BackgroundWound repair is one of the most complex biological processes of human life. Allogeneic cell-based engineered skin substitutes provide off-the-shelf temporary wound coverage and act as biologically active dressings, releasing growth factors, cytokines and extracellular matrix components essential for proper wound healing. However, they are susceptible to immune rejection and this is their major weakness.Thanks to their low immunogenicity and high effectiveness in regeneration, fetal skin cells represent an attractive alternative to the commonly used autologous and allogeneic skin grafts.Methods/designWe developed a new dressing comprising a collagen matrix seeded with a specific ratio of active fetal fibroblasts and keratinocytes. These produce a variety of healing growth factors and cytokines which will increase the speed of wound healing and induce an immunotolerant state, with a slight inflammatory reaction and a reduction in pain.The objective of this study is to demonstrate that the use of this biological dressing for wound healing at the split-thickness skin graft (STSG) donor site, reduces the time to healing, decreases other co-morbidities, such as pain, and improves the appearance of the scar.This investigation will be conducted as part of a randomized study comparing our new biological dressing with a conventional treatment in a single patient, thus avoiding the factors that may influence the healing of a graft donor site.DiscussionThis clinical trial should enable the development of a new strategy for STSG donor-wound healing based on a regenerative dressing. The pain experienced in the first few days of STSG healing is well known due to the exposure of sensory nerve endings. Reducing this pain will also reduce analgesic drug intake and the duration of sick leave.Our biological dressing will meet the essential need of surgeons to “re-crop” from existing donor sites, e.g., for thermal-burn patients. By accelerating healing, improving the appearance of the scar and reducing pain, we hope to improve the conditions of treatment for skin grafts.Trial registrationClinicalTrials.gov, ID: NCT03334656. Registered on 7 November 2017.

Background: Acne vulgaris has increased in women over the past 10 years; it currently affects 20-30% of women. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, the four types of systemic treatment approved for female acne include cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks. In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits luteinizing hormone (LH) production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, very few studies have been performed in a limited number of patients: the studies showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne. In that context, it is clearly of interest to perform the first double-blind randomized study of spironolactone versus cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone's efficacy in order to establish it as an alternative to cyclines. Methods: Two hundred female patients will be included. They must have acne vulgaris with at least 10 inflammatory lesions and no more than 3 nodules. After randomization, the patients will be treated by spironolactone or doxycycline for 3 months and after placebo. The study will be blind for the first 6 months and open for the last 6 months. Discussion: The treatment frequently used in female acne is systemic antibiotics with many courses, as it is a chronic inflammatory disease. In the context of the recent World Health Organisation (WHO) revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative in the treatment of adult female acne instead of using isotretinoin, which is more complex to manage. Trial registration: ClinicalTrials.gov: NCT03334682. Registered on 7 November 2017.

e14071 Background: Machine learning methods are new artificial intelligence tools with promising applications in healthcare. We developed and validated 4 machine learning models to predict the response to immunotherapy and targeted therapy in stage IIIc or IV melanoma patients. Methods: This work was conducted on data from 10 centers participating in the French network for Research and Clinical Investigation on Melanoma (RIC-Mel), launched in 2012. Thus, 935 patients, corresponding to 1978 systemic treatments have been extracted from RIC-Mel database. The following data were considered: age, sex, Breslow, melanoma type, ulceration, spontaneous regression, mitotic index, number of invaded lymph nodes, extracapsular extension, mutational status, melanoma stage, number of metastasis sites, lines of treatments, and time between first melanoma excision and metastatic relapse. Treatment response: complete response, partial response, stable disease, defined as class 1 and progressive disease as class 2. We split this cohort/database into a training set (80%) and test set (20%). The algorithm performances were evaluated on the test set by the percentage of treatments correctly classified in class 1 or 2. Four machine learning algorithms (linear model, random forest, XGBoost and LightGBM) were compared in terms of performance and interpretation for both types of treatments. Results: The accuracies of the best models for immunotherapy (LightGBM) and targeted therapy (random forest) were respectively 66% and 65%. The most significant variables for building the models were respectively: stage (IIIc or IV), response to previous treatments lines, age, number of metastasis sites and time between first melanoma excision and metastatic relapse. Conclusions: We present here the first machine learning models to predict the response to immunotherapy and targeted therapy in stage IIIc or IV melanoma patients. The most predictive variables are coherent with the literature. Future development will include data from 18FDG-PET/CT imaging and other predictive markers recently identified, as circulating DNA to improve the models performance.

Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from metalloproteases (MMPs). It is possible that their chelating activity may help to inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) In addition, tetracyclines are modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. The lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among tetracyclines, the advantages of doxycycline are triple: its long history of safety (infrequent side effects with no notable risks), the short duration of treatment and its low cost.Methods: By estimating the rate of patients presenting pulmonary signs requiring hospitalisation in at-risk patients infected with COVID-19 at 25%, we hypothesise that on doxycycline, this rate would decrease to 12%. The main objective involves 2 embedded hypotheses tested successively in case of rejection of the previous one: (i) Decrease the rate of patients requiring hospitalisation, (ii) Decrease the use of mechanical ventilatory assistance.Discussion: This study could have an impact on the management of COVID-19 risk factor patientsupstream of hospitals by general practitioners. These patients,if kept at home under experimental treatment, would participate in reducing the risk of dissemination of SAR-CoV-2in the population.Thus, this treatment would contribute to supporting the deconfinement strategy through blocking the viral infection early and reducing the contagious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.

No abstract

Background: The DYNAMIC study is based on three properties of tetracyclines. (1) Tetracyclines are known to chelate zinc from matrix metalloproteinases. It is possible their chelating activity may help inhibit COVID-19 infection by limiting its ability to replicate in the host. (2) As seen with dengue virus, tetracyclines may also be able to inhibit the replication of positive polarity single-stranded RNA viruses, such as COVID-19. (3) Tetracyclines are also modulators of innate immunity (anti-inflammatory activity), a property that has been used to treat inflammatory skin diseases for many years. They could therefore participate in limiting the cytokine storm induced by COVID-19. Moreover, the lipophilic nature of tetracyclines and their strong pulmonary penetration could allow them to inhibit viral replication at this level. Among the tetracyclines, doxycycline has three advantages: its long safety history (side effects are uncommon with no notable risks), its short treatment duration and its low cost.Methods: The trial will involve 330 patients who are positive for SARS-CoV-2 infection and have one or more risk factors for worsening the disease. These patients will be included in six hospitals covering the whole of France. For 14 days they will be given either 200mg of doxycycline a day or a placebo. Our hypothesis is a considerable reduction in the number of patients hospitalised due to COVID-19 thanks to the treatment of doxycycline.Discussion: This study could have an impact on general practitioners’ management of COVID-19 patients with risk factors prior to hospital admission. If kept at home under experimental treatment, these patients would help reduce the risk of spreading SARS-CoV-2 among the population. This treatment would therefore contribute to supporting the deconfinement strategy by blocking the viral infection early and reducing the infectious period.Trial Registration: On ClinicalTrials.gov, registration number NCT04371952, first published on 30 April 2020.

No abstract

Background: Acne vulgaris of adult females has increased over the past 10 years; it affects currently 20 to 30% of adult females. The physiopathology of adult female acne is distinguished from that of teenagers essentially by two factors: hormonal and inflammatory. On a therapeutic plan, in female acne, four types of systemic treatment approved in this indication include: cyclines (leading to bacterial resistance); zinc salts (less effective than cyclines); and antiandrogens (risks of phlebitis). The last alternative is represented by isotretinoin, but its use in women of childbearing potential is discouraged because of the teratogen risks.In this context, spironolactone could represent an interesting alternative. It blocks the 5-alpha-reductase receptors at the sebaceous gland and inhibits LH production at the pituitary level. It has no isotretinoin constraints and does not lead to bacterial resistance. Currently, a very few studies have been performed on a limited number of patients. They showed that at low doses (lower than 200 mg/day), spironolactone can be effective against acne.In that context, it seemed clearly interesting to perform the first double-blind randomized study of spironolactone vs cyclines, which remains the moderate acne reference treatment, and to demonstrate the superiority of spironolactone’s efficacy in order to establish it as an alternative to cyclines.Methods: Two hundred female patients will be included. They will have acne vulgaris with at least ten inflammatory lesions and no more than three nodules. After randomization, the patients will be treated by spironolactone or doxycycline for three months and after placebo. The study will be blind for the first six months and open for the last six months. Discussion: The treatment frequently used in female acne is systemic antibiotics with many courses as it is a chronic inflammatory disease. In the context of the recent WHO revelation about the serious, worldwide threat to public health of antibiotic resistance, this trial could give the physician another alternative for adult female acne before using isotretinoin, whose management is more complex. Trial registration: On ClinicalTrials.gov, registration number NCT03334682, first published on 7 November, 2017. Recruitment is still ongoing.