Management of psoriatic arthritis by dermatologists - a German nationwide survey.

BACKGROUND AND OBJECTIVES: Psoriatic arthritis (PsA) warrants early diagnosis and treatment for optimal results. This study aimed to elucidate routine monitoring activities for PsA with concurrent psoriasis (PsO) by dermatologists to gather data on how conditions for optimal treatment are ensured. PATIENTS AND METHODS: This non-interventional, prospective, epidemiological, cross-sectional study (2016-2019) included patients with confirmed PsA from dermatologists. Descriptive statistics were conducted for center and patient characteristics as well as for data of PsA monitoring and treatment stratified by different center types. RESULTS: 212 patients from 34 office-based physicians, five non-university hospitals, and nine university hospitals were included. The majority of the PsA patients were diagnosed by a rheumatologist (> 55% in each center type) at an early or intermediate stage (> 59%). Treatment was initiated most frequently by a dermatologist (office-based physicians: 69.6%, hospitals: 60.9%, university hospitals: 82.9%). Patients were treated with biologics more frequently in university hospitals (single therapy: 43.9%, in combination with systemic therapy: 26.8%) compared to private practices (single: 44.6%, combination: 13.5%) and non-university hospitals (single: 34.8%, combination: 8.7%). CONCLUSIONS: As PsA diagnosis was performed most frequently by rheumatologists whereas treatment was primarily initiated by dermatologists, an optimal collaboration between these specialists is crucial.

Efficacy and Treatment Satisfaction of Different Systemic Therapies in Children and Adolescents with Moderate-to-Severe Atopic Dermatitis: A Real-World Study.

For the treatment of moderate-to-severe atopic dermatitis in children and adolescents, the monoclonal antibody dupilumab and the selective JAK-1 inhibitor upadacitinib are two modern systemic therapies approved for long-term treatment. Both drugs have demonstrated high efficacy in randomized controlled trials, although evidence from real-world data in the pediatric population is limited. In a prospective analysis over 24 weeks, we investigated the efficacy, safety and treatment satisfaction of both systemic therapies in 23 patients (16 patients treated with dupilumab; 7 patients treated with upadacitinib). The median age of the patients was 16 years, with a median EASI of 18.8. A significant improvement in the EASI, VAS-itch, CDLQI, POEM and DFIQ from baseline to week 24 was demonstrated for both treatment options. No significant difference was observed between dupilumab and upadacitinib in any of the assessed scores. Less adverse events were recorded in the real-world setting compared with clinical trials. Our results confirm the efficacy and safety of dupilumab and upadacitinib as equivalent treatment options in children and adolescents in a real-world setting.

How wound environments trigger the release from Rifampicin-loaded liposomes.

BACKGROUND: Chronic wounds often contain high levels of proinflammatory cytokines that prolong the wound-healing process. Patients suffering from these conditions are likely to benefit from topical rifampicin therapy. Although recent research indicates considerable anti-inflammatory properties of the antibiotic, currently, there are no commercial topical wound healing products available. To address this medical need, a liposomal drug delivery system was developed. A mechanistic investigation outlined major influences of wound environments that affect the release kinetics and, as a consequence, local bioavailability. METHODS: Liposomes were prepared using the thin-film hydration method and subsequently freeze-dried at the pilot scale to improve their stability. We investigated the influence of oxidation, plasma proteins, and lipolysis on the in vitro release of rifampicin and its two main degradation products using the Dispersion Releaser technology. A novel simulated wound fluid provided a standardized environment to study critical influences on the release. It reflects the pathophysiological environment regarding pH, buffer capacity, and protein content. RESULTS: During storage, the liposomes efficiently protect rifampicin from degradation. After the dispersion of the vesicles in simulated wound fluid, despite the significant albumin binding (>70%), proteins have no considerable effect on the release. Also, the presence of lipase at pathophysiologically elevated concentrations did not trigger the liberation of rifampicin. Surprisingly, the oxidative environment of the wound bed represents the strongest accelerating influence and triggers the release. CONCLUSION: A stable topical delivery system of rifampicin has been developed. Once the formulation comes in contact with simulated wound fluid, drug oxidation accelerates the release. The influence of lipases that are assumed to trigger the liberation from liposomes depends on the drug-to-lipid ratio. Considering that inflamed tissues exhibit elevated levels of oxidative stress, the trigger mechanism identified for rifampicin contributes to targeted drug delivery.

Correct performance of subcutaneous injections in plaque psoriasis: comparison of trained and untrained patients with different application systems in routine clinical care.

BACKGROUND: Moderate-to-severe plaque psoriasis can be treated very successfully with systemic therapies. Often the therapeutics must be injected subcutaneously. This prospective observational study aimed to compare the correct preparation and performance of subcutaneous injections in trained and untrained patients with plaque psoriasis. MATERIALS AND METHODS: We asked 110 patients (29.1% women, 70.9% men, injection system: 75.5% prefilled syringe, 24.5% autoinjector) to what extent they were trained for self-injection. While participants injected a sham injection with their current system, we evaluated the preparation, execution, and follow-up using a newly developed scoring system. RESULTS: 87.3% (n = 96) of the participants declared that they had been trained for self-injection. No statistically significant difference was observed between the trained and untrained participants in performing the injection correctly (p = .458). The most common mistakes were the wrong preparation and follow-up of the injection. A bifactorial rank-variance analysis showed a negative influence of the factor injection system (prefilled syringe) on the total score (p = .005). CONCLUSION: We can indicate that patients with plaque psoriasis are well prepared for subcutaneous self-injection. Self-injection of systemic therapies is easy to perform, especially with patient-friendly systems, and does not require specialized training.

Management of Paediatric Psoriasis by Paediatricians: A Questionnaire-Based Survey.

INTRODUCTION: Paediatric plaque psoriasis (PedPso) in children and adolescents is often diagnosed and treated for the first time by paediatricians. An early onset of psoriasis is associated with a genetic family burden, higher severity of disease and increased risk of comorbidities, sometimes starting in childhood. However, little information is available on prevalence data and the clinical management of PedPso by paediatricians. METHODS: A total of 191 questionnaires were sent out to paediatricians regarding their management of PedPso, with a focus on prevalence, diagnosis, initiation of therapies, screening for comorbidities and collaboration with dermatologists. Of these, 95 (49.7%) were returned and evaluated anonymously. RESULTS: Only about one-half of the responding paediatricians reported being certain in their diagnosis of PedPso, even though they regularly see moderate-to-severely affected patients. The questionnaire revealed that there are clear differences in the general management of PedPso if the paediatrician is not certain of the diagnosis of psoriasis. Compared to paediatricians certain of their diagnosis, those who are uncertain less frequently perform whole-body inspection, screen for relevant comorbidities, such as psoriasis arthritis, metabolic syndrome or mental disorders, and prescribe the use of topical or systemic therapies. No responding paediatrician reported the use of modern systemic therapies, such as biologicals, even in severely affected children. The majority of respondents rated their cooperation with dermatologists as good. CONCLUSION: The certainty of the diagnosis, the use of system therapies and the screening for comorbidity could improve the care of PedPso through targeted training of paediatricians and intensified interdisciplinary cooperation with dermatologist.

Non-thermal near-infrared exposure photobiomodulates cellular responses to ionizing radiation in human full thickness skin models.

Ionizing and near-infrared radiation are both part of the therapeutic spectrum in cancer treatment. During cancer therapy ionizing radiation is typically used for non-invasive reduction of malignant tissue, while near-infrared photobiomodulation is utilized in palliative medical approaches, e.g. for pain reduction or impairment of wound healing. Furthermore, near-infrared is part of the solar wavelength spectrum. A combined exposure of these two irradiation qualities - either intentionally during medical treatment or unintentionally due to solar exposure - is therefore presumable for cancer patients. Several studies in different model organisms and cell cultures show a strong impact of near-infrared pretreatment on ionizing radiation-induced stress response. To investigate the risks of non-thermal near-infrared (NIR) pretreatment in patients, a human in vitro full thickness skin models (FTSM) was evaluated for radiation research. FTSM were pretreated with therapy-relevant doses of NIR followed by X-radiation, and then examined for DNA-double-strand break (DSB) repair, cell proliferation and apoptosis. Double-treated FTSM revealed a clear influence of NIR on X-radiation-induced stress responses in cells in their typical tissue environment. Furthermore, over a 24h time period, double-treated FTSM presented a significant persistence of DSBs, as compared to samples exclusively irradiated by X-rays. In addition, NIR pretreatment inhibited apoptosis induction of integrated fibroblasts, and counteracted the radiation-induced proliferation inhibition of basal keratinocytes. Our work suggests that cancer patients treated with X-rays should be prevented from uncontrolled NIR irradiation. On the other hand, controlled double-treatment could provide an alternative therapy approach, exposing the patient to less radiation.

Photodynamic Treatment of Oral Squamous Cell Carcinoma Cells with Low Curcumin Concentrations.

Objective: Curcumin is known for its anti-oxidative, anti-inflammatory and anti-tumorigenic qualities at concentrations ranging from 3.7µg/ml to 55µg/ml. Therefore it is pre-destined for tumour therapy. Due to high oral doses that have to be administered and the low bioavailability of curcumin new therapy concepts have to be developed. One of these therapy concepts is the combination of low curcumin concentrations and UVA or visible light. Aim of our study was to investigate the influence of this treatment regime on oral squamous cell carcinoma cells. Materials and Methods: A human oral squamous cell carcinoma cell line (HN) was pre-incubated with low curcumin concentrations (0.01µg/ml to 1µg/ml). Thereafter cell cultures were either left un-irradiated or were irradiated either with 1J/cm2 UVA or for 5min with visible light. Quantitative analysis of proliferation, membrane integrity, oxidative potential and DNA fragmentation were done. Results: It could be shown that low curcumin concentrations neither influenced proliferation, nor cell morphology, nor cell integrity nor apoptosis. When combining these curcumin concentrations with UVA or visible light irradiation cell proliferation as well as development of reactive oxygen species was reduced whereas DNA fragmentation was increased. Concentration as well as light entity specific effects could be observed. Conclusions: The present findings substantiate the potential of the combination of low curcumin concentrations and light as a new therapeutic concept to increase the efficacy of curcumin in the treatment of cancer of the oral mucosa.

Influence of Biodentine® - A Dentine Substitute - On Collagen Type I Synthesis in Pulp Fibroblasts In Vitro.

Preserving a patient's own teeth-even in a difficult situation-is nowadays preferable to surgical intervention and therefore promotes development of suitable dental repair materials. Biodentine®, a mineral trioxide aggregate substitute, has been used to replace dentine in a bioactive and biocompatible manner in both the dental crown and the root. The aim of our study was to evaluate the influence of Biodentine® on pulp fibroblasts in vitro. For this study, one to five Biodentine® discs with a diameter of 5.1mm were incubated in DMEM. To obtain Biodentine® suspensions the media were collected and replaced with fresh medium every 24h for 4 days. Primary pulp cells were isolated from freshly extracted wisdom teeth of 20-23 year old patients and incubated with the Biodentine® suspensions. Proliferation, cell morphology, cell integrity and cell viability were monitored. To evaluate the effect of Biodentine® on collagen type I synthesis, the secretion of the N-terminal domain of pro-collagen type I (P1NP) and the release of transforming growth factor-ß1 (TGF-ß1) were quantified. None of the Biodentine® suspensions tested influenced cell morphology, proliferation or cell integrity. The cell viability varied slightly depending on the suspension used. However, the concentrations of P1NP of all pulp fibroblast cultures treated for 24h with the moderate to high Biodentine® concentration containing suspensions of day 1 were reduced to 5% of the control. Furthermore, a significant TGF-ß1 reduction was observed after treatment with these suspensions. It could be shown that Biodentine® is biocompatible. However, dissolved particles of the moderate to high concentrated Biodentine® suspensions 24h after mixing induce a significant reduction of TGF-ß1 release and reduce the secretion of collagen type I of primary pulp fibroblasts.

Water-filtered near-infrared influences collagen synthesis of keloid-fibroblasts in contrast to normal foreskin fibroblasts.

Hypertrophic scar development is associated to impaired wound healing, imbalanced fibroblast proliferation and extracellular matrix synthesis. Stigmatization, physical restrictions and high recurrence rates are only some aspects that illustrate the severe influence impaired wound healing can have on patients' life. The treatment of hypertrophic scars especially keloids is still a challenge. In recent years water-filtered near-infrared irradiation (wIRA) composed of near-infrared (NIR) and a thermal component is applied for an increasing penal of clinical purposes. It is described to beneficially influence e.g. wound healing. But discrimination between the thermal and the NIR dependent components of these effects has not been conclusively elucidated. Aim of our study was therefore to investigate the influence of the light fraction on the thermal impact of wIRA irradiation in dermal cells. We concentrated our analysis on morphological properties and collagen synthesis. Foreskin fibroblasts and the keloid fibroblast cell line KF111 were exposed to temperatures between 37°C and 46°C with or without additional irradiation with 360J/cm(2) NIR. Our results show that viability was not influenced by irradiation. Independent of the analysed fibroblast species temperature dependent occurrence of spheric cells could be observed. These morphological changes were clearly counteracted by additional light exposure. Convective heat reduced collagen type I synthesis in both cell species depending on the applied temperature. Co-treatment with NIR significantly reversed this effect in keloid fibroblast cultures treated at 46°C whereas no difference could be observed in the foreskin fibroblasts. The observed influence on collagen type I synthesis was associated to a temperature dependent TGF-ß1 secretion reduction. Co-stimulation of keloid cultures with NIR at 46°C completely abolished the temperature dependent TGF-ß1 secretion reduction. In foreskin fibroblast cultures co-treatment with NIR had no additional influence on TGF-ß1 secretion. The observed influence of convective heat treatment with and without NIR on keloid and foreskin fibroblasts indicates a possible clinical application that has to be evaluated in further basic research and clinical studies in context of hypertrophic scar treatment.

European Emergency Data Project (EED Project): EMS data-based health surveillance system.

Emergency Medical Services (EMS) constitute a unique component of health care at the interface between primary and hospital care. EMS data within the pre-hospital setting represents an unparalleled source of epidemiological and health care information that have so far been neglected for public health monitoring. The European Emergency Data Project (EED Project) thus intends to identify common indicators for European EMS systems and to evaluate their suitability for integration into a comprehensive public health monitoring strategy. The article provides a brief overview on objectives and methodology in the form of a progress report.