Background: Prognosis of patients affected by metastatic esophageal–gastric junction (EGJ) or gastric cancer (GC) remains dismal. Trastuzumab, an anti-HER2 monoclonal antibody, is the only targeted agent approved for the first-line treatment of patients with HER2-overexpressing advanced EGJ or GC in combination with chemotherapy. However, patients invariably become resistant during this treatment. We recently identified the overexpression of fibroblast growth factor (FGF) receptor 3 (FGFR3) as a molecular mechanism responsible for trastuzumab resistance in GC models, providing the rationale for the inhibition of this receptor as a potential second-line strategy in this disease. Pemigatinib is a selective, potent, oral inhibitor of FGFR1, 2, and 3. Methods: The FiGhTeR trial is a phase II, single-arm, open-label study to assess safety and activity of the FGFR inhibitor pemigatinib as second-line treatment strategy in metastatic EGJ/GC patients progressing under trastuzumab-containing therapies. The primary endpoint is the 12-week progression-free survival rate. Plasma and tumor tissue samples will be collected for translational research analyses at baseline, during treatment, and at progression on pemigatinib. Discussion: Co-alterations in genes coding for different tyrosine-kinase receptors are emerging as relevant mechanisms of acquired resistance to anti-HER2 therapeutic strategies in GC. In particular, our group has recently identified that in GC models the overexpression of FGFR3 sustains the acquired resistance to trastuzumab. This trial aims to assess the safety, tolerability and activity of the FGFR inhibitor pemigatinib as a second-line treatment in metastatic EGJ/GC patients refractory to first-line trastuzumab-containing therapies. Furthermore, this study offers the opportunity to prospectively study mechanisms and pathways involved in trastuzumab resistance. Protocol number: CRC2017_02 EudraCT Number: 2017-004522-14

Objective of the present retrospective analysis was to evaluate resources consumption for psychotic patients treatment with olanzapine (OLZ), risperidone (RIS) or typical neuroleptics (NL) during year 2000 in the Dipartimento di Salute Mentale (DSM) of Ravenna. The screening of total number of psychotic patients followed in the Ravenna DSM during year 2000 generated 26 cases treated with OLZ, 22 treated with RIS and 17 treated with NL that were respecting criteria of equivalence for age and illness severity. For these patients we analyzed pharmacological, non pharmacological (medical visits, nurse visits, social assistance, rehabilitative sessions) and hospital interventions during the year of observation, choosing the point of view of the DSM for costs attribution. The analysis of pharmacological interventions evidentiated a major usage of associated neuroleptics in the RIS and NL groups in respect to OLZ (p<0,05 OLZ vs RIS and OLZ vs NL), other significant differences were about associated anticholinergics (OLZNL>RIS, p<0,05 for all comparisons). Hospital days during the year of observation in the three groups were 4,42 for OLZ patients, 7,71 for NL patients and 10,95 for RIS patients (p<0,05 for all comparisons: OLZ vs RIS, OLZ vs NL and RIS vs NL). The sum of pharmacological, non pharmacological and hospital costs (from 8.856.000 to 10.818.000 LIT) didn't generated statistically significant differences even if the OLZ group followed more intense rehabilitative activities (+71,65% vs RIS and +24,41% vs NL). Farmeconomia e percorsi terapeutici 2001; 2 (4): 217-222

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Tuberculosis resistant cases have been estimated to grow every year. Besides Mycobacterium tuberculosis, other mycobacterial species are responsible for an increasing number of difficult-to-treat infections. To increase efficacy of pulmonary treatment of mycobacterial infections an inhalable antibiotic powder targeting infected alveolar macrophages (AMs) and including an efflux pump inhibitor was developed. Low molecular weight sodium hyaluronate sub-micron particles were efficiently loaded with rifampicin, isoniazid and verapamil, and transformed in highly respirable microparticles (mean volume diameter: 1 μm) by spray drying. These particles were able to regenerate their original size upon contact with aqueous environment with mechanical stirring or sonication. The in vitro drugs release profile from the powder was characterized by a slow release rate, favorable to maintain a high drug level inside AMs. In vitro antimicrobial activity and ex vivo macrophage infection assays employing susceptible and drug resistant strains were carried out. No significant differences were observed when the powder, which did not compromise the AMs viability after a five-day exposure, was compared to the same formulation without verapamil. However, both preparations achieved more than 80% reduction in bacterial viability irrespective of the drug resistance profile. This approach can be considered appropriate to treat mycobacterial respiratory infections, regardless the level of drug resistance.

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