Background: Psoriasis has a negative impact on patients’ physical and mental health and can lead to anxiety and depression. Disease management strategies, including educational programs and eHealth devices, have been shown to improve health care for several chronic diseases. However, such disease management strategies are lacking in the routine care of patients with psoriasis. Objective: This study aims to study the impact of a novel intervention that combines an educational program with a disease management smartphone app on the mental health of patients with psoriasis. Methods: Patients with psoriasis in the intervention group received an educational program; attended visits on weeks 0, 12, 24, 36, and 60; and had access to the study app. Patients in the control group only attended the visits. The primary endpoint was a significant reduction of scores on the Hospital Anxiety and Depression Scale (HADS). Secondary end points were reductions in Dermatology Life Quality Index score, Psoriasis Area and Severity Index score, pruritus, and pain, as well as improvements in mood and daily activities. In addition, modulating effects of sex, age, disease duration, and app use frequency were evaluated. Results: A total of 107 patients were included in the study and randomized into the control group (53/107, 49.5%) or intervention group (54/107, 50.5%). Approximately 71.9% (77/107) of the patients completed the study. A significant reduction in HADS-Depression (HADS-D) in the intervention group was found at weeks 12 (P=.04) and 24 (P=.005) but not at weeks 36 (P=.12) and 60 (P=.32). Patient stratification according to app use frequency showed a significant improvement in HADS-D score at weeks 36 (P=.004) and 60 (P=.04) and in HADS-Anxiety (HADS-A) score at weeks 36 (P=.04) and 60 (P=.05) in the group using the app less than once every 5 weeks. However, in patients using the app more than once every 5 weeks, no significant reduction in HADS-D (P=.84) or HADS-A (P=.20) score was observed over the 60-week study period compared with that observed in patients in the control group. All findings were independent of sex, age, and disease duration. Conclusions: These findings support the use of a disease management smartphone app as a valid tool to achieve long-term improvement in the mental health of patients with psoriasis if it is not used too frequently. Further studies are needed to analyze the newly observed influence of app use frequency. Trial Registration: Deutsches Register Klinischer Studien DRKS00020755; https://tinyurl.com/nyzjyvvk

Melanoma immunotherapy is still not satisfactory due to immunosuppressive cell populations within the tumor stroma. Targeting tumor-associated macrophages (TAM) can help to restore an anti-tumor immunity. Previously, we could show that classical TAM markers expressed in vivo need a 7 day M-CSF/dexamethasone/IL-4 (MDI) stimulation for their induction in peripheral blood monocytes (pBM) in vitro. To identify possible novel therapeutic targets on TAM, gene expression analysis of MDI-treated pBM was performed. This identified up-regulation of the purinergic G-protein coupled receptor P2Y12, the therapeutic target of the clinically approved anti-thrombotic drugs cangrelor, clopidogrel, ticagrelor, and prasugrel. We generated a peptide antibody and validated its specificity using transgenic P2Y12⁺ U937 cells. With the help of this antibody, P2Y12 expression was confirmed on CD68⁺ CD163⁺ TAM of melanoma in situ. Functional analysis revealed that treatment of transgenic P2Y12⁺ U937 cells with the receptor agonist 2-MeSADP induced ERK1/2 and Akt phosphorylation and increased the secretion of the chemokines CXCL2, CXCL7, and CXCL8. These effects could be abolished with the P2Y12 antagonist PSB0739 or with Akt and ERK inhibitors. In addition, P2Y12⁺ macrophages migrated towards the ADP-rich culture medium of puromycin-treated dying B16F1 melanoma cells. Cangrelor treatment blocked migration. Taken together, our results indicate that P2Y12 is an important chemotaxis receptor, which triggers migration of macrophages towards nucleotide-rich, necrotic tumor areas, and modulates the inflammatory environment upon ADP binding.

Tumor‐associated macrophages (TAMs) represent alternatively activated (M2) macrophages that support tumor growth. Previously, we have described a special LYVE‐1⁺ M2 TAM subset in vitro and in vivo; gene profiling of this TAM subset identified MS4A8A as a novel TAM molecule expressed in vivo by TAM in mammary carcinoma and malignant melanoma. In vitro, Ms4a8a mRNA and MS4A8A protein expression was strongly induced in bone marrow‐derived macrophages (BMDMs) by combining M2 mediators (IL‐4, glucocorticoids) and tumor‐conditioned media (TCM). Admixture of MS4A8A⁺ TCM/IL‐4/GC‐treated BMDM significantly enhanced the tumor growth rate of subcutaneously transplanted TS/A mammary carcinomas. Upon forced overexpression of MS4A8A, Raw 264.7 macrophage‐like cells displayed a special gene signature. Admixture of these MS4A8A⁺ Raw 264.7 cells also significantly enhanced the tumor growth rate of subcutaneously transplanted mammary carcinomas. To identify the signaling pathways involved in synergistic induction of MS4A8A, the major signaling cascades with known functions in TAM were analyzed. Although inhibitors of NF‐κB activation and of the MAPK JNK and ERK did not show relevant effects, the p38α/β MAPK inhibitor SB203580 strongly and highly significantly (p > 0.001) inhibited MS4A8A expression on mRNA and protein level. In addition, MS4A8A expression was restricted in M2 BMDM from mice with defective GC receptor (GR) dimerization indicating that classical GR gene regulation is mandatory for MS4A8A induction. In conclusion, expression of MS4A8A within the complex signal integration during macrophage immune responses may act to fine tune gene regulation. Furthermore, MS4A8A⁺ TAM may serve as a novel cellular target for selective cancer therapy.

Background: Psoriasis is a chronic inflammatory skin disease. The visibility of erythematous plaques on the skin as well as the pain and itchiness caused by the skin lesions frequently leads to psychological distress in patients. Smartphone apps are widespread and easily accessible. Earlier studies have shown that apps can effectively complement current management strategies for patients with psoriasis. However, no analysis of such apps has been published to date. Objective: The aim of this study is to systematically identify and objectively assess the quality of current publicly available German apps for patients with psoriasis using the Mobile Application Rating Scale (MARS) and compile brief ready-to-use app descriptions. Methods: We conducted a systematic search and assessment of German apps for patients with psoriasis available in the Google Play Store and Apple App Store. The identified apps were randomly assigned to 1 of 3 reviewers, who independently rated them using the German MARS (MARS-G). The MARS-G includes 15 items from 4 different sections (engagement, functionality, aesthetics, and information) to create an overall mean score for every app. Scores can range from 1 for the lowest-quality apps to 5 for the highest-quality apps. Apps were ranked according to their mean MARS-G rating, and the highest-ranked app was evaluated independently by 2 patients with psoriasis using the user version of the MARS-G (uMARS-G). Furthermore, app information, including origin, main function, and technical aspects, was compiled into a brief overview. Results: In total, we were able to identify 95 unique apps for psoriasis, of which 15 were available in both app stores. Of these apps, 5 were not specifically intended for patients with psoriasis, 1 was designed for clinical trials only, and 1 was no longer available at the time the evaluation process began. Consequently, the remaining 8 apps were included in the final evaluation. The mean MARS-G scores ranged from 3.51 to 4.18. The app with the highest mean MARS-G score was Psoriasis Helferin (4.18/5.00). When rated by patients, however, the app was rated lower in all subcategories, resulting in a mean uMARS-G score of 3.48. Most apps had a commercial background and a focus on symptom tracking. However, only a fraction of the apps assessed used validated instruments to measure the user’s disease activity. Conclusions: App quality was heterogeneous, and only a minority of the identified apps were available in both app stores. When evaluated by patients, app ratings were lower than when evaluated by health care professionals. This discrepancy highlights the importance of involving patients when developing and evaluating health-related apps as the factors that make an app appealing to users may differ between these 2 groups. Trial Registration: Deutsches Register Klinischer Studien DRKS00020963; https://tinyurl.com/ye98an5b

Background: Patients with axial spondyloarthritis (axSpA) benefit from regular home-based exercise (HbE). In spite of recommendations, a relevant proportion of German axSpA patients does not adhere to recommended HbE practices. To enhance HbE care, we developed the novel digital therapeutic (DTx) “Axia” compliant with the European medical device regulation (MDR). Axia offers a modern app-based HbE solution with patient educative content and further integrated features. Objective: We aimed to assess Axia’s efficacy, attractiveness, and functionality through a survey among axSpA-patients involved in the first user tests. Methods: A mixed-method online questionnaire with 38 items was administered to 37 axSpA volunteers after using Axia. Numeric rating scales (NRS) and likelihood scales were primarily used. Results: HbE frequency significantly increased from a median of 1 day/week to 6 days/week (p < 0.001) by using Axia. Existing HbE practitioners also increased their frequency (median of 4 days/week before, 6 days/week with Axia, p < 0.05). Axia received a median rating of 5 out of 5 stars. On NRS scales, Axia scored a median of 9 for intuitiveness and design, and a median of 8 for entertainment. 64.9% reported improved range of motion, 43.2% reported reduced pain, and 93.6% enhanced disease-specific knowledge. All users recommended Axia to other patients. Conclusion: Axia increases axSpA patients HbE frequency, possibly due to its good intuitiveness and design, leading to reduction in pain and subjective improvement of range of motion. This warrants further investigation in large randomized controlled interventional trials to establish its efficacy conclusively and patients adherence to HbE.