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Concetta Cafiero,1,* Agnese Re,2,* Alessandra Micera,3,* Raffaele Palmirotta,4 Delio Monaco,5 Francesca Romano,6 Claudia Fabrizio,7 Raffaele Di Francia,8 Andrea Cacciamani,3 Pier Luigi Surico,9 Gerardo D’Amato,10 Salvatore Pisconti1 1Medical Oncology, SG Moscati Hospital, Taranto, Italy; 2CNR-IASI, Catholic University of Sacred Heart, Rome, Italy; 3Research Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, Rome, Italy; 4Department of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, Bari, Italy; 5Radiology, SG Moscati Hospital, Taranto, Italy; 6Department of Precision Medicine, Luigi Vanvitelli University of Campania, Napoli, Italy; 7Infectious Disease Unit, SG Moscati Hospital, Taranto, Italy; 8Italian Association of Pharmacogenomics and Molecular Diagnostics, Ancona, Italy; 9Oncology and Hematology Department, F Miulli Hospital, Acquaviva delle Fonti, Italy; 10Endocrine and Metabolic Surgery, A Gemelli Polyclinic Foundation, Rome, Italy*These authors contributed equally to this workCorrespondence: Alessandra MiceraResearch Laboratories in Ophthalmology, IRCCS — Fondazione Bietti, 6 via di Santo Stefano Rotondo, Rome 00184, ItalyTel +39-06-4554-1191Email alessandra.micera@fondazionebietti.itRaffaele PalmirottaDepartment of Biomedical Sciences and Clinical Oncology, Oncogenomic Research Center, Aldo Moro University of Bari, ItalyEmail raffaelepalmirotta@gmail.comAbstract: The latest developments in precision medicine allow the modulation of therapeutic approaches in different pathologies on the basis of the specific molecular characterization of the patient. This review of the literature coupled with in silico analysis was to provide a selected screening of interactions between single-nucleotide polymorphisms (SNPs) and drugs (repurposed, investigational, and biological agents) showing efficacy and toxicityin counteracting Covid-19 infection. In silico analysis of genetic variants related to each drug was performed on such databases as PharmGKB, Ensembl Genome Browser, www.drugs.com, and SNPedia, with an extensive literature review of papers (to May 10, 2020) on Covid-19 treatments using Medline, Embase, International Pharmaceutical Abstracts, PharmGKB, and Google Scholar. The clinical relevance of SNPs, known as both drug targets and markers, considering genetic variations with known drug responses, and the therapeutic consequences are discussed. In the context of clinical treatment of Covid-19, including infection prevention, control measures, and supportive care, this review highlights the importance of a personalized approach in the final selection of therapy, which is probably essential in the management of the Covid-19 pandemic.Keywords: Covid-19, SARS-CoV2, drug effects, pharmacogenomics, pharmacogenetics, in silico, ADR

Barbara Bortot, 1 Maurizio Mongiat, 2 Erica Valencic, 3 Simeone Dal Monego, 4 Danilo Licastro, 4 Matteo Crosera, 5 Gianpiero Adami, 5 Enrico Rampazzo, 6 Giuseppe Ricci, 7, 8 Federico Romano, 7 Giovanni Maria Severini, 1 Stefania Biffi 7 1Department of Medical Genetics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 2Department of Research and Diagnosis, Division of Molecular Oncology, Centro Di Riferimento Oncologico Di Aviano (CRO) IRCCS, Aviano, Italy; 3Department of Pediatrics, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 4ARGO Open Lab Platform for Genome Sequencing, AREA Science Park, Trieste, Italy; 5Department of Chemical and Pharmaceutical Sciences, University of Trieste, Trieste, Italy; 6Department of Chemistry “G. Ciamician”, University of Bologna, Bologna, Italy; 7Department of Obstetrics and Gynecology, Institute for Maternal and Child Health, IRCCS Burlo Garofolo, Trieste, Italy; 8Department of Medicine, Surgery and Health Sciences, University of Trieste, Trieste, ItalyCorrespondence: Stefania Biffi Email stefania.biffi@burlo.trieste.itBackground: Platinum resistance is a major challenge in the management of ovarian cancer. Even low levels of acquired resistance at the cellular level lead to impaired response to cisplatin. In ovarian cancer intraperitoneal therapy, nanoparticle formulation can improve the cisplatin’s pharmacokinetics and safety profile.Purpose: This work aimed to investigate the chemo-sensitivity of ovarian cancer SKOV3 cells upon short-term (72h) single treatment of cisplatin and cisplatin-loaded biodegradable nanoparticles (Cis-NP). The aim was then to determine the therapeutic properties of Cis-NP in vivo using a SKOV3-luc cells’ xenograft model in mice.Methods: Cell cytotoxicity was assessed after the exposure of the cell culture to cisplatin or Cis-NP. The effect of treatments on EMT and CSC-like phenotype was studied by analyzing a panel of markers by flow cytometry. Intracellular platinum concentration was determined by inductively coupled plasma mass spectrometry (ICS-MS), and gene expression was evaluated by RNAseq analysis. The efficacy of intraperitoneal chemotherapy was evaluated in a SKOV3-luc cells’ xenograft model in mice, through a combination of bioluminescence imaging, histological, and immunohistochemical analyses.Results: We observed in vitro that short-term treatment of cisplatin has a critical role in determining the potential induction of chemoresistance, and a nanotechnology-based drug delivery system can modulate it. The RNAseq actg 3nalysis underlines a protective effect of nanoparticle system according to their ability to down-regulate several genes involved in chemoresistance, cell proliferation, and apoptosis. The highest intracellular platinum concentration obtained with Cis-NP treatment significantly improved the efficacy. Consistent with in vitro results, we found that Cis-NP treatment in vivo can significantly reduce tumor burden and aggressiveness compared to the free drug.Conclusion: Nanoparticle-mediated cisplatin delivery may serve as an intracellular depot impacting the cisplatin pharmacodynamic performance at cellular levels. These features may contribute to improving the drawbacks of conventional intraperitoneal therapy, and therefore will require further investigations in vivo.Keywords: cisplatin resistance, ovarian cancer, SKOV3, nanoparticle, epithelial-mesenchymal transition, Ca125, apoptosis

Capture and total cross section measurements for 94,95,96Mo have been performed at the neutron time-of-flight facilities, n_TOF at CERN and GELINA at JRC-Geel. The measurements were performed using isotopically enriched samples with an enrichment above 95% for each of the 94,95,96Mo isotopes. The capture measurements were performed at n_TOF using C6D6 detectors and a new sTED detector. The transmission measurements were performed at a 10 m station of GELINA using a 6Li glass neutron detector. Preliminary results of these measurements are presented.

The neutron time-of-flight facility n_TOF is characterised by its high instantaneous neutron intensity, high-resolution and broad neutron energy spectra, specially conceived for neutron-induced reaction cross section measurements. Two Time-Of-Flight (TOF) experimental areas are available at the facility: experimental area 1 (EAR1), located at the end of the 185 m horizontal flight path from the spallation target, and experimental area 2 (EAR2), placed at 20 m from the target in the vertical direction. The neutron fluence in EAR2 is ˜ 300 times more intense than in EAR1 in the relevant time-of-flight window. EAR2 was designed to carry out challenging cross-section measurements with low mass samples (approximately 1 mg), reactions with small cross-sections or/and highly radioactive samples. The high instantaneous fluence of EAR2 results in high counting rates that challenge the existing capture systems. Therefore, the sTED detector has been designed to mitigate these effects. In 2021, a dedicated campaign was done validating the performance of the detector up to at least 300 keV neutron energy. After this campaign, the detector has been used to perform various capture cross section measurements at n_TOF EAR2.

The NEAR Station is a new experimental area developed at the n_TOF Facility at CERN. The activation station of NEAR underwent a characterization of the beam following the installation of the new n_TOF Spallation Target. The commissioning of the neutron beam comprises a set of simulations made with the FLUKA code and experimental verification. The experimental determination of the neutron spectrum was made using activation techniques with three separate set-ups. Two set-ups were based on the Multi-foil Activation technique (MAM-1 and MAM-2), and the third set-up relied on the process of neutron moderation and activation of a single material (ANTILoPE). The three set-ups are presented. Also the present plans and future perspectives of the activation station of NEAR are discussed.

The n_TOF facility hosts CERN’s pulsed neutron source, comprising two beam lines of different flight paths and one activation station. It is based on a proton beam delivered by the PS accelerator impinging on a lead spallation target. During Long Shutdown 2 (LS2) at CERN (2019-2021), a major upgrade of the spallation target was carried out in order to optimize the performances of the neutron beam. Therefore, the characteristics of n_TOF two experimental areas were investigated in detail. In this work, the focus is on the second experimental area (EAR2), located 20 m above the spallation target. Preliminary results of the neutron energy distribution and beam line energy resolution are presented, compared to previous experimental campaigns and Monte Carlo simulations with the FLUKA code. Moreover, preliminary results of the spatial beam profile measurements are shown.

Several international agencies recommend the study of new routes and new facilities for producing radioisotopes with application to nuclear medicine. 177Lu is a versatile radioisotope used for therapy and diagnosis (theranostics) of cancer with good success in neuroendocrine tumours that is being studied to be applied to a wider range of tumours. 177Lu is produced in few nuclear reactors mainly by the neutron capture on 176Lu. However, it could be produced at high-intensity celeratorbased neutron facilities. The energy of the neutrons in accelerator-based neutron facilities is higher than in thermal reactors.Thus, experimental data on the 176Yb(n,γ) cross-section in the eV and keV region are mandatory to calculate accurately the production of 177Yb, which beta decays to 177Lu. At present, there are not experimental data available from thermal to 3 keV of the 176Yb(n,γ) cross-section. In addition, there is no data in the resolved resonance region (RRR). This contribution shows the first results of the 176Yb capture measurement performed at the n_TOF facility at CERN.

Silvia Coretti,1 Federica Romano,1 Valentina Orlando,2 Paola Codella,1 Sabrina Prete,1 Eugenio Di Brino,1 Matteo Ruggeri1 1Post-Graduate School of Economics and Management (ALTEMS), Università Cattolica del Sacro Cuore, Rome, Italy; 2Center of Pharmacoeconomics (CIRFF), Department of Pharmacy, Federico II University, Naples, Italy Background: Hepatitis C is a liver infection caused by hepatitis C virus. Its main complications are cirrhosis and liver cancer. According to the World Health Organization (WHO), more than 185 million people worldwide are infected with hepatitis C virus and, of these, 350,000 die every year. Due to the high disease prevalence and the existence of effective (and expensive) medical treatments able to dramatically change the prognosis, early detection programs can potentially prevent the development of serious chronic conditions, improve health, and save resources. Objective: To summarize the available evidence on the cost-effectiveness of screening programs for hepatitis C. Methods: A literature search was performed on PubMed and Scopus search engines. Trip database was queried to identify reports produced by the major Health Technology Assessment (HTA) agencies. Three reviewers dealt with study selection and data extraction blindly. Results: Ten papers eventually met the inclusion criteria. In studies focusing on asymptomatic cohorts of individuals at general risk the cost/quality adjusted life year of screening programs ranged between US $4,200 and $50,000/quality adjusted life year gained, while in those focusing on specific risk factors the incremental cost-effectiveness ratio ranged between $848 and $128,424/quality adjusted life year gained. Age of the target population and disease prevalence were the main cost-effectiveness drivers. Conclusion: Our results suggest that, especially in the long run, screening programs represent a cost-effective strategy for the management of hepatitis C. Keywords: hepatitis C, screening, early detection, cost-effectiveness

S Bordonaro,1 F Romano,1 E Lanteri,1 F Cappuccio,1 R Indorato,2 A Butera,2 A D’Angelo,3 F Ferraù,3 P Tralongo11Medical Oncology Unit, Umberto I Hospital, Rete Assistenza Oncologica, Siracusa, 2Medical Oncology Unit, S Giovanni di Dio Hospital, Agrigento, 3Medical Oncology Unit, S Vincenzo Hospital, Taormina, ItalyIntroduction: The advent of oral chemotherapy agents has had a strong impact on several aspects of the management of cancer patients, including survival rates, health-care expenditure, and health-related quality of life. However, access to care and adherence to oral chemotherapy are central to optimal outcomes.Patients and methods: In this multicenter observational study, we assessed the effect of the “Active Home Care” initiative – a structured, active, home-based cancer-treatment program – on quality of life, health-care utilization, and patient adherence and satisfaction using self-administered questionnaires. Sixty-two patients treated with oral chemotherapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate) were enrolled in the program. Weekly home visits were scheduled, each one with a trained nurse who delivered the home-based chemotherapy and reviewed patients’ compliance and treatment toxicity. An oncologist evaluated patients and modified the dosage of oral chemotherapy based on toxicity reported during the previous cycle at bi-weekly visits.Results: A total of 460 home visits were performed between April 2012 and February 2013. The Active Home Care initiative was associated with significant improvements in physical functioning and symptoms, and reductions in the access to cancer facilities. Satisfaction with oral chemotherapy and care received was high. All patients reported having taken their medications according to their prescription, and no patient reported difficulties in managing the oral chemotherapy regimen. Conclusion: The Active Home Care program was associated with improvements in the quality of life of patients and caregivers, better adherence to treatment, and the effective management of therapy and cancer-related symptoms. Home-based cancer treatment may also optimize the utilization of health-care resources.Keywords: advanced cancer, home-based care, quality of life, adherence, patient satisfaction, effective therapy management

Sebastiano Bordonaro Fabio Raiti, Annamaria Di Mari, Calogera Lopiano, Fabrizio Romano, Vitalinda Pumo, Sebastiano Rametta Giuliano, Margherita Iacono, Eleonora Lanteri, Elena Puzzo, Sebastiano Spada, Paolo TralongoUOC Medical Oncology, RAO, ASP 8 Siracusa, ItalyBackground: Active home-based treatment represents a new model of health care. Chronic treatment requires continuous access to facilities that provide cancer care, with considerable effort, particularly economic, on the part of patients and caregivers. Oral chemotherapy could be limited as a consequence of poor compliance and adherence, especially by elderly patients.Methods: We selected 30 cancer patients referred to our department and treated with oral therapy (capecitabine, vinorelbine, imatinib, sunitinib, sorafenib, temozolomide, ibandronate). This pilot study of oral therapy in the patient’s home was undertaken by a doctor and two nurses with experience in clinical oncology. The instruments used were clinical diaries recording home visits, hospital visits, need for caregiver support, and a questionnaire specially developed by the European Organization for Research and Treatment of Cancer (EORTC), known as the QLQ-C30 version 2.0, concerning the acceptability of oral treatment from the patient’s perspective.Results: This program decreased the need to access cancer facilities by 98.1%, promoted better quality of life for patients, as reflected in increased EORTC QLQ-C30 scores over time, allowing for greater adherence to oral treatment as a result of control of drug administration outside the hospital. This model has allowed treatment of patients with difficult access to care (elderly, disabled or otherwise needed caregivers) that in the project represent the majority (78% of these).Conclusions: This model of active home care improves quality of life and adherence with oral therapy, reduces the need to visit the hospital, and consequently decreases the number of lost hours of work on the part of carers. Management of the service by the professionals involved revealed excellent control of the process by nursing staff, with minimal visits involving doctors.Keywords: cancer, treatment, home-based, quality of life, compliance

Fabrizio Romano, Mattia Garancini, Arianna Libera Ciravegna, Fabio Uggeri, Luca Degrate, Matteo Maternini, Franco UggeriDepartment of General Surgery (Chirurgia I), San Gerardo Hospital, University of Milan-Bicocca, Monza, ItalyAbstract: Splenectomy has been performed for a heterogeneous group of hematologic diseases with a therapeutic or diagnostic purpose or as part of the staging process in Hodgkin’s disease. Most patients undergoing therapeutic splenectomy are chronically ill with significant splenomegaly. This scenario can be associated with a high risk of postoperative morbidity and mortality due to the prolonged course of disease for patients with myelofibrosis; their susceptibility to infection, thrombosis, and hemorrhage; and the severe enlargement of their spleens. We have reviewed the main papers published about postoperative complications after splenectomy, analyzing the risk factors, prevention measures, and respective treatments. Great care must be taken in the management of patients presenting malignant diseases, splenomegaly, and hemostasis disorder. Moreover, despite the faster discharge that new surgical techniques now allow, close attention should be paid to symptoms reported by patients, in order to avoid potentially life-threatening complications such as portal vein thrombosis, pancreas injuries, and overwhelming postsplenectomy infection.Keywords: hematologic disease, complications, postoperative, laparoscopic

Ada Lo Schiavo,1 Rosa Valentina Puca,1 Francesca Romano,1 Roberto Cozzi2 1Department of Dermatology, Second University of Naples, Naples, Italy; 2Department of Dermatology, AORN "A Cardarelli", Naples, Italy Abstract: Statins, also known as 3-hydroxy-3-methylglutaril-CoA reductase inhibitors, are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Although they are generally considered safe, some serious adverse effects, such as myositis, myopathy, and rhabdomyolysis can rarely occur. Furthermore, recent data from long-term follow-up on patients who have been taking statins for a long period of time suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reactions is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. Herein we report the case of a 70 year-old man who developed a relapse of pemphigus erythematosus, a syndrome with features of both lupus erythematosus and pemphigus, after atorvastatin intake. Keywords: pemphigus erythematosus, autoimmune disease, treatment, pathogenesis, statins

Trichinellosis is one of the most serious foodborne parasitic zoonoses in Europe. Wild carnivorous and omnivorous hosts are the main reservoirs of Trichinella spp. nematodes in nature. In the winter of 2008-2009, an atypical clinical case of trichinellosis occurred for the consumption of pork from a wild boar (Sus scrofa) hunted in southwestern Alps in Italy. The symptomatic individual showed delayed development of oedemas in the lower limbs and eosinophilia, which appeared three months after infection. Muscle samples harboured 3.8 larvae/g, which were identified as Trichinella britovi. During the epidemiological investigation, anti-Trichinella IgG were detected in five hunters.

Nuclear fragmentation studies, historically driven by the interest of the nuclear physicists, are nowadays the subject of great attention for the hadrontherapy and the space radiation protection communities. In both fields, fragmentation cross sections are needed to predict the effects of the ion nuclear interactions within the patient’s and the astronaut’s body. Indeed, the the Monte Carlo codes used in planning tumor treatments and space missions must be tuned and validated by experimental data. However, only a limited set of fragmentation cross sections are available in literature, especially at Fermi energies. Therefore we have studied the production of secondary fragments in the 12C+12C and 12C+ 197Au reactions at 62 AMeV. Some of the measured cross sections are presented in this work.