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Background and Objectives: While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice. Methods: SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first-line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing the choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort. Results: Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since the start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching. Conclusions: This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.

Background and Objectives: While tyrosine kinase inhibitors (TKIs) have transformed CP-CML management, limited data exist on their use in clinical practice. Methods: SIMPLICITY (NCT01244750) is an observational study in CP-CML patients, exploring first-line (1L) TKI use and management patterns in the US and Europe. Over half of the patients recruited in Europe are from Italy (n=266). This is an analysis of the Italian cohort and a comparison with the rest of the European SIMPLICITY population. Baseline demographic, factors influencing the choice of first-line TKI, response monitoring patterns and predictors of monitoring, and treatment interruptions, discontinuations and switching by index TKIs are presented for the Italian cohort in the first year of treatment and compared with that for the overall European SIMPLICITY cohort. Results: Italian patients received 1L imatinib (IM; retrospective [(n=31]; prospective [n=106]), dasatinib (DAS; n=56) or nilotinib (NIL; n=73). Documented cytogenetic response monitoring by 12 months was lower than expected, but almost all patients had documented molecular response monitoring. Fewer patients discontinued first-line TKI by 12 months in Italy compared with the rest of the European SIMPLICITY population (p=0.003). Of those with ≥12 months follow-up since the start of 1L TKI, only 7.1% (n=19) of Italian patients switched to a second-line TKI, a third less than in the rest of the European SIMPLICITY population. Of interest, intolerance as opposed to resistance, was the main reason for switching. Conclusions: This analysis provides valuable insights into management and treatment patterns in Italian patients with CML within routine clinical practice.

Background Obesity is recognized as a leading global health problem, correlated with an increased risk for several chronic diseases. One strategy for weight control management includes the use of vegetables rich in bioactive compounds to counteract weight gain, improve the antioxidant status and stimulate lipid catabolism. Aim of the Study The aim of this study was to investigate the role of Raphanus sativus Sango sprout juice (SSJ), a Brassica extraordinarily rich in anthocyanins (AC) and isothiocyanates (ITCs), in a non-genetic model of obesity (high fat diet-HFD induced). Methods Control groups were fed with HFD or regular diet (RD). After a 10-week period, animals were assigned to experimental units and treated by gavage for 28 days as follows: HFD and RD control groups (rats fed HFD or RD and treated with vehicle only) and HFD-treated groups (rats fed HFD and treated with 15, 75 or 150 mg/kg b.w. of SSJ). Body weight and food consumption were recorded and serum lipid profile was measured (total cholesterol, triglycerides, and non-esterified fatty acids). Hepatic phase-I, phase-II as well as antioxidant enzymatic activities were assessed. Results SSJ lowered total cholesterol level, food intake and liver weight compared with HFD rodents. SSJ at medium dose proved effective in reducing body-weight (~19 g reduction). SSJ was effective in up-regulating the antioxidant enzymes catalase, NAD(P)H:quinone reductase, oxidised glutathione reductase and superoxide dismutase, which reached or exceeded RD levels, as well as the phase II metabolic enzyme UDP-glucuronosyl transferase (up to about 43%). HFD up-regulated almost every cytochrome P450 isoform tested, and a mild down-regulation to baseline was observed after SSJ intervention. Conclusion This work reveals, for the first time, the antioxidant, hypolipidemic and antiobesity potential of SSJ, suggesting its use as an efficient new functional food/nutraceutical product.

ackground: Small conductance Ca2+ activated K+ (SK) channel inhibition has generating conflicting results in the setting of left ventricular dysfunction (LVD). Objective: To evaluate the effect of the SK channel inhibitor AP14145 compared to dofetilide in LVD induced by atrial tachypacing (ATP) in pigs. Methods: A total of 18 pigs were divided into an atrial fibrillation (AF) group and a control group. AF pigs were atrially tachypaced for 4–8 weeks until sustained vernakalant-resistant AF developed. Signs of remodeling were investigated by echocardiography (after cardioversion), biomarkers and tissue analysis. Effect of 20 mg/kg AP14145, given alone or before 0.1 mg/kg dofetilide, or vice versa, were compared in terms of short term variability (STV) of the QT and RR intervals. Results: ATP resulted in a reduced ejection fraction (EF) (52±4 vs. 69±3%, p=0.003, AF vs. controls). This was accompanied by increased end diastolic and systolic LA volumes (50±8 vs. 29±2 ml, p=0.03 and 36±8 vs. 11±0.5 ml, p=0.0007) and LA area (18±2 vs. 11±0.5 cm2, p=0.0006). In pigs with AF, the STV of QT did not change when AP14145 was given alone or before dofetilide, but increased when dofetilide was given alone or after AP14145 (from 0.02±0.07 to 0.55±0.11, n=4, p=0.02). The baseline STV of RR was significantly reduced by AP14145 (from 0.31±0.14 to -0.33±0.11, n=4, p=0.01) and increased by dofetilide (1.5±0.16, n=4, p=0.04 and 0.01). Conclusions: Atrial tachypacing induced AF with concomitantly lowered EF and increased LA volume and area. These findings show that structural remodeling developed, yet SK inhibition by AP14145 did not induce any pro-arrhythmic effects in the ventricles, in contrast to the positive control dofetilide. Acknowledgement/Funding: Innovation Fund Denmark, the Carlsberg Foundation, the Wellcome Trust European Union's Horizon 2020 research and innovation programme

'Candidatus Neoehrlichia mikurensis' is an emerging tick-borne zoonotic agent that primarily affects immunocompromised human patients. Dogs and foxes are frequently exposed to ticks, and both species are in close proximity to humans. This is the first study to systematically investigate the occurrence of 'Candidatus Neoehrlichia mikurensis' in Canidae in Europa. We analyzed 1'739 blood samples from dogs in Switzerland, Italy, Spain and Portugal and 162 blood samples from free-ranging red foxes (Vulpes vulpes) in Switzerland. All samples were tested using a previously described multiplex real-time PCR for the Anaplasmataceae family, the 'Candidatus Neoehrlichia' genus and the 'Candidatus Neoehrlichia mikurensis' species. All Anaplasmataceae positive samples were subsequently tested using specific real-time PCRs for Anaplasma phagocytophilum, Anaplasma platys, Ehrlichia canis and Rickettsia helvetica. Among the tested animals, one dog from Zurich tested positive for 'Candidatus Neoehrlichia mikurensis'. The 12-year old West Highland white terrier had been splenectomized 3 months prior to the blood collection and presented with polyuria/polydipsia. Fanconi syndrome was diagnosed based on glucosuria with normoglycemia and hyperaminoaciduria. A. platys and E. canis were detected in 14/249 dogs from Sicily and Portugal; two of the dogs were coinfected with both agents. Four Swiss foxes tested positive for A. phagocytophilium. R. helvetica was detected for the first time in a red fox. In conclusion, 'Candidatus Neoehrlichia mikurensis' infection should be considered in sick dogs, particularly when immunocompromised. The pathogen seems not to be widespread in Canidae in the investigated countries. Conversely, other Anaplasmataceae were more readily detected in dogs and foxes.