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The recent identification of rearrangements of neurotrophic tyrosine receptor kinase (NTRK) genes and the development of specific fusion protein inhibitors, such as larotrectinib and entrectinib, have revolutionized the diagnostic and clinical management of patients presenting with tumours with these alterations. Tumours that harbour NTRK fusions are found in both adults and children and are either rare tumours with common NTRK fusions that may be diagnostic, or more common tumours with rare NTRK fusions. To assess the currently available evidence, 3key Spanish medical societies (the Spanish Society of Medical Oncology (SEOM), the Spanish Society of Pathology (SEAP) and the Spanish Society of Paediatric Haematology and Oncology (SEHOP) have brought together a group of experts to develop a consensus document that includes guidelines on the diagnostic, clinical and therapeutic aspects of NTRK-fusion tumours. It also discusses the challenges related to the routine detection of these genetic alterations in a mostly public health care system.

Purpose Osimertinib has proven efficacy in EGFR T790M mutation-positive non-small cell lung cancer (NSCLC) patients; however, its benefits have not been evaluated in a real-world setting. Methods ASTRIS is a single-arm, open-label, multinational study to evaluate the efficacy and safety of osimertinib for the treatment of EGFR T790M mutation-positive NSCLC. We present the study design and preliminary cut-off analysis results (as of October 2017) describing the baseline characteristics and methodology for T790M mutation detection in the Spanish cohort. Results The Spanish cohort included 131 patients from a total 3014 patients. Forty patients (28.1%) were still undergoing therapy at the time of cut-off; 68.7% were women and 97.7% were Caucasian, with a mean age of 64.8 (SD 11.7) years. The most common type of sample for evaluating T790M mutations was tissue (55.0%), and samples were obtained from the primary tumor in 61.1% of cases. Mutation analysis was performed by the local laboratory in 60.3% of cases and using the Roche Cobas® EGFR assay in 43.5% of cases. Conclusions ASTRIS is expected to confirm the benefits of osimertinib in a real-world setting. Data on real-world practices for the detection of the EGFR T790M mutation may provide additional information for the designing of guidelines for best practices.

In recent years, there has been an increasing interest in finding sustainable strategies for the efficient removal of contaminants from soils. The objective of this review is to examine the biochemical principles of specific genetic modifications in plants, their applications in the field for specific contaminants as phytotechnologies, and their international regulation. In addition, the review presents some biological aspects of rhizosphere-related phenomena, the interactions of organic and inorganic pollutants with plants, and the performance of the phytotechnologies across the continents. During the last few decades, at least eight genera of genetically modified plants (GMPs) have been tested and used for soil remediation with outstanding results. Arabidopsis, Nicotiana, and Oryza are the plant genera most widely studied. Specific plant genes such as metal transporters, chelators, metallothioneins, phytochelatins, and oxygenases have been transferred to plants to improve the elimination of contaminants in soil. We discuss some important aspects of gene manipulation and its application for removal of diverse contaminants. A key challenge faced by phytotechnologies is the final disposal of the generated biomass, from a safety aspect. We argue that the commercial success of phytotechnologies depends on the generation of valuable biomass on contaminated land and its use for bioenergy generation. The use of such technologies would promote a broader understanding of the importance of plants, especially GMPs, in the environment and their contribution to environmental sustainability.

Objectives: Concomitant chemo-radiation is the standard treatment for unresectable stage III non-small cell lung cancer (LA-NSCLC), The aim of this study was to assess the safety and efficacy of oral vinorelbine and cisplatin (OVP) compared with etoposide and cisplatin (EP), both in combination with radiotherapy, in this setting. Material and methods: An open-label, randomized phase II trial was undertaken including 23 hospitals in Spain. Adults with untreated unresectable stage III NSCLC were randomizedl:1 to receive: oral vinorelbine (days 1 and 8 with cisplatin on day 1 in 3-week cycles; 2 cycles of induction, 2 cycles in concomitance) or etoposide (days 1-5 and 29-32 with cisplatin on days 1 and 8 in 4-week cycles; 2 cycles in concomitance). Both groups received concomitant radiotherapy 2 Gy/day (66 Gy). The primary endpoint was progression free survival (PFS). Results: One hundred and forty patients were enrolled. Sixty-nine patients received OVP and 71 received EP. Globally adverse events grade 3/4 per cycle were fewer in the vinorelbine arm (19.4%) than in the etoposide arm (62.6%) (p < 0.001). One patient (1.5%) in the OVP arm and 12 pts (17.6%) in the EP arm presented esophagitis grade 3/4 (p = 0.002). Median PFS was similar in both groups (10.8 [95% CI 7.7-13.8] and 9.6 months [95% CI 4.4-14.8]; p = 0.457, respectively). Preliminary median overall survival was 30 months in the OVP arm and 31.9 months in the EP arm (p = 0.688). Conclusions: Our findings show that OVP could be considered a standard combination with similar efficacy and better safety profile for the treatment of LA-NSCLC patients.

Immunodiagnosis in sheep presents problems of sensitivity and specificity, limiting its applicability in surveillance systems. The objective of this study was to develop a sensitive, specific and accessible technique for diagnosing cystic echinococcosis in naturally infected sheep and to evaluate the validity of necropsy as a reference test. A total of 247 sheep were studied at slaughterhouses, confirming the parasitological diagnosis with histology. Serum was processed with enzyme immunoassay (EIA) using three antigen preparations: total hydatid liquid (LHT), purified fraction of LHT (S2B) and purified lipoprotein (B). Western Blot (WB) was used as a control. EIA proved effective for differentiating Echinococcus granulosus from larval stage of Taenia hydatigena and intestinal cestodes in all three antigen preparations. Serums from macroscopically negative sheep were reactive to EIA and positive with WB. In the whole flock, sensitivity was 89.2% for LHT, 80.0% for S2B and 86.4% for B. Sensitivity in lambs was 78.6% for LHT, 75.0% for S2B and 64.3% for B. Macroscopic diagnosis at the time of slaughter was found to have limitations as a reference test for immunodiagnosis of cystic equinococcosis in sheep, so it was necessary to include histology and WB as reference tests. LHT was the antigen preparation of greatest value and EIA proved to be a sensitive and specific technique, adequate for surveillance systems and for evaluating control programmes.

In this work, the impact of a hydatidosis control programme for dogs on the intermediate ovine host was specifically analysed to determine the levels of prevalence achieved and the dynamics of parasite transmission, as well as to evaluate the quality of diagnostic systems in slaughterhouses. A field study was conducted in four slaughterhouses (Valcheta, Los Menucos, Jacobacci, Bariloche) that process animals coming from all the departments within the work area. The control programme for dogs entailed treating dogs with 5 mg/kg praziquantel at 2-month intervals for 20 years. Sample size was determined with a 10% error margin and a 95% significance level. Harvested viscera (liver, lungs, kidneys) were preserved in 5% formaldehyde and sent to the laboratory for diagnostic confirmation of both positive and negative specimens. The 61% initial prevalence dropped to 18.3% at the end of the 10-year period, observed differences proving significant (Chi-square=15.454, P=0.00). There were statistically significant increases in infection prevalence with age (Pearson’s Chi-square=133.61, P=0.00). Overall, 37.2% of hydatidosis cases diagnosed in slaughterhouses were considered non-hydatid by histological study. On the other hand, 1.1% of those diagnosed as healthy were found to be infected with hydatidosis. The number of hydatid cysts per animal increased with age: 0.04 in lambs and 1.22 in adults (linear regression equation, −0.0539+0.0127×age), whereas the average for the whole period was 3.7% in lambs and 20.5% in adults. Viability studies indicated that 63.8% of parasitised animals had viable cysts, out of which 53.3% were fertile. Diagnosis of infection in sheep made by means of an adjusted statistical design and with histological confirmation of the presumptive diagnosis made in slaughterhouses demonstrated the flaws of the official systems for epidemic surveillance of hydatidosis. However, there was no overall significant difference in slaughterhouse and laboratory data. Ro was 0.53 and could imply a decrease in reproductive capacity of the parasite and steady state extinction.

Novel spiro-branched sugar derivatives bearing a spiro-5′-(4′-amino-2′-oxazolone) or a spiro-5′-(4′-amino-1′,2′,3′-oxathiazole-2′,2′-dioxide) rings at position-3 of the sugar moiety have been prepared. The synthesis has been achieved by a one-pot procedure from a conveniently protected sugar cyanohydrin derivative by reaction with chlorosulfonyl isocyanate or sulfamoyl chloride, respectively. The tautomeric preference in solution of these novel 3-spiro sugars are described as derived from NMR spectroscopy. Also a comparative theoretical study, by ab-initio methods, of the steric and electronic properties of the spiro rings present in these sugar derivatives has been performed.

Aim: There is a need to develop biomarkers to predict the outcome of patients with metastatic colorectal cancer (CRC) treated with chemotherapy (Ch) plus Bevacizumab (B). It has been reported that during exposure to B there is a switch in the plasma levels of angiogenesis growth factors and related cytokines called angiogenic switch (AS). It is not known if changes in these circulating factors affect the response of patients with CRC to Ch + B. The aim of this study is to determine the influence of AS in the PFS in pts with metastatic CRC treated with Ch + B. Methods: Treatment naive, ECOG 0-1, metastatic CRC pts were eligible. Patients received induction treatment with XELOX-B or XELIRI-B at standard doses x 6 cycles followed by maintenance treatment with B plus Capecitabine until progression. Angiogenic related cytokines (HGF, PIGF, MCP-3, MM-9, Eotaxin, bFGF and IL-18) were prospectively analyzed at baseline and at the time of each CT evaluation (every eight weeks). AS + was defined by A) doubling of PIGF compared to baseline or B) PIGF elevation with a simultaneous elevation of any two of bFGF, HGF, MCP-3, IL-18 or MMP-9 compared to baseline. Results: Of 62 patients enrolled, 24 (36.7%) have progressed. Median PFS is 15.6 (95% CI: 8.3 to 16.4) months for the entire population. Twenty-five pts (40.3%) were AS + , out of which 23 were detected at first on-study evaluation (week 8). 18 were classified as AS+ based on both criteria, 4 based on criteria A) and 3 based on criteria B). One year (95% CI) PFS for AS+ pts was 82.6% (53.0% to 94.4%) versus 32.9% (13.9% to 53.5%) for AS- pts (p Conclusions: There is a statistically significant improved PFS amongst metastatic CRC AS+ pts treated with first line Ch + B combination compared with AS–pts. Disclosure: All authors have declared no conflicts of interest.

Polarographic diffusion coefficients are reported for cadmium ion in the solvents NH 4 NO 3 -2 H 2 O, NH 4 NO 3 -4 H 2 O and Ca(N0 3 ) 2 · 4 H 2 O At 50† and in mixtures of Ca(NO 3 ) 2 · 4 H 2 O with KNO 3 at 100†. The diffusion coefficients in NH 4 NO 3 -2 H 2 O and NH 4 NO 3 -4 H 2 O were 6.15 × 10 −6 and 1.51 × 10 −5 Cm 2 Sec −1 . In the much more viscous solvent, Ca(NO 3 ) 2 · 4 H 2 O, The diffusion coefficients were 0.312 × 10 −6 and 1.33 × 10 −6 cm 2 sec −1 at 50° And 100°. The diffusion coefficient appeared to be independent of solvent composition in the melts KNO 3 -Ca(NO 3 ) 2 · 4 H 2 O with mole fractions of Ca(N0 3 ) 2 · 4 H 2 O between 0.45 and 1.00 at 100°. The temperature dependence of D cd in Ca(NO 3 ) 2 · 4 H 2 O corresponded to an activation energy of 7.05 keal mole −1 and was consistent with parameters reported for the temperature-dependence of conductance and viscosity in this solvent.