Clinical, pharmacokinetic and pharmacodynamic evaluations of metronomic UFT and cyclophosphamide plus celecoxib in patients with advanced refractory gastrointestinal cancers

Aims. To evaluate UFT and cyclophosphamide (CTX) based metronomic chemotherapy plus celecoxib (CXB) for the treatment of patients with heavily pre-treated advanced gastrointestinal malignancies. Methods. Thirty-eight patients received 500 mg/mq2 CTX i.v bolus on day 1 and, from day 2, 50 mg/day CTX p.o. plus 100 mg/twice a day UFT p.o. and 200 mg/twice a day CXB p.o. Tegafur, 5-FU, 5-FUH2, GHB and uracil pharmacokinetics were assessed. Plasma vascular endothelial growth factor (VEGF), soluble VE-cadherin (sVE-C) and thrombospondin-1 (TSP-1) levels were detected by ELISA and real-time PCR of CD133 gene expression on peripheral blood mononuclear cell was also performed. Results Seventeen patients (45%) obtained stable disease (SD) with a median duration of 5.8 ms (range, 4.2–7.4). Median progression free survival (PFS) and overall survival (OS) were 2.7 ms (95% CI, 1.6–3.9 ms) and 7.1 ms (95% CI, 4.3–9.9 ms), respectively. No toxicities of grade >1 were observed. Pharmacokinetics of 27 patients (13/14, SD/progressive disease, PD) after the first treatment of UFT revealed that 5-FU AUC and Cmax values greater than 1.313 h x microg/ml and 0.501 microg/ml, respectively, were statistically correlated with stabilization of disease and prolonged PFS/OS. VEGF and sVE-C plasma levels were greater in the PD group when compared to SD group. CD133 expression increased only in the PD patients. Conclusion. Metronomic UFT and CTX with CXB in heavily pre-treated gastrointestinal patients were well tolerated and associated with interesting activity. Potential predictive pharmacokinetic parameters and pharmacodynamic biomarkers have been found

Copernicus Ocean State Report, issue 6

The 6th issue of the Copernicus OSR incorporates a large range of topics for the blue, white and green ocean for all European regional seas, and the global ocean over 1993–2020 with a special focus on 2020

Bromide and Acids: A Comprehensive Study on Their Role on the Hydrogen Peroxide Direct Synthesis

Hydrogen peroxide direct synthesis was studied using different concentrations of NaBr and H₃PO₄ (promoters) with a commercial Pd/C catalyst. The aim of the study was to understand the role of the acids and bromide on the catalyst and thus the effect on the direct synthesis. The experimental work was done in a continuous trickle bed reactor (TBR) using different concentrations of promoters. The effect of the promoters on the catalyst (Pd leaching and bromide adsorption) was monitored by inductively coupled plasma (ICP) on the solution obtained from the reaction environment. ICP analysis coupled with the monitoring of conversion, selectivity, and productivity helped to understand the effect of the promoters and to check the possibility to discriminate better the reaction network mechanism with different reaction conditions. Pd leaching was correlated to catalyst activity and bromide/phosphoric acid ratio. This work provides new and original evidence on the role of promoters, allowing one to understand better how to push the direct synthesis and how to control the catalyst ability to produce H₂O₂ rather than H₂O

Radiation Therapy-Induced Cardiovascular Disease Treated by a Percutaneous Approach

We report the case of a 51-year-old woman, treated with radiotherapy at the age of two years, for a pulmonary sarcoma. Subsequently she developed severe aortic stenosis and bilateral ostial coronary artery disease, symptomatic for dyspnea (NYHA III functional class). Due to the prohibitive surgical risk, she underwent successful stenting in the right coronary artery and left main ostia with drug eluting stents and, afterwards, transcatheter aortic valve replacement with transfemoral implantation of a 23 mm Edwards SAPIEN XT valve. The percutaneous treatment was successful without complications and the patient is in NYHA II functional class at 2 years’ follow-up, fully carrying out normal daily activities

Delayed Gadolinium-Enhanced Cardiac Magnetic Resonance in Patients With Chronic Myocarditis Presenting With Heart Failure or Recurrent Arrhythmias

ObjectivesWe evaluated the effectiveness of contrast-enhanced cardiac magnetic resonance (CE-CMR) in detecting chronic myocarditis (CM).BackgroundChronic myocarditis represents a common evolution of acute myocarditis. Although CE-CMR has been revealed to be effective in identifying areas of myocardial damage in acute myocarditis, its role in the diagnosis of chronic myocardial inflammation has not yet been investigated.MethodsTwenty-three patients with CM underwent CE-CMR and endomyocardial biopsy (EMB). Chronic myocarditis was defined by the presence of: 1) chronic (>6 months) heart failure symptoms and/or repetitive ventricular arrhythmias; 2) no history of recent flu-like symptoms or infections; and 3) histologic evidence of active myocarditis (AM) or borderline myocarditis (BM) according to Dallas criteria. Contrast-enhanced cardiac magnetic resonance included black-blood T2-weighted (BBT2w) images without and with fat saturation and delayed three-dimensional T1 turbo field-echo inversion-recovery sequences obtained 15 min after gadolinium injection.ResultsHistology showed AM in 14 patients and BM in 9 patients. FatSat BBT2w revealed the presence of edema in five (36%) patients with AM but not in BM patients. Areas of late enhancement (LE) were observed in 12 (84%) subjects with AM and in 4 (44%) cases with BM. A mid-wall LE pattern was the most frequent finding in both groups while a subepicardial distribution of LE was observed only in patients with AM.ConclusionsContrast-enhanced cardiac magnetic resonance identified areas of myocardial inflammation in up to 70% of patients with biopsy-proven CM. We suggest that CE-CMR may be a useful non-invasive diagnostic tool in patients with CM, and it may indicate and even guide the execution of left ventricular EMB with relevant prognostic and therapeutic implications