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Several statistical methods are nowadays available for the analysis of gene expression data recorded through microarray technology. In this article, we take a closer look at several Gaussian mixture models which have recently been proposed to model gene expression data. It can be shown that these are special cases of a more general model, called the mixture of structural equation models (mixture of SEMs), which has been developed in psychometrics. This model combines mixture modelling and SEMs by assuming that component-specific means and variances are subject to a SEM. The connection with SEM is useful for at least two reasons: (1) it shows the basic assumptions of existing methods more explicitly and (2) it helps in straightforward development of alternative mixture models for gene expression data with alternative mean/covariance structures. Different specifications of mixture of SEMs for clustering gene expression data are illustrated using two benchmark datasets. [ABSTRACT FROM AUTHOR]

In the last few years, model-based clustering techniques have become widely used in the context of microarray data analysis. In this empirical context, a potential purpose for statistical approaches is the identification of clusters of genes that are co-expressed under subsets of experimental conditions. We discuss a hierarchical mixture model to combine advantages of allowing for dependence within gene clusters and for simultaneous clustering of genes and experimental conditions. Thanks to the adopted hierarchical structure, we may distinguish gene clusters from mixture components, where the latter may represent intra-cluster gene-specific extra-Gaussian departures. To cluster experimental conditions, instead, we suggest a suitable parameterization of component-specific means by using a binary row stochastic matrix representing condition membership. The performance of the proposed approach is discussed on both simulated and real datasets. [ABSTRACT FROM AUTHOR]

In healthy aging research, typically multiple health outcomes are measured, representing health status. The aim of this paper was to develop a model-based clustering approach to identify homogeneous sibling pairs according to their health status. Model-based clustering approaches will be considered on the basis of linear mixed effect model for the mixture components. Class memberships of siblings within pairs are allowed to be correlated, and within a class the correlation between siblings is modeled using random sibling pair effects. We propose an expectation-maximization algorithm for maximum likelihood estimation. Model performance is evaluated via simulations in terms of estimating the correct parameters, degree of agreement, and the ability to detect the correct number of clusters. The performance of our model is compared with the performance of standard model-based clustering approaches. The methods are used to classify sibling pairs from the Leiden Longevity Study according to their health status. Our results suggest that homogeneous healthy sibling pairs are associated with a longer life span. Software is available for fitting the new models. Copyright © 2011 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Objective: This study, derived from the phase 3 SAFE trial (ClinicalTrials.gov identifier: NCT2236806), explores subclinical cardiac damage in breast cancer patients receiving anthracycline-based chemotherapy and left-sided breast radiation therapy (RT)., Materials and Methods: Eligible patients were randomized to a cardioprotective pharmacological therapy (bisoprolol, ramipril, or both) or placebo, with cardiac surveillance at multiple time-point using standard and 3-dimensional echocardiography. Dosimetric parameters were analysed, including mean heart dose (MHD) and various metrics for heart substructures, employing advanced contouring techniques and auto-contouring software., Results: In the analysis of left-sided breast RT patients, the study encompassed 39 out of 46 irradiated individuals, focusing on GLS and 3D-LVEF outcomes with ≥ 10% worsening, defined as subclinical heart damage. Distinct RT schedules were used, with placebo exhibiting the highest ≥ 10% worsening (36.4%). In terms of treatment arms, bisoprolol exhibited 11.1% worsening, while ramipril 16.7% and bisoprolol + ramipril 25%. For patients with no subclinical damage, the mean MHD was 1.5 Gy; for patients with subclinical heart damage, the mean MHD was 1.6 Gy (p = 0.94). Dosimetric parameters related to heart and heart substructures (left anterior descending artery, right and left atrium, right and left ventricle) showed no statistically significant differences between patients with and without subclinical damage., Conclusion: Our results emphasize the crucial role of cardioprotective measures in mitigating adverse effects, highlighting RT as having negligible influence on cardiac performance. An extended follow-up assessment of the whole series is warranted to determine whether a subclinical effect could significantly influence clinical outcomes and cardiac events., Competing Interests: Declarations. Conflict of interest: Icro Meattini declares occasional small fees received for advisory boards supported by Eli Lilly, Novartis, Astra Zeneca, Daiichi Sankyo, Gilead, SeaGen, Pfizer, and Menarini StemLine. Roberto Pellegrini is an employee of Elekta AB (Stockholm, Sweden). Isacco Desideri, Jacopo Nori, and Lorenzo Livi are editors in this journal. Ethical approval: This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of University of Florence. Consent to participate: Informed consent was obtained from all individual participants included in the study. Consent to publish: The authors affirm that human research participants provided informed consent for publication., (© 2024. Italian Society of Medical Radiology.)

Background: Data published in 2015 showed that patients with early breast cancer (EBC) and a low-risk (LR) Recurrence Score® (RS) result by the 21-gene Oncotype DX® assay ("the test") did not derive benefit from adding chemotherapy (CT) to endocrine therapy (HT), while those with a high-risk (HR) RS result did. However, the role of CT remained uncertain in patients with intermediate-risk (IR) cancers. We designed a study to assess the test's ability to categorize patients with EBC with uncertain biological behavior into the groups (LR and HR) for which the value of additional chemotherapy was defined., Methods: The POST trial was a multicenter, prospective cohort study conducted in 14 Breast Centers of the Tuscany region of Italy. Consecutive patients with pT1-2 pN0-N1mi hormone receptor-positive/HER2-negative EBC and uncertain biological behavior based on standard parameters were enrolled. Patients were categorized based on RS results into LR, IR, and HR groups if RS result was < 11, 11-25, and > 25, respectively. Treatment recommendations by multidisciplinary meeting assessed before and after RS results were available., Results: Of 246 tested samples, 78 were classified as LR or HR, with most of the patients (65.4 %) being at IR. Following test results, the recommendation changed in 15.9 % of cases. Among patients initially recommended for CT or for discussion about the role of CT, respectively 64.3 % and 75.9 % ultimately received recommendation for HT alone., Conclusions: Our study suggests that RS results can refine treatment decisions for patients with EBC exhibiting uncertain biological behavior initially recommended or considered for CT. (250/250)., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Networks consist of interconnected units, known as nodes, and allow to formally describe interactions within a system. Specifically, bipartite networks depict relationships between two distinct sets of nodes, designated as sending and receiving nodes. An integral aspect of bipartite network analysis often involves identifying clusters of nodes with similar behaviors. The computational complexity of models for large bipartite networks poses a challenge. To mitigate this challenge, we employ a Mixture of Latent Trait Analyzers (MLTA) for node clustering. Our approach extends the MLTA to include covariates and introduces a double EM algorithm for estimation. Applying our method to COVID-19 data, with sending nodes representing patients and receiving nodes representing preventive measures, enables dimensionality reduction and the identification of meaningful groups. We present simulation results demonstrating the accuracy of the proposed method.

Ovarian cancer (OC) is the most lethal of all gynecological cancers. Due to vague symptoms, OC is mostly detected at advanced stages, with a 5-year survival rate (SR) of only 30%; diagnosis at stage I increases the 5-year SR to 90%, suggesting that early diagnosis is essential to cure OC. Currently, the clinical need for an early, reliable diagnostic test for OC screening remains unmet; indeed, screening is not even recommended for healthy women with no familial history of OC for fear of post-screening adverse events. Salivary diagnostics is considered a major resource for diagnostics of the future. In this work, we searched for OC biomarkers (BMs) by comparing saliva samples of patients with various stages of OC, breast cancer (BC) patients, and healthy subjects using an unbiased, high-throughput proteomics approach. We analyzed the results using both logistic regression (LR) and machine learning (ML) for pattern analysis and variable selection to highlight molecular signatures for OC and BC diagnosis and possibly re-classification. Here, we show that saliva is an informative test fluid for an unbiased proteomic search of candidate BMs for identifying OC patients. Although we were not able to fully exploit the potential of ML methods due to the small sample size of our study, LR and ML provided patterns of candidate BMs that are now available for further validation analysis in the relevant population and for biochemical identification.

Background and Purpose: Data on immunoresponse after SARS-CoV-2 vaccines for patients treated with exclusive radiotherapy (RT) are scarce. Since RT may affect the immune system, we conducted the MORA trial (Antibody response and cell-mediated immunity of MOderna mRNA-1273 vaccine in patients treated with RAdiotherapy)., Materials and Methods: Data regarding humoral and cellular immune response of patients treated with RT were prospectively collected after the second and third dose of mRNA vaccines., Results: Ninety-two patients were enrolled. With a median of 147 days after the second dose, the median SARS-CoV-2 IgG titer was 300 BAU/mL: six patients were seronegative (Spike IgG titer ≤ 40 BAU/mL), whereas 24, 46 and 16 were poor responders (Spike IgG titer:41-200 BAU/mL), responders (Spike IgG titer:201-800 BAU/mL) and ultraresponders (Spike IgG titer > 800 BAU/mL), respectively. Among seronegative patients, two patients were negative also for cell mediated response, as tested with IFN-γ release Assay (IGRA) test. With a median of 85 days after the third dose, the median SARS-CoV-2 IgG titer was 1632 BAU/mL in 81 patients: only two patients were seronegative, whereas 16 and 63 patients were responders and ultraresponders, respectively. Among the 2 persistently seronegative patients, IGRA test was negative in one who had previously received anti-CD20 therapy. Documented paucisymptomatic (n = 3) or asymptomatic (n = 4) infection occurred after the third dose, during the Omicron wave., Conclusion: In patients treated with exclusive RT, even during the Omicron breakthrough, robust humoral response and clinical protection from severe SARS-CoV-2 disease were achievable with three doses of mRNA vaccine., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The structural collapse of a street lighting pole represents an aspect that is often underestimated and unpredictable, but of relevant importance for the safety of people and things. These events are complex to evaluate since several sources of damage are involved. In addition, traditional inspection methods are ineffective, do not correctly quantify the residual life of poles, and are inefficient, requiring enormous costs associated with the vastness of elements to be investigated. An advantageous alternative is to adopt a distributed type of Structural Health Monitoring (SHM) technique based on the Internet of Things (IoT). This paper proposes the design of a low-cost system, which is also easy to integrate in current infrastructures, for monitoring the structural behavior of street lighting poles in Smart Cities. At the same time, this device collects previous structural information and offers some secondary functionalities related to its application, such as meteorological information. Furthermore, this paper intends to lay the foundations for the development of a method that is able to avoid the collapse of the poles. Specifically, the implementation phase is described in the aspects concerning low-cost devices and sensors for data acquisition and transmission and the strategies of information technologies (ITs), such as Cloud/Edge approaches, for storing, processing and presenting the achieved measurements. Finally, an experimental evaluation of the metrological performance of the sensing features of this system is reported. The main results highlight that the employment of low-cost equipment and open-source software has a double implication. On one hand, they entail advantages such as limited costs and flexibility to accommodate the specific necessities of the interested user. On the other hand, the used sensors require an indispensable metrological evaluation of their performance due to encountered issues relating to calibration, reliability and uncertainty.

Opinion Statement: Prophylaxis and treatment of thrombosis in leukemic patients still represent a major challenge with several clinical questions yet to be solved. Indeed, the paucity of evidence makes the management of venous thromboembolic events difficult and not uniform. Due to thrombocytopenia, patients with acute myeloid leukemia (AML) are underrepresented in trials investigating prophylaxis and treatment of thrombosis in cancer, and prospective data are lacking. Likewise, the therapeutic approach with anti-coagulants in leukemic patients is inferred from guidelines originally developed in the solid cancer setting and clear recommendations in the thrombocytopenic population are limited. Importantly, the discrimination of patients at high risk of bleeding from those with a predominant risk of thrombosis remains extremely difficult with no predictive score validated so far. Thus, the management of thrombosis often relies on clinician experience, and it is tailored to the individual patient, constantly balancing thrombotic and hemorrhagic risks. Who would benefit from primary prophylaxis and how a thrombotic event should be appropriately treated are some of the unanswered questions that the future guidelines and trials should address. Moreover, a greater effort should be made to identify robust predictive factors able to guide clinicians in the management of this potential serious complication for AML patients., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity., Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients., Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value., Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70.

Background: International and national oncology societies had released recommendations in favor of COVID-19 vaccination in cancer patients. In the context of the national vaccination campaign targeting the so called extremely vulnerable, we aimed to assess the safety and efficacy of the mRNA vaccines in a cohort of 623 patients., Methods: Between March 26 and April 04, 2021, the Pfizer and BioNTech BNT162b2 mRNA and the Moderna mRNA-1273 vaccines were given as a two-dose prime-boost regimen. Starting on September 25th 2021 a third dose was offered to patients in whom a suboptimal immunogenicity with COVID-19 vaccination could be expected. Safety assessments were performed by phone call 7 days after each dose. Electronic health records were accessed to review demographic information, disease history, treatment detail, and outcome events of participants patients'., Findings: No toxicities were reported in 63.7%, 54%, and in 48.7% patients with cancer after each dose. Mild-to-moderate pain at the injection site was the most commonly adverse event. After the second dose, 46% of the 610 patients reported toxicity, with more systemic side-effects observed. Fever was reported in 45% of patients, with a temperature ≥ 38 °C in 21.4% of them. Of the 335 patients receiving a third vaccine dose, 51% reported toxicity, with 13% of patients reporting more than one effect. Logistic regression analysis reported mixed results, with limited variables or categories reporting a significant odd ratio. The type of vaccine reported a significant value at first dose (OR = 0.12; CI 0.52, 0.26; p = 0.00). Thirty-four cases of COVID-19 infection were reported with only one patient requiring a short-term hospitalization for monitoring., Interpretation: The safety profile of the mRNA vaccines does not raise any specific concerns and support prioritization of vaccination for cancer patients., Competing Interests: Conflict of interest statement The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2022. Published by Elsevier Ltd.)

The frequency of thrombosis in AML has been evaluated only in a few studies and no validated predictive model is currently available. Recently, DIC score was shown to identify patients at higher thrombotic risk. We aimed to evaluate the frequency of thromboembolism in AML patients treated with intensive chemotherapy and to assess the ability of genetic and clinical factors to predict the thrombotic risk. We performed a retrospective observational study including 222 newly diagnosed adult AML (210) and high-risk MDS (12), treated with intensive chemotherapy between January 2013 and February 2020. With a median follow-up of 44 months, we observed 50 thrombotic events (90% were venous, VTE). The prevalence of thrombosis was 22.1% and the 6-months cumulative incidence of thrombosis was 10%. The median time to thrombosis was 84 days and 52% of the events occurred within 100 days from AML diagnosis. Khorana and DIC score failed to stratify patients according to their thrombotic risk. Only history of a thrombotic event (p = 0.043), particularly VTE (p = 0.0053), platelet count above 100 × 10 9 /L at diagnosis (p = 0.036) and active smoking (p = 0.025) significantly and independently increased the risk of thrombosis, the latter particularly of arterial events. AML genetic profile did not affect thrombosis occurrence. Results were confirmed considering only thromboses occurring within day 100 from diagnosis. DIC score at diagnosis, but not thrombosis, was independently associated with reduced survival (p = 0.004). Previous VTE, platelet count above 100 × 10 9 /L and active smoking were the only factors associate with increased thrombotic risk in AML patients treated intensively, but further studies are needed to validate these results., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

In the field of Smart Cities, especially for Smart Street Lighting and Smart Mobility, the use of low-cost devices is considered an advantageous solution due to their easy availability, cost reduction and, consequently, technological and methodological development. However, this type of transducers shows many critical issues, e.g., in metrological and reliability terms, which can significantly compromise their functionality and safety. Such issue has a large relevance when temperature and humidity are cause of a rapid aging of sensors. The aim of this work is to evaluate the effects of accelerated aging in extreme climatic conditions on the performance of a control system, based on a low-cost ultrasonic distance sensor, for public-lighting management in Smart Cities. The presented architecture allows for the detection of vehicles, pedestrians and small animals and contains a dedicated algorithm, developed in an Edge/Cloud environment, that is able to display the acquired measurements to users connected on the web. The obtained results highlight that the effect of accelerated aging is to significantly reduce the linearity of the calibration curve of the sensor and, moreover, to exponentially increase the number of outliers and invalid measurements. These limitations can be overcome by developing an appropriate self-calibration strategy.

Background: In the last years immunotherapy has revolutionized the treatment of non-small cell lung cancer (NSCLC) not supported by a driver mutation. Immunotherapy related adverse events (irAEs) have a unique toxicity profiles distinct from the toxicities of classical chemotherapy treatment relating to their mechanism of action. We analyzed some serious and uncommon life-threatening irAEs, needing a change in the therapeutic strategy., Method: Between October 2018 and October 2020, 63 NSCLC patients underwent immunotherapy. Thirty-eight patients underwent first-line Pembrolizumab, 200 mg every 21 days (Group A). Twenty patients were treated in second line with Pembrolizumab 200 mg every 21 days or Nivolumab 240 mg every 14 days or Atezolizumab 800 mg every 14 days (Group B). Five stage III patients treated after radio chemotherapy with Durvalumab 1500 mg every 14 days (Group C)., Results: We experienced: a) 2 bowel perforations (3.2%), necessitating Hartmann's resection. Only one of the two patients restored immunotherapy; b) 1 chronic renal insufficiency (1.6%, creatinine up to 8 mg/dL) and 2 severe hypertransaminasemias (3.2%, up to 65 U/L), requiring the immediate and definitive interruption of ICIs; c) 2 pericardial effusions (3.2%), of which one needed subxiphoid pericardiocentesis for cardiac tamponade. Patient restored immunotherapy after resolution of the acute event., Conclusions: Immunotherapy include monoclonal antibodies reducing the suppression of effector T cells and improving the tumor-specific immune responses. Most common irAEs are evident in mild and reversible form, but sometimes life-threatening irEAs show up. Therefore, further clinical trials needed to increase knowledge of drugs and prevent unexpected irAEs.

Importance: Several studies have evaluated cardioprotective strategies to prevent myocardial dysfunction in patients who are receiving cardiotoxic therapies. However, the optimal approach still represents a controversial issue., Objective: To determine whether pharmacological cardioprevention could reduce subclinical heart damage in patients with breast cancer who are being treated with anthracycline-based chemotherapy., Design, Setting, and Participants: The SAFE trial was a 4-arm, randomized, phase 3, double-blind, placebo-controlled, national multicentric study conducted at 8 oncology departments in Italy. It was a prespecified interim analysis on the first 174 patients who had completed cardiac assessment at 12 months. The study recruitment was conducted between July 2015 and June 2020. The interim analysis was performed in 2020. Patients were eligible for trial inclusion if they had indication to receive primary or postoperative systemic therapy using an anthracycline-based regimen. Patients with a prior diagnosis of cardiovascular disease were excluded., Interventions: Cardioprotective therapy (bisoprolol, ramipril, or both drugs compared with placebo) was administered for 1 year from the initiation of chemotherapy or until the end of trastuzumab therapy in case of ERBB2-positive patients. Doses for all groups were systematically up-titrated up to the daily target dose of bisoprolol (5 mg, once daily), ramipril (5 mg, once daily), and placebo, if tolerated., Main Outcomes and Measures: The primary end point was defined as detection of any subclinical impairment (worsening ≥10%) in myocardial function and deformation measured with standard and 3-dimensional (3D) echocardiography, left ventricular ejection fraction (LVEF), and global longitudinal strain (GLS)., Results: The analysis was performed on 174 women (median age, 48 years; range, 24-75 years) who had completed a cardiological assessment at 12 months and reached the end of treatment. At 12 months, 3D-LVEF worsened by 4.4% in placebo arm and 3.0%, 1.9%, 1.3% in the ramipril, bisoprolol, ramipril plus bisoprolol arms, respectively (P = .01). Global longitudinal strain worsened by 6.0% in placebo arm and 1.5% and 0.6% in the ramipril and bisoprolol arms, respectively, whereas it was unchanged (0.1% improvement) in the ramipril plus bisoprolol arm (P < .001). The number of patients showing a reduction of 10% or greater in 3D-LVEF was 8 (19%) in the placebo arm, 5 (11.5%) in the ramipril arm, 5 (11.4%) in the bisoprolol, arm and 3 (6.8%) in the ramipril plus bisoprolol arm; 15 patients (35.7%) who received placebo showed a 10% or greater worsening of GLS compared with 7 (15.9; ramipril), 6 (13.6%; bisoprolol), and 6 (13.6%; ramipril plus bisoprolol) (P = .03)., Conclusions and Relevance: The interim analysis of this randomized clinical trials suggested that cardioprotective pharmacological strategies in patients who were affected by breast cancer and were receiving an anthracycline-based chemotherapy are well tolerated and seem to protect against cancer therapy-related LVEF decline and heart remodeling., Trial Registration: ClinicalTrials.gov identifier: NCT2236806.

Competing Interests: We declare no competing interests. We thank Piero Paolini (Head of Operative Emergency Service, Azienda USL Toscana Centro) and Simone Magazzini (Head of Emergency and Critical Care, Azienda USL Toscana Centro) for their collaboration. We also thank all the volunteers who participated in the reference group. SS also thanks Matteo Giopp, Teo Giopp, and Bernardo Giopp. We did not receive any funding for this work.

Background: Adjuvant hormone treatment of postmenopausal breast cancer is mainly based on aromatase inhibitors. Adverse events associated with such class of drugs are particularly severe in elderly patients. Therefore, we investigated the possibility of ab initio predict which elderly patients could encounter toxicity., Methods: In light of national and international oncological guidelines recommending the use of screening tests for multidimensional geriatric assessment in elderly patients aged ≥70 years and eligible for active cancer treatment, we assessed whether the Vulnerable Elder Survey (VES)-13 and the Geriatric (G)-8 could be predictors of toxicity associated with aromatase inhibitors. Seventy-seven consecutive patients aged ≥70 diagnosed with non-metastatic hormone-responsive breast cancer and therefore eligible for adjuvant hormone therapy with aromatase inhibitors, were screened with the VES-13 and the G-8, and underwent a six-monthly clinical and instrumental follow-up in our medical oncology unit, from September 2016 to March 2019 (30 months). Said patients were identified as vulnerable (VES-13 score ≥3 or G-8 score ≤14) and fit (VES-13 score <3 or G-8 score >14). The likelihood of experiencing toxicity is greater among vulnerable patients., Results: The correlation between the VES-13 or the G-8 tools and the presence of adverse events is equal to 85.7% (p = 0.03). The VES-13 demonstrated 76.9% sensitivity, 90.2% specificity, 80.0% positive predictive value, 88.5% negative predictive value. The G-8 demonstrated 79.2% sensitivity, 88.7% specificity, 76% positive predictive value, 90.4% negative predictive value., Conclusion: The VES-13 and the G-8 tools could be valuable predictors of the onset of toxicity associated with aromatase inhibitors in the adjuvant treatment of breast cancer in elderly patients aged ≥70., Competing Interests: None

Viscosupplementation by hyaluronic acid (HA) is recommended for non-surgical management of knee osteoarthritis (OA). This study investigated the efficacy and safety of a single i.a. (32 mg/4 ml) Hymovis MO.RE. injection, a new HA derivative hydrogel, for the treatment of adult regular sports players affected by knee OA arising from overuse injuries. Patients were prospectively enrolled if regularly practicing sports and diagnosed with Kellgren-Lawrence grade I-III OA. They received a single Hymovis MO.RE. intra-articular (i.a.) injection and were evaluated 30, 90, 180, and 360 days thereafter. The assessment involved measuring changes in knee function, pain, the activity of daily living (ADL), and quality of life (QOL) by using the Knee injury and Osteoarthritis Outcome Score (KOOS), GAIT analysis, the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) scores for knee pain (WOMAC A) and function (WOMAC C), and a visual analogue scale (VAS) pain score. The study involved thirty-one patients, 23 women and eight men, whose median age was 49. KOOS function subscore, as well as GAIT cadence and velocity, showed a statistically significant increase at each time-point after injection ( p < 0.0001). WOMAC, KOOS pain, symptoms, ADL, and QOL scores also significantly improved at all control visits. No severe adverse events or treatment-related events were detected. A single Hymovis MO.RE. (32 mg/4 ml) intra-articular injection provides a rapid, lasting, and safe response in regular sports players affected by knee OA, possibly representing a viable therapeutic option for this demanding patient subgroup. Further investigations are necessary to confirm these findings., Competing Interests: NG is an employee of Fidia Farmaceutici SpA. (Abano Terme, PD, Italy). However, Fidia Farmaceutici SpA did not participate in the decision to submit this manuscript for publication. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Bernetti, Agostini, Alviti, Giordan, Martella, Santilli, Paoloni and Mangone.)

Olaparib is the first poly(ADP-ribose) polymerase inhibitor approved as maintenance therapy of recurrent ovarian cancer (OC) patients with a BRCA mutation. To achieve the maximum clinical benefit, adherence to olaparib must be persistent. However, in clinical practice, this is challenged by the frequent suboptimal management of toxicities. In view of the expanding use of olaparib also in Italy, physicians must learn how to adequately and promptly manage drug toxicities not to unnecessarily interrupt or reduce the dose. The experts agreed that nausea,vomiting, anemia, and fatigue are the most frequent events experienced by OC patients on olaparib, and that these toxicities usually develop early during treatment, are mainly of grade 1-2 and transient and can be managed with simple non-pharmacological interventions. By sharing their real-world experiences, the panel prepared, for each toxicity, an algorithm organized by grade and besides the procedures indicated in the local label, included supportive care interventions based also on nutritional and lifestyle modifications and psycho-oncology consultation. Moreover, in view of the tablet entry into the Italian market, the full and reduced dosages of capsules and tablets were compared. This practical guidance is intended to be a tool to support especially less-experienced physicians in the management of these complex patients, with the aim to help preventing the worsening of patients' conditions and the unnecessary interruption/reduction of olaparib dosage, which may jeopardize treatment efficacy.