Efficacy of Spironolactone Compared with Doxycycline in Moderate Acne in Adult Females: Results of the Multicentre, Controlled, Randomized, Double-blind Prospective and Parallel Female Acne Spironolactone vs doxyCycline Efficacy (FASCE) Study.

Acne in adult females is triggered mainly by hormones. Doxycycline is a reference treatment in acne. Spironolactone targets the androgen receptor of sebaceous glands and is prescribed off-label for female adult acne. This multicentre, controlled, randomized, double-blind prospective and parallel study assessed the efficacy of spironolactone compared with doxycycline in adult female acne. A total of 133 women with moderate acne were randomized to receive treatment with: (i) doxycycline and benzoyl peroxide for 3 months followed by a 3-month treatment with its placebo and benzoyl peroxide, or (ii) spironolactone and benzoyl peroxide for 6 months. Successfully treated patients continued with benzoyl peroxide or spironolactone alone for a further 6 months. Primary endpoints were treatment success at month 4 and month 6 with the AFAST score. At all visits, the ECLA score, lesion counts, local and systemic safety and quality of life were assessed. Spironolactone performed better at month 4 and showed a statistically significant better treatment success after 6 months than doxycycline (p = 0.007). Spironolactone was 1.37-times and 2.87-times more successful compared with doxycycline at respective time-points. AFAST and ECLA scores, as well as lesion counts always improved more with spironolactone. Patients' quality of life was better with spironolactone at month 4 and month 6. Spironolactone was very well tolerated. This is the first study to show that, in female adults with moderate acne, treatment with spironolactone is significantly more successful than doxycycline and very well tolerated.

[Can academic structures improve access to CAR-T cells?] / Les structures académiques peuvent-elles permettre une amélioration de l'accessibilité aux CAR-T cells ?

In France, hospital cell therapy units have not been authorised to routinely produce chimeric antigen receptor T lymphocytes (CAR-T cells), which would then be referred to as academic CAR-T cells. CAR-T cells are classified as advanced therapy medicinal products and correspond to genetically modified T lymphocytes ex vivo. The CAR-T cell production process is complex and requires scientific and technical expertise to meet the acceptance criteria of the pharmaceutical quality system. The most commonly used method for genetically modifying T lymphocytes is viral transduction (lentiviral or retroviral), which requires prior access to a batch of good manufacturing practice (GMP) grade viral vector. Because of its cost, this reagent is the main limiting factor for developing CAR-T cells. A CAR-T cell produced by an industrial company is expensive (around €350,000 per injection) and the time taken by the manufacturer to make it available to the clinician can vary from three to five weeks. By meeting the economic and ecological challenges, can academic structures improve access to CAR-T cells? In this article, we present the elements necessary for the feasibility of setting up CAR-T cell production in an academic structure.

Insulin Growth Factor-1 Status in Hidradenitis Suppurativa: A French Institutional Pilot Study.

BACKGROUND: Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease of the follicles in the apocrine glands and is associated with a deficiency in the innate immunity of the skin. It is characterized by the occurrence of nodules, abscesses, fistulas, scars. OBJECTIVE: Although a relationship has already been demonstrated between HS and innate immunity, IGF-1 status in patients with HS is still unknown. The objective of this pilot study was to determine IGF-1 status in patients with HS as well as its potential relationship with the clinical profile of the disease. METHODS: This monocentric and cross-sectional study involved 39 patients hospitalized at the Dermatology Department of CHU Nantes between November 2014 and January 2018. Clinical data and IGF1 status were collected during the follow-up consultation. RESULTS: Forty-nine percent of the patients had very low levels of IGF-1. At the clinical level, these patients were young and with a short duration of disease. The major difference was that IGF1-deficient patients had a higher BMI than others. The others factors differing between the two patient groups did not reach statistical significance. CONCLUSION: This exploratory pilot study indicates that HS with a low level of IGF-1 could represent a specific phenotype of patients with HS. These preliminary results have to be confirmed with a larger cohort, as they could have practical consequences in the therapeutic care of these patients.

FASCE, the benefit of spironolactone for treating acne in women: study protocol for a randomized double-blind trial.

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.

CICAFAST: comparison of a biological dressing composed of fetal fibroblasts and keratinocytes on a split-thickness skin graft donor site versus a traditional dressing: a randomized controlled trial.

BACKGROUND: Wound 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/DESIGN: We 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. DISCUSSION: This 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 REGISTRATION: ClinicalTrials.gov, ID: NCT03334656 . Registered on 7 November 2017.

[Successful completion of an ISO 9001 v 2015 certification process in clinical investigation research]. / Réussir une démarche de certification ISO 9001 v 2015 en investigation clinique.

Clinical investigation at the University Hospital of Nantes is carried out within the investigation department, which consists of coordination and 24 clinical research teams gathered at four different hospital sites. The Clinical Investigation Units are all equipped with a Quality Management System. This has been in place for more than 12 years and was initially created for the Clinical Investigation Units of the Clinical Investigation Centre (CIC 1413) in Nantes and then transposed in 2013, to the emerging Clinical Investigation Units. OBJECTIVE: In order to evaluate the performance of this quality approach applied to all UHC investigations, the Investigation Department is committed to obtaining an ISO 9001:2015 certification. METHODS: The quality division of the investigation department conducted the project according to a methodology, based on internal and external evaluations to determine an inventory and the retro-planning of the certification approach. RESULTS: The scope of the certification involved the investigation department of the University Hospital: 24 clinical investigation units, over 500 medical staff, 150 non-medical staff. In our certification approach, the client was the promoter of the clinical study. The process lasted 18 months and included phases of training and awareness-raising for all the staff involved. The quality management system of the investigation department has been revised and improved in accordance with current regulations. The Investigation Department obtained the ISO 9001:2015 certification for all clinical investigations at the Nantes University Hospital in June 2017 without any non-compliance. CONCLUSION: Our work shows that the investigation department has successfully adapted the ISO 9001:2015 standard to institutional clinical research. The certification for specific activities in clinical investigation is the guarantee of an optimized and relevant organization for the safety of volunteers, participating in clinical research as well as the scientific quality of the research and contributes to the satisfaction of sponsors.

Foetal skin cells in wound healing: a promising tool for clinical application.

The skin is the first protective barrier of our body. Wound healing is therefore an essential mechanism. However, this phenomenon can be impaired when wounds are too large or chronic, for example, in diabetes. Interestingly, adult skin heals with scars, whereas foetuses present scarless regeneration. The objective of this review is to highlight the difference in healing pathways between foetal and adult skin and to present the recent therapeutic strategies envisaged using foetal properties in the clinic. The main features that distinguish foetal wound healing from adult wound healing are less tissue inflammation, faster reepithelialisation, and less contraction of the neodermis, allowing foetal tissues to regenerate. Recently, new therapies in regenerative medicine have been introduced using these foetal properties. For the first time, our team has developed CICAFAST, an innovative dressing composed of foetal keratinocytes and fibroblasts, which has been tested on a skin graft donor site in a clinical Phase 1/2 trial.