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Valentina Burgio,1 Massimo Iavarone,2 Giovanni Giuseppe Di Costanzo,3 Fabio Marra,4 Sara Lonardi,5,6 Emiliano Tamburini,7 Fabio Piscaglia,8 Gianluca Masi,9,10 Ciro Celsa,11 Francesco Giuseppe Foschi,12 Marianna Silletta,13 Daniela Caterina Amoruso,14 Margherita Rimini,15 Mariangela Bruccoleri,2 Raffaella Tortora,3 Claudia Campani,4 Caterina Soldà,6 Massimo Giuseppe Viola,16 Antonella Forgione,8 Fabio Conti,12 Francesca Salani,9,10 Silvia Catanese,9,10 Carmelo Marco Giacchetto,17 Claudia Fulgenzi,13 Carmine Coppola,14 Pietro Lampertico,18 Antonio Pellino,6,19 Gabriele Rancatore,17 Giuseppe Cabibbo,17 Francesca Ratti,20 Federica Pedica,21 Angelo Della Corte,22 Massimo Colombo,18 Francesco De Cobelli,23 Luca Aldrighetti,20 Stefano Cascinu,1,23 Andrea Casadei-Gardini1,23 1Department of Medical Oncology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 2Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; 3Department of Hepatology, Naples, 80131, Italy; 4Dipartimento di Medicina Sperimentale e Clinica, Università di Firenze, Firenze, Italy; 5Early Phase Clinical Trial Unit, Department of Oncology, Veneto Institute of Oncology IOV-IRCCS, Padua, Italy; 6Medical Oncology Unit 1, Department of Oncology, Veneto Institute of Oncology IOV - IRCCS, Padua, Italy; 7Department of Oncology and Palliative Care, Cardinale Hospital, Naples, Italy; 8Division of Internal Medicine, Hepatobiliary and Immunoallergic Disease, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy; 9Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, Pisa, Italy; 10Unit of Medical Oncology 2, Azienda Ospedaliero-Universitaria Pisana, Pisa, Italy; 11Department of Surgical, Oncological and Oral Sciences (Di.Chir.On.S.), University of Palermo, Palermo, 90127, Italy; 12Internal Medicine, Infermi Hospital, Faenza (AUSL ROMAGNA), Ravenna, Italy; 13Department of Oncology, Campus Bio Medico, Roma, Italy; 14Hepatology Unit, Internal Medicine, Area Stabiese Hospital, Naples, Italy; 15Department of Oncology and Hematology, Division of Oncology, University of Modena and Reggio Emilia, Modena, 4121, Italy; 16Department of General Surgery and Emergency Surgery, Cardinale Hospital, Tricase, Italy; 17Section of Gastroenterology & Hepatology, Department of Health Promotion, Mother and Child Care, Internal Medicine and Medical Specialties, PROMISE, University of Palermo, Palermo, 90127, Italy; 18Liver Center, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 19Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy; 20Hepatobiliary Surgery Division, Liver Center, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 21Department of Experimental Oncology, Pathology Unit, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 22Department of Radiology, Vita-Salute San Raffaele University, IRCCS San Raffaele Scientific Institute, Milan, 20132, Italy; 23School of Medicine, Vita-Salute San Raffaele University, Milan, 20132, ItalyCorrespondence: Andrea Casadei-GardiniDepartment of Medical Oncology, IRCCS San Raffaele Hospital, Via Olgettina n. 60, Milan, ItalyEmail casadeigardini@gmail.comBackground: Lenvatinib has been approved in Italy since October 2019 as a first-line therapy for advanced hepatocellular carcinoma (HCC) and to date data on effectiveness and safety of lenvatinib are not available in our region. To fill this gap, we performed a multicentric analysis of the real-world treatment outcomes with the propensity score matching in a cohort of Italian patients with unresectable HCC who were treated with either sorafenib or lenvatinib.Aims and Methods: To evaluate the effectiveness of sorafenib and lenvatinib as primary treatment of advanced HCC in clinical practice we performed a multicentric analysis of the treatment outcomes of 288 such patients recruited in 11 centers in Italy. A propensity score was used to mitigate confounding due to referral biases in the assessment of mortality and progression-free survival.Results: Over a follow-up period of 11 months the Cox regression model showed 48% reduction of death risk for patients treated with lenvatinib (95% CI: 0.34– 0.81; p = 0.0034), compared with those treated with sorafenib. The median PFS was 9.0 and 4.9 months for lenvatinib and sorafenib arm, respectively. Patients treated with lenvatinib showed a higher percentage of response rate (29.4% vs 2.8%; p < 0.00001) compared with patients treated with sorafenib. Sorafenib was shown to be correlated with more HFSR, diarrhea and fatigue, while lenvatinib with more hypertension and fatigue.Conclusion: Our study highlighted for the first time the efficacy and safety of lenvatinib in an Italian cohort of patients.Keywords: hepatocarcinoma, sorafenib, lenvatinib

Gabriele Masi,1 Pamela Fantozzi,1 Arianna Villafranca,1 Annalisa Tacchi,1 Federica Ricci,1 Laura Ruglioni,1 Emanuela Inguaggiato,1 Chiara Pfanner,1 Samuele Cortese2 1IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy; 2Clinical and Experimental Sciences (CNS and Psychiatry), Faculty of Medicine, University of Southampton, Southampton, UK Purpose: Methylphenidate (MPH), the first-line medication in children with attention-deficit/hyperactivity disorder (ADHD), is associated with increased risk of sleep disorders. Melatonin has both hypnotic and chronobiotic properties that influence circadian rhythm sleep disorders. This study explores the effectiveness of melatonin in children with ADHD who developed sleep problems after starting MPH. Patients and methods: This study, based on a clinical database, included 74 children (69 males, mean age 11.6±2.2 years) naturalistically treated with MPH (mean dosage 33.5±13.5 mg/d). The severity of sleep disorder (sleep onset delay) was recorded at baseline and after a follow-up of at least 4 weeks using a seven-point Likert scale according to the Clinical Global Impression Severity score. Effectiveness of melatonin on sleep (mean dosage 1.85±0.84 mg/d) after 4 weeks was assessed using a seven-point Likert scale according to the Clinical Global Impression Improvement (CGI-I) score, and patients who scored 1 (very much improved) or 2 (much improved) were considered responders. Results: Clinical severity of sleep disorders was 3.41±0.70 at the baseline and 2.13±1.05 after the follow-up (P

Gabriele Masi,1 Annarita Milone,1 Giulia Scrinzi,2 Maria Mucci,1 Valentina Viglione,1 Gabriella Bruni,1 Stefano Berloffa,1 Simone Pisano3 1IRCCS Stella Maris Foundation, Developmental Psychiatry and Psychopharmacology Unit, Pisa, Italy; 2Child Neuropsychiatry Unit, Department of Surgical Sciences, Dentistry, Gynecology and Pediatrics, University of Verona, Verona, Italy; 3Clinic of Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery, University of Salerno, Salerno, Italy Background: Although lithium is currently approved for the treatment of bipolar disorders in youth, long term data, are still scant. The aim of this study was to describe the safety and efficacy of lithium in referred bipolar adolescents, who were followed up at the 4th (T1) and 8th (T2) month of treatment.Methods: The design was naturalistic and retrospective, based on a clinical database, including 30 patients (18 males, mean age 14.2±2.1 years).Results: Mean blood level of lithium was 0.69±0.20 mEq/L at T1 and 0.70±0.18 mEq/L at T2. Both Clinical Global Impression-Severity (CGI-S) and Children Global Assessment Scale (C-GAS) scores improved from baseline (CGI-S 5.7±0.5, C-GAS 35.1±3.7) to T1 (CGI-S 4.2±0.70, C-GAS 46.4±6.5; P

Gabriele Masi,1 Simone Pisano,2 Paola Brovedani,1 Gioia Maccaferri,1 Azzurra Manfredi,1 Annarita Milone,1 Annalaura Nocentini,3 Lisa Polidori,1 Laura Ruglioni,1 Pietro Muratori1 1IRCCS Fondazione Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Italy; 2Clinic of Child and Adolescent Neuropsychiatry, Department of Medicine and Surgery, University of Salerno, Baronissi, Italy; 3Department of Sciences of Education and Psychology, University of Florence, Florence, Italy Purpose: Our aims were to explore the developmental trajectories of callous–unemotional (CU) traits using a growth curve analysis in Italian children with disruptive behavior disorders treated with a multimodal intervention, and to test both predictors and distal outcomes of CU traits trajectories. Patients and method: One hundred and sixty-eight children were enrolled, of whom 24 were lost in the follow-up and 144 were followed up from ages 8–9 to 14–15 years with four assessment points. Patients included 128 males (88.9%) with a mean age of 8.7 years, 96 with oppositional defiant disorder (66.7%) and 48 with conduct disorder (CD) (33.3%). The developmental trajectories of CU traits were assessed with the Inventory of Callous–Unemotional Traits (ICU). Results: Our findings revealed that CU features were likely to fit a quadratic model from childhood to adolescence. The CU traits tended to decrease during childhood, with stabilization in adolescence and a significant variability in the growth curves. Pretreatment CD and higher levels of externalizing behavioral problems were associated with higher level of CU traits at baseline, whereas positive parenting was associated with lower levels. No significant effects were found for all the other predictors (socioeconomic status, negative parenting, combined pharmacotherapy). Regarding outcomes into adolescence, both higher levels of CU traits at the baseline and a lower decrease of CU traits across time points predicted a higher risk of CD diagnosis, and higher rate of referrals to mental health services and of substance use. Furthermore, pretreatment CD and negative parenting predicted a higher risk of substance use into adolescence. Conclusion: Our findings suggest that a close monitoring of CU traits in referred children with disruptive behavior disorders may help to detect the patients at higher risk of poor outcome. Keywords: conduct disorder, oppositional defiant disorder, callous–unemotional traits, aggressive behavior, child psychiatry, psychopathy

Maria-Cristina Porfirio,1 Juliana Paula Gomes de Almeida,2 Maddalena Stornelli,1 Silvia Giovinazzo,1 Diane Purper-Ouakil,3 Gabriele Masi4 1Unit of Child Neurology and Psychiatry, “Tor Vergata” University of Rome, Italy; 2Unit of Child Neurology, Irmandade Santa Casa de Misericordia Hospital São Paulo, Brazil; 3Unit of Child and Adolescent Psychiatry, Saint Eloi Hospital, Montpellier, France; 4IRCCS Stella Maris, Scientific Institute of Child Neurology and Psychiatry, Calambrone, Pisa, Italy Abstract: In the last two decades, second-generation antipsychotics (SGAs) were more frequently used than typical antipsychotics for treating both psychotic and nonpsychotic psychiatric disorders in both children and adolescents, because of their lower risk of adverse neurological effects, that is, extrapyramidal symptoms. Recent studies have pointed out their effect on weight gain and increased visceral adiposity as they induce metabolic syndrome. Patients receiving SGAs often need to be treated with other substances to counteract metabolic side effects. In this paper, we point out the possible protective effect of add-on melatonin treatment in preventing, mitigating, or even reversing SGAs metabolic effects, improving quality of life and providing safer long-term treatments in pediatric patients. Melatonin is an endogenous indolamine secreted during darkness by the pineal gland; it plays a key role in regulating the circadian rhythm, generated by the suprachiasmatic nuclei (SCN) of the hypothalamus, and has many other biological functions, including chronobiotic, antioxidant and neuroprotective properties, anti-inflammatory and free radical scavenging effects, and diminishing oxidative injury and fat distribution. It has been hypothesized that SGAs cause adverse metabolic effects that may be restored by nightly administration of melatonin because of its influence on autonomic and hormonal outputs. Interestingly, atypical anti-psychotics (AAPs) can cause several sleep disorders, and circadian misalignment can influence hormones involved in the metabolic regulation, such as insulin, leptin, and ghrelin; furthermore, a relationship between obesity and sleep curtailment has been demonstrated, as well as sleep deprivation in rats has been associated with hyperphagia. Metabolic effects of melatonin, both central and peripheral, direct and indirect, target most metabolic disorders reported during and after SGA treatment in children, adolescents, and adults. Further systematic studies on psychiatric patients are needed to explore the effect of add-on melatonin on metabolic side effects of SGAs, independent of energy intake, diet, and exercise. Keywords: melatonin, metabolic syndrome, second-generation antipsychotics

The following research took place during the 2018 − ‘19 season in ‘Italia' table grape vineyard in Apulia. Four treatments were compared: no fertilized (T), organic amendment fertilized (B) at rate of 5.0 ton/hectare, equivalent at the rate of 100 Kg N ha−1, 75 Kg P2O5 ha−1 and 75 Kg K202 ha−1; mineral fertilized (M) at the same rate of N, P2O5 and K2O of organic fertilized vines and finally a cover crops treatment with a mixture of vetch, pea and lentil (S). Leaf gas exchange during summer season shown significant differences in term of net CO2 assimilation, stomatal conductance, transpiration onto organic fertilized vines respect to control vines. Vines fertilized with organic amendment shown a better water status during warmest summer days since organic compounds improve the soil-water holding capacity. Compared to unfertilized vines, vines fertilized with organic amendment have shown a significant increase in yield per vine (+ 32%) in relation to the highest cluster weight and the highest sugar content respect to mineral fertilized vines. Our results indicates that application of an high level of soil organic amendment on ‘Italia' table grape vines increase grapevines yield, berry solid soluble solid and have improved soil properties, contrasting summer drought effect.

The drastic reduction of agrobiodiversity has induced all countries in the world to implement numerous initiatives to safeguard genetic resources. The biodiversity issue is also one of the priority objectives of the global action plan for the conservation and sustainable use of FAO's cytogenetic resources and of the International Treaty on Plant Genetic Resources for Food and Agriculture. In Italy, the primary competence on genetic resources of agricultural interest is entrusted to the Ministry of Agricultural. In 2004, the Ministry entrusted the coordination of the RGV/FAO Project to CREA. The main objectives of the project, in addition to the inventory of accessions present in the collections of the structures involved, are their morphological, agronomic and molecular characterization and the productive enhancement with particular reference to the autochthonous varieties at risk of extinction. The project in question includes the activities of recovery and characterization of the viticultural germplasm illustrated in the present work. The 12 vines described here, like others yet to be rediscovered, are strongly linked to small winegrowers and indissolubly characterial of a territory in Campania Region that from the socio-cultural (rather fragmented agricultural system) and environmental orography point of view, like the national one, is very diversified.

The rechallenge strategy is based on the concept that a subset of patients with RAS wild‐type (WT) metastatic colorectal cancer (mCRC) could still benefit of epidermal growth factor receptor (EGFR) inhibition, after progression to an anti‐EGFR based‐therapy. We performed a pooled analysis of two‐phase II prospective trials to determine the role of rechallenge in third‐line mCRC patients with RAS/BRAF WT baseline circulating tumor DNA (ctDNA). Individual data of 33 and 13 patients from CAVE and CRICKET trials that received as third‐line therapy cetuximab rechallenge were collected. Overall survival (OS), Progression‐free survival (PFS), Overall response rate (ORR), Stable disease (SD) >6 months were calculated. Adverse events were reported. For the whole 46 patient population, median PFS (mPFS) was 3.9 months (95% Confidence Interval, CI 3.0–4.9) with median OS (mOS) of 16.9 months (95% CI 11.7–22.1). For CRICKET patients, mPFS was 3.9 months (95% CI 1.7–6.2); mOS was 13.1 months (95% CI 7.3–18.9) with OS rates at 12, 18, and 24 months of 62%, 23%, and 0%, respectively. For CAVE patients, mPFS was 4.1 months (95% CI 3.0–5.2); mOS was 18.6 months (95% CI 11.7–25.4) with OS rates at 12, 18, 24 months of 61%, 52%, 21%, respectively. Skin rash was more frequently reported in CAVE trial (87.9% vs. 30.8%; p = 0.001), whereas a increased incidence of hematological toxicities was observed in CRICKET trial (53.8%% vs. 12.1%; p = 0.003). Third‐line cetuximab rechallenge in combination with either irinotecan or avelumab in RAS/BRAF WT ctDNA mCRC patients represents a promising therapy. [ABSTRACT FROM AUTHOR]