Prediction of high on-treatment platelet reactivity in clopidogrel-treated patients with acute coronary syndromes.

BACKGROUND: About 40% of clopidogrel-treated patients display high platelet reactivity (HPR). Alternative treatments of HPR patients, identified by platelet function tests, failed to improve their clinical outcomes in large randomized clinical trials. A more appealing alternative would be to identify HPR patients a priori, based on the presence/absence of demographic, clinical and genetic factors that affect PR. Due to the complexity and multiplicity of these factors, traditional statistical methods (TSMs) fail to identify a priori HPR patients accurately. The objective was to test whether Artificial Neural Networks (ANNs) or other Machine Learning Systems (MLSs), which use algorithms to extract model-like 'structure' information from a given set of data, accurately predict platelet reactivity (PR) in clopidogrel-treated patients. METHODS: A complete set of fifty-nine demographic, clinical, genetic data was available of 603 patients with acute coronary syndromes enrolled in the prospective GEPRESS study, which showed that HPR after 1month of clopidogrel treatment independently predicted adverse cardiovascular events in patients with Syntax Score >14. Data were analysed by MLSs and TSMs. ANNs identified more variables associated PR at 1month, compared to TSMs. RESULTS: ANNs overall accuracy in predicting PR, although superior to other MLSs was 63% (95% CI 59-66). PR phenotype changed in both directions in 35% of patients across the 3 time points tested (before PCI, at hospital discharge and at 1month). CONCLUSIONS: Despite their ability to analyse very complex non-linear phenomena, ANNs or MLS were unable to predict PR accurately, likely because PR is a highly unstable phenotype.

[Atheroembolic renal disease]. / La malattia renale ateroembolica.

Atheroembolic renal disease can be defined as renal failure due to occlusion of the renal arterioles by cholesterol crystal emboli usually dislodged from ulcerated atherosclerotic plaques of the aorta. Atheroembolic renal disease is part of multisystem disease, since the embolization usually involves other organ systems such as the gastrointestinal system, central nervous system, and lower extremities. The kidney is frequently involved because of the proximity of the renal arteries to the abdominal aorta, where erosion of atheromatous plaques is most likely to occur. Embolization may occur spontaneously or after angiographic procedures, vascular surgery, and anticoagulation. In the last decade, atheroembolic renal disease has become a recognizable cause of renal disease. An ante-mortem diagnosis of the disease is possible in a significant proportion of cases as long as the level of diagnostic suspicion is high. The disease can severely affect kidney and patient survival. Although no specific treatment has been proven efficacious, use of statins may be justifiable and such therapy would be a reasonable choice for future treatment trials.

A novel 19F-NMR method for the investigation of the antioxidant capacity of biomolecules and biofluids.

A new assay for the measurement of the antioxidant capacity of biomolecules by high resolution 19F-NMR spectroscopy is presented here. This method is based on the use of trifluoroacetanilidic detectors, namely trifluoroacetanilide, N-(4-hydroxyphenyl)-trifluoroacetamide and 2-hydroxy-4-trifluoroacetamidobenzoic acid. Upon hydroxyl radical attack, such fluorinated detectors yield trifluoroacetamide and trifluoroacetic acid that can be quantitatively determined by 19F-NMR spectroscopy. Trifluoroacetamide was found to be a reliable reporter of hydroxyl radical attack on the fluorinated detectors, whereas N-(4-hydroxyphenyl)-trifluoroacetamide was found to be the most sensitive detector amongst the ones considered. Therefore, N-(4-hydroxyphenyl)-trifluoroacetamide has been used in competition experiments to assess the antioxidant capacity of a number of low and high molecular weight antioxidants. The antioxidant capacity of a given compound has been scaled in terms of an adimensional parameter, kF, that represents the ratio between the scavenger abilities of the fluorinated detector and the competitor. kF values obtained for low-molecular-mass compounds fall in the range 0.17 < kF < 1.5 and are in good agreement with second order rate constants (k2OH) for the reaction of the antioxidant with hydroxyl radicals. The kF value for serum albumin is much larger (46.9) than that predicted from the reported k2OH value. This finding supports the view that the protein can very effectively scavenge hydroxyl radicals as well as secondary radicals. Human blood serum showed that its antioxidant capacity is even higher than that shown by aqueous solutions of albumin at physiologic concentration suggesting a further contribution from other macromolecular serum components.

Intraperitoneal chemotherapy with carboplatin and recombinant interferon alpha in ovarian cancer.

Twenty-five patients with Stage III ovarian cancer were entered into a trial with intraperitoneal combinations of carboplatin (400 mg/cqm) and recombinant interferon alfa (50 MU). All patients had received prior intravenous platinum-based chemotherapy and underwent 2nd look laparotomy at study entry. Our study indicates that this combination chemotherapy is safely administered by the intraperitoneal route. Myelotoxicity was frequent, but rarely of grade 3. No major local toxicity was recorded by accessing the peritoneal cavity with a temporary catheter. The response to treatment was promising in the group of patients with less then 2 cm residual disease at study entry (15 patients); in this group, all patients had no clinical evidence of disease at the completion of the therapy. In 2 cases reexploration was performed and pCR was recorded. Only one patient of this group relapsed during a mean follow-up of 21 months. Two pCRS were also recorded in the group of patients with more than 2 cm at 2nd look (9 patients), although relapse occurred after 9 and 15 months respectively. In the remaining patients of this group, persistence of disease was observed after intraperitoneal chemotherapy.