In highly immunocompromised patients, the effectiveness of 3 mg/kg of liposomal amphotericin B per day as first-line therapy for invasive aspergillosis is demonstrated, with a response rate of 50% and a 12-week survival rate of 72%. The regimen of 10 mg/kg per day demonstrated no additional benefit and higher rates of nephrotoxicity.

International audienceInvasive fungal infections are a main cause of morbidity and mortality in cancer patients undergoing intensive chemotherapy regimens. Early antifungal treatment is mandatory to improve survival. Today, a number of effective and better-tolerated but more expensive antifungal agents compared to the former gold standard amphotericin B deoxycholate are available. Clinical decision-making must consider results from numerous studies and published guidelines, as well as licensing status and cost pressure. New developments in antifungal prophylaxis improving survival rates result in a continuous need for actualization. The treatment options for invasive infections include fluconazole, voriconazole, and amphotericin B and its lipid formulations, as well as echinocandins. Voriconazole, amphotericin B, amphotericin B lipid formulations, caspofungin, itraconazole, and posaconazole are available for the treatment of invasive aspergillosis. Additional procedures, such as surgical interventions, immunoregulatory therapy, and granulocyte transfusions, have to be considered. The Infectious Diseases Working Party of the German Society of Hematology and Oncology here presents its 2008 recommendations discussing the dos and do-nots, as well as the problems and possible solutions, of evidence criteria selection

The PC needs of patients with advanced COPD are comparable with LC patients, and breathlessness severity and distress are even higher. The care for COPD patients requires further improvement to address symptom burden and PC needs.

In patients with MBC receiving chemotherapy and initial Hb less than 12.9 g/dL, epoetin beta increased Hb. No difference was detected in overall survival. Because of its superiority design, this study cannot, however, exclude clinically important differences in survival with absolute certainty.

Duration of neutropenia, high-dose cytarabine, prior antibiotic therapy and a partial response to the first IFI therapy were risk factors for recurrent IFI and should be considered in AML patients with prior pulmonary IFI undergoing further chemotherapy.

BackgroundA prospective observational registry assessed real world experience with caspofungin monotherapy or combination therapy for the initial or salvage treatment of proven or probable invasive aspergillosis (IA).MethodsData were collected from April 2006 to September 2007 for patients treated with caspofungin for a single episode of IA. Clinical effectiveness was categorized as favorable (complete or partial) or unfavorable (stable disease or failure) at the end of caspofungin therapy (EOCT).ResultsConsecutive patients (n = 103) with proven or probable IA (per EORTC/MSG criteria) were identified from 11 countries. Malignancy (76.7%), neutropenia (64.1%), allogeneic hematopoietic stem cell transplantation (HSCT, 22.3%), solid organ transplantation (8.7%), autologous HSCT (4.9%), and HIV/AIDS (2.9%) were the most common underlying conditions. Most patients (84.5%) had pulmonary IA. Aspergillus fumigatus was the most frequently isolated species. The majority of patients received caspofungin monotherapy (82.5%) primarily as salvage therapy (82.4%). The main reason for switching to salvage therapy was clinical failure of the first-line therapy (69%). A favorable response at EOCT was seen in 56.4% (57/101) of patients overall, including 56.5% (48/85) and 56.3% (9/16) of patients receiving caspofungin monotherapy and combination therapy, respectively. Favorable response rates in clinically relevant subgroups were: malignancy, 51.9% (41/79); allogeneic HSCT, 56.5% (13/23); and neutropenia at time of hospitalization, 53.0% (35/66). There was a 72.3% (73/101) survival at 7 days after EOCT. Serious adverse events related to caspofungin were reported in 4 cases (3.9%); 3 patients (2.9%) discontinued treatment due to an adverse event related to caspofungin.ConclusionsCaspofungin was both effective and well tolerated among high-risk patient groups such as those with neutropenia and active malignancies.

Two novel soluble polymer-bound oligo-L-leucines 2 and 5, which can be retained by a membrane reactor system, have been prepared and used as catalysts for the continuously operated asymmetric epoxidation of chalcone. The optimized batch reaction conditions yield epoxychalcone in high enantioselectivities (up to 94%) and conversions (over 99%) after 15 minutes.Epoxides are widely used compounds in organic synthesis. 1 For this reason several approaches to effect enantioselective epoxidation have been made. 2 Among the welldeveloped methods, the Juliá-Colonna epoxidation, which utilizes chiral polyamino acids (in particular poly-L-leucine) as heterogeneous catalysts, has emerged as the first reliable method for the asymmetric epoxidation of electron-deficient olefins, exhibiting exceptionally high chiral induction for chalcone. 3Degussa and their partners from the University of Liverpool have worked intensively on the improvement of heterogeneous Juliá-Colonna oxidation. A noteworthy modification includes the introduction of percarbonate in dimethoxyethane as a cheap oxidant/solvent system for the use in some polyamino acid-catalysed epoxidations. 4The poly-L-leucine catalyst remained insoluble under all the reaction conditions applied. The first homogeneous version of the Juliá-Colonna epoxidation of trans-chalcone was reported recently. 5 However, the conversion observed was only 39% after 1 hour and 80% after 24 hours with an ee of 95-98%.Since the chiral information has to be transferred from the catalyst to the olefinic substrate, homogeneous asymmetric catalysis is a more attractive method for the synthesis of chiral epoxides. However, up to now, no process has made the step from an academically promising method to an application on larger scale.The interest of Degussa in developing methods for asymmetric synthesis in a chemzyme membrane reactor 6 promoted further investigation of the homogeneous enantioselective epoxidation of a,b-unsaturated ketones.We reasoned that the preparation of polymer enlarged oligo(L-leucine)s which were soluble in common organic solvents and large enough to be retained in a membrane reactor could allow us to develop a continuously operated asymmetric epoxidation of trans-chalcone.There are two major approaches to synthesize homogeneously soluble polymer-enlarged catalysts, that is using either linear polymers or dendrimers as carriers.We have focused our work on linear polymers, because they demand less synthetic effort. Thus, we prepared two types of soluble polymer enlarged oligo(L-leucine)s 2 and 5 (Scheme 1, Scheme 2). The approach to catalyst 2 involved the co-polycondensation of 1 equivalent of commercially available O,O-bis(2-aminoethyl)-polyethyleneglycol 20000 1 with 16 equivalents of L-leucine-N-carboxyanhydride in CHCl 3 . 7 Scheme 1 Synthesis of homogeneously soluble oligo(L-leucine) 2.We found that the resulting polyethyleneglycol-supported oligo(L-leucine) 2 can act as an efficient homogeneous chiral catalyst in the epoxidation of trans-chalcone 6 employing the urea ...

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