Beta-Blocker Use in Older Hospitalized Patients Affected by Heart Failure and Chronic Obstructive Pulmonary Disease: An Italian Survey From the REPOSI Register

Beta (β)-blockers (BB) are useful in reducing morbidity and mortality in patients with heart failure (HF) and concomitant chronic obstructive pulmonary disease (COPD). Nevertheless, the use of BBs could induce bronchoconstriction due to β2-blockade. For this reason, both the ESC and GOLD guidelines strongly suggest the use of selective β1-BB in patients with HF and COPD. However, low adherence to guidelines was observed in multiple clinical settings. The aim of the study was to investigate the BBs use in older patients affected by HF and COPD, recorded in the REPOSI register. Of 942 patients affected by HF, 47.1% were treated with BBs. The use of BBs was significantly lower in patients with HF and COPD than in patients affected by HF alone, both at admission and at discharge (admission, 36.9% vs. 51.3%; discharge, 38.0% vs. 51.7%). In addition, no further BB users were found at discharge. The probability to being treated with a BB was significantly lower in patients with HF also affected by COPD (adj. OR, 95% CI: 0.50, 0.37-0.67), while the diagnosis of COPD was not associated with the choice of selective β1-BB (adj. OR, 95% CI: 1.33, 0.76-2.34). Despite clear recommendations by clinical guidelines, a significant underuse of BBs was also observed after hospital discharge. In COPD affected patients, physicians unreasonably reject BBs use, rather than choosing a β1-BB. The expected improvement of the BB prescriptions after hospitalization was not observed. A multidisciplinary approach among hospital physicians, general practitioners, and pharmacologists should be carried out for better drug management and adherence to guideline recommendations

A general method for radiomic features selection - A SPECT simulation study

Introduction There are several radiological techniques, and, in this study, we focused the Single Photon Emission Computed Tomography (SPECT) imaging. It is possible to reconstruct the unknown tracer distribution inside the body by applying tomographic reconstruction algorithms such as Filtered Back Projection (FBP) and Ordered Subset Expectation Maximisation (OSEM) to the acquired data. Nowadays, thanks to technological innovations, a new branch of research has rapidly evolved: the radiomics. In practice, radiomics tries to assess whether the “textural features” of images in regions related to specific diseases could provide added value in a diagnostic process, in the evaluation of prognosis or could guide therapeutic choices. A general concern that has to be accounted for when performing a clinical study is whether changes in acquisition and reconstruction parameters could affect the value of the features. To the best of our knowledge, in literature, there is no unique method for identifying robust features; here, a generalised method to study the effects of the variation of reconstruction parameters on radiomic features is proposed and applied to asses stability and reliability in SPECT imaging. Materials and methods Only simulation studies could asses the link between features extracted from reconstructed images and their original values. From a preliminary statistical analysis, it emerged that at least 66 phantoms (representing different original textures) were needed to achieve a statistical power higher than 90%. These synthetic phantoms derived from abdominal CT scans and “Visible Human Project” image sets. Then, using a proper model, we simulated SPECT acquisitions of each phantom and reconstructed the corresponding images changing parameters in FBP and OSEM tomographic algorithms. Features extraction was conducted with PyRadiomics, an open-source software. Six feature classes were considered, based on Intensity, Grey-Level Co-occurrence Matrix (GLCM), Grey Level Dependence Matrix (GLDM), Grey Level Run Length Matrix (GLRLM), Grey Level Size Zone Matrix (GLSZM) and Neighbourhood Grey-Tone Difference Matrix (NGTDM). Ultimately, 93 different radiomics features for each phantom were calculated. In this way, data-set has a series of repeated measurements and the method of Generalised Estimating Equations (GEE) is suitable for analysing databases with a similar structure. In this study, two different GEE models were developed: one to analyse if the radiomic features calculated in the reconstructed images (Vr) reproduce the same feature in the original VOI (Vo); another to study if they are stable or not with reconstruction parameters variations. Results 32 different reconstructions for each available phantom were obtained, for a total of 2112 images stacks. The results of the two GEE models, features could be classified according to four possible groups: a) feature with a correlation between Vo and Vr, without reconstruction parameters variation effect; b) features without a correlation between Vo and Vr and without a significant impact of the reconstruction parameters variation; c) features with a statistically significant correlation between Vo and Vr and with the effect of the reconstruction parameters variation on the Vr value; d) reconstruction parameters variation affects Vr. Moreover, there is not a correlation between the values obtained from the reconstructed images and Vo. Discussion In literature, as far as we know, there are no trustworthy works of the reproducibility or repeatability applied to SPECT imaging. Here, with software simulations, we tried to answer the following two questions: 1) Are the features extracted from the reconstructed images (Vr) correlated to those of the original images (Vo)? 2) Are the features extracted from the reconstructed images robust when the reconstruction parameters vary? To answer these questions, two GEE models were developed. Most features showed a correlation between Vo and Vr, but with a relevant impact of reconstruction parameters variation. For clinical studies, in our opinion, features like a) would be the optimal choice. However, also features like c) could be used, but researchers have to handle with care these features for which the reconstruction parameters variations affect Vr. Using the remaining features is not recommended as the lack of correlation between Vo and Vr makes random any link with clinical end-points, so it could be difficult to reproduce any result on cohorts of patients other than the one used to develop the radiomic model. Conclusions From this study, it emerges how reconstruction parameters could affect radiomic features in SPECT imaging. In our opinion, researchers should take into account this dependency in both retrospective and prospective radiomic studies. Ultimately, the method described in this work, although complicated, represents a logical approach to carry out propaedeutic evaluations about the selection of imaging parameters or radiomic features to be used for clinical studies

Bone structure texture analysis as a potential tool to estimate radiation induced insufficiency fracture risk.

the possible role of bone structure TA(texuture analysis as a potential tool to estimate radiation induced insufficiency fracture risk, but further prospective studies on a large population are needed to best estimate the actual preliminary data

Texture analysis of parotid gland as a predictive factor of radiation induced xerostomia: A subset analysis.

CT image biomarkers (IBMs) seem to be very interesting in evaluation of radiation response to treatment [4,5] and deserve proper investigations with further prospective studies and validated with external data sets

Prognostic Value of MR Imaging Texture Analysis in Brain Non-Small Cell Lung Cancer Oligo-Metastases Undergoing Stereotactic Irradiation.

BACKGROUND : Stereotactic irradiation is widely used in brain oligo-metastases treatment. The aim of this study is to evaluate the prognostic value of magnetic resonance imaging (MRI) texture analysis (TA) of brain metastases (BM) of non-small cell lung cancer (NSCLC). MATERIALS AND METHODS : This study included thirty-eight consecutive patients undergoing stereotactic irradiation, that is, stereotactic fractionated radiotherapy (SRT) or radiosurgery (SRS), from January 2011 to December 2014 for 1-2 brain BM from NSCLC. Whole-brain radiotherapy (WBRT) was not delivered. The diagnostic MRI DICOM (Digital Imaging and Communications in Medicine) images were collected and analyzed with a homemade ImageJ macro, and typical TA parameters (mean, standard deviation, skewness, kurtosis, entropy, and uniformity) were evaluated for: brain progression-free survival; modality of brain metastatic progression (local progression or/and new metastases); and overall survival, after SRT/SRS. RESULTS: After SRT/SRS 14 patients (36.8%) experienced recurrence in the brain, with a recurrence in the irradiated site (five patients, 13.2%), new metastases (11 patients, 28.9%), local recurrence and new metastases (two patients, 5.25%). Nineteen patients (50%) died of tumor progression or other causes. Entropy and uniformity were significantly associated with local progression, whereas kurtosis was significantly associated with both local progression and new brain metastases. CONCLUSIONS : These results appear promising, since the knowledge of factors correlated with the modality of brain progression after stereotactic irradiation of brain oligo-metastatic foci of NSCLC might help in driving the best treatment in these patients (association of SRT/SRS with WBRT? Increase of SRT/SRS dose?). Our preliminary data needs confirmation in large patient series

Water/cortical bone decomposition: A new approach in dual energy CT imaging for bone marrow oedema detection. A feasibility study

Introduction Many studies aimed at validating the application of Dual Energy Computed Tomography (DECT) in clinical practice where conventional CT is not exhaustive. An example is given by bone marrow oedema detection, in which DECT based on water/calcium (W/Ca) decomposition was applied. In this paper a new DECT approach, based on water/cortical bone (W/CB) decomposition, was investigated. Materials and methods Eight patients suffering from marrow oedema were scanned with MRI and DECT. Two-materials density decomposition was performed in ROIs corresponding to normal bone marrow and oedema. These regions were drawn on DECT images using MRI informations. Both W/Ca and W/CB were considered as material basis. Scatter plots of W/Ca and W/CB concentrations were made for each ROI in order to evaluate if oedema could be distinguished from normal bone marrow. Thresholds were defined on the scatter plots in order to produce DECT images where oedema regions were highlighted through color maps. The agreement between these images and MR was scored by two expert radiologists. Results For all the patients, the best scores were obtained using W/CB density decomposition. Conclusions In all cases, DECT color map images based on W/CB decomposition showed better agreement with MR in bone marrow oedema identification with respect to W/Ca decomposition. This result encourages further studies in order to evaluate if DECT based on W/CB decomposition could be an alternative technique to MR, which would be important when short scanning duration is relevant, as in the case of aged or traumatic patients

Bone texture analysis using CT-simulation scans to individuate risk parameters for radiation-induced insufficiency fractures

This study deals with the role of texture analysis as a predictive factor of radiation-induced insufficiency fractures in patients undergoing pelvic radiation. Introduction: This study aims to assess the texture analysis (TA) of computed tomography (CT) simulation scans as a predictive factor of insufficiency fractures (IFs) in patients with pelvic malignancies undergoing radiation therapy (RT). Methods: We performed an analysis of patients undergoing pelvic RT from January 2010 to December 2014, 24 of whom had developed pelvic bone IFs. We analyzed CT-simulation images using ImageJ macro software and selected two regions of interest (ROIs), which are L5 body and the femoral head. TA parameters included mean (m), standard deviation (SD), skewness (sk), kurtosis (k), entropy (e), and uniformity (u). The IFs patients were compared (1:2 ratio) with controlled patients who had not developed IFs and matched for sex, age, menopausal status, type of tumor, use of chemotherapy, and RT dose. A reliability test of intra- and inter-reader ROI TA reproducibility with the intra-class correlation coefficient (ICC) was performed. Univariate and multivariate analyses (logistic regression) were applied for TA parameters observed both in the IFs and the controlled groups. Results: Inter- and intra-reader ROI TA was highly reproducible (ICC > 0.90). Significant TA parameters on paired t test included L5 m (p = 0.001), SD (p = 0.002), k (p = 0.006), e (p = 0.004), and u (p = 0.015) and femoral head m (p < 0.001) and SD (p = 0.001), whereas on logistic regression analysis, L5 e (p = 0.003) and u (p = 0.010) and femoral head m (p = 0.027), SD (p = 0.015), and sex (p = 0.044). Conclusions: In our experience, bone CT TA could be correlated to the risk of radiation-induced IFs. Studies on a large patient series and methodological refinements are warranted

Bone texture analysis using CT-simulation scans to individuate risk parameters for radiation-induced insufficiency fractures.

This study deals with the role of texture analysis as a predictive factor of radiation-induced insufficiency fractures in patients undergoing pelvic radiation. Introduction: This study aims to assess the texture analysis (TA) of computed tomography (CT) simulation scans as a predictive factor of insufficiency fractures (IFs) in patients with pelvic malignancies undergoing radiation therapy (RT). Methods: We performed an analysis of patients undergoing pelvic RT from January 2010 to December 2014, 24 of whom had developed pelvic bone IFs. We analyzed CT-simulation images using ImageJ macro software and selected two regions of interest (ROIs), which are L5 body and the femoral head. TA parameters included mean (m), standard deviation (SD), skewness (sk), kurtosis (k), entropy (e), and uniformity (u). The IFs patients were compared (1:2 ratio) with controlled patients who had not developed IFs and matched for sex, age, menopausal status, type of tumor, use of chemotherapy, and RT dose. A reliability test of intra- and inter-reader ROI TA reproducibility with the intra-class correlation coefficient (ICC) was performed. Univariate and multivariate analyses (logistic regression) were applied for TA parameters observed both in the IFs and the controlled groups. Results: Inter- and intra-reader ROI TA was highly reproducible (ICC > 0.90). Significant TA parameters on paired t test included L5 m (p = 0.001), SD (p = 0.002), k (p = 0.006), e (p = 0.004), and u (p = 0.015) and femoral head m (p < 0.001) and SD (p = 0.001), whereas on logistic regression analysis, L5 e (p = 0.003) and u (p = 0.010) and femoral head m (p = 0.027), SD (p = 0.015), and sex (p = 0.044). Conclusions: In our experience, bone CT TA could be correlated to the risk of radiation-induced IFs. Studies on a large patient series and methodological refinements are warranted

Therapeutic afucosylated monoclonal antibody and bispecific T-cell engagers for T-cell acute lymphoblastic leukemia

Background T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive disease with a poor cure rate for relapsed/resistant patients. Due to the lack of T-cell restricted targetable antigens, effective immune-therapeutics are not presently available and the treatment of chemo-refractory T-ALL is still an unmet clinical need. To develop novel immune-therapy for T-ALL, we generated an afucosylated monoclonal antibody (mAb) (ahuUMG1) and two different bispecific T-cell engagers (BTCEs) against UMG1, a unique CD43-epitope highly and selectively expressed by T-ALL cells from pediatric and adult patients. Methods UMG1 expression was assessed by immunohistochemistry (IHC) on a wide panel of normal tissue microarrays (TMAs), and by flow cytometry on healthy peripheral blood/bone marrow-derived cells, on 10 different T-ALL cell lines, and on 110 T-ALL primary patient-derived cells. CD43-UMG1 binding site was defined through a peptide microarray scanning. ahuUMG1 was generated by Genetic Glyco-Engineering technology from a novel humanized mAb directed against UMG1 (huUMG1). BTCEs were generated as IgG1-(scFv)(2) constructs with bivalent (2+2) or monovalent (2+1) CD3 epsilon arms. Antibody dependent cellular cytotoxicity (ADCC), antibody dependent cellular phagocytosis (ADCP) and redirected T-cell cytotoxicity assays were analysed by flow cytometry. In vivo antitumor activity of ahUMG1 and UMG1-BTCEs was investigated in NSG mice against subcutaneous and orthotopic xenografts of human T-ALL. Results Among 110 T-ALL patient-derived samples, 53 (48.1%) stained positive (24% of TI/TII, 82% of TIII and 42.8% of TIV). Importantly, no expression of UMG1-epitope was found in normal tissues/cells, excluding cortical thymocytes and a minority (&lt;5%) of peripheral blood T lymphocytes. ahUMG1 induced strong ADCC and ADCP on T-ALL cells in vitro, which translated in antitumor activity in vivo and significantly extended survival of treated mice. Both UMG1-BTCEs demonstrated highly effective killing activity against T-ALL cells in vitro. We demonstrated that this effect was specifically exerted by engaged activated T cells. Moreover, UMG1-BTCEs effectively antagonized tumor growth at concentrations &gt;2 log lower as compared with ahuUMG1, with significant mice survival advantage in different T-ALL models in vivo. Conclusion Altogether our findings, including the safe UMG1-epitope expression profile, provide a framework for the clinical development of these innovative immune-therapeutics for this still orphan disease