Cyclophosphamide vs rituximab for eradicating inhibitors in acquired hemophilia A: A randomized trial in 108 patients.

BACKGROUND: Acquired hemophilia A (AHA) is a rare autoimmune disorder due to autoantibodies against Factor VIII, with a high mortality risk. Treatments aim to control bleeding and eradicate antibodies by immunosuppression. International recommendations rely on registers and international expert panels. METHODS: CREHA, an open-label randomized trial, compared the efficacy and safety of cyclophosphamide and rituximab in association with steroids in patients with newly diagnosed AHA. Participants were treated with 1 mg/kg prednisone daily and randomly assigned to receive either 1.5-2 mg/kg/day cyclophosphamide orally for 6 weeks, or 375 mg/m2 rituximab once weekly for 4 weeks. The primary endpoint was complete remission over 18 months. Secondary endpoints included time to achieve complete remission, relapse occurrence, mortality, infections and bleeding, and severe adverse events. RESULTS: Recruitment was interrupted because of new treatment recommendations after 108 patients included (58 cyclophosphamide, 50 rituximab). After 18 months, 39 cyclophosphamide patients (67.2 %) and 31 rituximab patients (62.0 %) were in complete remission (OR 1.26; 95 % CI, 0.57 to 2.78). In the poor prognosis group (FVIII < 1 IU/dL, inhibitor titer > 20 BU mL-1), significantly more remissions were observed with cyclophosphamide (22 patients, 78.6 %) than with rituximab (12 patients, 48.0 %; p = 0.02). Relapse rates, deaths, severe infections, and bleeding were similar in the 2 groups. In patients with severe infection, cumulative doses of steroids were significantly higher than in patients without infection (p = 0.03). CONCLUSION: Cyclophosphamide and rituximab showed similar efficacy and safety. As first line, cyclophosphamide seems preferable, especially in poor prognosis patients, as administered orally and less expensive. FUNDING: French Ministry of Health. CLINICALTRIALS: gov number: NCT01808911.

Sub-wavelength energy concentration with electrically generated mid-infrared surface plasmons.

While freely propagating photons cannot be focused below their diffraction limit, surface-plasmon polaritons follow the metallic surface to which they are bound, and can lead to extremely sub-wavelength energy volumes. These properties are lost at long mid-infrared and THz wavelengths where metals behave as quasi-perfect conductors, but can in principle be recovered by artificially tailoring the surface-plasmon dispersion. We demonstrate - in the important mid-infrared range of the electromagnetic spectrum - the generation onto a semiconductor chip of plasmonic excitations which can travel along long distances, on bent paths, to be finally focused into a sub-wavelength volume. The demonstration of these advanced functionalities is supported by full near-field characterizations of the electromagnetic field distribution on the surface of the active plasmonic device.

Semiconductor surface plasmon sources.

Surface-plasmon polaritons (SPPs) are propagating electromagnetic modes bound at a metal-dielectric interface. We report on electrical generation of SPPs by reproducing the analogue in the near field of the slit-doublet experiment, in a device which includes all the building blocks required for a fully integrated plasmonic active source: an electrical generator of SPPs, a coupler, and a passive metallic waveguide. SPPs are generated upon injection of electrical current, and they are then launched at the edges of a passive metallic strip. The interference fringes arising from the plasmonic standing wave on the surface of the metallic strip are unambiguously detected with apertureless near-field scanning optical microscopy.

A semiconductor laser device for the generation of surface-plasmons upon electrical injection.

Surface plasmons are electromagnetic waves originating from electrons and light oscillations at metallic surfaces. Since freely propagating light cannot be coupled directly into surface-plasmon modes, a compact, semiconductor electrical device capable of generating SPs on the device top metallic surface would represent an advantage: not only SP manipulation would become easier, but Au-metalized surfaces can be easily functionalized for applications. Here, we report a demonstration of such a device. The direct proof of surface-plasmon generation is obtained with apertureless near-field scanning optical microscopy, which detects the presence of an intense, evanescent electric field above the device metallic surface upon electrical injection.