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BackgroundThere is limited evidence on the best available treatment options for capillary malformations (CMs), mainly due to the absence of uniform outcome measures in trials on therapies. A core outcome set (COS) enables standard reporting of trial outcomes, which facilitates comparison of treatment results.ObjectivesTo develop a core outcome domain set (CDS), as part of a core outcome set (COS), for clinical research on CMs.MethodsSixty-seven potentially relevant outcome subdomains were recognized based on the literature, focus group sessions, and input from the COSCAM working group. These outcome subdomains were presented in an online Delphi study to CM experts (medical specialists and authors of relevant literature) and (parents of) patients with CM (international patient associations). During three e-Delphi study rounds, the participants repeatedly scored the importance of these outcome subdomains on a seven-point Likert scale. Participants could also propose other relevant outcome subdomains. Consensus was defined as ≥ 80% agreement as to the importance of an outcome subdomain among both stakeholder groups. The CDS was finalized during an online consensus meeting.ResultsIn total 269 participants from 45 countries participated in the first e-Delphi study round. Of these, 106 were CM experts from 32 countries, made up predominantly of dermatologists (59%) and plastic surgeons (18%). Moreover, 163 (parents of) patients with CM from 28 countries participated, of whom 58% had Sturge-Weber syndrome. During the two subsequent e-Delphi study rounds, 189 and 148 participants participated, respectively. After the entire consensus process, consensus was reached on 11 outcome subdomains: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence.ConclusionsWe recommend the CDS to be used as a minimum reporting standard in all future trials of CM therapy. Our next step will be to select suitable outcome measurement instruments to score the core outcome subdomains. What is already known about this topic? Besides physical and functional sequelae, capillary malformations (CMs) often cause emotional and social burden. The lack of uniform outcome measures obstructs proper evaluation and comparison of treatment strategies. As a result, there is limited evidence on the best available treatment options. The development of a core outcome set (COS) may improve standardized reporting of trial outcomes. What does this study add? A core outcome domain set (CDS), as part of a COS, was developed for clinical research on CMs. International consensus was reached on the recommended core outcome subdomains to be measured in CM trials: colour/redness, thickness, noticeability, distortion of anatomical structures, glaucoma, overall health-related quality of life, emotional functioning, social functioning, tolerability of intervention, patient satisfaction with treatment results, and recurrence. This CDS enables the next step in the development of a COS, namely to reach consensus on the core outcome measurement instruments to score the core outcome subdomains. What are the clinical implications of this work? The obtained CDS will facilitate standardized reporting of treatment outcomes, thereby enabling proper comparison of treatment results. This comparison is likely to provide more reliable information for patients about the best available treatment options.

ImportanceLaser-assisted drug delivery (LADD) is used for various medical and cosmetic applications. However, there is insufficient evidence-based guidance to assist clinicians performing LADD.ObjectiveTo develop recommendations for the safe and effective use of LADD.Evidence reviewA systematic literature review of Cochrane Central Register of Controlled Trials, Embase, and MEDLINE was conducted in December 2019 to identify publications reporting research on LADD. A multidisciplinary panel was convened to draft recommendations informed by the systematic review; they were refined through 2 rounds of Delphi survey, 2 consensus meetings, and iterative review by all panelists until unanimous consensus was achieved.FindingsOf the 48 published studies of ablative fractional LADD that met inclusion criteria, 4 were cosmetic studies; 21, oncologic; and 23, medical (not cosmetic/oncologic), and 6 publications of nonablative fractional LADD were included at the request of the expert panel, producing a total of 54 studies. Thirty-four studies (63.0%) were deemed to have low risk of bias, 17 studies (31.5%) had moderate risk, and 3 (5.5%) had serious risk. The key findings that informed the guidelines developed by the expert panel were as follows: LADD is safe in adults and adolescents (≥12 years) with all Fitzpatrick skin types and in patients with immunosuppression; it is an effective treatment for actinic keratosis, cutaneous squamous cell carcinoma in situ, actinic cheilitis, hypertrophic scars, and keloids; it is useful for epidermal and dermal analgesia; drug delivery may be increased through the application of heat, pressure, or occlusion, or by using an aqueous drug solution; laser settings should be selected to ensure that channel diameter is greater than the delivered molecule; antibiotic prophylaxis is not recommended, except with impaired wound healing; antiviral prophylaxis is recommended when treating the face and genitalia; and antifungal prophylaxis is not recommended. The guideline's 15 recommendations address 5 areas of LADD use: (I) indications and contraindications; (II) parameters to report; (III) optimization of drug delivery; (IV) safety considerations; and (V) prophylaxis for bacterial, viral, and fungal infections.Conclusions and relevanceThis systematic review and Delphi consensus approach culminated in an evidence-based clinical practice guideline for safe and effective use of LADD in a variety of applications. Future research will further improve our understanding of this novel treatment technique.

IntroductionWhile laser technology has expanded the armamentarium of treatment for various skin diseases during the past years, heterogeneity in study outcomes hampers comparability and appropriate evidence synthesis. Part of these issues can be addressed by developing a generic outcome set. Using the Delphi method, this study aims to seek consensus between key stakeholders on relevant generic outcomes (what to measure) for implementation in the international registry on Laser trEAtments in Dermatology (LEAD). The registry is focused on collecting research data on various laser treatments for skin disorders.Methods and analysisBy reviewing the literature and involvement of key stakeholder groups and adult patients in need or after laser surgery and health professionals, a preliminary list of outcomes will be generated and categorised into domains. Using these outcomes, an international three-round Delphi study will be performed to rate the importance of outcomes in the selection of a generic outcome set. Participants are allowed to provide new outcomes to the preliminary list for revisions during the first Delphi round. Finally, results will be discussed during a consensus meeting to agree on generic outcomes to be used in the LEAD registry.Ethics and disseminationAn ethics approval was not applicable (W19_290 # 18.336). The study is registered with the Cochrane Skin Core OUtcome Set INitiative) and the Core Outcome Measures in Effectiveness Trials initiative. Procedures will be conducted according to the Declaration of Helsinki. The findings will be disseminated through peer-reviewed publications and conference presentations.

Background Severe keloids are difficult to treat. Corticosteroid injections with needles are painful and associated with frequent recurrences. Therefore, more effective, safe and patient-friendly alternative treatments are urgently needed. Objectives To assess the efficacy, tolerability and patient satisfaction of intralesional bleomycin treatment using a needle-free electronic pneumatic jet injector (EPI) in severe keloids. Methods Patients with severe keloids were included in this double-blind, randomized, placebo-controlled trial with split-lesion design. Three EPI treatments with bleomycin or saline were administered every 4 weeks in the intervention and control sides. Outcome measures were change in scar volume assessed by three-dimensional imaging, Patient and Observer Scar Assessment Scale (POSAS), skin perfusion with laser speckle contrast imaging (LSCI), spilled volume, procedure-related pain, adverse events and patient satisfaction. Results Fourteen patients (nine female, five male) were included. The estimated mean keloid volume was significantly reduced by 20% after EPI-assisted bleomycin, compared with a slight increase of 3% in the control side (P < 0.01). The estimated mean POSAS patient and observer scores decreased by respectively 28% and 20% (P = 0.03 and P = 0.001). LSCI showed no significant change in perfusion. EPI treatment was preferred over previous needle injections in 85% of patients. The estimated mean spilled volume after EPI was around 50%, and numerical rating scale pain scores were moderate. Adverse events included bruising, hyperpigmentation and transient superficial necrosis. Conclusions A course of three EPI-assisted bleomycin injections is efficacious and well tolerated in severe keloids. Moreover, EPI was preferred by most patients and may serve as a patient-friendly alternative treatment. [ABSTRACT FROM AUTHOR]

Recent studies have demonstrated that ablative fractional laser (AFL) can inhibit the hedgehog pathway, enhance immune infiltration and clear basal cell carcinomas (BCCs) in murine models. In this study, we applied RNA sequencing to further characterise the impact of AFL on the transcriptome of murine skin containing early‐stage microscopic BCCs, contrasting it with the effects of topical application of the hedgehog inhibitor vismodegib. Our results showed that BCC induction in murine skin was primarily linked to gene upregulation (significantly upregulated genes: 277, significantly downregulated genes: 24). Characterisation of these genes with Ingenuity Pathway Analysis showed that tumour induction was associated with activation of BCC and Sonic Hedgehog signalling. Both AFL and vismodegib treatments reversed these changes, with vismodegib demonstrating superior performance by reversing most of the upregulated genes (AFL: 59/277; vismodegib: 180/277). Surprisingly, Ingenuity Pathway Analysis also revealed that both AFL and vismodegib treatments caused considerable immune cell infiltration. Based on gene set enrichment analysis and cell type deconvolution, AFL treatment resulted in the largest immune cell recruitment, which for both treatments primarily consisted of infiltrating neutrophils, macrophages and monocytes. In conclusion, the distinct effects observed in BCC skin following AFL and vismodegib treatment suggest key differences between the two interventions. Future applications of AFL or vismodegib treatments could leverage their individual effects, for example by combining the effect of AFL on the immune system with other topical treatments. [ABSTRACT FROM AUTHOR]

Background: The development of artificial intelligence (AI) is rapidly expanding, showing promise in the dermatological field. Skin checks are a resource‐heavy challenge that could potentially benefit from AI‐tool assistance, particularly if provided in widely available AI solutions. A novel smartphone application(app)‐based AI system, "SCAI," was developed and trained to recognize spots in paired images of skin, pursuing identification of new skin lesions. This pilot study aimed to investigate the feasibility of the SCAI‐app to identify simulated skin changes in vivo. Materials and methods: The study was conducted in a controlled setting with healthy volunteers and standardized, simulated skin changes (test spots), consisting of customized 3‐mm adhesive spots in three colors (black, brown, and red). Each volunteer had a total of eight test spots adhered to four areas on back and legs. The SCAI‐app collected smartphone‐ and template‐guided standardized images before and after test spot application, using its backend AI algorithms to identify changes between the paired images. Results: Twenty‐four volunteers were included, amounting to a total of 192 test spots. Overall, the detection algorithms identified test spots with a sensitivity of 92.0% (CI: 88.1–95.9) and a specificity of 95.5% (CI: 95.0–96.0). The SCAI‐app's positive predictive value was 38.0% (CI: 31.0–44.9), while the negative predictive value was 99.7% (CI: 99.0–100). Conclusion: This pilot study showed that SCAI‐app could detect simulated skin changes in a controlled in vivo setting. The app's feasibility in a clinical setting with real‐life skin lesions remains to be investigated, where the challenge with false positives in particular needs to be addressed. [ABSTRACT FROM AUTHOR]