Hereditary Thoracic Aortic Diseases

Advances in both imaging techniques and genetics have led to the recognition of a wide variety of aortic anomalies that can be grouped under the term 'hereditary thoracic aortic diseases'. The present review aims to summarize this very heterogeneous population's clinical, genetic, and imaging characteristics and to discuss the implications of the diagnosis for clinical counselling (on sports activity or pregnancy), medical therapies and surgical management

Prognostic and Predictive Role of Neutrophil to lymphocyte Ratio in Second Line Immunotherapy of Non-small Cell Lung Cancer

n/

Quartiere di quartieri

Peer Reviewe

Overcoming Underpowering in the Outcome Analysis of Repaired—Tetralogy of Fallot: A Multicenter Database from the CMR/CT Working Group of the Italian Pediatric Cardiology Society (SICPed)

Background: Managing repaired tetralogy of Fallot (TOF) patients is still challenging despite the fact that published studies identified prognostic clinical or imaging data with rather good negative predictive accuracy but weak positive predictive accuracy. Heterogeneity of the initial anatomy, the surgical approach, and the complexity of the mechanism leading to dilation and ventricular dysfunction explain the challenge of predicting the adverse event in this population. Therefore, risk stratification and management of this population remain poorly standardized. Design: The CMR/CT WG of the Italian Pediatric Cardiology Society set up a multicenter observational clinical database of repaired TOF evaluations. This registry will enroll patients retrospectively and prospectively assessed by CMR for clinical indication in many congenital heart diseases (CHD) Italian centers. Data collection in a dedicated platform will include surgical history, clinical data, imaging data, and adverse cardiac events at 6 years of follow-up. Summary: The multicenter repaired TOF clinical database will collect data on patients evaluated by CMR in many CHD centers in Italy. The registry has been set up to allow future research studies in this population to improve clinical/surgical management and risk stratification of this population

Safety of extended interval dosing immune checkpoint inhibitors:a multicenter cohort study

BACKGROUND: Real-life spectrum and survival implications of immune-related adverse events (irAEs) in patients treated with extended interval dosing (ED) immune checkpoint inhibitors (ICIs) are unknown. METHODS: Characteristics of 812 consecutive solid cancer patients who received at least 1 cycle of ED monotherapy (pembrolizumab 400 mg Q6W or nivolumab 480 mg Q4W) after switching from canonical interval dosing (CD; pembrolizumab 200 mg Q3W or nivolumab 240 mg Q2W) or treated upfront with ED were retrieved. The primary objective was to compare irAEs patterns within the same population (before and after switch to ED). irAEs spectrum in patients treated upfront with ED and association between irAEs and overall survival were also described. RESULTS: A total of 550 (68%) patients started ICIs with CD and switched to ED. During CD, 225 (41%) patients developed any grade and 17 (3%) G3 or G4 irAEs; after switching to ED, any grade and G3 or G4 irAEs were experienced by 155 (36%) and 20 (5%) patients. Switching to ED was associated with a lower probability of any grade irAEs (adjusted odds ratio [aOR] = 0.83, 95% confidence interval [CI] = 0.64 to 0.99; P = .047), whereas no difference for G3 or G4 events was noted (aOR = 1.55, 95% CI = 0.81 to 2.94; P = .18). Among patients who started upfront with ED (n = 232, 32%), 107 (41%) developed any grade and 14 (5%) G3 or G4 irAEs during ED. Patients with irAEs during ED had improved overall survival (adjusted hazard ratio [aHR] = 0.53, 95% CI = 0.34 to 0.82; P = .004 after switching; aHR = 0.57, 95% CI = 0.35 to 0.93; P = .025 upfront). CONCLUSIONS: Switching ICI treatment from CD and ED did not increase the incidence of irAEs and represents a safe option also outside clinical trials.</p

APOLLO 11 Project, Consortium in Advanced Lung Cancer Patients Treated With Innovative Therapies: Integration of Real-World Data and Translational Research

Introduction: Despite several therapeutic efforts, lung cancer remains a highly lethal disease. Novel therapeutic approaches encompass immune-checkpoint inhibitors, targeted therapeutics and antibody-drug conjugates, with different results. Several studies have been aimed at identifying biomarkers able to predict benefit from these therapies and create a prediction model of response, despite this there is a lack of information to help clinicians in the choice of therapy for lung cancer patients with advanced disease. This is primarily due to the complexity of lung cancer biology, where a single or few biomarkers are not sufficient to provide enough predictive capability to explain biologic differences; other reasons include the paucity of data collected by single studies performed in heterogeneous unmatched cohorts and the methodology of analysis. In fact, classical statistical methods are unable to analyze and integrate the magnitude of information from multiple biological and clinical sources (eg, genomics, transcriptomics, and radiomics). Methods and objectives: APOLLO11 is an Italian multicentre, observational study involving patients with a diagnosis of advanced lung cancer (NSCLC and SCLC) treated with innovative therapies. Retrospective and prospective collection of multiomic data, such as tissue- (eg, for genomic, transcriptomic analysis) and blood-based biologic material (eg, ctDNA, PBMC), in addition to clinical and radiological data (eg, for radiomic analysis) will be collected. The overall aim of the project is to build a consortium integrating different datasets and a virtual biobank from participating Italian lung cancer centers. To face with the large amount of data provided, AI and ML techniques will be applied will be applied to manage this large dataset in an effort to build an R-Model, integrating retrospective and prospective population-based data. The ultimate goal is to create a tool able to help physicians and patients to make treatment decisions. Conclusion: APOLLO11 aims to propose a breakthrough approach in lung cancer research, replacing the old, monocentric viewpoint towards a multicomprehensive, multiomic, multicenter model. Multicenter cancer datasets incorporating common virtual biobank and new methodologic approaches including artificial intelligence, machine learning up to deep learning is the road to the future in oncology launched by this project

Combined action potential- and dynamic-clamp for accurate computational modelling of the cardiac IKr current

In the present work Action-Potential clamp (APC) and Dynamic clamp (DC) were used in combination in order to optimize the Luo-Rudy (LRd) mathematical formulation of the guinea-pig rapid delayed rectifier K(+) current (IKr), and to validate the optimized model. To this end, IKr model parameters were adjusted to fit the experimental E4031-sensitive current (IE4031) recorded under APC in guinea-pig myocytes. Currents generated by LRd model (ILRd) and the optimized one (IOpt) were then compared by testing their suitability to replace IE4031 under DC. Under APC, ILRd was significantly larger than IE4031 (mean current densities 0.51±0.01 vs 0.21±0.05pA/pF; p<0.001), mainly because of different rectification. IOpt mean density (0.17±0.01pA/pF) was similar to the IE4031 one (NS); moreover, IOpt accurately reproduced IE4031 distribution along the different AP phases. Models were then compared under DC by blocking native IKr (5μM E4031) and replacing it with ILRd or IOpt. Whereas injection of ILRd overshortened AP duration (APD90) (by 25% of its pre-block value), IOpt injection restored AP morphology and duration to overlap pre-block values. This study highlights the power of APC and DC for the identification of reliable formulations of ionic current models. An optimized model of IKr has been obtained which fully reversed E4031 effects on the AP. The model strongly diverged from the widely used Luo-Rudy formulation; this can be particularly relevant to the in silico analysis of AP prolongation caused by IKr blocking or alterations

Spectrometric performances of high quantum efficiency multi and single anode PMTs coupled to LaBr3(Ce) crystal

High quantum efficiency semiconductor photodetectors have recently drawn the attention of the scientific community for their potential in the realization of a new class of scintillation imagers with very high energy and spatial resolution performance. However, this goal does not seem within easy reach, due to various technological issues such as, for example, the difficulty to scale the characteristics of a single detector to an imager with suitable dimensions. Lately a definite technical improvement in increasing quantum efficiency up to 42% for position sensitive photomultipliers was achieved. The aim of this work is thus to test this new technological progress and to study the possible implications in imaging applications. Four Hamamatsu PMTs were tested: two multi anode photomultipliers, one with a bialkali (27% quantum efficiency) and the other one with a super-bialkali photocathode (38% quantum efficiency), and two 1 x 1 in. PMTs, both equipped with an ultra bialkali photocathode (42% quantum efficiency). In particular one of the ultra bialkali PMT has also an increased efficiency of first dynode charge collection. The results were compared with the ones obtained with a reference PMT (Hamamatsu R6231), mainly used in spectroscopy. The PMTs were coupled to LaBr3(Ce), NaI(Tl) and LSO(Ce) continuous scintillation crystals. The tests were done using two independent electronic chains: one dedicated for spectroscopic application and a second one, using a multi wire 64 channel readout, for imaging applications. The super-bialkali MA-PMTs have shown high energy resolution, both with spectroscopic and imaging setup, highlighting the appropriateness of these devices for the development of imaging devices with high spectroscopic performance. (C) 2013 Elsevier B.V. All rights reserved

Reliability of high quantum efficiency MA-PMT for spectrometric quality assurance of scintillation imagers

The outstanding semiconductor photodetectors with high quantum efficiency have interested the scientific community for their potential of assembling a new class of scintillation imagers with very high energy and spatial resolution performances at low cost. Recently we assisted also to a strong technological advance in Photo Multiplier Tube (PMT) by increasing of photocathode Quantum Efficiency (QE) up to 42% peak value. From a pragmatic point of view the aim of this work is to test if this technology is ready for imaging applications and mainly focused on the investigation of energy resolution and pulse height linearity performances. Two Multi Anode PMTs (MA-PMT) were tested: a standard Hamamatsu 88500 and a new modified one, equipped with SuperBiAlkali (SBA) photocathode, with enhanced QE. The PMTs were coupled to a LaBr3(Ce) continuous crystal dedicated for imaging application. The MA-PMT responses were tested utilizing two electronic chains: one dedicated for spectroscopy, where the 64 PMT outputs were reduced to only one signal, and a second one, utilizing 64 channels readout for imaging. These MA-PMTs have shown very good linearity response, up to 1 MeV photon energy, and high performances in term of energy resolution, demonstrating that this technology is particularly indicated to develop imaging devices with enhanced spectroscopic response