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Hepatocellular carcinoma (HCC) is the seventh most common cancer worldwide and the second leading cause of cancer-related mortality. HCC typically arises within a cirrhotic liver, but in about 20% of cases occurs in absence of cirrhosis. Among non-cirrhotic risk factors, non-alcoholic fatty liver disease (NAFLD) currently represents the most important emerging cause of HCC in developed countries. It has been estimated that annual incidence of HCC among patients with non-cirrhotic NAFLD is approximately 0.1–1.3 per 1000 patients/year and ranges from 0.5% to 2.6% among patients with non-alcoholic steatohepatitis (NASH) cirrhosis. However, only a few clinical trials enrolling HCC patients actually distinguished NAFLD/NASH-related cases from other non-cirrhotic causes and therefore evidence is still lacking in this subset of patients. This review aims to describe the biology underpinning NAFLD development, to investigate the main molecular pathways involved in its progression to NASH and HCC and to describe how different pathogenetic mechanisms underlying the onset of HCC can have an impact in clinical practice. We hereby also provide an overview of current HCC treatment options, with a particular focus on the available data on NAFLD-related cases in practice-changing clinical trials.

Atopic dermatitis (AD) is characterized by itching or pruritus, erythematous lesions, pruritus, and a skin barrier defect. Repeated scratching can trigger the itch-scratch cycle. Itching is associated with an adverse impact on quality of life. The first-line treatment of AD includes the use of topical corticosteroids for atopic dermatitis. However, parents of children with atopic dermatitis are often reluctant to accept the use of topical corticosteroids due to their concern of adverse effects flare-up. Relizema™ cream is a prescription emollient device (PED) multi-ingredients moisturizer formulation that has been indicated for the treatment of signs and symptoms of dermatitis. It is approved as medical device (MD) class IIa in Europe and it is registered as a topical medical device in countries of Asia Pacific. A consensus meeting of 9 dermatologists from multiple countries in Asia Pacific region treating atopic dermatitis was conducted. The dermatologists presented their cases of atopic dermatitis. PED was reported by patients to offer good relief of symptoms and improve skin softness unlike other moisturizers. In fact, a few patients reported relief with Relizema™ cream after using other moisturizers which were not demonstrating clinical effectiveness. Patients reported they noticed a softness in their skin after the application of the PED. PED was effective even in patients with lichenified skin. The formulation which is enriched with antioxidants helped relieve eczema. Due to its steroid-free formulation, the PED can be continued as a part of long-term maintenance treatment to maintain healthy skin conditions, prolong remission, and prevent recurrence.

Historically, metastatic melanoma was considered a highly lethal disease. However, recent advances in drug development have allowed a significative improvement in prognosis. In particular, BRAF/MEK inhibitors and anti-PD1 antibodies have completely revolutionized the management of this disease. Nonetheless, not all patients derive a benefit or a durable benefit from these therapies. To overtake this challenges, new clinically active compounds are being tested in the context of clinical trials. CDK4/6 inhibitors are drugs already available in clinical practice and preliminary evidence showed a promising activity also in melanoma. Herein we review the available literature to depict a comprehensive landscape about CDK4/6 inhibitors in melanoma. We present the molecular and genetic background that might justify the usage of these drugs, the preclinical evidence, the clinical available data, and the most promising ongoing clinical trials.

Background Endocrine therapy (ET) plus cyclin-dependent-kinases 4/6 inhibitors (CDK4/6i) represents the standard treatment for luminal-metastatic breast cancer (MBC). However, prospective head-to-head comparisons are still lacking for 1st line (L) options, and it is still crucial to define the best strategy between 1st and 2nd L. Materials and methods 717 consecutive luminal-MBC pts treated between 2008 and 2020 were analyzed at the Oncology Department of Aviano and Udine, Italy. Differences about survival outcomes (OS, PFS and PPS) were tested by log-rank test. The attrition rate (AR) between 1st and 2ndL was calculated. Results At 1stL, pts were treated with ET (49%), chemotherapy (CT) (31%) and ET-CDKi (20%) while, at 2ndL, 33% received ET, 33% CT and 8% ET-CDKi. Overall AR was 10%, 7% for CT, 8% for ET and 17% for ET-CDKi. By multivariate analysis, 1stL ET-CDK4/6i showed a better mPFS1 and OS. Moreover, 2ndL ET-CDK4/6i demonstrated better mPFS2 compared to ET and CT. Notably, 1stL ET-CDKi resulted in higher mPFS than 2ndL ET-CDKi. Intriguingly, 1stL ET-CDK4/6i was associated with worse mPPS compared to CT and ET. Secondarily, 1stL ET-CDK4/6i followed by CT had worse OS compared to 1stL ET-CDK4/6i followed by ET. Notably, none of baseline characteristics at 2ndL influenced 2ndL treatment choice (ET vs. CT) after ET-CDKi. Conclusion Our real-world data demonstrated that ET-CDKi represents the best option for 1stL luminal-MBC compared to ET and CT. Also, the present study pointed out that 2ndL ET, potentially combined with other molecules, could be a feasible option after CDK4/6i failure, postponing CT on later lines., Highlights • To define the best treatment strategy for 1st and 2nd L is crucial for luminal mBC. • 1st L CDK4/6i-based therapies represent the standard treatment in luminal mBC. • This study confirmed the key role of 1st L CDK4/6i on a real-world cohort. • This study suggested a preeminent role for ET after first-line CDK4/6i. • The 2nd line ET with other molecules could allow to further postpone CT.

La bronquiolitis es una patología frecuente en la práctica clínica pediátrica. Constituye una de las principales entidades clínicas dentro de las infecciones respiratorias agudas bajas (IRAB). Se define como el primer episodio de sibilancias con manifestaciones clínicas de infección viral en un niño menor de dos años y afecta principalmente a lactantes menores de 6 meses. El tratamiento es fundamentalmente de soporte con oxigenoterapia e hidratación, quedando el resto de las terapéuticas bajo una profunda controversia acerca de su real efectividad. Metodología: Desde la exposición de un escenario clínico se planteó una pregunta estructurada para luego realizar una búsqueda bibliográfica con el fin de dar respuesta a la pregunta sobre la efectividad en el tratamiento del bronquiolitis con broncodilatadores. Se realizó una búsqueda en PubMed utilizando los Mesh (Medical Subject Headings) "bronchodilators AND bronchiolitis", se aplicaron distintos filtros, tras lo cual se llegó al número final de 23 artículos. Tras una lectura de los títulos y resúmenes de los artículos, se escogió el artículo "Bronchodilators for bronchiolitis". Análisis del artículo: Nos hemos centrado las siguientes variables con el fin de responder a la pregunta clínica: la mejoría en el score clínico, la reducción de la tasa de internación y la saturometría de oxígeno. Realizamos luego un análisis secundario de los datos de las distintas variables con el fin de definir los valores de riesgo relativo (RR), reducción de riesgo absoluto (RRA), reducción del riesgo relativo (RRR) y el número necesario a tratar (NNT) con sus respectivos intervalos de confianza del 95% (IC 95%). También se llevó a cabo un análisis estadístico para evaluar la variable de saturación de oxígeno. Recomendación final: No está recomendado el uso de broncodilatadores en el manejo del bronquiolitis, ya que no mejoran ninguna de las variables analizadas. Los broncodilatadores no sólo no tienen eficacia, sino que suponen un gasto y presentan efectos adversos indeseables

Background: The recent COVID-19 outbreak in Italy required timely adoption of efficient triage procedures (TPs) with the aim to minimize the risk of infection spreading in the hospitals We developed a written questionnaire (items explored: fever, respiratory symptoms, previous contacts or personal positivity for COVID-19) together with body temperature (BT) measurement, to intercept patients (pts) with suspect of COVID-19 infection Methods: We conducted a monocentric observational study of a consecutive series of outpatients with diagnosis of solid tumor, accessing the Day Unit of Oncology Department at Udine Academic Cancer Center (Northern Italy) from 30 March 2020 to 30 April 2020 In this abstract we present the preliminary results of the TPs performed until 10 April 2020 Results: 1054 TPs were performed out of 586 pts, with a median of 2 TPs per pt Median age was 64 9 years, males were 35 4% Overall, 82 5% of TPs were made because of access for therapy, 10 7% for programmed procedures, radiological exams or non-oncological consultations, 1 2% for unplanned presentation (e g urgencies) The stage of neoplasm was early in 30 7% and advanced in 69 3% of pts TPs were made in pts receiving chemotherapy (58 2%), immunotherapy (10 8%), targeted therapy (18 9%), other therapies (5 2%) and in pts without active oncological therapy (6 9%) The questionnaires resulted positive in 5 5% of cases;2 9% were positive for fever, 2 9% for respiratory symptoms, 0 1% for previous contact with a case of COVID-19 Concomitant presence of 2 or more items was observed in 0 5% of questionnaires Of note, 6 TPs required medical evaluation despite a negative questionnaire and were considered to be clinically suspect BT≥37°C was observed in 7 TPs Overall, the oncologic program was postponed in 0 9% of the TPs, while in 0 5% a test for SARS-CoV-2 was performed for clinical suspect: no one resulted positive At multivariate analysis, factors associated with positive triage were diagnosis of thoracic cancer (OR 2 06;95%CI 1 02-4 12;p=0 04) and prior test for SARS-CoV-2 (OR 2 81;95%CI 1 46-5 41;p=0 001) Conclusions: A well-structured triage for COVID-19 could reduce the risk for further spreading of infection in Oncology facilities with limited impact on scheduled activities Legal entity responsible for the study: The authors Funding: Has not received any funding Disclosure: F Puglisi: Honoraria (self): MSD;Honoraria (self), Advisory/Consultancy, Research grant/Funding (self), Travel/Accommodation/Expenses: Roche;Honoraria (self), Advisory/Consultancy: Eli Lilly;Honoraria (self): Takeda;Pfizer;Advisory/Consultancy: Amgen;Novartis;Pierre Fabre;Research grant/Funding (self): Astrazeneca;Eisai;Travel/Accommodation/Expenses: Celgene;Servier C Andreetta: Advisory/Consultancy: AstraZeneca;GlaxoSmithKline;MSD A M Minisini: Advisory/Consultancy: Novartis;MSD;Pierre Fabre G Fasola: Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Bristol-Myers Squibb srl;Eli Lilly SpA ;Servier Italia SpA ;Speaker Bureau/Expert testimony: Astrazeneca;Travel/Accommodation/Expenses: Merck Sharp and Dohme S p A ;Boehringer-Ingelheim S p A All other authors have declared no conflicts of interest

International audience; PurposeWe evaluated a new single-use digital flexible cystoscope with an integrated grasper designed for double-J stent removal, Isiris™, addressing success rate, image quality, deflection, maneuverability and grasper functionality.MethodsIn September 2015, a prospective cohort study was conducted in six tertiary European reference centers. All consecutive patients included underwent double-J stent removal and were 18 years or older. Success rate was defined by complete stent removal. Image quality, deflection, maneuverability and grasper functionality were rated with a Likert scale.ResultsA total of 83 procedures were performed. 82% of procedures were performed in the endoscopy room, while the others were in the operating room since a consecutive endourological intervention was planned. The median duration of stent implantation was 28 days [14; 60]. In five patients, stent removal was not possible. Four patients had an incrusted double-J stent, and in one patient, the stent migrated into the ureter. After unsuccessful attempts of stent removal with conventional flexible cystoscope and grasper, the five patients had to be scheduled for an ureterorenoscopy procedure to remove the stent. In the other 78 patients, all double-J stents were removed successfully. Image quality, deflection, maneuverability and grasper functionality were rated as “very good” in 72.3, 78.3, 72.3 and 73.5%, respectively.ConclusionThis multicenter clinical evaluation of Isiris™ displayed good image quality, active deflection, maneuverability and grasper functionality. Further evaluation of stent removal outcomes, cost analysis and microbiology will help to delineate the possible place of Isiris™ in the current practice.

Background Cancer multidisciplinary team meetings (MDMs) are commonly acknowledged as a good clinical practice. One of the roles of MDMs is to identify the best diagnostic and therapeutic strategies for patients (pts) with new diagnosis of early breast cancer (EBC). In this setting, the purpose of the study was to define whether there was agreement between the planned program (i.e. MDMs-based decision) and that actually applied (i.e. actual therapeutic choice, ATC). In addition, the study explored factors associated with discordance. Methods We conducted a monocentric retrospective study of a consecutive series of 291 pts with new diagnosis of EBC, discussed at MDMs at the University Hospital of Udine (Italy), from January 2017 to June 2018. Results Median age was 62 years (range 27-88 years). Among invasive EBC patients, the most frequent phenotype was luminal-A (38%), followed by luminal-B (33%), HER2-positive (12%) and triple negative (5%). Thirty-four pts (12%) had diagnosis of in situ carcinoma (DCIS). Median time from MDMs discussion to first oncological examination was two weeks. Rate of discordance between MDMs-based decision and final choice, during face to face consultation with the oncologist, was 15.8% (46/291). Among cases with discordance, 19 pts (41.3%) had age > 70 years; 8 pts (17%) had a diagnosis of DCIS, 13 pts (28%) luminal-B carcinoma, 12 pts (26%) luminal-A, 9 pts (20%) HER2-positive and 4 pts (9%) triple negative EBC. The most frequent reason for changing the MDMs-based program was clinical decision by the oncologist at the first evaluation (87%). Follow-up was preferred to the chemotherapy proposed within the MDMs by 15% of pts, and to the endocrine therapy in 39% cases (among these, 44.5% had diagnosis of DCIS). In our study 16/46 pts (35%) had a therapeutic change from chemotherapy to endocrine therapy: among these pts, 7/16 had a luminal-B and 6/16 had a HER2-positive disease. Further analysis aiming at evaluating variables which could predict discordance between MDMs proposal and face to face oncological consultation are ongoing. Conclusions The results of our study could be useful for enhance the role of MTD and identify unmet needs in decision making process in EBC. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background High BMI is associated with better survival in metastatic melanoma patients (MM pts), while sarcopenia is linked to poorer outcome in pts with stage III. The aim of this study was to examine the prognostic impact of body-mass index (BMI), baseline sarcopenia, loss of skeletal muscle mass (LSMM) on overall survival (OS) in MM pts who received immunotherapy (IT). Methods The retrospective series included 42 consecutive MM pts (Jan 2011-Dec 2018) treated with IT in a single referral center. Sarcopenia was defined according to Prado’s criteria. Skeletal muscle index (SMI) was calculated as cross-sectional-area of muscle (cm2), using CT-scan, at the L3 level divided by the square of the height (m2). Early LSMM, during IT, was defined as a decrease in SMI > =10% from baseline at first evaluation. BMI was calculated as weight (kg) divided by the square of height (m2) and categorized according to standard WHO definitions. Weight loss was analyzed as continuous variable. Results At baseline, 27 pts (64,3%) were male, 26 pts (61.9%) were =25. Out of 42 pts, 30 (71.4%) had a CT-scan at first evaluation, and 30% of them had an early LSMM. Median OS was 11.38 months. Both in univariate and multivariate analysis, ECOG PS > =1, and early LSMM > =10% were significantly associated with worse OS. Conversely, pts with weight loss had better OS (Table). Table . 1367P OS univariate analysis OS multivariate analysis Factors HR p 95% Confidence Interval HR p 95% Confidence Interval PS ECOG³1 3.02 0.01 (1.29-7.08) 3.99 0.043 (1.04-15.31) Weight loss 0.88 0.03 (0.78-0.98) 0.85 0.02 (0.74-0.97) Early LSMM > =10% 4.24 0.006 (1.50-11.97) 3.09 0.04 (1.04-9.22) Conclusions Early LSMM > =10% and ECOG PS > =1 may negatively influence the outcome of MM pts treated with IT. Further prospective studies are needed to confirm these data. Legal entity responsible for the study Maria Grazia Vitale. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Background Patients (pts) with melanoma brain metastases (BM) have a historically poor prognosis, with a reported median overall survival (mOS) of 4-6 months. Aim of this study is to evaluate predictive factors of survival in pts with melanoma BM. Secondly, a multivariate model was used to define groups with distinct prognosis. Methods Consecutive pts with melanoma BM treated in two Italian cancer centers were included in this 10-year retrospective cohort study (2008-2018). Baseline clinicopathological factors, systemic and loco-regional treatments were registered. The Kaplan-Meier method and the Cox model were used to analyze the association of prognostic factors and OS. Results 150 pts with melanoma BM were enrolled in this study: 42% with a single BM, 51.3% with ≥ 3 extracranial metastatic sites and 38% with an ECOG performance status (PS) of 0. About 50.7% of pts had a BRAF mutation. Notably, 56% of pts were asymptomatic at BM diagnosis, and 40% presented high LDH levels at baseline. Overall, mOS after BM diagnosis was 5.78 months (95% CI 4.80-6.67), and median intracranial progression-free survival was 4.63 months (95% CI 3.81-5.12). According to treatment modality, stereotactic radiosurgery/neurosurgery plus systemic therapy showed the best outcome (mOS 12.32 months, 95% CI 7.92-25.30). A multivariate model was used to identify baseline prognostic factors independently associated with OS (Table). Conversely, sex and symptomatic BM did not significantly impact on OS. Predicted survival functions defined 3 distinct prognostic groups (P Table . 1363P Covariates HR 95% CI P Points BRAF wild type 1.95 1.22-3.12 1 BM > 1 2.20 1.35-3.59 1 LDH ≥ 2 x upper normal limit 1.83 1.07-3.11 0.026 1 ECOG PS > 0 2.68 1.62-4.43 0.0001 1 Extracranial metastatic sites ≥ 3 1.91 1.17-3.1 1 Age ≥ 65 1.86 1.15-3.02 0.012 1 Conclusions This score can be useful for stratifying prognosis in pts with melanoma BM. Prospective studies are needed to validate this score and to explore how it may guide treatment strategy. Legal entity responsible for the study Dipartimento di Oncologia, Azienda Sanitaria Universitaria Integrata di Udine. Funding Has not received any funding. Disclosure F. Puglisi: Honoraria (self), Advisory / Consultancy: Amgen; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eisai; Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Ipsen; Honoraria (self), Research grant / Funding (self): Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Research grant / Funding (self): Roche; Honoraria (self): Pierre Fabre; Advisory / Consultancy: Merck Sharp & Dohme; Advisory / Consultancy: Takeda; Research grant / Funding (self): Astrazeneca. All other authors have declared no conflicts of interest.

Resumen Introduccion y Objetivos: el tumor vesical t1g3 constituye el grupo de tumores superficiales mas agresivo. Nuevos factores pronosticos en el campo de la citogenetica y la biologia molecular han sido analizados, con resultados a menudo contradictorios, siendo escasos los trabajos especificos en tumores t1g3. Nuestro objetivo es determinar si en este grupo de tumores los marcadores inmunohistoquimicos presentan valor predictivo de progresion clinicamente util, y por tanto con validez para indicar una actitud terapeutica precoz mas idonea. Material y metodos Estudio retrospectivo de una serie de 83 pacientes afectos de tumor vesical t1g3, sobre los que analizamos un total de 14 variables; entre los nuevos factores predictivos: la determinacion inmunohistoquimica de las proteinas reguladoras del ciclo celular: p53, p21 y bcl-2, asi como la proteina Ki-67 como marcador de proliferacion celular. Mediante analisis de regresion logistica establecemos las variables pronosticas independientes para progression tumoral. Resultados El punto de corte establecido para Ki67 y p53 fue el 40% de celulas inmunomarcadas, 20% para p21 y 10% para Bcl-2. El analisis univariante puso de manifiesto diferentes tasas de progresion y tiempos libres de progression en funcion de la inmunotincion de Ki67 y p53; sin embargo, la regresion logistica demostro que solo la inmunohistoquimica de p53 presentaba valor predictivo independiente. Conclusiones La determinacion inmunohistoquimica de p53 presenta valor predictivo de progresion clinicamente util en tumors vesicales t1g3, de manera que su determinacion puede constituir un factor fundamental en las estrategias de tratamiento de estos tumores.

[EN] There are numerous passive strategies for reducing energy consumption in Spanish traditional vernacular architecture, depending on external conditions and also on the intended use of the interior of these constructions. In the case study analyzed, localized in an interior area of Spain, known as La Mancha, a set of vernacular buildings have been studied. Solar protection and solar gain, for example, are the key resources related to solar control. While cross ventilation, self-ventilation, or induced ventilation are related to the energy efficiency of the airflow. Other mechanisms identified are, for example, thermal insulation and thermal inertia of the materials. All these K-factors have been checked and parameterized in order to understand these vernacular strategies. Finally, thanks to a comparison of such resources, the study achieved a set of criteria for the use of these solutions in contemporary local architecture., The authors would like to thank the European Union framework 7th program for making this work possible via the LIMA project as well as to the following fellowships: The R&D FPI-UPV (P.A.I.D. program of the Universitat Politecnica de Valencia) and the FPU by the Spanish Ministerio de Educacion, Cultura y Deporte.

Se efectuó un experimento de campo con el objetivo de seleccionar cepas de rizobios inoculadas en trigo (Triticum aestivum, L., var. Cuba-204). Se evaluaron varios indicadoress agroproductivos de la planta, tales como: peso seco aéreo, longitud del tallo, rendimiento de granos, peso de 1000 granos y rendimiento de nitrógeno. Como criterio de selección de los mejores tratamientos se consideraron los valores estadísticamente superiores al control fertilizado. Se utilizaron cuatro cepas de referencia, pertenecientes a diferentes géneros y especies de rizobios, y 10 cepas nativas, pertenecientes al género Sinorhizobium, que fueron aisladas de raíces de leguminosas (Melilotus y Medicago), adaptadas a ecosistemas ganaderos de Alberta, Canadá. Una de las cepas fue aislada de leguminosas adaptadas a suelos contaminados con hidrocarburos de esa misma zona geográfica. Las cepas crecieron en LMA y resuspendidas en CLM hasta lograr una UFC de 10(6) _ 10(8) cél/mL. Se utilizaron métodos estándar para la inoculación de cereales. Se aplicó un diseño experimental de bloques completamente aleatorizado, con 16 tratamientos y cuatro réplicas. Uno de los tratamientos se fertilizó con 150 kg/ha (NH4NO3). Se utilizó análisis de varianza. Las diferencias entre medias fueron halladas por la prueba LSD de Fisher (pA field experiment was carried out in order to select rhizobial strains inoculated to wheat (Triticum aestivum, L., var. Cuba-204). Several parameters of agricultural significance were assessed, such as: aerial dry weight, length of stems, grain yield, weight of 1 000 grains and nitrogen yield. As selection criterion of the best treatments, the statistically higher values compared to the fertilized control were considered. Four reference strains, belonging to several rhizobial genus and species were used, as well as ten native strains, belonging to Sinorhizobium that were isolated from roots of legumes (Melilotus and Medicago), adapted to Canadian livestock ecosystems in Alberta. One of the strains was isolated from legumes adapted to soils contaminated with hydrocarbons located in the same geographic zone. The strains grew YMA and re-suspended in YMB until they reached a 6 8 CFU of 10 - 10 cells/mL. Standard methods for the inoculation of cereals were used. A complete randomized block experimental design with 16 treatments and four replications within plots was used. A treatment was fertilized with 150 kg/ha (NH NO ). Variance analysis was applied while differences between treatments were 4 3 found through LSD (Fisher’s test) (p