Patient-Centered Chronic Wound Care Mobile Apps: Systematic Identification, Analysis, and Assessment.

Background: The prevalence of chronic wounds is predicted to increase within the aging populations in industrialized countries. Patients experience significant distress due to pain, wound secretions, and the resulting immobilization. As the number of wounds continues to rise, their adequate care becomes increasingly costly in terms of health care resources worldwide. eHealth support systems are being increasingly integrated into patient care. However, to date, no systematic analysis of such apps for chronic wounds has been published. Objective: The aims of this study were to systematically identify and subjectively assess publicly available German- or English-language mobile apps for patients with chronic wounds, with quality assessments performed by both patients and physicians. Methods: Two reviewers independently conducted a systematic search and assessment of German- or English-language mobile apps for patients with chronic wounds that were available in the Google Play Store and Apple App Store from April 2022 to May 2022. In total, 3 apps met the inclusion and exclusion criteria and were reviewed independently by 10 physicians using the German Mobile App Rating Scale (MARS) and the System Usability Scale (SUS). The app with the highest mean MARS score was subsequently reviewed by 11 patients with chronic wounds using the German user version of the MARS (uMARS) and the SUS. Additionally, Affinity for Technology Interaction (ATI) scale scores were collected from both patients and physicians. Results: This study assessed mobile apps for patients with chronic wounds that were selected from a pool of 118 identified apps. Of the 73 apps available in both app stores, 10 were patient oriented. After excluding apps with advertisements or costs, 3 apps were evaluated by 10 physicians. Mean MARS scores ranged from 2.64 (SD 0.65) to 3.88 (SD 0.65) out of 5, and mean SUS scores ranged from 50.75 (SD 27) to 80.5 (SD 17.7) out of 100. WUND APP received the highest mean MARS score (mean 3.88, SD 0.65 out of 5) among physicians. Hence, it was subsequently assessed by 11 patients and achieved a similar rating (uMARS score: mean 3.89, SD 0.4 out of 5). Technical affinity, as measured with the ATI scale, was slightly lower in patients (score: mean 3.62, SD 1.35 out of 6) compared to physicians (score: mean 3.88, SD 1.03 out 6). Conclusions: The quality ratings from physicians and patients were comparable and indicated mediocre app quality. Technical affinity, as assessed by using the ATI scale, was slightly lower for patients. Adequate apps for patients with chronic wounds remain limited, emphasizing the need for improved app development to meet patient needs. The ATI scale proved valuable for assessing technical affinity among different user groups.

Federated Learning for Decentralized Artificial Intelligence in Melanoma Diagnostics.

Importance: The development of artificial intelligence (AI)-based melanoma classifiers typically calls for large, centralized datasets, requiring hospitals to give away their patient data, which raises serious privacy concerns. To address this concern, decentralized federated learning has been proposed, where classifier development is distributed across hospitals. Objective: To investigate whether a more privacy-preserving federated learning approach can achieve comparable diagnostic performance to a classical centralized (ie, single-model) and ensemble learning approach for AI-based melanoma diagnostics. Design, Setting, and Participants: This multicentric, single-arm diagnostic study developed a federated model for melanoma-nevus classification using histopathological whole-slide images prospectively acquired at 6 German university hospitals between April 2021 and February 2023 and benchmarked it using both a holdout and an external test dataset. Data analysis was performed from February to April 2023. Exposures: All whole-slide images were retrospectively analyzed by an AI-based classifier without influencing routine clinical care. Main Outcomes and Measures: The area under the receiver operating characteristic curve (AUROC) served as the primary end point for evaluating the diagnostic performance. Secondary end points included balanced accuracy, sensitivity, and specificity. Results: The study included 1025 whole-slide images of clinically melanoma-suspicious skin lesions from 923 patients, consisting of 388 histopathologically confirmed invasive melanomas and 637 nevi. The median (range) age at diagnosis was 58 (18-95) years for the training set, 57 (18-93) years for the holdout test dataset, and 61 (18-95) years for the external test dataset; the median (range) Breslow thickness was 0.70 (0.10-34.00) mm, 0.70 (0.20-14.40) mm, and 0.80 (0.30-20.00) mm, respectively. The federated approach (0.8579; 95% CI, 0.7693-0.9299) performed significantly worse than the classical centralized approach (0.9024; 95% CI, 0.8379-0.9565) in terms of AUROC on a holdout test dataset (pairwise Wilcoxon signed-rank, P < .001) but performed significantly better (0.9126; 95% CI, 0.8810-0.9412) than the classical centralized approach (0.9045; 95% CI, 0.8701-0.9331) on an external test dataset (pairwise Wilcoxon signed-rank, P < .001). Notably, the federated approach performed significantly worse than the ensemble approach on both the holdout (0.8867; 95% CI, 0.8103-0.9481) and external test dataset (0.9227; 95% CI, 0.8941-0.9479). Conclusions and Relevance: The findings of this diagnostic study suggest that federated learning is a viable approach for the binary classification of invasive melanomas and nevi on a clinically representative distributed dataset. Federated learning can improve privacy protection in AI-based melanoma diagnostics while simultaneously promoting collaboration across institutions and countries. Moreover, it may have the potential to be extended to other image classification tasks in digital cancer histopathology and beyond.

S2k guidelines on diagnosis and treatment of linear IgA dermatosis initiated by the European Academy of Dermatology and Venereology.

INTRODUCTION: Linear IgA dermatosis (LAD) is a rare subepidermal autoimmune bullous disease (AIBD) defined by predominant or exclusive immune deposits of immunoglobulin A at the basement membrane zone of skin or mucous membranes. This disorder is a rare, clinically and immunologically heterogeneous disease occurring both in children and in adults. The aim of this project is to present the main clinical features of LAD, to propose a diagnostic algorithm and provide management guidelines based primarily on experts' opinion because of the lack of large methodologically sound clinical studies. METHODS: These guidelines were initiated by the European Academy of Dermatology and Venereology (EADV) Task Force Autoimmune Bullous Diseases (AIBD). To achieve a broad consensus for these S2k consensus-based guidelines, a total of 29 experts from different countries, both European and non-European, including dermatologists, paediatric dermatologists and paediatricians were invited. All members of the guidelines committee agreed to develop consensus-based (S2k) guidelines. Prior to a first virtual consensus meeting, each of the invited authors elaborated a section of the present guidelines focusing on a selected topic, based on the relevant literature. All drafts were circulated among members of the writing group, and recommendations were discussed and voted during two hybrid consensus meetings. RESULTS: The guidelines summarizes evidence-based and expert opinion-based recommendations (S2 level) on the diagnosis and treatment of LAD. CONCLUSION: These guidelines will support dermatologists to improve their knowledge on the diagnosis and management of LAD.

Dermatologist-like explainable AI enhances trust and confidence in diagnosing melanoma.

Artificial intelligence (AI) systems have been shown to help dermatologists diagnose melanoma more accurately, however they lack transparency, hindering user acceptance. Explainable AI (XAI) methods can help to increase transparency, yet often lack precise, domain-specific explanations. Moreover, the impact of XAI methods on dermatologists' decisions has not yet been evaluated. Building upon previous research, we introduce an XAI system that provides precise and domain-specific explanations alongside its differential diagnoses of melanomas and nevi. Through a three-phase study, we assess its impact on dermatologists' diagnostic accuracy, diagnostic confidence, and trust in the XAI-support. Our results show strong alignment between XAI and dermatologist explanations. We also show that dermatologists' confidence in their diagnoses, and their trust in the support system significantly increase with XAI compared to conventional AI. This study highlights dermatologists' willingness to adopt such XAI systems, promoting future use in the clinic.

VEXAS-Syndrome, a newly described autoinflammatory systemic disease with dermatologic manifestations.

VEXAS syndrome is a recently identified autoinflammatory systemic disease caused by an acquired somatic mutation of the X-linked UBA1 gene, the key enzyme of the first step of ubiquitylation. The acronym VEXAS stands for the characteristics Vacuoles, E1 enzyme, X-linked, autoinflammatory and somatic. The disease occurs in advanced adulthood preferentially in men and is characterized by hematological, rheumatological and dermatological symptoms. The latter include neutrophil-rich lesions reminiscent of Sweet's syndrome, erythema nodosum- and panniculitis-like skin manifestations and recurrent polychondritis of the nose and auricles. The presence of cytoplasmic vacuoles in myeloid and erythroid precursors in the bone marrow is characteristic. In up to half of the cases, VEXAS syndrome is associated with myelodysplastic syndrome. Dermatologists should be familiar with the clinical picture, as skin symptoms are often the first indicator of the disease. Molecular diagnostics are essential for confirming the diagnosis and risk stratification of affected patients. In this minireview we provide an overview of the pathophysiology, diagnosis and therapy of VEXAS syndrome and illustrate its clinical picture with two own cases.

A center-based, ambulatory care concept for hidradenitis suppurativa improves patient outcomes and is also cost-effectiveness.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease affecting approximately 1% of the population. The patient journey through the German health care system leads to high disease burden and substantial treatment costs. The EsmAiL study showed that an innovative, interprofessional, multimodal care-concept reduces disease activity and burden of HS compared to standard care. This paper examines the costs of treating HS in Germany and compares them with those of the innovative care concept implemented in EsmAiL. METHODS: EsmAiL was a two-arm, multicenter, prospective randomized controlled trial including 553 adults with HS. The study was registered in the German Clinical Trials Registry (DRKS00022135). The control group (CG) remained in standard care, whereas the intervention group (IG) was referred to specialized so-called 'acne-inversa-centres (AiZ)' where patients were treated with a structured, interdisciplinary approach. The present paper analyses the treatment costs for a subpopulation based on health insurance cost data from the two largest German health insurers. Quality-Adjusted Life Years (QALY) was assessed based on Dermatology Life Quality Index (DLQI). RESULTS: Total annual treatment costs per patient were €3,966.07 in standard care (n = 89) and €3,974.37 in the innovative care (n = 93). The costs per additional QALY amounted to €12,698.72 in the IG. Given the conventional and established threshold of €22,600 to €33,900 per QALY, the innovative treatment in AiZ proved to be cost-effective. CONCLUSION: Treatment costs of HS are substantial and increase with disease severity. The new form of care is cost-effective and is expected to decrease costs in the long run.

A structured, multimodal form of care reduces costs in the treatment of Hidradenitis suppurativa compared to standard care.

The gut microbiome in bullous pemphigoid: implications of the gut-skin axis for disease susceptibility.

Bullous pemphigoid (BP) is an autoimmune blistering disease that primarily affects the elderly. An altered skin microbiota in BP was recently revealed. Accumulating evidence points toward a link between the gut microbiota and skin diseases; however, the gut microbiota composition of BP patients remains largely underexplored, with only one pilot study to date, with a very limited sample size and no functional profiling of gut microbiota. To thoroughly investigate the composition and function of the gut microbiota in BP patients, and explore possible links between skin conditions and gut microbiota, we here investigated the gut microbiota of 66 patients (81.8% firstly diagnosed) suffering from BP and 66 age-, sex-, and study center-matched controls (CL) with non-inflammatory skin diseases (132 total participants), using 16S rRNA gene and shotgun sequencing data. Decreased alpha-diversity and an overall altered gut microbial community is observed in BP patients. Similar trends are observed in subclassifications of BP patients, including first diagnoses and relapsed cases. Furthermore, we observe a set of BP disease-associated gut microbial features, including reduced Faecalibacterium prausnitzii and greater abundance of pathways related to gamma-aminobutyric acid (GABA) metabolism in BP patients. Interestingly, F. prausnitzii is a well-known microbiomarker of inflammatory diseases, which has been reported to be reduced in the gut microbiome of atopic dermatitis and psoriasis patients. Moreover, GABA plays multiple roles in maintaining skin health, including the inhibition of itching by acting as a neurotransmitter, attenuating skin lesions by balancing Th1 and Th2 levels, and maintaining skin elasticity by increasing the expression of type I collagen. These findings thus suggest that gut microbiota alterations present in BP may play a role in the disease, and certain key microbes and functions may contribute to the link between gut dysbiosis and BP disease activity. Further studies to investigate the underlying mechanisms of the gut-skin interaction are thus clearly warranted, which could aid in the development of potential therapeutic interventions.

Comorbidity in bullous pemphigoid: up-date and clinical implications.

Bullous pemphigoid is the most common autoimmune blistering disease in industrialized countries and particularly affects the elderly. In this patient population, comorbid diseases are frequent and may complicate management and treatment of bullous pemphigoid. A better understanding why distinct diseases are more frequent in bullous pemphigoid patients may lead to new pathophysiological insights and - as a consequence - result in better patient care. The association of bullous pemphigoid with neurological and psychiatric diseases is well known and confirmed by several case-control studies. Association with further diseases such as malignancy and metabolic diseases are still discussed controversially. In recent years new relationships between bullous pemphigoid and autoimmune as well as inflammatory skin diseases have been reported. This review provides a systematic overview on studies addressing comorbidity in bullous pemphigoid patients. Increasing the awareness of both, common and rare comorbid diseases, may enable clinicians to optimize patient support and individualized treatment of bullous pemphigoid.

Tumor-derived GDF-15 blocks LFA-1 dependent T cell recruitment and suppresses responses to anti-PD-1 treatment.

Immune checkpoint blockade therapy is beneficial and even curative for some cancer patients. However, the majority don't respond to immune therapy. Across different tumor types, pre-existing T cell infiltrates predict response to checkpoint-based immunotherapy. Based on in vitro pharmacological studies, mouse models and analyses of human melanoma patients, we show that the cytokine GDF-15 impairs LFA-1/ß2-integrin-mediated adhesion of T cells to activated endothelial cells, which is a pre-requisite of T cell extravasation. In melanoma patients, GDF-15 serum levels strongly correlate with failure of PD-1-based immune checkpoint blockade therapy. Neutralization of GDF-15 improves both T cell trafficking and therapy efficiency in murine tumor models. Thus GDF-15, beside its known role in cancer-related anorexia and cachexia, emerges as a regulator of T cell extravasation into the tumor microenvironment, which provides an even stronger rationale for therapeutic anti-GDF-15 antibody development.

Expression of Connexin 43 in Granular Cell Tumors of the Skin, Tongue and Esophagus.

BACKGROUND: Granular cell tumors (GCT) are rare neoplasms of Schwann cell origin occurring in the skin and in other organs. The etiopathogenesis of GCT is yet poorly understood. Connexin 43 (Cx43) is the most broadly expressed gap junction protein in humans, the tumoral role of which has been investigated in several types of tumors. Its role in GCT of the skin, oral cavity and gastrointestinal tract is as yet unknown. METHODS: Herein, we present a study on the immunohistochemical expression of Cx43 in GCT of the skin (n = 15), tongue (n = 4) and esophagus (n = 3). Immunolabeling was scored positive (weak (+), moderate (++) or strong (+++)). RESULTS: Cx43 was expressed by all cases of GCT of the skin, tongue and esophagus (22/22), showing moderate to strong staining. All tissue sections of GCT were characterized by a diffuse, cytoplasmic staining pattern of the tumor cells. None of those showed membranous or nuclear staining. CONCLUSION: Our results suggest that Cx43 probably plays an important role in the development of this rare tumor entity.

A centre-based ambulatory care concept for hidradenitis suppurativa improves disease activity, disease burden and patient satisfaction: results from the randomized controlled EsmAiL trial.

BACKGROUND: Hidradenitis suppurativa (HS) is an inflammatory disease of the inverse skin regions that occurs in young women, in particular, and affects approximately 1% of the population. Outpatient care is often inadequate and usually cannot prevent progression. OBJECTIVES: To evaluate in the EsmAiL ('Evaluation eines strukturierten und leitlinienbasierten multmodalen Versorgungskonzepts für Menschen mit Akne inversa') trial whether an innovative care concept can decrease disease activity and burden, and improve patient satisfaction. METHODS: EsmAiL was conducted as a two-arm, multicentre, prospective, randomized controlled trial that included 553 adults with HS. Inclusion criteria were a minimum of three inflammatory lesions and at least a moderate impact of the disease on quality of life. The control group (CG) remained under standard care, while patients in the intervention group (IG) were treated according to a trial-specific, multimodal concept. The primary endpoint was the absolute change in International Hidradenitis Suppurativa Severity Score System (IHS4). RESULTS: In total, 274 patients were randomized to the IG and 279 to the CG. Altogether, 377 attended the final assessment after 12 months of intervention. Participants in the IG (n = 203) achieved a mean improvement in IHS4 of 9.3 points, while the average decrease in IHS4 in patients in the CG (n = 174) was 5.7 points (P = 0.003). Patients treated under the new care concept also reported a statistically significantly higher decrease in pain, Dermatology Life Quality Index and Hospital Anxiety and Depression Scale scores compared with those in the CG (P < 0.001). Patient satisfaction was also statistically significantly higher in the IG compared with the CG (P < 0.001). CONCLUSIONS: The establishment of standardized treatment algorithms in so-called 'acne inversa centres' in the ambulatory setting has a substantial, positive impact on the course of HS and significantly improves patient satisfaction.