Effect of inulin on breath hydrogen, postprandial glycemia, gut hormone release, and appetite perception in RYGB patients: a prospective, randomized, cross-over pilot study.

BACKGROUND AND OBJECTIVE: Large intestinal fermentation of dietary fiber may control meal-related glycemia and appetite via the production of short-chain fatty acids (SCFA) and the secretion of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY). We investigated whether this mechanism contributes to the efficacy of the Roux-en-Y gastric bypass (RYGB) by assessing the effect of oligofructose-enriched inulin (inulin) vs. maltodextrin (MDX) on breath hydrogen (a marker of intestinal fermentation), plasma SCFAs, gut hormones, insulin and blood glucose concentrations as well as appetite in RYGB patients. METHOD: Eight RYGB patients were studied on two occasions before and ~8 months after surgery using a cross-over design. Each patient received 300 ml orange juice containing 25 g inulin or an equicaloric load of 15.5 g MDX after an overnight fast followed by a fixed portion snack served 3 h postprandially. Blood samples were collected over 5 h and breath hydrogen measured as well as appetite assessed using visual analog scales. RESULTS: Surgery increased postprandial secretion of GLP-1 and PYY (P ≤ 0.05); lowered blood glucose and plasma insulin increments (P ≤ 0.05) and reduced appetite ratings in response to both inulin and MDX. The effect of inulin on breath hydrogen was accelerated after surgery with an increase that was earlier in onset (2.5 h vs. 3 h, P ≤ 0.05), but less pronounced in magnitude. There was, however, no effect of inulin on plasma SCFAs or plasma GLP-1 and PYY after the snack at 3 h, neither before nor after surgery. Interestingly, inulin appeared to further potentiate the early-phase glucose-lowering and second-meal (3-5 h) appetite-suppressive effect of surgery with the latter showing a strong correlation with early-phase breath hydrogen concentrations. CONCLUSION: RYGB surgery accelerates large intestinal fermentation of inulin, however, without measurable effects on plasma SCFAs or plasma GLP-1 and PYY. The glucose-lowering and appetite-suppressive effects of surgery appear to be potentiated with inulin.

577-nm high-power optically pumped semiconductor laser is safe and effective in the treatment of inflammatory acne: a prospective, single-center, split-face comparative study.

OBJECTIVE: This study aimed to appraise the efficacy of a 577-nm high-power optically pumped semiconductor laser (HOPSL) for the treatment of inflammatory acne. METHODS: The study included 50 patients with acne vulgaris (inflammatory type), 14 men, and 36 women; patient ages ranged from 16 to 35 years. The left side of the face was treated with a single pass of a 577-nm high-power optically pumped semiconductor laser (HOPSL) every 2 weeks for 3 sessions. The severity of acne examined prior to the first session and 4 weeks after the last session (Investigator's Global Assessment of acne severity, IGA; single lesion count). RESULTS: At baseline, no statistically significant difference in the severity of inflammatory acne lesions between both sides was observed. One month after the final session, a significant improvement (IGA reduction of > 50%) of the overall severity of acne was observed in 49 patients (98%) on the laser-treated side versus 41 (82%) the control side of the face (P < .05). Hence, we found a significant reduction in the mean percentage of inflammatory papules, pustules, and nodules on the laser-treated versus the control side (79.33 vs 56.92, 78.04 vs 43.33, 64.85 vs 21.93%, respectively) (P < 0.05). Side effects in the form of erythema and irritation during sessions were transient and tolerated by the patients. CONCLUSION: The 577-nm high-power optically pumped semiconductor laser is effective and safe for the treatment of inflammatory lesions (papules, pustules, and nodules) in acne patients.

CCL20-CCR6 axis directs sperm-oocyte interaction and its dysregulation correlates/associates with male infertility‡.

The interaction of sperm with the oocyte is pivotal during the process of mammalian fertilization. The limited numbers of sperm that reach the fallopian tube as well as anatomic restrictions indicate that human sperm-oocyte encounter is not a matter of chance but a directed process. Chemotaxis is the proposed mechanism for re-orientating sperm toward the source of a chemoattractant and hence to the oocyte. Chemokines represent a superfamily of small (8-11 kDa), cytokine-like proteins that have been shown to mediate chemotaxis and tissue-specific homing of leukocytes through binding to specific chemokine receptors such as CCRs. Here we show that CCR6 is abundantly expressed on human sperms and in human testes. Furthermore, radioligand-binding experiments showed that CCL20 bound human sperm in a specific manner. Conversely, granulosa cells of the oocyte-surrounding cumulus complex as well as human oocytes represent an abundant source of the CCR6-specific ligand CCL20. In human ovaries, CCL20 shows a cycle-dependent expression pattern with peak expression in the preovulatory phase and CCL20 protein induces chemotactic responses of human sperm. Neutralization of CCL20 in ovarian follicular fluid significantly impairs sperm migratory responses. Conversely, analyses in infertile men with inflammatory conditions of the reproductive organs demonstrate a significant increase of CCL20/CCR6 expression in testis and ejaculate. Taken together, findings of the present study suggest that CCR6-CCL20 interaction may represent an important factor in directing sperm-oocyte interaction.

[Aesthetic Filler Injections and the Management of Side Effects]. / Ästhetische Behandlungen mit Fillern und das Management von Nebenwirkungen.

Over the past years aesthetic procedures have been evolving as an important part of daily dermatological practice. Herein, fillers represent an integral component of a modern, multimodal aesthetic treatment approach. Advances in the understanding of the aging face and modern fillers offer a broad variety of indications ranging from augmentation to hydration or collagen-induction. At the same time the range of available injection materials, products and techniques has grown to mere unmanageable dimensions. Finally, dermatologists are frequently confronted with the consequences of improper filler treatments or late side effects of early filler materials which have already disappeared from the market and even the experienced injector may encounter treatment-associated side effects. Here, we review the most important current and historic filler materials, including indications, injection techniques, adverse effects and the respective management recommendations.

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.

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.

BACKGROUND: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated. METHODS/DESIGN: In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events). DISCUSSION: This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13.

Molecular effects of fractional ablative erbium:YAG laser treatment with multiple stacked pulses on standardized human three-dimensional organotypic skin models.

The molecular changes in gene expression following ablative laser treatment of skin lesions, such as atrophic scars and UV-damaged skin, are not completely understood. A standardized in vitro model of human skin, to study the effects of laser treatment on human skin, has been recently developed. Therefore, the aim of the investigation was to examine morphological and molecular changes caused by fractional ablative erbium:YAG laser treatment on an in vitro full-thickness 3D standardized organotypic model of human skin. A fractional ablative erbium:YAG laser was used to irradiate organotypic human 3D models. Laser treatments were performed at four different settings using a variety of stacked pulses with similar cumulative total energy fluence (60 J/cm2). Specimens were harvested at specified time points and real-time PCR (qRT-PCR) and microarray studies were performed. Frozen sections were examined histologically. Three days after erbium:YAG laser treatment, a significantly increased mRNA expression of matrix metalloproteinases and their inhibitors (MMP1, MMP2, MMP3, TIMP1, and TIMP2), chemokines (CXCL1, CXCL2, CXCL5, and CXCL6), and cytokines such as IL6, IL8, and IL24 could be detected. qRT-PCR studies confirmed the enhanced mRNA expression of IL6, IL8, IL24, CXCLs, and MMPs. In contrast, the mRNA expression of epidermal differentiation markers, such as keratin-associated protein 4, filaggrin, filaggrin 2, and loricrin, and antimicrobial peptides (S100A7A, S100A9, and S100A12) as well as CASP14, DSG2, IL18, and IL36ß was reduced. Four different settings with similar cumulative doses have been tested (N10%, C10%, E10%, and W25%). These laser treatments resulted in different morphological changes and effects on gene regulations. Longer pulse durations (1000 µs) especially had the strongest impact on gene expression and resulted in an upregulation of genes, such as collagen-1A2, collagen-5A2, and collagen-6A2, as well as FGF2. Histologically, all treatment settings resulted in a complete regeneration of the epidermis 3 days after irradiation. Fractional ablative erbium:YAG laser treatment with a pulse stacking technique resulted in histological alterations and shifts in the expression of various genes related to epidermal differentiation, inflammation, and dermal remodeling depending on the treatment setting applied. A standardized in vitro 3D model of human skin proved to be a useful tool for exploring the effects of various laser settings both on skin morphology and gene expression during wound healing. It provides novel data on the gene expression and microscopic architecture of the exposed skin. This may enhance our understanding of laser treatment at a molecular level.

[Cutaneous side effects of targeted cancer drugs]. / Kutane Nebenwirkungen zielgerichteter onkologischer Arzneimittel.

In the past decades many new drugs were approved for the treatment of cancer and have been established as essential parts of various therapeutic regimens. In particular targeted therapies and immune checkpoint inhibitors that aim at specific carcinogenic signaling pathways or modulate the tumor-immune response have revolutionized cancer therapy. Despite their targeted actions, these drugs may lead to diverse adverse reactions. In particular, cutaneous toxicities represent a serious threat to patients' quality of life and may lead to dose reduction or therapy cessation. In most cases, basic management is performed by the treating oncologist. Nevertheless, more severe reactions may require the expertise of a dermatologist. In this review, we present specific cutaneous adverse reactions of new drug classes such as epidermal growth factor receptor inhibitors (EGFR-I), multikinase inhibitors (MKI), BRAF inhibitors, MEK inhibitors, and immune checkpoint inhibitors (anti-PD1-, anti-CTLA4-antibodies). Furthermore, we give recommendations concerning the prevention and management of respective cutaneous reactions.

A novel native collagen dressing with advantageous properties to promote physiological wound healing.

OBJECTIVE: Chronic hard-to-heal wounds generate high costs and resource use in western health systems and are the focus of intense efforts to improve healing outcomes. Here, we introduce a novel native collagen (90 %):alginate (10 %) wound dressing and compare it with the established oxidised dressings Method: Matrices were analysed by atomic force microscopy (AMF), scanning electron microscopy (SEM), and immunoelectron microscopy for collagen types I, III and V. Viability assays were performed with NIH-3T3 fibroblasts. Matrix metalloproteinase (MMP) binding was analysed, and the effect of the wound dressings on platelet-derived growth factor B homodimer (PDGF-BB) was investigated. RESULTS: Unlike oxidised regenerated cellulose (ORC)/collagen matrix and ovine forestomach matrix (OFM), the three-dimensional structure of the native collagen matrix (NCM) was found to be analogous to intact, native, dermal collagen. Fibroblasts seeded on the NCM showed exponential growth whereas in ORC/collagen matrix or OFM, very low rates of proliferation were observed after 7 days. MMP sequestration was effective and significant in the NCM. In addition, the NCM was able to significantly stabilise PDGF-BB in vitro. CONCLUSION: We hypothesise that the observed microstructure of the NCM allows for an effective binding of MMPs and a stabilisation and protection of growth factors and also promotes the ingrowth of dermal fibroblasts, potentially supporting the re commencement of healing in previously recalcitrant wounds. DECLARATION OF INTEREST: This work was supported by BSN Medical, Hamburg, Germany.

Alopecia in patients treated with molecularly targeted anticancer therapies.

BACKGROUND: The introduction of molecularly targeted anticancer therapies presents new challenges, among which dermatologic adverse events are noteworthy. Alopecia in particular is frequently reported, but the true incidence is not known. PATIENTS AND METHODS: We sought to ascertain the incidence and risk of developing alopecia during treatment with approved inhibitors of oncogenic pathways and molecules [anaplastic lymphoma kinase, breakpoint cluster region-abelson, B-rapidly accelerated fibrosarcoma, Bruton's tyrosine kinase, cytotoxic T-lymphocyte antigen-4, epidermal growth factor receptor, human epidermal growth factor receptor-2, Janus kinase, MAPK/ERK (extracellular signal-regulated kinase) Kinase, mammalian target of rapamycin, smoothened, vascular endothelial growth factor, vascular endothelial growth factor receptor, platelet derived growth factor receptor; proteasomes; CD20, CD30, CD52]. Electronic database (PubMed, Web of Science) and ASCO meeting abstract searches were conducted to identify clinical trials reporting alopecia. Meta-analysis was conducted utilizing fixed- or random-effects models. RESULTS: The calculated overall incidence of all-grade alopecia was 14.7% [95% confidence interval (CI) 12.6% to 17.2%]-lowest with bortezomib, 2.2% (95% CI 0.4% to 10.9%), and highest with vismodegib, 56.9% (95% CI 50.5% to 63.1%). There was an increased risk of all-grade alopecia [relative risk (RR), 7.9 (95% CI 6.2-10.09, P ≤ 0.01)] compared with placebo, but when compared with chemotherapy, the risk was lower [RR, 0.32 (95% CI 0.2-0.55, P ≤ 0.01)]. CONCLUSIONS: Targeted therapies are associated with an increased risk of alopecia.

Allergic sensitization to pegylated interferon-α results in drug eruptions.

BACKGROUND: The introduction of pegylated interferon (PEG-IFN)-α in the treatment of chronic hepatitis C has led to an increase in sustained virological response. Despite reduced immunogenicity of the pegylated form in comparison with native interferon (IFN)-α, a high frequency of adverse cutaneous reactions has been reported with pegylated IFN-α. Here, we aimed to investigate the immunological mechanisms underlying pegylated IFN-α-induced drug eruptions. METHODS: Hepatitis C patients suffering from drug eruptions in association with administration of pegylated interferons were enrolled in the study (n = 22). Subjects were tested for sensitivity to pegylated IFN-α2a , pegylated IFN-α2b , or ribavirin using intradermal, scratch, and/or patch tests, as well as lymphocyte activation tests (LATs). Skin biopsies obtained from pegylated IFN-α-associated exanthemas, as well as from localized inflammatory skin reactions at pegylated IFN-α injection sites, were analyzed for the expression of relevant chemokines by quantitative real-time PCR and immunohistochemistry. RESULTS: A subset of patients suffering from pegylated IFN-α-associated exanthemas displayed positive intradermal tests to PEG-IFNs but not to conventional IFN (11/22). In selected patients, this observation correlated with the presence of pegylated IFN-specific T cells (3/11). Chemokine profiles of inflammatory skin reactions at the injection sites reflected an IFN-α-signature, whereas lesional skin of exanthemas showed induction of TH2-associated chemokines. CONCLUSIONS: Our results indicate that specific sensitizations are one cause of exanthemas under therapy with PEG-IFNs. Clinical proof-of-concept analyses demonstrate that affected patients may benefit from a switch to conventional, nonpegylated drugs, enabling IFN-α therapy continuation without drug-associated skin eruptions.

[Successful therapy of condylomata acuminata with ingenol mebutate]. / Erfolgreiche Therapie von Condylomata acuminata mit Ingenolmebutat.

Condylomata acuminata (CA) are one of the most common sexually transmitted infections in the sexually active population. Due to the stigmatizing character of the disease and the high rate of relapse after therapy, CA may significantly affect patients' quality of life. Here, we report the case of successful treatment of multiple CA of the penis and scrotum in a 53-year-old man with ingenol mebutate gel.

[Successful drug desensitization after vemurafenib-induced rash]. / Erfolgreiche Medikamentendesensibilisierung nach Vemurafenib-induziertem Arzneimittelexanthem.

The BRAF inhibitor vemurafenib was approved in 2011 for the treatment of inoperable or metastatic melanoma. Vemurafenib therapy is associated with several side effects, such as arthralgia, secondary skin tumors or inflammatory rashes. In particular cutaneous toxicities represent a serious threat to patients' adherence. Here, we present the case of a successful drug desensitization in a patient that presented with a vemurafenib-induced rash. Lymphocyte activation tests failed to detect drug-specific T cells, suggesting that the development of the rash was based upon a nonallergic drug hypersensitivity reaction. A program of slow desensitization was initiated and subsequently, vemurafenib was tolerated at the full effective and recommended dosage.

[Successful treatment of a professional tattoo with the R20 method]. / Erfolgreiche Lasertherapie einer Tätowierung mit der R20-Methode.

A 54-year-old man presented for the removal of a professional tattoo on the right upper arm. We initiated a comparative treatment with a q-switched 694-nm Ruby laser (TattooStar® Effect, Asclepion® Lasertechnologies, Jena, Germany, Spot: 4 mm, Fluence: 4 J/cm(2)) using the so-called R20-method. The tattoo was divided into three equal parts and was treated with up to three passes in one session at intervals of 20 min. After 3 sessions, which were conducted at intervals of 4 weeks, the areas that had been treated with multiple passes per session showed a significantly stronger fading compared to the area that had been treated with single passes. The patient reported a slight, transient blistering in the area that had been treated with three passes. Nevertheless, we did not observe any scarring or other irreversible complications. Our observation demonstrates the efficacy of the R20-method for the laser-removal of tattoos.

[Management of complications after aesthetic hyaluronic acid injections]. / Management von Komplikationen nach ästhetischen Hyaluronsäureinjektionen.

The use of hyaluronic acid fillers for treatment of rhytides (wrinkles) is widespread in aesthetic dermatology and is considered a safe procedure; however, complications can occur especially if the injections are carried out by an inexperienced person and/or with a lack of anatomical knowledge. The two cases presented here exemplify this problem. In conclusion, both cases demonstrate complications after uncritical injection of hyaluronic acid fillers into "risk" or "expert" regions. While the patients in these two cases recovered completely, the injection of filler substances can also lead to the risk of potentially permanent side effects, such as granuloma, necrosis with scar tissue formation and even blindness. The frequency and severity of complications often show a direct correlation with the qualification or expertise of the person treating and hence injection treatments should be performed solely by physicians.