Cancer patients requiring interruption of long-term warfarin because of surgery or chemotherapy induced thrombocytopenia: the use of fixed sub-therapeutic doses of low-molecular weight heparin.

No data are available regarding the management of cancer patients requiring interruption of long-term vitamin-K antagonist (VKA) therapy. For this purpose, we tested the efficacy and safety of fixed doses of low-molecular weight heparin (LMWH) in substitution of VKA because of invasive procedures or chemotherapy-induced thrombocytopenia. In cancer patients on VKA, therapy was discontinued 5 ± 1 days before surgery or chemotherapy. Heparin was given at prophylactic dosage in patients at low risk and at fixed subtherapeutic doses (3,800 or 4,000 UI anti-FXa, b.i.d.) in those at high-risk for thrombosis. LMWH was reinitiated 12 hr after surgery and VKA the day after. In patients receiving chemotherapy, LMWH was reinitiated 12/24 hr after obtaining a stable platelet count ≥ 30,000 mmc(3) and VKA after a stable platelet count ≥ 50,000 mmc(3) . Thromboembolism and major bleeding events were recorded from the time of VKA suspension to 30 ± 2 days postprocedure or until the next chemotherapy. Overall, 156 patients (56.4% at low risk and 43.5% at high risk for thrombosis) were enrolled; 34.6% underwent major surgery, 40.4% nonmajor surgery, and 25% chemotherapy. Thrombotic events occurred in five patients [3.2%, 95% confidence interval (CI): 1.41-7.27], four belonging to the high-risk and one to the low-risk group. Major bleeding occurred in five patients (3.2%, 95 CI: 1.41-7.27), all belonging to the high-risk group (three during major surgery and two during chemotherapy). In conclusion, LMWH given at fixed subtherapeutic is a feasible and relatively safe approach for bridging therapy in cancer patients on long-term VK

Clinical implications of discordant early molecular responses in CML patients treated with imatinib

A reduction in BCR-ABL1/ABL1IS transcript levels to <10% after 3 months or <1% after 6 months of tyrosine kinase inhibitor therapy are associated with superior clinical outcomes in chronic myeloid leukemia (CML) patients. In this study, we investigated the reliability of multiple BCR-ABL1 thresholds in predicting treatment outcomes for 184 subjects diagnosed with CML and treated with standard-dose imatinib mesylate (IM). With a median follow-up of 61 months, patients with concordant BCR-ABL1/ABL1IS transcripts below the defined thresholds (10% at 3 months and 1% at 6 months) displayed significantly superior rates of event-free survival (86.1% vs. 26.6%) and deep molecular response (≥ MR4; 71.5% vs. 16.1%) compared to individuals with BCR-ABL1/ABL1IS levels above these defined thresholds. We then analyzed the outcomes of subjects displaying discordant molecular transcripts at 3-and 6-month time points. Among these patients, those with BCR-ABL1/ABL1IS values >10% at 3 months but <1% at 6 months fared significantly better than individuals with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (event-free survival 68.2% vs. 32.7%; p < 0.001). Likewise, subjects with BCR-ABL1/ABL1IS at 3 months >10% but <1% at 6 months showed a higher cumulative incidence of MR4 compared to patients with BCR-ABL1/ABL1IS <10% at 3 months but >1% at 6 months (75% vs. 18.2%; p < 0.001). Finally, lower BCR-ABL1/GUSIS transcripts at diagnosis were associated with BCR-ABL1/ABL1IS values <1% at 6 months (p < 0.001). Our data suggest that when assessing early molecular responses to therapy, the 6-month BCR-ABL1/ABL1IS level displays a superior prognostic value compared to the 3-month measurement in patients with discordant oncogenic transcripts at these two pivotal time points

Drug-Related Cardiotoxicity for the Treatment of Haematological Malignancies in Elderly.

Meyer Paul Hugo. Diderot oder die Ambivalenz der Aufklärung, Neumann, 1987. In: Recherches sur Diderot et sur l'Encyclopédie, n°4, 1988. pp. 164-165

Solar photo-Fenton at mild conditions to treat a mixture of six emerging pollutants

The applicability of photo-Fenton to degrade a mixture of emerging pollutants (EPs) namely amoxycillin, acetaminophen, acetemiprid, caffeine, clofibric acid and carbamazepine has been studied at different scenarios. At high concentrations, acidic photo-Fenton was able to achieve a fast removal of the EPs. Although, complete mineralization was not reached, the toxicity of the solution was decreased according to the respiration of activated sludge and luminescence of Vibrio fischeri assays, although according to this last assay a transitory enhancement of the toxicity was found, attributable to the formation of toxic byproducts such as phenols, chlorophenols and chlorinated pyrydines. Experiments carried out with 5 mg/l of each EP showed that at neutral media the process was two orders of magnitude less efficient than at acidic pH, although it was still able to remove the EPs. The aqueous matrix has a remarkable effect on the process as the presence of humic acids increased the reaction rate and inorganic salts played an inhibitory role. Finally, experiments performed with 10 lg/l of each EP showed that under those experimental conditions nearly complete removal of the EPs was reached with neutral photo-Fenton after 120 min of irradiation; in this case, humic substances played a disfavorable role.We want to thank the financial support of Spanish Ministerio de Ciencia e Innovacion (CTQ 2009-13459-0O5-03) and (CTQ 2009-3459-C05-01).Bernabeu García, A.; Palacios Guillem, S.; Vicente Candela, R.; Vercher Pérez, RF.; Malato Rodríguez, S.; Arques Sanz, A.; Amat Payá, AM. (2012). Solar photo-Fenton at mild conditions to treat a mixture of six emerging pollutants. Chemical Engineering Journal. 198:65-72. https://doi.org/10.1016/j.cej.2012.05.056S657219

Microcontaminant degradation in municipal wastewater treatment plant secondary effluent by EDDS assisted photo-Fenton at near-neutral pH: An experimental design approach

This work aims to evaluate the applicability of EDDS (ethylenediamine-N,N'-disuccinic acid) as an iron chelating agent for photo-Fenton treatment of municipal wastewater spiked with organic contaminants at near-neutral pH. A series of laboratory scale experiments are conducted under simulated sunlight in accordance with a central composite experimental design in order to define the most favorable conditions in terms of initial iron concentration (maintaining a molar ratio 1:2 of Fe:EDDS), H2O2 and pH. The system is evaluated in terms of degradation efficiency, H2O2 consumption and iron availability. The simulated system has been compared in terms of degradation efficiency with a 60 L compound parabolic collector (CPC), and significant correlation has been observed. An approach for estimating near-optimal regions of operability is also demonstrated. (C) 2015 Elsevier B.V. All rights reserved

Residual vein thrombosis for assessing duration of anticoagulation after unprovoked deep vein thrombosis of the lower limbs: the extended DACUS study.

Abstract The safest duration of anticoagulation after idiopathic deep vein thrombosis (DVT) is unknown. We conducted a prospective study to assess the optimal duration of vitamin K antagonist (VKA) therapy considering the risk of recurrence of thrombosis according to residual vein thrombosis (RVT). Patients with a first unprovoked DVT were evaluated for the presence of RVT after 3 months of VKA administration; those without RVT suspended VKA, while those with RVT continued oral anticoagulation for up to 2 years. Recurrent thrombosis and/or bleeding events were recorded during treatment (RVT group) and 1 year after VKA withdrawal (both groups). Among 409 patients evaluated for unprovoked DVT, 33.2% (136 of 409 patients) did not have RVT and VKA was stopped. The remaining 273 (66.8%) patients with RVT received anticoagulants for an additional 21 months; during this period of treatment, recurrent venous thromboembolism and major bleeding occurred in 4.7% and 1.1% of patients, respectively. After VKA suspension, the rates of recurrent thrombotic events were 1.4% and 10.4% in the no-RVT and RVT groups, respectively (relative risk = 7.4; 95% confidence interval = 4.9-9.9). These results indicate that in patients without RVT, a short period of treatment with a VKA is sufficient; in those with persistent RVT, treatment extended to 2 years substantially reduces, but does not eliminate, the risk of recurrent thrombosis

Effect of Related and Unrelated Donor Haematopoietic Stem-Cell Transplantation on Outcome in Adults With High Risk Hematological Disease: An intention-to-treat Analysis of 410 Patients at a Single Center Institution

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Pregnancy complications in acquired thrombotic thrombocytopenic purpura : a case-control study

BackgroundPregnant women with a history of acquired thrombotic thrombocytopenic purpura (TTP) are considered at risk for disease recurrence and might be at risk for miscarriage, similar to other autoimmune disorders. However, the exact entity of these risks and their causes are unknown. The aim of this study was to evaluate risk factors associated with adverse pregnancy outcome, in terms of both gravidic TTP and miscarriage, in women affected by previous acquired TTP.MethodsWe conducted a nested case\ubfcontrol study in women with a history of acquired TTP enrolled in the Milan TTP registry from 1994 to October 2012, with strict inclusion criteria to reduce referral and selection bias.ResultsFifteen out of 254 women with acquired TTP were included, namely four cases with gravidic TTP, five with miscarriage, and six controls with uncomplicated pregnancy. In the cases, ADAMTS13 activity levels in the first trimester were moderately-to-severely reduced (median levels <3% in gravidic TTP and median levels 20% [range 14-40%] in the women with miscarriage) and anti-ADAMTS13 antibodies were invariably present, while in the control group ADAMTS13 activity levels were normal (median 90%, range 40-129%), with absence of detectable anti-ADAMTS13 antibodies. Reduced levels of ADAMTS13 activity (<25%) in the first trimester were associated with an over 2.9-fold increased risk for gravidic TTP and with an over 1.2-fold increased risk for miscarriage (lower boundary of the confidence interval of the odds ratio). In addition, the presence of anti-ADAMTS13 antibodies during pregnancy was associated with an over 6.6-fold increased risk for gravidic TTP and with an over 4.1-fold increased risk for miscarriage.ConclusionsADAMTS13 activity evaluation and detection of anti-ADAMTS13 antibody could help to predict the risk of complications in pregnant women with a history of acquired TTP