La nozione di gruppo ai fini dell'Imposta sul Valore Aggiunto

I caratteri dell'Iva di gruppo nella normativa comunitaria: la disciplina relativa all'opzione sull'Iva di gruppo prevista dall'art. 11 della Direttiva n. 2006/112/CE del Consiglio del 28 novembre 2006. L'adozione del gruppo IVA da parte degli Stati Membri. Profili comparatistici. La normativa nazionale in materia di Iva di gruppo. Prospettive connesse all'attuazione nell'ordinamento italiano delle previsioni contenute nell'art. 11 della Direttiva n. 2006/112/CE.I caratteri dell'Iva di gruppo nella normativa comunitaria: la disciplina relativa all'opzione sull'Iva di gruppo prevista dall'art. 11 della Direttiva n. 2006/112/CE del Consiglio del 28 novembre 2006. L'adozione del gruppo IVA da parte degli Stati Membri. Profili comparatistici. La normativa nazionale in materia di Iva di gruppo. Prospettive connesse all'attuazione nell'ordinamento italiano delle previsioni contenute nell'art. 11 della Direttiva n. 2006/112/CE.LUISS PhD Thesi

Vaginal atrophy in breast cancer survivors: attitude and approaches among oncologists

Abstract Background Vulvovaginal atrophy (VVA) is a relevant problem for breast cancer survivors (BCSs), in particular for those who receive aromatase inhibitors (AIs). We conducted a survey, to assess the attitude of oncologists toward the diagnosis and treatment of VVA in BCSs. Materials and Methods In 2015, 120 computer-assisted Web interviews were performed among breast oncologists. Results According to oncologists' perceptions, 60% of postmenopausal BCSs and 39.4% of premenopausal BCSs will suffer from VVA. Despite that none of the physicians considered VVA as a transient event or a secondary problem in BCSs, only half of the oncologists (48%) directly illustrated VVA to the patients as a possible consequence. Forty-one percent of the oncologists refer BCSs to gynaecologist to define VVA treatment, whereas 35.1% manages it alone. Nonhormonal treatments are preferred by most oncologists (71%). The main reason not to prescribe vaginal estrogen therapy in BCSs is the fear of increased cancer recurrence, the possible interference with tamoxifen, or AIs and the fear of medical litigation. Conclusion VVA is a relevant problem for BCSs. Great effort should be done to correctly inform health care providers about VVA problems and on the different possible available treatments

pH-triggered conduction of amine-functionalized single ZnO wire integrated on a customized nanogap electronic platform

The electrical conductance response of single ZnO microwire functionalized with amine-groups was tested upon an acid pH variation of a solution environment after integration on a customized gold electrode array chip. ZnO microwires were easily synthesized by hydrothermal route and chemically functionalized with aminopropyl groups. Single wires were deposited from the solution and then oriented through dielectrophoresis across eight nanogap gold electrodes on a platform single chip. Therefore, eight functionalized ZnO microwire-gold junctions were formed at the same time, and being integrated on an ad hoc electronic platform, they were ready for testing without any further treatment. Experimental and simulation studies confirmed the high pH-responsive behavior of the amine-modified ZnO-gold junctions, obtaining in a simple and reproducible way a ready-to-use device for pH detection in the acidic range. We also compared this performance to bare ZnO wires on the same electronic platform, showing the superiority in pH response of the amine-functionalized material

Pharmacoutilization of epoetins in na\uc3\uafve patients with hematological malignancies in an unselected italian population under clinical practice setting: A comparative analysis between originator and biosimilars

Aim: The purpose of this study was to assess the prescription of epoetins and consumption of health care resources (in terms of drug treatments) in na\uc3\uafve patients with hematological malignancies in a real-world setting; in particular, we compared the results between reference product and biosimilar products. Methods: An observational retrospective study based on administrative and laboratory databases of three local health units was conducted. All adults diagnosed with hematological malignancies and who had received at least one epoetin (either reference product or biosimilars) prescription for the first time between 1 January 2010 and 30 April 2012 (enrollment period) were included. The date of the first prescription of epoetin within the enrollment period was defined as index date (ID). Patients were followed up for 4 weeks after ID (follow-up period) and were investigated for the 1-year period before the ID. The difference between the last hemoglobin (Hb) measurement after ID and the one prior to ID (\uce\u94Hb) was evaluated. The drug cost analysis was conducted from the perspective of the Italian National Health System. Results: Overall, 69 patients were included in the study; 48 of them received reference epoetin product and 21 received biosimilars as first prescription. Among reference product users, the mean \uc2\ub1 standard deviation (SD) age was 62.5\uc2\ub114.7 years; this cohort of patients was slightly significantly younger than the biosimilar users (71.8\uc2\ub111.8 years). The mean \uc2\ub1SD overall Hb level prior to treatment was lower among patients who started with biosimilar products (9.6\uc2\ub11.1 g/dL) compared to those who started with a reference product (10.1\uc2\ub12.1 g/dL). No significant differences in \uce\u94Hb were observed between biosimilar and originator groups during the followup period. The mean \uef\u82\u81\uef\u81\ubd\uef\u80 SD cost per patient was \ue2\u82\uac667.98\uc2\ub1573.93 and \ue2\u82\uac340.85\uc2\ub1235.73 for the reference product and biosimilar users, respectively (p=0.065). Conclusion: Our study showed that the use of biosimilar products might contribute to controlling health care costs (in terms of drug treatments) for patients with hematological malignancies being maintained by high-quality anemia therapy. Our findings also showed some discordances regarding the most appropriate therapeutic approach in daily clinical practice

Evaluation of the Impact of Catheter Ablation Procedure on Outcomes and Economic Burden in Patients with Atrial Fibrillation: Real-World Data from Italian Administrative Databases

A real-world analysis among the Italian population has been carried out to estimate the number of atrial fibrillation (AF) patients undergoing catheter ablation and to evaluate their clinical outcome and economic burden. A retrospective analysis on administrative Italian databases has been performed. Between January 2011 and December 2019, all patients diagnosed with AF were considered and those undergoing catheter ablation were identified. Overall, 3084 (3.54%) of AF patients with at least one catheter ablation were included (mean age 63.2, 67.3% males). A significant decrease in the use of AF-related medications and in hospitalizations, mainly related to AF and heart failure, was observed during the 3-year post-ablation period. The average total cost per patient during the 1-year before ablation period was significantly higher compared to the 1-year post-ablation cost (EUR 5248 vs. 4008, respectively; p < 0.001). After propensity score matching, the overall mortality of patients who underwent ablation was significantly lower compared to that assessed in patients not treated with the procedure (9.386/1000 vs. 23.032/1000 person-year, respectively; p < 0.001). Moreover, the mean total costs were significantly higher in patients who did not undergo ablation compared to those who received ablation (EUR 5516 vs. 4008, respectively; p < 0.001). This real-world data analysis shows that in Italy, although catheter ablation is performed in a minority of AF patients, it is associated with significantly better post-procedure clinical outcomes and a significant reduction in healthcare-related costs

Epirubicin. A new entry in the list of fetal cardiotoxic drugs? Intrauterine death of one fetus in a twin pregnancy. Case report and review of literature

BACKGROUND: Current knowledge indicate that epirubicin administration in late pregnancy is almost devoid of any fetal cardiotoxicity. We report a twin pregnancy complicated by breast cancer in which epirubicin administration was causatively linked to the death of one twin who was small for gestational age (SGA) and in a condition of oligohydramnios and determined the onset of a transient cardiotoxicity of the surviving fetus/newborn. CASE PRESENTATION: A 38-year-old caucasic woman with a dichorionic twin pregnancy was referred to our center at 20 and 1/7 weeks for a suspected breast cancer, later confirmed by the histopathology report. At 31 and 3/7 weeks, after the second chemotherapy cycle, ultrasound examination evidenced the demise of one twin while cardiac examination revealed a monophasic diastolic ventricular filling, i.e. a diastolic dysfunction of the surviving fetus who was delivered the following day due to the occurrence of grade II placental abruption. The role of epirubicin cardiotoxicity in the death of the first twin was supported by post-mortem cardiac and placental examination and by the absence of structural or genomic abnormalities that may indicate an alternative etiology of fetal demise. The occurrence of epirubicin cardiotoxicity in the surviving newborn was confirmed by the report of high levels of troponin and transient left ventricular septal hypokinesia. CONCLUSION: Based on our findings we suggest that epirubicin administration in pregnancy should be preceded by the screening of some fetal conditions like SGA and oligohydramnios that may increase its cardiotoxicity and that, during treatment, the diastolic function of the fetal right ventricle should be specifically monitored by a pediatric cardiologist; also, epirubicin and desamethasone for lung maturation should not be closely administered since placental effects of glucocorticoids may increase epirubicin toxicity

Targeting of RET oncogene by naphthalene diimide-mediated gene promoter G-quadruplex stabilization exerts anti-tumor activity in oncogene-addicted human medullary thyroid cancer

Medullary thyroid cancer (MTC) relies on the aberrant activation of RET proto-oncogene. Though targeted approaches (i.e., tyrosine kinase inhibitors) are available, the absence of complete responses and the onset of resistance mechanisms indicate the need for novel therapeutic interventions. Due to their role in regulation of gene expression, G-quadruplexes (G4) represent attractive targets amenable to be recognized or stabilized by small molecules. Here, we report that exposure of MTC cells to a tri-substituted naphthalene diimide (NDI) resulted in a significant antiproliferative activity paralleled by inhibition of RET expression. Biophysical analysis and gene reporter assays showed that impairment of RET expression was consequent to the NDI-mediated stabilization of the G4 forming within the gene promoter. We also showed for the first time that systemic administration of the NDI in mice xenotransplanted with MTC cells resulted in a remarkable inhibition of tumor growth in vivo. Overall, our findings indicate that NDI-dependent RET G4 stabilization represents a suitable approach to control RET transcription and delineate the rationale for the development of G4 stabilizing-based treatments for MTC as well as for other tumors in which RET may have functional and therapeutic implications

Analysis of drug utilization and health care resource consumption in patients with psoriasis and psoriatic arthritis before and after treatment with biological therapies

To describe the therapeutic pathways of patients with psoriasis (PSO) and psoriatic arthritis (PsA) before and after treatment with biological therapies in a real-world setting and to determine the relative consumption of health care resources