modified Rankin Scale. Results: Among 532 consecutive WFNS grades IV-V aSAH patients, CI occurred in 106 (19.9%). CI (adjusted OR 0.59 0.35-0.98; p 0.045) independently predicted increased disability. Volume of SAH (aOR 1.02, 95% C.I. 1.00-1.04; p 0.015), anterior communicating aneurysm, ACoA, (aOR 6.2, 95% C.I. 1.4-27.3; p 0.015) and need of angiographic treatment (aOR 2.2, 95% C.I. 1.3-3.8; p 0.002) resulted independently predictive of CI occurrence. CI volume emerged as the strongest predictor of increased disability (aOR 1.03 95% C.I. 1.01-1.05; p < .001) and mortality (aOR 1.009 95% CI 1.002-1.02; P 0.018) in the CI affected population. Conclusions: ACoA, SAH volume and need for DSA treatment predicted CI, whose detrimental role on outcome is mainly driven by its volumetric extension. CI volume resulted independently predictive of mortality and increased disability in early brain injury survivors
Congenital aniridia: European COST action ANIRIDIA-NET guidelines for diagnosis, management and care
No full textCongenital aniridia is a rare ocular disorder affecting the majority of eye structures and can be associated with systemic manifestations. The main visible phenotypic characteristic is the partial or complete absence of the iris; however, foveal hypoplasia is a more frequent and reliable clinical sign. Other ocular comorbidities are associated with the disease, such as cataract, keratopathy and optic nerve hypoplasia. Mutation in the PAX6 gene is the most common cause of congenital aniridia, but other causative mutations exist. The main ocular symptoms experienced by those with congenital aniridia are photophobia, glare, low visual acuity, dryness/irritation of the ocular surface and nystagmus. Management and follow-up of patients with congenital aniridia can be challenging due to the lack of effective therapeutic options and the complexity of ocular manifestations and outcomes. These guidelines for the diagnosis, management and care of congenital aniridia have been developed at the European level, thanks to ANIRIDIA-NET, based on a review of the scientific literature on clinical and molecular characterization, therapeutic options as well as non-medical approaches
Comprehensive one-day management of prostate cancer patients: PRO-FAST single-fraction ablative, urethral-sparing, HDR-like, robotic SBRT
No full textBackground: Radiotherapy (RT) is a standard curative treatment for prostate cancer (PCa) and there is growing evidence of the high efficacy of moderate and ultra-hypofractionated RT. Reducing treatment duration to one week or less is a major advance, but very few studies have explored single-fraction therapy. This study evaluates the feasibility, safety, and efficacy of single-fraction stereotactic body RT (SBRT) while delivering the entire procedure in one day, with a potentially high benefit in terms of patient comfort and therapy cost and logistics. Methods: This prospective, non-randomized monocentric trial uses Robotic Radiosurgery (CyberKnife v.7 system) to deliver a single 24 Gy fraction to the prostate (± seminal vesicles) with a "urethral sparing HDR-like" technique, and target tracking. The first phase will enroll 13 PCa patients following Simon's optimal design. Treatment is to be stopped if ≥ 2 patients develop ≥ G3 toxicity (CTCAE v5.0) within a month from RT end; otherwise, 52 more patients will be added, totaling 65. To account for minimal drop-out, 5 extra patients will be enrolled, reaching 70. All procedures are performed in a single day, including fiducial implantation, imaging acquisition, contouring, planning, dosimetry quality control, and treatment. Apart from treatment feasibility in terms of one-month acute toxicity, secondary endpoints include late toxicity, biochemical and clinical control. Discussion: Few others have investigated the 24 Gy single-fraction schedule using different delivery modalities (not including tracking), which has proved to be non-inferior to 5 fraction SBRT. Our approach aims to maintain (and possibly improve) the previously reported acute, subacute and late toxicity as well as disease control, adding evidence in favor of single-fraction delivery. Another significant goal of the study is the demonstration that all the complex treatment procedures can be safely delivered in a single day. This would be especially appealing for patients far from radiotherapy centers and those with work commitments not allowing daily hospital visits. The study of response to RT can also provide useful information about PCa radiobiology. Planned additional analyses may help in better assessing the clinical value of PSMA PET/CT in the selection of high-risk patients with true limited disease, and in identifying radiomic features associated to outcome. Trial registration: The study was prospectively registered at clinicaltrials.gov (NCT05936736)
Linking signaling dynamics and cell fate decisions through single-cell imaging: evidence and challenges
No full textAge-dependent response to initial highly effective treatment in relapsing multiple sclerosis
No full textObjectives: To assess the impact of age on the superiority of highly effective (HE) disease-modifying treatments (DMTs) compared to platform DMTs in a real-world population of relapsing MS patients (pwMS). Methods: A total of 20,984 pwMS were extracted from the Italian Multiple Sclerosis Register with a diagnosis of Clinically Isolated Syndrome or Relapsing-Remitting MS, at least four Expanded Disability Status Scale (EDSS) evaluations and 2 years follow-up, starting DMT. The baseline was the nearest visit to the first DMT starting date. The risk of first 24-week confirmed disability accumulation (CDA) on EDSS in HE versus platform DMTs after 2 years and the entire follow-up was assessed through Cox regression models. Results: After 1:1 propensity score matching, we evaluated 1698 pwMS initiating HE-DMTs and 1698 initiating platforms. After 2 years follow-up, the proportion of CDA events was lower in patients on HE-DMTs (12.2%) than those on platform DMTs (15%), as confirmed by Cox regression analysis (hazard ratio (HR) = 0.22, 95% confidence interval (CI) = 0.10-0.47; p < 0.001). HE-DMTs were more effective in patients under 45 years of age (HR = 0.49, 95% CI = 0.39-0.63; p < 0.001), but not in patients over 45 (HR = 0.77, 95% CI = 0.54-1.08, p = 0.125). Notably, prolonged exposure to any DMT during follow-up reduced disability accumulation even in patients over 45 (HR = 0.13, 95% CI = 0.02-0.99; p = 0.050). Conclusion: This real-world study of relapsing pwMS demonstrates that the benefit of initial HE treatment diminishes with age. However, even in older patients, DMT exposure, regardless of the efficacy level, appears to reduce disability accumulation, and so, on an individual level, initial HE treatment could still be more effective
L’inferno (non) sono gli altri. Sartre e l’etica dell’impegno
No full textIn questo saggio si analizza come l’espressione “l’inferno sono gli altri” venga spesso fraintesa come sintomo di un pessimismo esistenziale. In realtà, per Sartre è il punto di partenza per un’etica dell’impegno che mette in luce la responsabilità verso l’altro e la necessità di riconoscere la sua singolarità. Attraverso una lucida critica al manicheismo, Sartre sottolinea che l’identificazione del male nell’Altro deriva da un’oggettivazione etico-politica, radicata in una logica di oppressione e disumanizzazione. Si propone così un umanesimo anti-umanista (ossia, anti-borghese), fondato sul riconoscimento autentico della libertà e della sua irriducibile unicità
Lymphomas: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up
No full textThis ESMO CPG provides key recommendations and algorithms for managing DLBCL, FL, HL, MCL, MZL, PCNSL and PTCL. •It covers epidemiology, diagnosis, staging, risk assessment, treatment of primary and refractory disease and follow-up. •Treatment algorithms for each lymphoma type are provided. •The author group encompasses a multidisciplinary group of experts from different institutions and countries in Europe. •Recommendations are based on available scientific data and the authors’ collective expert opinion. © 2025 European Society for Medical Oncology
Transcatheter Approaches to Atrial Functional Mitral Regurgitation: How Far Have We Come?
Get PDFFunctional mitral regurgitation (MR) is associated with increased cardiovascular morbidity and mortality and over the past decade, the diagnosis of atrial functional mitral regurgitation (aFMR) has been increasingly observed in the elderly, especially in those with atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF). Annular enlargement, perturbations of annular contraction, and atriogenic leaflet tethering distinguish the pathophysiology of aFMR from the one of ventricular origin. However, no consensus provides recommendations regarding the differential diagnosis and the subsequent management of aFMR. The advent of transcatheter mitral valve repair has paved the way for various treatments including edge-to-edge repair (TEER), mitral annuloplasty, and replacement, with optimistic results on short-medium-term outcome provided by preliminary studies. In parallel, rhythm control of AF for paroxysmal and persistent types, should be pursued to induce reverse remodeling and restoring the normal leaflet coaptation. In this setting, catheter ablation aiming for electrical isolation of the pulmonary veins is the most widely recognized and effective strategy for maintaining sinus rhythm. Nevertheless, arrhythmia-free survival is lower in patients with persistent and long-term persistent AF, leading to the adoption of hybrid strategies combining transcatheter endocardial ablation and thoracoscopic epicardial surgical ablation. This review provides an update on the diagnosis and treatment of aFMR, focusing on available transcatheter approaches that can be performed in the catheterization lab and electrophysiology lab
Organ perfusion pressure predicts outcomes in cardiogenic shock patients
No full textAims: The diagnosis of cardiogenic shock (CS) relies upon signs and/or symptoms of end-organ hypoperfusion. The combination of hypoperfusion and systemic congestion identifies patients at particularly high risk. This study evaluated organ perfusion pressure (OPP), calculated as mean arterial pressure minus invasive central venous pressure, as a predictor of outcomes in CS. Methods and results: All consecutive patients with acute myocardial infarction-related CS (AMI-CS) or acutely decompensated heart failure-related CS (ADHF-CS) enrolled in the multicentre Altshock-2 registry between January 2020 and November 2023 were included. The primary outcome was in-hospital all-cause mortality. Overall, 316 patients were included (mean age: 64 ± 13 years, 62 [20%] female, median left ventricular ejection fraction: 22% [interquartile range, IQR 15–30%], 261 [85.9%] SCAI stage C or worse, median OPP at presentation: 57.0 mmHg [IQR 47.0–69.8 mmHg]). A total of 117 (37%) patients died during the hospitalization. Low OPP (i.e. <57.0 mmHg) was associated with significantly higher in-hospital all-cause mortality (hazard ratio [HR] 1.757, 95% confidence interval [CI] 1.208–2.556, p = 0.003), whereas low mean arterial pressure alone was not (HR 1.323, 95% CI 0.901–1.941, p = 0.153). After multivariable adjustment for significant clinical data available at first bedside assessment (age and Sequential Organ Failure Assessment score), low OPP still predicted significantly higher in-hospital all-cause mortality (HR per mmHg decrease: 1.016, 95% CI 1.004–1.029, p = 0.010). Low OPP appeared particularly powerful in predicting higher in-hospital all-cause mortality among ADHF-CS patients (HR 3.172, p = 0.002). Conclusion: In this multicentre, observational, prospective study on patients hospitalized for CS, lower OPP on admission was associated with significantly higher in-hospital all-cause mortality