Analysis of the relative frequencies of the multipartite BNYVV genomic RNAs in different plants and tissues.

Multipartite virus genomes are composed of two or more segments, each packaged into an independent viral particle. A potential advantage of multipartitism is the regulation of gene expression through changes in the segment copy number. Soil-borne beet necrotic yellow vein virus (BNYVV) is a typical example of multipartism, given its high number of genomic positive-sense RNAs (up to five). Here we analyse the relative frequencies of the four genomic RNAs of BNYVV type B during infection of different host plants (Chenopodium quinoa, Beta macrocarpa and Spinacia oleracea) and organs (leaves and roots). By successfully validating a two-step reverse-transcriptase digital droplet PCR protocol, we show that RNA1 and -2 genomic segments always replicate at low and comparable relative frequencies. In contrast, RNA3 and -4 accumulate with variable relative frequencies, resulting in distinct RNA1 : RNA2 : RNA3 : RNA4 ratios, depending on the infected host species and organ.

Poor comparability of coagulation screening test with specific measurement in patients receiving direct oral anticoagulants: results from a multicenter/multiplatform study.

Essentials Prothrombin and partial thromboplastin time (PT/PTT) measure direct oral anticoagulants (DOACs). PT, PTT and specific tests for DOACs were performed on patients treated for atrial fibrillation. Normal PT/PTT don't exclude DOAC activity and their prolongation doesn't confirm DOAC action. The use of PT or PTT to evaluate DOAC activity could cause dangerous misinterpretations. SUMMARY: Background Prothrombin time (PT) and activated partial thromboplastin time (APTT) have been proposed to measure the effect of oral anti-activated factor X (FXa) or anti-activated FII drugs, respectively. Aims To evaluate the relationships and responsiveness of PT and APTT versus direct oral anticoagulant (DOAC) concentrations measured with specific coagulation tests performed with different platforms in four Italian anticoagulation clinics. Methods Six hundred and thirty-five patients with atrial fibrillation participated in the study: 240 were receiving dabigatran, 264 were receiving rivaroxaban, and 131 were receiving apixaban. Blood was taken at trough and peak within the first month (15-25 days) of treatment. PT, APTT, diluted thrombin time (dTT) calibrated for dabigatran and anti-FXa calibrated for rivaroxaban or apixaban were determined. Results For dabigatran, the correlation between APTT and dTT ranged from r = 0.80 to r = 0.62. For rivaroxaban, the correlation between the anti-FXa assay and PT ranged from r = 0.91 to r = 0.73. For apixaban, the correlation between the anti-FXa assay and PT was lower than for the two other drugs (r = 0.81 to r = 0.54). Despite the above significant correlations, the responsiveness of PT or APTT was relatively poor. A discrepancy between global testing and DOAC plasma concentrations was shown in a considerable proportion of patients, depending on the platform and drug, with values ranging from 6% to 62%. Conclusions Overall, poor responsiveness of the screening tests to DOAC concentrations was observed. PT and APTT normal values cannot exclude DOAC anticoagulant activity, and PT or APTT prolongation is not always associated with DOAC anticoagulant effect as determined with specific tests.

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer.

BACKGROUND: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. PATIENTS AND METHODS: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). RESULTS: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. CONCLUSIONS: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01640782.

Need of more frequent International Normalized Ratio monitoring in elderly patients on long-term anticoagulant therapy after influenza vaccination.

Previous findings suggest the safety of influenza vaccination for patients on oral anticoagulant therapy (OAT). However, some studies reported a moderate reduction or increase of the anticoagulation. We assessed the effect of influenza vaccination on anticoagulation levels. Seventy-three patients on stable long-term OAT were recruited. Patients were compared with a control group of 72 patients observed during the same period. No differences in the anticoagulation levels were found in patients and in controls during the 3 months before and after the vaccination. However, in patients older than 70 years we observed a reduction of anticoagulation intensity achieved in the month after the vaccination, with a prolonged time spent below the therapeutic range (10% before and 27% after, P = 0.001), and this behaviour was still observed 3 months after vaccination. Influenza vaccination is safe in patients on OAT, but it is associated with a slight reduction in warfarin effect in the elderly, suggesting the need of more frequent International Normalized Ratio monitoring after vaccination in these subjects.