Treatment of onychomycosis using a 1064-nm diode laser with or without topical antifungal therapy: a single-center, retrospective analysis in 56 patients.

BACKGROUND: Currently available treatment options for onychomycosis such as topical and systemic antifungals are often of limited efficacy, difficult to administer or associated with relevant side effects. Non-ablative laser therapy is proposed to represent a safe alternative without the disadvantages of drugs. Yet, to date, the efficacy of laser therapy for onychomycosis is discussed controversially. Against this background, we performed a systematic retrospective analysis of our clinical experience of 4 years of onychomycosis treatment applying a long-pulsed 1.064-nm diode laser. METHODS: We retrospectively evaluated the records of 56 patients with microscopic and culturally proven onychomycosis affecting a toenail of the hallux and other toes, who had been treated with a long-pulsed 1.064-nm diode laser (FOX, A.C.R. Laser GmbH, Nuremberg) during the time period of July 2013-December 2016 with or without concomitant topical antifungals. Thereof, 27 patients received laser treatment and 29 patients received laser treatment in combination with local antifungals. We conducted a mean of 3.9 laser treatments at 2-6-week intervals. The primary endpoint of our analysis was clinical improvement; secondary endpoints were complete remission of fungal pathogens in fungal culture and in microscopy. RESULTS: Clinical improvement was achieved in 56% of patients treated with laser only after a mean of 4.5 treatments and in 69% of patients treated with laser in combination with topical antifungals after a mean of 3.6 treatments. Cultural healing was detected in 63% of patients treated with laser only after a mean of 5.4 treatments, vs. 86% of patients treated with laser and concomitant topical antifungals after a mean of 4.8 treatments. Microscopic healing (complete healing) with the absence of fungal pathogens was achieved in 11% of patients after a mean of 4.7 treatments with laser only, vs. 21% of patients treated with laser and concomitant topical antifungals after a mean of 4 treatments. No relevant adverse effects were observed. CONCLUSIONS: The 1.064-nm diode laser is an effective and safe option for the treatment of onychomycosis. Of note, the combination with topical antifungals will increase overall treatment efficacy and reduce the time to healing. Particularly, patients with contraindications against systemic antifungals may benefit from this multimodal therapeutic approach. Our data, moreover, suggest that treatment efficacy is positively correlated with the total number of laser treatments.

Anti-CD20 monoclonal antibody-dependent phagocytosis of chronic lymphocytic leukaemia cells by autologous macrophages.

Unconjugated monoclonal antibodies (mAbs) are an important component of effective combination therapies for chronic lymphocytic leukaemia (CLL). Antibody-dependent phagocytosis (ADP) is a major mediator of mAb cytotoxicity, but there is limited knowledge of the determinants of ADP efficacy. We used macrophages derived in vitro from autologous circulating monocytes to test the effects of mAb structure and concentration, target : effector cell ratio, duration of co-incubation and CLL cell CD20 expression on ADP. Next-generation anti-CD20 mAbs (ofatumumab, ublituximab, obinutuzumab, ocaratuzumab) were significantly more effective at inducing ADP compared to rituximab, but none were as effective as the anti-CD52 mAb alemtuzumab. Ofatumumab (10 µg/ml) used as a representative next-generation anti-CD20 mAb achieved an ADP plateau at 3 h co-incubation with a target : effector ratio of 10 : 1 (mean = 2.1 CLL cells/macrophage, range = 1.5-3.5). At 0.156 µg/ml (the lowest concentration tested) ofatumumab ADP was significantly higher than alemtuzumab. However, ofatumumab-induced ADP did not increase significantly at higher mAb concentrations. We show that anti-CD20 mAb ADP efficacy is determined by the mAb characteristics, target : effector ratio and incubation time. We suggest that preclinical evaluation of anti-CD20 mAbs to understand the determinants of ADP could be useful in designing future combination therapies for CLL.

[Multiple erythema migrans and facial nerve paralysis: clinical manifestations of early disseminated Lyme borreliosis]. / Multilokuläre Erythemata migrantia und Fazialisparese : Klinische Manifestationsformen der disseminierten Frühinfektion der Lyme-Borreliose.

Lyme borreliosis is a common vector-borne disease in Europe. The infection follows different stages with a broad variability of clinical symptoms and manifestations in different organs. A 49-year-old man presented with flu-like symptoms, facial nerve paralysis and multiple erythematous macular on his trunk and extremities. We diagnosed Lyme disease (stage II) with facial nerve paralysis and multiple erythema migrans. Intravenous ceftriaxone led to complete healing of hissymptoms within 2 weeks.

[Current status of oral immunomodulatory and immunosuppressive agents]. / Aktueller Stand der oralen Therapie mit immunmodulatorischen und immunsuppressiven Medikamenten.

Various dermatological disorders require treatments with immunosuppressive or immunomodulatory agents. Nevertheless, several studies demonstrate low prescription rates for systemic treatments. This low usage may be a result of physicians' low levels of confidence in administering systemic treatments. However, immunosuppressive treatments represent safe options when potential side effects as well as pharmacological interactions are considered. This review overviews the most important oral immunosuppressive or immunomodulatory agents and summarizes their mode of actions, indications, and adverse effects. Biologics that require intravenous or subcutaneous application are not included, but novel and new agents likely to be released soon are considered.

[NK/T-cell lymphoma, nasal type with cutaneous dissemination]. / NK/T-Zell-Lymphom vom nasalen Typ mit kutaner Dissemination.

Extranodal NK/T-cell lymphoma, nasal type, is a lymphoproliferative disorder originating from peripheral T-cells or natural killer (NK) cells. While it is a rare disease in Europe, it is more frequent in Asia and South America. It is associated with Epstein-Barr virus (EBV) infection and characterized by an extremely aggressive course and poor prognosis. We report a 46-year-old Caucasian woman who presented with multiple subcutaneous, painful nodules on the trunk first noticed a few weeks earlier. In addition to dermatological findings, the patient reported a 4-months history of necrotizing nasopharyngeal inflammation of unclear origin. Due to nonspecific histological and clinical findings mimicking a chronic inflammatory condition, a diagnosis of Wegener disease was made and immunosuppressive therapy with azathioprine was initiated. However the disease progressed under therapy. Histopathological reevaluation and immunophenotyping revealed a disseminated NK/T-cell lymphoma, nasal type. In the case of an unspecific chronic inflammatory process in the nasopharyngeal space one should always consider the possibility of this rare lymphoma, even in Europe.

Role of the novel mTOR inhibitor RAD001 (everolimus) in anaplastic thyroid cancer.

Activation of the phosphatidylinositol-3-kinase (PI3K) signaling cascade is increasingly recognized as a common feature of thyroid follicular neoplasms. Among the PI3K downstream effectors, the main kinase, directly responsible for the increased cell growth and proliferation, is called mammalian target of rapamycin (mTOR). This central kinase might be directly inhibited via rapamycin and its derivatives. The aim of the present study was to examine whether RAD001 (everolimus) can selectively suppress the proliferation of different anaplastic thyroid cancer (ATC) cells. Five different human ATC cell lines were exposed to different concentrations of RAD001. Importantly, we found a dose-dependent growth inhibition in two ATC cell lines at concentrations of 43.5 and 94.5 nM although not as intensive as within the RAD001 responding K562cell line. The other cell lines revealed a GI (50) between 168 to 234 nM. In parallel, quantitative PCR of PCNA displayed a reduced expression of PCNA within the responding cell lines, respectively. In summary, we found a good responding effect in a part of ATC cell lines, which may have a clinical impact.